The date of this prospectus is                        , 2017.2018.

Table of Contents

TABLE OF CONTENTS

Table of Contents

ABOUT THIS PROSPECTUS

        This prospectus is part of a registration statement that we have filed with the Securities and Exchange Commission (the "SEC") pursuant to which the selling stockholders named herein may, from time to time, offer and sell or SEC, utilizing a "shelf" registration process. Under this shelf registration process, we may offerotherwise dispose of the shares of our common stock and preferred stock, various series of debt securities and/or warrants, rights or purchase contracts to purchase any of such securities, either individually orcovered by this prospectus. You should not assume that the information contained in units, in one or more offerings, with a total value of up to $175,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we offer a type or series of securities under this prospectus we will provide a prospectus supplement that will contain specific information about the terms of that offering.

        This prospectus does not contain all of the information included in the registration statement. For a more complete understanding of the offering of the securities, you should referis accurate on any date subsequent to the registration statement, including its exhibits. Thedate set forth on the front cover of this prospectus supplement may also add, update or changethat any information contained orwe have incorporated by reference inis correct on any date subsequent to the date of the document incorporated by reference, even though this prospectus. However, no prospectus supplement will offeris delivered or shares of common stock are sold or otherwise disposed of on a security thatlater date. It is not registeredimportant for you to read and describedconsider all information contained in this prospectus, at the time of its effectiveness. This prospectus, together with the applicable prospectus supplements andincluding the documents incorporated by reference into this prospectus, includes all material information relating to the offering of securities under this prospectus.therein, in making your investment decision. You should carefullyalso read this prospectus, the applicable prospectus supplement,and consider the information andin the documents incorporated herein by reference and the additional informationto which we have referred you under the headingcaptions "Where You Can Find MoreAdditional Information" before making an investment decision.

        You should rely only on the information we have provided or incorporatedand "Information Incorporated by referenceReference" in this prospectus or any prospectus supplement.prospectus.

        We have not authorized anyone to provide you with information different from that contained or incorporated by reference in this prospectus. Noany dealer, salespersonsalesman or other person is authorized to give any information or to represent anything notmake any representation other than those contained or incorporated by reference in this prospectus. You must not rely onupon any unauthorized information or representation.representation not contained or incorporated by reference in this prospectus. This prospectus isdoes not constitute an offer to sell onlyor the solicitation of an offer to buy any of our shares of common stock other than the shares of our common stock covered hereby, nor does this prospectus constitute an offer to sell or the solicitation of an offer to buy any securities in any jurisdiction to any person to whom it is unlawful to make such offer or solicitation in such jurisdiction. Persons who come into possession of this prospectus in jurisdictions outside the United States are required to inform themselves about, and to observe, any restrictions as to the offering and the distribution of this prospectus applicable to those jurisdictions.

        Unless we have indicated otherwise, or the context otherwise requires, references in this prospectus supplement and the accompanying prospectus to "OvaScience," the "Company," "we," "us" and "our" refer to OvaScience, Inc. and its subsidiaries.

Table of Contents

INFORMATION INCORPORATED BY REFERENCE

        We are allowed to incorporate by reference information contained in documents that we file with the SEC. This means that we can disclose important information to you by referring you to those documents and that the information in this prospectus is not complete and you should read the information incorporated by reference for more detail. Information in this prospectus supersedes information incorporated by reference that we filed with the Commission prior to the date of this prospectus, while information that we file later with the SEC will automatically update and supersede the information in this prospectus.

        We incorporate by reference the documents listed below and any future filings we will make with the SEC under Section 13(a), 13(c), 14 or 15(d) of the Exchange Act (i) after the date of the initial filing of the registration statement of which this prospectus is a part and prior to effectiveness of such registration statement, and (ii) from the date of this prospectus but prior to the termination of the offering of the securities offered hereby,covered by this prospectus (other than Current Reports or portions thereof furnished under Item 2.02 or 7.01 of Form 8-K):

•

Our proxy statement filed on Schedule 14A dated November 5, 2018 in connection with the Company's special meeting of stockholders;



•

The supplement to our proxy statement filed on Schedule 14A dated November 19, 2018 in connection with the Company's special meeting of stockholders;



•

Our Annual Report on Form 10-K for the fiscal year ended December 31, 2017;



•

Our proxy statement on Schedule 14A filed on April 30, 2018 in connection with the Company's annual meeting of stockholders;



•

Our Quarterly Reports on Form 10-Q for the quarters ended March 31, 2018, June 30, 2018 and September 30, 2018;



•

Our Current Reports on Form 8-K and 8-K/A filed with the SEC on January 3, 2018, January 8, 2018, February 1, 2018, March 15, 2018, May 3, 2018, June 26, 2018, August 9, 2018, November 1, 2018, November 19, 2018 and November 26, 2018 (other than any portions thereof deemed furnished and not filed); and



•

The description of our common stock set forth in the registration statement on Form 8-A registering our common stock under Section 12 of the Exchange Act, which was filed with the Commission on April 25, 2013, including any amendments or reports filed for purposes of updating such description.

        We will provide to each person, including any beneficial owner, to whom a prospectus is delivered, a copy of any or all of the information that is incorporated by reference in this prospectus but only under circumstances andnot delivered with this prospectus, including exhibits that are specifically incorporated by reference in jurisdictions where it is lawfulsuch documents. You may request a copy of such documents, which will be provided to do so.you at no cost, by writing or telephoning us at the following address or telephone number:

OvaScience, Inc.
9 Fourth Avenue
Waltham, MA 02451
(617) 500-2802
Attn: Jonathan Gillis

        You should rely only on the information incorporated by reference or provided in this prospectus. We have not authorized anyone to provide you with different information. You should not assume that the information in this prospectus or any prospectus supplement is accurate only as of any date other than the date on the front of this document. Any statement contained in a document incorporated in this prospectus will be deemed to

Table of Contents

be modified or superseded for purposes of this prospectus to the documentextent that a statement contained in this prospectus modifies or supersedes that statement. Any statement that is modified or superseded will not constitute a part of this prospectus, except as modified or superseded.

        Copies of the documents incorporated by reference may also be found on our website at www.ovascience.com. Except with respect to the documents expressly incorporated by reference above which are accessible at our website, the information contained on our website is not a part of, and that anyshould not be construed as being incorporated by reference into, this prospectus.

        The information we have incorporated herein by reference includes information about Millendo. Following the Effective Time, the business of Millendo will continue as the business of the combined organization. Additionally, it has been determined that Millendo will be the accounting acquirer in the Merger, based upon the terms of the Merger Agreement and other factors including: (i) holders of Millendo stock and other persons holding securities convertible, exercisable or exchangeable directly or indirectly for Millendo Common Stock were initially estimated to own at least 82% of OvaScience immediately following the Effective Time, (ii) Millendo will hold the majority (seven of eight) of board seats of the combined company and (iii) Millendo's management will hold all key positions in the management of the combined company. Because of these factors, OvaScience has incorporated by reference to information about the Millendo business and operations into this prospectus.

Table of Contents

Table of Contents

Table of Contents

Table of Contents

DESCRIPTION OF THE MERGER

        On August 9, 2018, OvaScience announced that it had entered into an Agreement and Plan of Merger and Reorganization, as may be amended from time to time (the "Merger Agreement") with Millendo under which Millendo will merge with OvaScience in an all-stock transaction (the "Merger"). If the Merger is completed, a wholly owned subsidiary of OvaScience ("Merger Sub") will merge with and into Millendo, with Millendo surviving as a wholly owned subsidiary of OvaScience. In connection with the Merger, holders of OvaScience stock have been asked to approve an amendment to OvaScience's restated certificate of incorporation effecting a reverse stock split of OvaScience Common Stock at a ratio mutually agreed to between OvaScience and Millendo in the range of one new share for every 5 to 15 shares outstanding (the "Reverse Stock Split").

        Immediately prior to closing of the Merger (the "Effective Time"), each share of Millendo preferred stock and Millendo class-1 common stock will be converted into Millendo Common Stock. At the Effective Time, each share of Millendo's common stock, par value $0.001 per share ("Millendo Common Stock") outstanding immediately prior to the Effective Time (excluding shares held by stockholders who have exercised and perfected appraisal rights or dissenters' rights, but including shares of Millendo Common Stock that will be issued pursuant to certain existing Millendo shareholders in a pre-closing private placement of Millendo Common Stock (the "Pre-Closing Financing")) will be converted into the right to receive a number of shares of OvaScience Common Stock based on an exchange ratio set forth in the Merger Agreement (the "Exchange Ratio"). OvaScience will assume all outstanding and unexercised options to purchase shares of Millendo Common Stock (each, a "Millendo Option," and each holder of a Millendo Option, a "Millendo Optionholder") and warrants to purchase Millendo Common Stock, and each such Millendo Options and warrants will be converted into an option or warrant, respectively, to purchase shares of OvaScience Common Stock, with the number of shares of OvaScience Common Stock subject to such option or warrant and the exercise price being appropriately adjusted to reflect the Exchange Ratio.

        The final Exchange Ratio will be determined pursuant to a formula described in more detail in the Merger Agreement. As of the date of the documentexecution of the Merger Agreement, it was estimated that immediately after the consummation of the Merger, based solely on the sample Exchange Ratio of 0.1173 set forth below, holders of shares of Millendo Common Stock, Millendo Optionholders and other persons holding securities and rights directly or indirectly convertible, exercisable or exchangeable for Millendo Common Stock (collectively, "Millendo Securityholders") would own approximately 82% of Fully Diluted Closing OvaScience Common Stock, and holders of shares of OvaScience Common Stock, holders of options to purchase shares of OvaScience Common Stock and other persons holding securities and rights directly or indirectly convertible, exercisable or exchangeable for OvaScience Common Stock (collectively, "OvaScience Securityholders") would own approximately 18% of Fully Diluted Closing OvaScience Common Stock (as defined below), subject to adjustment of the Exchange Ratio as set forth in the Merger Agreement.

        The percentages set forth above assume that the initial estimate of the Exchange Ratio is not changed; however, the Exchange Ratio is subject to change as set forth in the Merger Agreement. The initial estimate of the Exchange Ratio set forth below assumed (i) that OvaScience would have between $40 million and $42 million in net cash immediately prior to Closing, (ii) a Pre-Closing Financing amount of $30.0 million, (iii) OvaScience outstanding shares and options as of the Closing would be equal to 3,721,460 (on a post reverse stock split basis), (iv) Millendo shares as of the Closing would be equal to 148,171,273 (on a fully-diluted, as-converted basis) and (v) a reverse stock split of every 10 shares of outstanding OvaScience Common Stock being combined and reclassified into one share of OvaScience Common Stock.

        The Exchange Ratio is calculated using a formula intended to allocate a percentage of the combined organization to existing Millendo Securityholders. Based on the assumptions described above,

Table of Contents

the Exchange Ratio would have been equal to approximately 0.1173 post-reverse split shares of OvaScience Common Stock for each share of Millendo Common Stock, which Exchange Ratio is subject to change based on the amount of OvaScience net cash, changes in the capitalization of OvaScience or Millendo prior to the Closing and the amount raised by Millendo in the Pre-Closing Financing (and as a result, OvaScience Securityholders and Millendo Securityholders could own more or less of the combined organization). After the initial signing of the Merger Agreement, the valuations for Millendo and OvaScience were reduced.

        OvaScience currently estimates that, assuming for this purpose a closing date of November 30, 2018, (i) it will have approximately $37.6 million in net cash immediately prior to Closing, (ii) the Pre-Closing Financing amount will be approximately $29.5 million, (iii) OvaScience outstanding shares and options as of the Closing will be equal to 3,727,669 (on a post reverse stock split basis) and (iv) the Millendo shares as of the Closing on a fully diluted and as-converted basis will be equal to 152,629,595. Accordingly, it is currently estimated that the Exchange Ratio at Closing will be approximately 0.1070 and, based solely on such Exchange Ratio, at Closing: (a) Millendo Securityholders as of immediately prior to the Merger (not including the shares issued in the Pre-Closing Financing) will own approximately 67.1% of the Fully Diluted Closing OvaScience Common Stock (as defined below), (b) the shares issued in the Pre-Closing Financing to Millendo Securityholders as of immediately prior to the Merger will represent approximately 13.1% of the Fully Diluted Closing OvaScience Common Stock, (c) the OvaScience Securityholders as of immediately prior to the Merger (excluding for this purpose certain out-of-the-money OvaScience Options) will own approximately 18.6% of the Fully Diluted Closing OvaScience Common Stock, and (d) the shares available for issuance under the Millendo Plan as of immediately prior to the Merger will represent approximately 1.2% of the Fully Diluted Closing OvaScience Common Stock, in each case, subject to adjustment of the Exchange Ratio as set forth in the Merger Agreement and described herein. Additionally, it is anticipated that the Post-Closing Financing (as defined below) will close shortly after the Closing, which would dilute, and thereby reduce, each then existing OvaScience Securityholder's proportionate holdings. Assuming that the Post-Closing Financing closes immediately after the Merger as well as the other aforementioned assumptions, it is expected that (a) Millendo Securityholders as of immediately prior to the Merger (not including the shares issued in the Pre-Closing Financing) will own approximately 61.7% of the Fully Diluted Post-Financing OvaScience Common Stock (as defined below), (b) the shares issued in the Pre-Closing Financing to Millendo Securityholders as of immediately prior to the Merger will represent approximately 12.0% of the Fully Diluted Post-Financing OvaScience Common Stock, (c) the OvaScience Securityholders as of immediately prior to the Merger (excluding for this purpose certain out-of-the-money OvaScience Options) will own approximately 17.1% of the Fully Diluted Post-Financing OvaScience Common Stock, (d) the shares issued in the Post-Closing Financing to the Post-Closing Financing Investor (as defined below) will represent approximately 8.1% of the Fully Diluted Post-Financing OvaScience Common Stock, and (e) the shares available for issuance under the Millendo Plan as of immediately prior to the Merger will represent approximately 1.1% of the Fully Diluted Post-Financing OvaScience Common Stock, in each case, subject to adjustment of the Exchange Ratio as set forth in the Merger Agreement and described herein. "Fully Diluted Closing OvaScience Common Stock" as used herein means (x) Orion Outstanding Shares (as defined in the Merger Agreement, which figure excludes the shares available for issuance under the 2012 Plan and a portion of the out-of-the-money OvaScience Options) plus (y) Company Outstanding Shares (as defined in the Merger Agreement, which figure includes the shares available for issuance under the Millendo Plan). "Fully Diluted Post-Financing OvaScience Common Stock" as used herein means (x) Orion Outstanding Shares (as defined in the Merger Agreement, which figure excludes the shares available for issuance under the 2012 Plan and a portion of the out-of-the-money OvaScience Options) plus (y) Company Outstanding Shares (as defined in the Merger Agreement, which figure includes the shares available for issuance under the Millendo Plan) plus (z) the Post-Closing Financing shares.

Table of Contents

        The Closing will occur no later than the second business day after the last of the conditions to the Merger has been satisfied, or at such other time as OvaScience and Millendo agree. OvaScience and Millendo anticipate that the consummation of the Merger will occur in the fourth quarter of 2018. However, because the Merger is subject to a number of conditions, neither OvaScience nor Millendo can predict exactly when the Closing will occur or if it will occur at all. After completion of the Merger, assuming that OvaScience receives the required stockholder approval of its proposal to change the name of the company, OvaScience will be renamed "Millendo Therapeutics, Inc."

        On September 25, 2018, OvaScience and Millendo entered into the First Amendment to the Merger Agreement (the "First Amendment"). The First Amendment provides, among other things, that shares of OvaScience Common Stock to be issued in exchange for shares of Millendo Common Stock to be issued in the Pre-Closing Financing would not be registered pursuant to the Registration Statement on Form S-4, originally filed by OvaScience on September 26, 2018. The First Amendment also increased the size of the board of directors of the combined company by one seat. Further, it provides, among other things, that shares of OvaScience Common Stock to be issued in exchange for shares of Millendo Common Stock to be issued to certain of the investors in the Pre-Closing Financing that were not previously stockholders of Millendo would be registered pursuant to a separate resale registration statement on Form S-3.

        On November 1, 2018, OvaScience and Millendo entered into the Second Amendment to the Merger Agreement (the "Second Amendment"). The Second Amendment was proposed by Millendo in order to lower Millendo's valuation from $191.9 million to $155.0 million in connection with the Post-Closing Financing. The Second Amendment provides that as a result of the reduction in Millendo's valuation, the Pre-Closing Financing, including the conversion of any convertible promissory notes issued after the date of the Second Amendment, would be consummated at a price per share for Millendo Common Stock of not less than $1.2096. The Second Amendment also provides that Millendo's Valuation would equal the sum of $155 million plus any proceeds received in the Pre-Closing Financing, and that OvaScience's Valuation would be lowered to $45.5 million, subject to certain adjustments set forth in the Merger Agreement. The Second Amendment additionally (i) provides that the definition of Millendo outstanding shares used for purposes of the exchange ratio shall include shares of Millendo Common Stock available for issuance under its stock option plans, (ii) provides for an adjustment to the Company's net cash in connection with certain litigation matters, and (iii) revises the definition of the Company's outstanding lease obligations with respect to its principal office space. It also revises certain representations and warranties being made by Millendo.

        The description of the Merger Agreement is not complete and is qualified in its entirety by reference to Merger Agreement, which has been filed as an annex to our proxy statement on Schedule 14A, filed with the SEC on November 5, 2018 and which is incorporated by reference regardless of the time of delivery of this prospectus or any sale of a security.

        We further note that theherein. See "Where You Can Find Additional Information" and "Information Incorporated by Reference." The representations, warranties and covenants made by us in any agreement that is filed as an exhibit to any document that is incorporated by reference in the accompanying prospectusMerger Agreement were made solely for the benefit of the parties to such agreement, including, in some cases, for the purpose of allocating risk among the parties to such agreements,thereto, and should not be deemed to be a representation, warranty or covenant to you. Moreover, such representations, warranties or covenants were accurate onlymade as of the date when made.an earlier date. Accordingly, such representations, warranties and covenants should not be relied on as accurately representing the current state of our affairs.

        This prospectus may not be used to consummate sales of our securities, unless it is accompanied by a prospectus supplement. To the extent there are inconsistencies between any prospectus supplement, this prospectus and any documents incorporated by reference, the document with the most recent date will control.

        Unless the context otherwise requires, "OvaScience," "OVAS," "the Company," "we," "us," "our" and similar terms refer to OvaScience, Inc. and our subsidiaries.

Table of Contents

Table of Contents

Table of Contents

RISK FACTORS

        Investing in our securities involves significant risk. The prospectus supplement applicable to each offering of our securities will contain a discussion of the risks applicable to an investment in OvaScience. Prior to making a decision about investing in our securities, you should carefully consider the specific factors discussed under the heading "Risk Factors" in the applicable prospectus supplement, together with all of the other information contained or incorporated by reference in the prospectus supplement or appearing or incorporated by reference in this prospectus. You should also consider the risks, uncertainties and assumptions discussed under the heading "Risk Factors" included in our most recent annual report on Form 10-K, as revised or supplemented by our subsequent quarterly reports on Form 10-Q or our current reports on Form 8-K that we have filed with the SEC, all of which are incorporated herein by reference, and which may be amended, supplemented or superseded from time to time by other reports we file with the SEC in the future. The risks and uncertainties we have described are not the only ones we face. Additional risks and uncertainties not presently known to us or that we currently deem immaterial may also affect our operations. The occurrence of any of these risks might cause you to lose all or part of your investment in the offered securities.

RATIO OF EARNINGS TO FIXED CHARGES

        Any time debt securities are offered pursuant to this prospectus, we will provide a table setting forth our ratio of earnings to fixed charges on a historical basis in the applicable prospectus supplement, if required.

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

        This prospectus and the documents incorporated by reference in this prospectus include forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. Words such as, but not limited to, "believe," "expect," "anticipate," "estimate," "intend," "may," "plan," "potential," "predict," "project," "targets," "likely," "will," "would," "could," "should," "continue," and similar expressions or phrases, or the negative of those expressions or phrases, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Although we believe that we have a reasonable basis for each forward-looking statement contained in this prospectus and incorporated by reference in this prospectus, we caution you that these statements are based on our projections of the future that are subject to known and unknown risks and uncertainties and other factors that may cause our actual results, level of activity, performance or achievements expressed or implied by these forward-looking statements, to differ. The sections in our periodic reports, including our Annual Report on Form 10-K for the fiscal year ended December 31, 2016, entitled "Business," "Risk Factors," and "Management's Discussion and Analysis of Financial Condition and Results of Operations," as well as other sections in this prospectus and the documents or reports incorporated by reference in this prospectus, discuss some of the factors that could contribute to these differences. These forward-looking statements include, among other things, statements about:

•

the risks implicit in the development process of preparing bovine and human eggs for fertilization;



•

regulatory risks associated with obtaining authorization to fertilize human EggPC^SM cells for research;

Table of Contents

•

the possibility that internationalin vitro fertilization ("IVF") clinics that we work with may determine not to provide or continue providing the AUGMENT treatment or OvaPrime treatment, or to delay providing such treatments, or to limit the population of patients receiving the treatments based on clinical efficacy, safety or commercial, logistic, economic, available data, regulatory or other reasons;



•

challenges associated with enrolling and completing clinical trials, the science underlying our treatments (including the AUGMENT, OvaPrime and OvaTure treatments), which is unproven;



•

scientific and regulatory challenges associated with characterizing and fertilizing an EggPC cell-derived egg;



•

our ability to obtain regulatory approval or licenses where necessary for our treatments;



•

our ability to develop our treatments on the timelines we expect, if at all;



•

our ability to commercialize our treatments on the timelines we expect, if at all;



•

our expectation that the AUGMENT treatment and OvaPrime treatment are exempt from premarket review and approval applicable to drugs, biologics, medicinal products and medical devices under applicable regulations in those countries where we have introduced or plan to introduce the AUGMENT treatment or the OvaPrime treatment;



•

our plans to develop further clinical evidence for the AUGMENT treatment and the OvaPrime treatment;



•

our anticipated timing of announcing results from studies or trials;



•

the science underlying our treatment and treatments in development (including the AUGMENT, OvaPrime and OvaTure treatments), which is unproven;



•

our ability to obtain regulatory approval or licenses where necessary for our potential treatments;



•

the size and growth of the market for our fertility treatments and our ability to serve those markets;



•

the rate and degree of market acceptance of any future fertility treatments that we develop;



•

our ability to adjust our operations to manage our organizational changes and comply with applicable securities laws and regulations;



•

our ability to obtain additional financing;



•

the accuracy of our estimates regarding expenses, future revenues, capital requirements and the need for additional financing; and



•

our ability to attract and retain key scientific or management personnel.

        We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. We have included important cautionary statements in this prospectus or in the documents incorporated by reference in this prospectus, particularly in the "Risk Factors" section, that we believe could cause actual results or events to differ materially from the forward-looking statements that we make. For a summary of such factors, please refer to the section entitled "Risk Factors" in this prospectus, as updated and supplemented by the discussion of risks and uncertainties under "Risk Factors" contained in any supplements to this prospectus and in our most recent annual report on Form 10-K, as revised or supplemented by our subsequent quarterly reports on Form 10-Q or

Table of Contents

our current reports on Form 8-K, as well as any amendments thereto, as filed with the SEC and which are incorporated herein by reference. The information contained in this document is believed to be current as of the date of this document. We do not intend to update any of the forward-looking statements after the date of this document to conform these statements to actual results or to changes in our expectations, except as required by law.

        In light of these assumptions, risks and uncertainties, the results and events discussed in the forward-looking statements contained in this prospectus or in any document incorporated herein by reference might not occur. Investors are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this prospectus or the date of the document incorporated by reference in this prospectus. We are not under any obligation, and we expressly disclaim any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise. All subsequent forward-looking statements attributable to us or to any person acting on our behalf are expressly qualified in their entirety by the cautionary statements contained or referred to in this section.

USE OF PROCEEDS

        Unless otherwise indicated in the applicable prospectus supplement, we intend to use any net proceeds from the sale of securities under this prospectus to fund activities relating to the development and commercialization of our fertility treatments, and for other general corporate purposes, including, but not limited to, working capital, capital expenditures, investments, acquisitions, should we choose to pursue any, and collaborations. We have not determined the amounts we plan to spend on any of the areas listed above or the timing of these expenditures. As a result, our management will have broad discretion to allocate the net proceeds, if any, we receive in connection with securities offered pursuant to this prospectus for any purpose. Pending application of the net proceeds as described above, we may initially invest the net proceeds in short-term, investment-grade, interest-bearing securities or apply them to the reduction of short-term indebtedness.

PLAN OF DISTRIBUTION

        We may offer securities under this prospectus from time to time pursuant to underwritten public offerings, negotiated transactions, block trades or a combination of these methods. We may sell the securities (1) through underwriters or dealers, (2) through agents or (3) directly to one or more purchasers, or through a combination of such methods. We may distribute the securities from time to time in one or more transactions at:

•

a fixed price or prices, which may be changed from time to time;



•

market prices prevailing at the time of sale;



•

prices related to the prevailing market prices; or



•

negotiated prices.

        We may directly solicit offers to purchase the securities being offered by this prospectus. We may also designate agents to solicit offers to purchase the securities from time to time, and may enter into arrangements for "at-the-market," equity line or similar transactions. We will name in a prospectus supplement any underwriter or agent involved in the offer or sale of the securities.

        If we utilize a dealer in the sale of the securities being offered by this prospectus, we will sell the securities to the dealer, as principal. The dealer may then resell the securities to the public at varying prices to be determined by the dealer at the time of resale.

        If we utilize an underwriter in the sale of the securities being offered by this prospectus, we will execute an underwriting agreement with the underwriter at the time of sale, and we will provide the

Table of Contents

name of any underwriter in the prospectus supplement which the underwriter will use to make resales of the securities to the public. In connection with the sale of the securities, we, or the purchasers of the securities for whom the underwriter may act as agent, may compensate the underwriter in the form of underwriting discounts or commissions. The underwriter may sell the securities to or through dealers, and the underwriter may compensate those dealers in the form of discounts, concessions or commissions.

        With respect to underwritten public offerings, negotiated transactions and block trades, we will provide in the applicable prospectus supplement information regarding any compensation we pay to underwriters, dealers or agents in connection with the offering of the securities, and any discounts, concessions or commissions allowed by underwriters to participating dealers. Underwriters, dealers and agents participating in the distribution of the securities may be deemed to be underwriters within the meaning of the Securities Act, and any discounts and commissions received by them and any profit realized by them on resale of the securities may be deemed to be underwriting discounts and commissions. We may enter into agreements to indemnify underwriters, dealers and agents against civil liabilities, including liabilities under the Securities Act, or to contribute to payments they may be required to make in respect thereof.

        If so indicated in the applicable prospectus supplement, we will authorize underwriters, dealers or other persons acting as our agents to solicit offers by certain institutions to purchase securities from us pursuant to delayed delivery contracts providing for payment and delivery on the date stated in each applicable prospectus supplement. Each contract will be for an amount not less than, and the aggregate amount of securities sold pursuant to such contracts shall not be less nor more than, the respective amounts stated in each applicable prospectus supplement. Institutions with whom the contracts, when authorized, may be made include commercial and savings banks, insurance companies, pension funds, investment companies, educational and charitable institutions and other institutions, but shall in all cases be subject to our approval. Delayed delivery contracts will not be subject to any conditions except that:

•

the purchase by an institution of the securities covered under that contract shall not at the time of delivery be prohibited under the laws of the jurisdiction to which that institution is subject; and



•

if the securities are also being sold to underwriters acting as principals for their own account, the underwriters shall have purchased such securities not sold for delayed delivery. The underwriters and other persons acting as our agents will not have any responsibility in respect of the validity or performance of delayed delivery contracts.

        One or more firms, referred to as "remarketing firms," may also offer or sell the securities, if a prospectus supplement so indicates, in connection with a remarketing arrangement upon their purchase. Remarketing firms will act as principals for their own accounts or as our agents. These remarketing firms will offer or sell the securities in accordance with the terms of the securities. Each prospectus supplement will identify and describe any remarketing firm and the terms of its agreement, if any, with us and will describe the remarketing firm's compensation. Remarketing firms may be deemed to be underwriters in connection with the securities they remarket. Remarketing firms may be entitled under agreements that may be entered into with us to indemnification by us against certain civil liabilities, including liabilities under the Securities Act, and may be customers of, engage in transactions with or perform services for us in the ordinary course of business.

        Certain underwriters may use this prospectus and any accompanying prospectus supplement for offers and sales related to market-making transactions in the securities. These underwriters may act as principal or agent in these transactions, and the sales will be made at prices related to prevailing market prices at the time of sale. Any underwriters involved in the sale of the securities may qualify as "underwriters" within the meaning of Section 2(a)(11) of the Securities Act. In addition, the

Table of Contents

underwriters' commissions, discounts or concessions may qualify as underwriters' compensation under the Securities Act and the rules of the Financial Industry Regulatory Authority, Inc., or FINRA.

        Shares of our common stock sold pursuant to the registration statement of which this prospectus is a part will be authorized for listing and trading on The NASDAQ Global Market. The applicable prospectus supplement will contain information, where applicable, as to any other listing, if any, on The NASDAQ Global Market or any securities market or other securities exchange of the securities covered by the prospectus supplement. Underwriters may make a market in our common stock, but will not be obligated to do so and may discontinue any market making at any time without notice. We can make no assurance as to the liquidity of or the existence, development or maintenance of trading markets for any of the securities.

        In order to facilitate the offering of the securities, certain persons participating in the offering may engage in transactions that stabilize, maintain or otherwise affect the price of the securities. This may include over-allotments or short sales of the securities, which involve the sale by persons participating in the offering of more securities than we sold to them. In these circumstances, these persons would cover such over-allotments or short positions by making purchases in the open market or by exercising their over-allotment option. In addition, these persons may stabilize or maintain the price of the securities by bidding for or purchasing the applicable security in the open market or by imposing penalty bids, whereby selling concessions allowed to dealers participating in the offering may be reclaimed if the securities sold by them are repurchased in connection with stabilization transactions. The effect of these transactions may be to stabilize or maintain the market price of the securities at a level above that which might otherwise prevail in the open market. These transactions may be discontinued at any time.

        The underwriters, dealers and agents may engage in other transactions with us, or perform other services for us, in the ordinary course of their business.

DESCRIPTION OF COMMON STOCK

        We are authorized to issue 100,000,000 shares of common stock, par value $0.001 per share. As of February 27, 2017, we had 35,641,505 shares of common stock outstanding and approximately 80 stockholders of record.

        The following summary of certain provisions of our common stock does not purport to be complete. You should refer to the section of this prospectus entitled "Certain Provisions of Delaware Law and of the Company's Certificate of Incorporation and Bylaws" and our restated certificate of incorporation and our amended and restated bylaws, both of which are included as exhibits to the registration statement of which this prospectus is a part. The summary below is also qualified by provisions of applicable law.

General

        Holders of our common stock are entitled to one vote for each share held on all matters submitted to a vote of stockholders and do not have cumulative voting rights. An election of directors by our stockholders shall be determined by a plurality of the votes cast by the stockholders entitled to vote on the election. Holders of common stock are entitled to receive proportionately any dividends as may be declared by our board of directors, subject to any preferential dividend rights of any series of preferred stock that we may designate and issue in the future. All shares of common stock outstanding as of the date of this prospectus and, upon issuance and sale, all shares of common stock that we may offer pursuant to this prospectus, will be fully paid and nonassessable.

        In the event of our liquidation or dissolution, the holders of common stock are entitled to receive proportionately our net assets available for distribution to stockholders after the payment of all debts

Table of Contents

and other liabilities and subject to the prior rights of any outstanding preferred stock. Holders of common stock have no preemptive, subscription, redemption or conversion rights. There are no redemption or sinking fund provisions applicable to the common stock. Our outstanding shares of common stock are validly issued, fully paid and nonassessable. The rights, preferences and privileges of holders of common stock are subject to and may be adversely affected by the rights of the holders of shares of any series of preferred stock that we may designate and issue in the future.

Transfer Agent and Registrar

        The transfer agent and registrar for our common stock is Computershare Trust Company, N.A., with offices at 250 Royall Street, Canton, Massachusetts 02021.

Stock Exchange Listing

        Our common stock is listed for quotation on The NASDAQ Global Market under the symbol "OVAS."

DESCRIPTION OF PREFERRED STOCK

        We are authorized to issue 5,000,000 shares of preferred stock, par value $0.001 per share. As of the date of this prospectus, no shares of our preferred stock were outstanding or designated. The following summary of certain provisions of our preferred stock does not purport to be complete. You should refer to our restated certificate of incorporation and our amended and restated bylaws, both of which are included as exhibits to the registration statement of which this prospectus is a part. The summary below is also qualified by provisions of applicable law.

General

        Our board of directors may, without further action by our stockholders, from time to time, direct the issuance of shares of preferred stock in series and may, at the time of issuance, determine the rights, preferences and limitations of each series, including voting rights, dividend rights and redemption and liquidation preferences. Satisfaction of any dividend preferences of outstanding shares of preferred stock would reduce the amount of funds available for the payment of dividends on shares of our common stock. Holders of shares of preferred stock may be entitled to receive a preference payment in the event of any liquidation, dissolution or winding-up of our company before any payment is made to the holders of shares of our common stock. In some circumstances, the issuance of shares of preferred stock may render more difficult or tend to discourage a merger, tender offer or proxy contest, the assumption of control by a holder of a large block of our securities or the removal of incumbent management. Upon the affirmative vote of our board of directors, without stockholder approval, we may issue shares of preferred stock with voting and conversion rights which could adversely affect the holders of shares of our common stock.

        If we offer a specific series of preferred stock under this prospectus, we will describe the terms of the preferred stock in the prospectus supplement for such offering and will file a copy of the restated certificate establishing the terms of the preferred stock with the SEC. To the extent required, this description will include:

•

the title and stated value;



•

the number of shares offered, the liquidation preference, if any, per share and the purchase price;



•

the dividend rate(s), period(s) and/or payment date(s), or method(s) of calculation for such dividends;

Table of Contents

•

whether dividends will be cumulative or non-cumulative and, if cumulative, the date from which dividends will accumulate;



•

the procedures for any auction and remarketing, if any;



•

the provisions for a sinking fund, if any;



•

the provisions for redemption, if applicable;



•

any listing of the preferred stock on any securities exchange or market;



•

whether the preferred stock will be convertible into our common stock, and, if applicable, the conversion price (or how it will be calculated) and conversion period;



•

whether the preferred stock will be exchangeable into debt securities, and, if applicable, the exchange price (or how it will be calculated) and exchange period;



•

voting rights, if any, of the preferred stock;



•

a discussion of any material and/or special U.S. federal income tax considerations applicable to the preferred stock;



•

the relative ranking and preferences of the preferred stock as to dividend rights and rights upon liquidation, dissolution or winding up of the affairs of the Company; and



•

any material limitations on issuance of any class or series of preferred stock ranking pari passu with or senior to the series of preferred stock as to dividend rights and rights upon liquidation, dissolution or winding up of the Company.

Transfer Agent and Registrar

        The transfer agent and registrar for our preferred stock will be set forth in the applicable prospectus supplement.

DESCRIPTION OF DEBT SECURITIES

        The following description, together with the additional information we include in any applicable prospectus supplements, summarizes the material terms and provisions of the debt securities that we may offer under this prospectus. While the terms we have summarized below will apply generally to any future debt securities we may offer pursuant to this prospectus, we will describe the particular terms of any debt securities that we may offer in more detail in the applicable prospectus supplement. If we so indicate in a prospectus supplement, the terms of any debt securities offered under such prospectus supplement may differ from the terms we describe below, and to the extent the terms set forth in a prospectus supplement differ from the terms described below, the terms set forth in the prospectus supplement shall control.

        We may sell from time to time, in one or more offerings under this prospectus, debt securities, which may be senior or subordinated. We will issue any such senior debt securities under a senior indenture that we will enter into with a trustee to be named in the senior indenture. We will issue any such subordinated debt securities under a subordinated indenture, which we will enter into with a trustee to be named in the subordinated indenture. We have filed forms of these documents as exhibits to the registration statement, of which this prospectus is a part. We use the term "indentures" to refer to either the senior indenture or the subordinated indenture, as applicable. The indentures will be qualified under the Trust Indenture Act of 1939, as in effect on the date of the indenture. We use the term "debenture trustee" to refer to either the trustee under the senior indenture or the trustee under the subordinated indenture, as applicable.

Table of Contents

        The following summaries of material provisions of the senior debt securities, the subordinated debt securities and the indentures are subject to, and qualified in their entirety by reference to, all the provisions of the indenture applicable to a particular series of debt securities.

General

        Each indenture provides that debt securities may be issued from time to time in one or more series and may be denominated and payable in foreign currencies or units based on or relating to foreign currencies. Neither indenture limits the amount of debt securities that may be issued thereunder, and each indenture provides that the specific terms of any series of debt securities shall be set forth in, or determined pursuant to, an authorizing resolution and/or a supplemental indenture, if any, relating to such series.

        We will describe in each prospectus supplement the following terms relating to a series of debt securities:

•

the title or designation;



•

the aggregate principal amount and any limit on the amount that may be issued;



•

the currency or units based on or relating to currencies in which debt securities of such series are denominated and the currency or units in which principal or interest or both will or may be payable;



•

whether we will issue the series of debt securities in global form, the terms of any global securities and who the depositary will be;



•

the maturity date and the date or dates on which principal will be payable;



•

the interest rate, which may be fixed or variable, or the method for determining the rate and the date interest will begin to accrue, the date or dates interest will be payable and the record dates for interest payment dates or the method for determining such dates;



•

whether or not the debt securities will be secured or unsecured, and the terms of any secured debt;



•

the terms of the subordination of any series of subordinated debt;



•

the place or places where payments will be payable;



•

our right, if any, to defer payment of interest and the maximum length of any such deferral period;



•

the date, if any, after which, and the price at which, we may, at our option, redeem the series of debt securities pursuant to any optional redemption provisions;



•

the date, if any, on which, and the price at which we are obligated, pursuant to any mandatory sinking fund provisions or otherwise, to redeem, or at the holder's option to purchase, the series of debt securities;



•

whether the indenture will restrict our ability to pay dividends, or will require us to maintain any asset ratios or reserves;



•

whether we will be restricted from incurring any additional indebtedness;



•

a discussion of any material or special U.S. federal income tax considerations applicable to a series of debt securities;



•

the denominations in which we will issue the series of debt securities, if other than denominations of $1,000 and any integral multiple thereof; and

Table of Contents

•

any other specific terms, preferences, rights or limitations of, or restrictions on, the debt securities.

        We may issue debt securities that provide for an amount less than their stated principal amount to be due and payable upon declaration of acceleration of their maturity pursuant to the terms of the indenture. We will provide you with information on the federal income tax considerations and other special considerations applicable to any of these debt securities in the applicable prospectus supplement.

Conversion or Exchange Rights

        We will set forth in the prospectus supplement the terms, if any, on which a series of debt securities may be convertible into or exchangeable for our common stock or our other securities. We will include provisions as to whether conversion or exchange is mandatory, at the option of the holder or at our option. We may include provisions pursuant to which the number of shares of our common stock or our other securities that the holders of the series of debt securities receive would be subject to adjustment.

Consolidation, Merger or Sale; No Protection in Event of a Change of Control or Highly Leveraged Transaction

        The indentures do not contain any covenant that restricts our ability to merge or consolidate, or sell, convey, transfer or otherwise dispose of all or substantially all of our assets. However, any successor to or acquirer of such assets must assume all of our obligations under the indentures or the debt securities, as appropriate.

        Unless we state otherwise in the applicable prospectus supplement, the debt securities will not contain any provisions that may afford holders of the debt securities protection in the event we have a change of control or in the event of a highly leveraged transaction (whether or not such transaction results in a change of control), which could adversely affect holders of debt securities.

Events of Default Under the Indenture

        The following are events of default under the indentures with respect to any series of debt securities that we may issue:

•

if we fail to pay interest when due and our failure continues for 90 days and the time for payment has not been extended or deferred;



•

if we fail to pay the principal, or premium, if any, when due and the time for payment has not been extended or delayed;



•

if we fail to observe or perform any other covenant set forth in the debt securities of such series or the applicable indentures, other than a covenant specifically relating to and for the benefit of holders of another series of debt securities, and our failure continues for 90 days after we receive written notice from the debenture trustee or holders of not less than a majority in aggregate principal amount of the outstanding debt securities of the applicable series; and



•

if specified events of bankruptcy, insolvency or reorganization occur as to us.

        No event of default with respect to a particular series of debt securities (except as to certain events of bankruptcy, insolvency or reorganization) necessarily constitutes an event of default with respect to any other series of debt securities. The occurrence of an event of default may constitute an event of default under any bank credit agreements we may have in existence from time to time. In addition, the occurrence of certain events of default or an acceleration under the indenture may constitute an event of default under certain of our other indebtedness outstanding from time to time.

Table of Contents

        If an event of default with respect to debt securities of any series at the time outstanding occurs and is continuing, then the trustee or the holders of not less than a majority in principal amount of the outstanding debt securities of that series may, by a notice in writing to us (and to the debenture trustee if given by the holders), declare to be due and payable immediately the principal (or, if the debt securities of that series are discount securities, that portion of the principal amount as may be specified in the terms of that series) of and premium and accrued and unpaid interest, if any, on all debt securities of that series. Before a judgment or decree for payment of the money due has been obtained with respect to debt securities of any series, the holders of a majority in principal amount of the outstanding debt securities of that series (or, at a meeting of holders of such series at which a quorum is present, the holders of a majority in principal amount of the debt securities of such series represented at such meeting) may rescind and annul the acceleration if all events of default, other than the non-payment of accelerated principal, premium, if any, and interest, if any, with respect to debt securities of that series, have been cured or waived as provided in the applicable indenture (including payments or deposits in respect of principal, premium or interest that had become due other than as a result of such acceleration). We refer you to the prospectus supplement relating to any series of debt securities that are discount securities for the particular provisions relating to acceleration of a portion of the principal amount of such discount securities upon the occurrence of an event of default.

        Subject to the terms of the indentures, if an event of default under an indenture shall occur and be continuing, the debenture trustee will be under no obligation to exercise any of its rights or powers under such indenture at the request or direction of any of the holders of the applicable series of debt securities, unless such holders have offered the debenture trustee reasonable indemnity. The holders of a majority in principal amount of the outstanding debt securities of any series will have the right to direct the time, method and place of conducting any proceeding for any remedy available to the debenture trustee, or exercising any trust or power conferred on the debenture trustee, with respect to the debt securities of that series, provided that:

•

the direction so given by the holder is not in conflict with any law or the applicable indenture; and



•

subject to its duties under the Trust Indenture Act, the debenture trustee need not take any action that might involve it in personal liability or might be unduly prejudicial to the holders not involved in the proceeding.

        A holder of the debt securities of any series will only have the right to institute a proceeding under the indentures or to appoint a receiver or trustee, or to seek other remedies if:

•

the holder previously has given written notice to the debenture trustee of a continuing event of default with respect to that series;



•

the holders of at least a majority in aggregate principal amount of the outstanding debt securities of that series have made written request, and such holders have offered reasonable indemnity to the debenture trustee to institute the proceeding as trustee; and



•

the debenture trustee does not institute the proceeding, and does not receive from the holders of a majority in aggregate principal amount of the outstanding debt securities of that series (or at a meeting of holders of such series at which a quorum is present, the holders of a majority in principal amount of the debt securities of such series represented at such meeting) other conflicting directions within 60 days after the notice, request and offer.

        These limitations do not apply to a suit instituted by a holder of debt securities if we default in the payment of the principal, premium, if any, or interest on, the debt securities.

        We will periodically file statements with the applicable debenture trustee regarding our compliance with specified covenants in the applicable indenture.

Table of Contents

Modification of Indenture; Waiver

        The debenture trustee and we may change the applicable indenture without the consent of any holders with respect to specific matters, including:

•

to fix any ambiguity, defect or inconsistency in the indenture; and



•

to change anything that does not materially adversely affect the interests of any holder of debt securities of any series issued pursuant to such indenture.

        In addition, under the indentures, the rights of holders of a series of debt securities may be changed by us and the debenture trustee with the written consent of the holders of at least a majority in aggregate principal amount of the outstanding debt securities of each series (or, at a meeting of holders of such series at which a quorum is present, the holders of a majority in principal amount of the debt securities of such series represented at such meeting) that is affected. However, the debenture trustee and we may make the following changes only with the consent of each holder of any outstanding debt securities affected:

•

extending the fixed maturity of the series of debt securities;



•

reducing the principal amount, reducing the rate of or extending the time of payment of interest, or any premium payable upon the redemption of any debt securities;



•

reducing the principal amount of discount securities payable upon acceleration of maturity;



•

making the principal of or premium or interest on any debt security payable in currency other than that stated in the debt security; or



•

reducing the percentage of debt securities, the holders of which are required to consent to any amendment or waiver.

        Except for certain specified provisions, the holders of at least a majority in principal amount of the outstanding debt securities of any series (or, at a meeting of holders of such series at which a quorum is present, the holders of a majority in principal amount of the debt securities of such series represented at such meeting) may on behalf of the holders of all debt securities of that series waive our compliance with provisions of the indenture. The holders of a majority in principal amount of the outstanding debt securities of any series may on behalf of the holders of all the debt securities of such series waive any past default under the indenture with respect to that series and its consequences, except a default in the payment of the principal of, premium or any interest on any debt security of that series or in respect of a covenant or provision, which cannot be modified or amended without the consent of the holder of each outstanding debt security of the series affected;provided,however, that the holders of a majority in principal amount of the outstanding debt securities of any series may rescind an acceleration and its consequences, including any related payment default that resulted from the acceleration.

Discharge

        Each indenture provides that we can elect to be discharged from our obligations with respect to one or more series of debt securities, except for obligations to:

•

the transfer or exchange of debt securities of the series;



•

replace stolen, lost or mutilated debt securities of the series;



•

maintain paying agencies;



•

hold monies for payment in trust;



•

compensate and indemnify the trustee; and

Table of Contents

•

appoint any successor trustee.

        In order to exercise our rights to be discharged with respect to a series, we must deposit with the trustee money or government obligations sufficient to pay all the principal of, the premium, if any, and interest on, the debt securities of the series on the dates payments are due.

Form, Exchange, and Transfer

        We will issue the debt securities of each series only in fully registered form without coupons and, unless we otherwise specify in the applicable prospectus supplement, in denominations of $1,000 and any integral multiple thereof. The indentures provide that we may issue debt securities of a series in temporary or permanent global form and as book-entry securities that will be deposited with, or on behalf of, The Depository Trust Company or another depositary named by us and identified in a prospectus supplement with respect to that series.

        At the option of the holder, subject to the terms of the indentures and the limitations applicable to global securities described in the applicable prospectus supplement, the holder of the debt securities of any series can exchange the debt securities for other debt securities of the same series, in any authorized denomination and of like tenor and aggregate principal amount.

        Subject to the terms of the indentures and the limitations applicable to global securities set forth in the applicable prospectus supplement, holders of the debt securities may present the debt securities for exchange or for registration of transfer, duly endorsed or with the form of transfer endorsed thereon duly executed if so required by us or the security registrar, at the office of the security registrar or at the office of any transfer agent designated by us for this purpose. Unless otherwise provided in the debt securities that the holder presents for transfer or exchange or in the applicable indenture, we will make no service charge for any registration of transfer or exchange, but we may require payment of any taxes or other governmental charges.

        We will name in the applicable prospectus supplement the security registrar, and any transfer agent in addition to the security registrar, that we initially designate for any debt securities. We may at any time designate additional transfer agents or rescind the designation of any transfer agent or approve a change in the office through which any transfer agent acts, except that we will be required to maintain a transfer agent in each place of payment for the debt securities of each series.

        If we elect to redeem the debt securities of any series, we will not be required to:

•

issue, register the transfer of, or exchange any debt securities of that series during a period beginning at the opening of business 15 days before the day of mailing of a notice of redemption of any debt securities that may be selected for redemption and ending at the close of business on the day of the mailing; or



•

register the transfer of or exchange any debt securities so selected for redemption, in whole or in part, except the unredeemed portion of any debt securities we are redeeming in part.

Information Concerning the Debenture Trustee

        The debenture trustee, other than during the occurrence and continuance of an event of default under the applicable indenture, undertakes to perform only those duties as are specifically set forth in the applicable indenture. Upon an event of default under an indenture, the debenture trustee under such indenture must use the same degree of care as a prudent person would exercise or use in the conduct of his or her own affairs. Subject to this provision, the debenture trustee is under no obligation to exercise any of the powers given it by the indentures at the request of any holder of debt securities unless it is offered reasonable security and indemnity against the costs, expenses and liabilities that it might incur.

Table of Contents

Payment and Paying Agents

        Unless we otherwise indicate in the applicable prospectus supplement, we will make payment of the interest on any debt securities on any interest payment date to the person in whose name the debt securities, or one or more predecessor securities, are registered at the close of business on the regular record date for the interest.

        We will pay principal of and any premium and interest on the debt securities of a particular series at the office of the paying agents designated by us, except that unless we otherwise indicate in the applicable prospectus supplement, will we make interest payments by check which we will mail to the holder. Unless we otherwise indicate in a prospectus supplement, we will designate the corporate trust office of the debenture trustee in the City of New York as our sole paying agent for payments with respect to debt securities of each series. We will name in the applicable prospectus supplement any other paying agents that we initially designate for the debt securities of a particular series. We will maintain a paying agent in each place of payment for the debt securities of a particular series.

        All money we pay to a paying agent or the debenture trustee for the payment of the principal of or any premium or interest on any debt securities which remains unclaimed at the end of two years after such principal, premium or interest has become due and payable will be repaid to us, and the holder of the security thereafter may look only to us for payment thereof.

Governing Law

        The indentures and the debt securities will be governed by and construed in accordance with the laws of the State of New York, except to the extent that the Trust Indenture Act is applicable.

Subordination of Subordinated Debt Securities

        Our obligations pursuant to any subordinated debt securities will be unsecured and will be subordinate and junior in priority of payment to certain of our other indebtedness to the extent described in a prospectus supplement. The subordinated indenture does not limit the amount of senior indebtedness we may incur. It also does not limit us from issuing any other secured or unsecured debt.

DESCRIPTION OF WARRANTS

General

        We may issue warrants to purchase shares of our common stock, preferred stock and/or debt securities in one or more series together with other securities or separately, as described in the applicable prospectus supplement. Below is a description of certain general terms and provisions of the warrants that we may offer. Particular terms of the warrants will be described in the warrant agreements and the prospectus supplement relating to the warrants.

        The applicable prospectus supplement will contain, where applicable, the following terms of and other information relating to the warrants:

•

the specific designation and aggregate number of, and the price at which we will issue, the warrants;



•

the currency or currency units in which the offering price, if any, and the exercise price are payable;



•

the designation, amount and terms of the securities purchasable upon exercise of the warrants;



•

if applicable, the exercise price for shares of our common stock and the number of shares of common stock to be received upon exercise of the warrants;

Table of Contents

•

if applicable, the exercise price for shares of our preferred stock, the number of shares of preferred stock to be received upon exercise, and a description of that series of our preferred stock;



•

if applicable, the exercise price for our debt securities, the amount of debt securities to be received upon exercise, and a description of that series of debt securities;



•

the date on which the right to exercise the warrants will begin and the date on which that right will expire or, if you may not continuously exercise the warrants throughout that period, the specific date or dates on which you may exercise the warrants;



•

whether the warrants will be issued in fully registered form or bearer form, in definitive or global form or in any combination of these forms, although, in any case, the form of a warrant included in a unit will correspond to the form of the unit and of any security included in that unit;



•

any applicable material U.S. federal income tax consequences;



•

the identity of the warrant agent for the warrants and of any other depositaries, execution or paying agents, transfer agents, registrars or other agents;



•

the proposed listing, if any, of the warrants or any securities purchasable upon exercise of the warrants on any securities exchange;



•

if applicable, the date from and after which the warrants and the common stock, preferred stock and/or debt securities will be separately transferable;



•

if applicable, the minimum or maximum amount of the warrants that may be exercised at any one time;



•

information with respect to book-entry procedures, if any;



•

the anti-dilution provisions of the warrants, if any;



•

any redemption or call provisions;



•

whether the warrants may be sold separately or with other securities as parts of units; and



•

any additional terms of the warrants, including terms, procedures and limitations relating to the exchange and exercise of the warrants.

Transfer Agent and Registrar

        The transfer agent and registrar for any warrants will be set forth in the applicable prospectus supplement.

DESCRIPTION OF RIGHTS

General

        We may issue rights to our stockholders to purchase shares of our common stock, preferred stock or the other securities described in this prospectus. We may offer rights separately or together with one or more additional rights, debt securities, preferred stock, common stock, warrants or purchase contracts, or any combination of those securities in the form of units, as described in the applicable prospectus supplement. Each series of rights will be issued under a separate rights agreement to be entered into between us and a bank or trust company, as rights agent. The rights agent will act solely as our agent in connection with the certificates relating to the rights of the series of certificates and will not assume any obligation or relationship of agency or trust for or with any holders of rights certificates or beneficial owners of rights. The following description sets forth certain general terms and provisions

Table of Contents

of the rights to which any prospectus supplement may relate. The particular terms of the rights to which any prospectus supplement may relate and the extent, if any, to which the general provisions may apply to the rights so offered will be described in the applicable prospectus supplement. To the extent that any particular terms of the rights, rights agreement or rights certificates described in a prospectus supplement differ from any of the terms described below, then the terms described below will be deemed to have been superseded by that prospectus supplement. We encourage you to read the applicable rights agreement and rights certificate for additional information before you decide whether to purchase any of our rights. We will provide in a prospectus supplement the following terms of the rights being issued:

•

the date of determining the stockholders entitled to the rights distribution;



•

the aggregate number of shares of common stock, preferred stock or other securities purchasable upon exercise of the rights;



•

the exercise price;



•

the aggregate number of rights issued;



•

whether the rights are transferrable and the date, if any, on and after which the rights may be separately transferred;



•

the date on which the right to exercise the rights will commence, and the date on which the right to exercise the rights will expire;



•

the method by which holders of rights will be entitled to exercise;



•

the conditions to the completion of the offering, if any;



•

the withdrawal, termination and cancellation rights, if any;



•

whether there are any backstop or standby purchaser or purchasers and the terms of their commitment, if any;



•

whether stockholders are entitled to oversubscription rights, if any;



•

any applicable material U.S. federal income tax considerations; and



•

any other terms of the rights, including terms, procedures and limitations relating to the distribution, exchange and exercise of the rights, as applicable.

        Each right will entitle the holder of rights to purchase for cash the principal amount of shares of common stock, preferred stock or other securities at the exercise price provided in the applicable prospectus supplement. Rights may be exercised at any time up to the close of business on the expiration date for the rights provided in the applicable prospectus supplement.

        Holders may exercise rights as described in the applicable prospectus supplement. Upon receipt of payment and the rights certificate properly completed and duly executed at the corporate trust office of the rights agent or any other office indicated in the prospectus supplement, we will, as soon as practicable, forward the shares of common stock, preferred stock or other securities, as applicable, purchasable upon exercise of the rights. If less than all of the rights issued in any rights offering are exercised, we may offer any unsubscribed securities directly to persons other than stockholders, to or through agents, underwriters or dealers or through a combination of such methods, including pursuant to standby arrangements, as described in the applicable prospectus supplement.

Rights Agent

        The rights agent for any rights we offer will be set forth in the applicable prospectus supplement.

Table of Contents

DESCRIPTION OF PURCHASE CONTRACTSTHE PRIVATE PLACEMENT

        We        On November 1, 2018, OvaScience and Millendo entered into a Stock Purchase Agreement (as may issuebe amended from time to time, the "Purchase Agreement") with certain investors (the "Investors"), which provided for the sale and issuance of shares (the "Shares") of OvaScience Common Stock (the "Post-Closing Financing") for an aggregate purchase contracts, including contracts obligating holders toprice of approximately $20 million at a per share purchase from us, and for us to sell to holders, a specific or variable numberprice of our debt securities, shares of common stock, preferred stock, warrants or rights, or securities of an entity unaffiliated with us, or any combination(i) $1.2096divided by (ii) the Exchange Ratio. The consummation of the above, at a future date or dates. Alternatively,Post-Closing Financing and the purchase contracts may obligate us to purchase from holders, and obligate holders to sell to us, a specific or variable number of our debt securities, shares of common stock, preferred stock, warrants, rights or other property, or any combinationtransactions contemplated by the Purchase Agreement are conditioned upon the satisfaction of the above. The price of the securities or other property subject to the purchase contracts may be fixed at the time the purchase contracts are issued or may be determined by reference to a specific formula describedconditions set forth in the purchase contracts. We may issue purchase contracts separately or as a part of units each consisting of a purchase contract and one or more of our other securities described in this prospectus or securities of third parties, including U.S. Treasury securities, securing the holder's obligations under the purchase contract. The purchase contracts may require us to make periodic payments to holders or vice versaPurchase Agreement. OvaScience and the payments may be unsecured or pre-funded on some basis. The purchase contracts may require holdersInvestors intend to securecomplete the holder's obligations in a manner specified inPost-Closing Financing after the applicable prospectus supplement.

        The applicable prospectus supplement will describe the terms of any purchase contracts in respect of which this prospectus is being delivered, including, to the extent applicable, the following:

•

whether the purchase contracts obligate the holder or us to purchase or sell, or both purchase and sell, the securities subject to purchase under the purchase contract, and the nature and amount of each of those securities, or the method of determining those amounts;



•

whether the purchase contracts are to be prepaid;



•

whether the purchase contracts are to be settled by delivery, or by reference or linkage to the value, performance or level of the securities subject to purchase under the purchase contract;



•

any acceleration, cancellation, termination or other provisions relating to the settlement of the purchase contracts;



•

any applicable material U.S. federal income tax considerations; and



•

whether the purchase contracts will be issued in fully registered or global form.

        The preceding description sets forth certain general terms and provisions of the purchase contracts to which any prospectus supplement may relate. The particular terms of the purchase contracts to which any prospectus supplement may relate and the extent, if any, to which the general provisions may apply to the purchase contracts so offered will be described in the applicable prospectus supplement. To the extent that any particular terms of the purchase contracts described in a prospectus supplement differ from any of the terms described above, then the terms described above will be deemed to have been superseded by that prospectus supplement. We encourage you to read the applicable purchase contract for additional information before you decide whether to purchase any of our purchase contracts.

DESCRIPTION OF UNITS

        The following description, together with the additional information that we include in any applicable prospectus supplements summarizes the material terms and provisions of the units that we may offer under this prospectus. While the terms we have summarized below will apply generally to any units that we may offer under this prospectus, we will describe the particular terms of any series of units in more detail in the applicable prospectus supplement. The terms of any units offered under a prospectus supplement may differ from the terms described below.

        We will incorporate by reference from reports that we file with the SEC, the form of unit agreement that describesEffective Time. Under the terms of the series of units we are offering, and any supplemental agreements, beforePost-Closing Financing, the issuanceShares issued in the Post-Closing Financing will be issued pursuant to an exemption from the registration requirements of the related seriesSecurities Act of units.1933, as amended. The following summariesresale of material termsthe Shares by the Investors are being registered for resale on this registration statement.

        On November 28, 2018, OvaScience, Millendo and the Investors entered into the First Amendment to the Purchase Agreement (the "First Amendment to the Purchase Agreement"), pursuant to which the parties agreed to amend certain provisions of the unitsPurchase Agreement that would have allowed the Investors to waive certain conditions to the closing of the Post-Closing Financing. The parties also amended the fee reimbursement provisions.

        Concurrently with the execution of the Purchase Agreement, OvaScience entered into a Registration Rights Agreement (as may be amended from time to time, the "Registration Rights Agreement") with the Investors, pursuant to which OvaScience agreed to file, as promptly as reasonably possible after the execution of the Registration Rights Agreement, a registration statement (the "Resale Registration Shelf") with the SEC covering the resale of the shares sold to the Investors in the Post-Closing Financing and to use its reasonable best efforts to have the registration statement declared effective as promptly as practicable following the filing of the Resale Registration Shelf.

        Under the Registration Rights Agreement, OvaScience also agreed to use its reasonable best efforts to maintain the effectiveness of the Resale Registration Shelf until the earliest of (a) the date as of which Investors may sell all of their securities covered by the Resale Registration Shelf without restriction pursuant to Rule 144 or (b) all Shares covered by the Resale Registration Shelf otherwise cease to be registrable securities, as defined in the Registration Rights Agreement.

        The descriptions of the Purchase Agreement, the First Amendment to the Purchase Agreement and the Registration Rights Agreement are subject to,not complete and are qualified in their entirety by reference to all the provisions ofPurchase Agreement, the unit agreement and any supplemental agreements applicable to a particular series of units. We urge you to read the applicable prospectus supplements relatedFirst Amendment to the particular series of units that we may offer under this prospectus, as well as any related free writing prospectusesPurchase Agreement and the complete unit agreement and any supplemental agreements that contain the termsRegistration Rights Agreement, each of the units.

General

        We may issue units consisting of common stock, preferred stock, one or more debt securities, warrants, rights or purchase contacts for the purchase of common stock, preferred stock and/or debt securities in one or more series, in any combination. Each unit will be issued so that the holder of the unit is also the holder of each security included in the unit. Thus, the holder of a unit willwhich have the rights and obligations of a holder of each security included in the unit. The unit agreement under which a unit is issued may provide that the securities included in the unit may not be held or transferred separately, at any time or at any time before a specified date.

        We will describe in the applicable prospectus supplement the terms of the series of units being offered, including:

•

the designation and terms of the units and of the securities comprising the units, including whether and under what circumstances those securities may be held or transferred separately;



•

any provisions of the governing unit agreement that differ from those described below; and



•

any provisions for the issuance, payment, settlement, transfer or exchange of the units or of the securities comprising the units.

        The provisions described in this section, as well as those set forth in any prospectus supplement or as described under "Description of Common Stock," "Description of Preferred Stock," "Description of Debt Securities," "Description of Warrants," "Description of Rights" and "Description of Purchase Contracts" will apply to each unit, as applicable, and to any common stock, preferred stock, debt security, warrant, right or purchase contract included in each unit, as applicable.

Unit Agent

        The name and address of the unit agent for any units we offer will be set forth in the applicable prospectus supplement.

Issuance in Series

        We may issue units in such amounts and in such numerous distinct series as we determine.

Enforceability of Rights by Holders of Units

        Each unit agent will act solely as our agent under the applicable unit agreement and will not assume any obligation or relationship of agency or trust with any holder of any unit. A single bank or trust company may act as unit agent for more than one series of units. A unit agent will have no duty or responsibility in case of any default by us under the applicable unit agreement or unit, including any duty or responsibility to initiate any proceedings at law or otherwise, or to make any demand upon us. Any holder of a unit may, without the consent of the related unit agent or the holder of any other unit, enforce by appropriate legal action its rights as holder under any security included in the unit.

Table of Contents

CERTAIN PROVISIONS OF DELAWARE LAW AND OF THE COMPANY'S CERTIFICATE OF INCORPORATION AND BYLAWS

Anti-Takeover Provisions

Delaware Law

        We are subject to Section 203 of the Delaware General Corporation Law. Subject to certain exceptions, Section 203 prevents a publicly held Delaware corporation from engaging in a "business combination" with any "interested stockholder" for three years following the date that the person became an interested stockholder, unless the interested stockholder attained such status with the approval of our board of directors or unless the business combination is approved in a prescribed manner. A "business combination" includes, among other things, a merger or consolidation involving us and the "interested stockholder" and the sale of more than 10% of our assets. In general, an "interested stockholder" is any entity or person beneficially owning 15% or more of our outstanding voting stock and any entity or person affiliated with or controlling or controlled by such entity or person.

Staggered Board

        Our restated certificate of incorporation and by-laws divide our board of directors into three classes with staggered three year terms. In addition, our restated certificate of incorporation and by-laws provide that directors may be removed only for cause and only by the affirmative vote of the holders of 75% of our shares of capital stock present in person or by proxy and entitled to vote. Under our restated certificate of incorporation and by-laws, any vacancy on our board of directors, including a vacancy resulting from an enlargement of our board of directors, may be filled only by vote of a majority of our directors then in office. Furthermore, our restated certificate of incorporation provides that the authorized number of directors may be changed only by the resolution of our board of directors, subject to the rights of any holders of preferred stock to elect directors. The classification of our board of directors and the limitations on the ability of our stockholders to remove directors, change the authorized number of directors and fill vacancies could make it more difficult for a third party to acquire, or discourage a third party from seeking to acquire, control of our company.

Authorized but Unissued Shares

        The authorized but unissued shares of common stock and preferred stock are available for future issuance without stockholder approval, subject to any limitations imposed by the listing standards of any exchange on which our shares are listed. These additional shares may be used for a variety of corporate finance transactions, acquisitions and employee benefit plans. The existence of authorized but unissued and unreserved common stock and preferred stock could make more difficult or discourage an attempt to obtain control of us by means of a proxy contest, tender offer, merger or otherwise.

Special Meeting of Stockholders; Advance Notice Requirements for Stockholder Proposals and Director Nominations; Stockholder Action

        Our restated certificate of incorporation provides that we will indemnify each person who was or is a party or threatened to be made a party to any threatened, pending or completed action, suit or proceeding, other than an action by or in the right of us, by reason of the fact that he or she is or was, or has agreed to become, a director or officer, or is or was serving, or has agreed to serve, at our request as a director, officer, partner, employee or trustee of, or in a similar capacity with, another corporation, partnership, joint venture, trust or other enterprise (all such persons being referred tobeen filed as an "Indemnitee"), or by reason of any action alleged to have been taken or omitted in such capacity, against all expenses, including attorneys' fees, judgments, fines and amounts paid in settlement actually and reasonably incurred in connection with such action, suit or proceeding and any appeal therefrom, if

Table of Contents

such Indemnitee acted in good faith and in a manner he or she reasonably believed to be in, or not opposed to, our best interests, and, with respect to any criminal action or proceeding, he or she had no reasonable cause to believe his or her conduct was unlawful.

Super Majority Voting

        The General Corporation Law of the State of Delaware provides generally that the affirmative vote of a majority of the shares entitled to vote on any matter is required to amend a corporation's certificate of incorporation or by-laws, unless a corporation's certificate of incorporation or by-laws, as the case may be, require a greater percentage. Our by-laws may be amended or repealed by a majority vote of our board of directors or the affirmative vote of the holders of at least 75% of the votes that all our stockholders would be entitled to cast in any election of directors. In addition, the affirmative vote of the holders of at least 75% of the votes that all our stockholders would be entitled to cast in any election of directors is required to amend or repeal or to adopt any provisions inconsistent with certain of the provisions of our restated certificate of incorporation.

Limitation of Liability and Indemnification

        Our restated certificate of incorporation and our amended and restated bylaws provide that each person who was or is made a party or is threatened to be made a party to or is otherwise involved (including, without limitation, as a witness) in any action, suit or proceeding, whether civil, criminal, administrative or investigative, by reason of the fact that he or she is or was one of our directors or officers or is or was serving at our request as a director, officer, or trustee of another corporation, or of a partnership, joint venture, trust or other enterprise, including service with respect to an employee benefit plan, whether the basis of such proceeding is alleged action in an official capacity as a director, officer or trustee or in any other capacity while serving as a director, officer or trustee, shall be indemnified and held harmless by us to the fullest extent authorized by the Delaware General Corporation Law against all expense, liability and loss (including attorneys' fees, judgments, fines, ERISA excise taxes or penalties and amounts paid in settlement) reasonably incurred or suffered by such.

        Section 145 of the Delaware General Corporation Law permits a corporation to indemnify any director or officer of the corporation against expenses (including attorneys' fees), judgments, fines and amounts paid in settlement actually and reasonably incurred in connection with any action, suit or proceeding brought by reason of the fact that such person is or was a director or officer of the corporation, if such person acted in good faith and in a manner that he or she reasonably believed to be in, or not opposed to, the best interests of the believe his or her conduct was unlawful. In a derivative action (i.e., one brought by or on behalf of the corporation), indemnification may be provided only for expenses actually and reasonably incurred by any director or officer in connection with the defense or settlement of such an action or suit if such person acted in good faith and in a manner that he or she reasonably believed to be in, or not opposed to, the best interests of the corporation, except that no indemnification shall be provided if such person shall have been adjudged to be liable to the corporation, unless and only to the extent that the Delaware Chancery Court or the court in which the action or suit was brought shall determine that such person is fairly and reasonably entitled to indemnity for such expenses despite such adjudication of liability.

        Pursuant to Section 102(b)(7) of the Delaware General Corporation Law, Article Ninth of our restated certificate of incorporation eliminates the liability of a director to us or our stockholders for monetary damages for such a breach of fiduciary duty as a director, except for liabilities arising:

•

from any breach of the director's duty of loyalty to us or our stockholders;



•

from acts or omissions not in good faith or which involve intentional misconduct or a knowing violation of law;

Table of Contents

•

under Section 174 of the Delaware General Corporation Law; and



•

from any transaction from which the director derived an improper personal benefit.

        We have entered into indemnification agreements with our directors and certain officers, in addition to the indemnification provided in our restated certificate of incorporation and our amended and restated bylaws, and intend to enter into indemnification agreements with any new directors and executive officers in the future. We have purchased and intend to maintain insurance on behalf of any person who is or was a director or officer against any loss arising from any claim asserted against him or her and incurred by him or her in any such capacity, subject to certain exclusions.

        The foregoing discussion of our restated certificate of incorporation, amended and restated bylaws, indemnification agreements, indemnity agreement, and Delaware law is not intended to be exhaustive and is qualified in its entirety by such restated certificate of incorporation, amended and restated bylaws, indemnification agreements, indemnity agreement, or law.

        Insofar as indemnification for liabilities arising under the Securities Act may be permitted to our directors, officers and controlling persons pursuant to the foregoing provisions, or otherwise, we have been advised that in the opinion of the SEC such indemnification is against public policy as expressed in the Securities Act and is, therefore, unenforceable.

LEGAL MATTERS

        Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C., Boston, Massachusetts, will pass upon the validity of the issuance of the securities to be offered by this prospectus.

EXPERTS

        Ernst & Young LLP, independent registered public accounting firm, has audited our consolidated financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2016, and the effectiveness of our internal control over financial reporting as of December 31, 2016, as set forth in their reports, which are incorporated by reference in this prospectus and the registration statement. Our financial statements are incorporated by reference in reliance on Ernst & Young LLP's report, given on their authority as experts in accounting and auditing.

WHERE YOU CAN FIND MORE INFORMATION

        We are subject to the reporting requirements of the Securities Exchange Act of 1934, as amended, and file annual, quarterly and current reports, proxy statements and other information with the SEC. You may read and copy these reports, proxy statements and other information at the SEC's public reference facilities at 100 F Street, N.E., Room 1580, Washington, D.C. 20549. You can request copies of these documents by writing to the SEC and paying a fee for the copying cost. Please call the SEC at 1-800-SEC-0330 for more information about the operation of the public reference facilities. SEC filings are also available at the SEC's web site athttp://www.sec.gov. This prospectus is only part of a registration statement on Form S-3 that we have filed with the SEC under the Securities Act of 1933, as amended, and therefore omits certain information contained in the registration statement. We have also filed exhibits and schedules with the registration statement that are excluded from this prospectus, and you should refer to the applicable exhibit or schedule for a complete description of any statement referring to any contract or other document. You may inspect a copy of the registration statement, including the exhibits and schedules, without charge, at the public reference room or obtain a copy from the SEC upon payment of the fees prescribed by the SEC.

        We also maintain a website atwww.ovascience.com, through which you can access our SEC filings. The information set forth on our website is not part of this prospectus.

Table of Contents

INCORPORATION OF DOCUMENTS BY REFERENCE

        The SEC allows us to "incorporate by reference" information that we file with them. Incorporation by reference allows us to disclose important information to you by referring you to those other documents. The information incorporated by reference is an important part of this prospectus, and information that we file later with the SEC will automatically update and supersede this information. We filed a registration statement on Form S-3 under the Securities Act of 1933, as amended, with the SEC with respect to the securities we may offer pursuant to this prospectus. This prospectus omits certain information contained in the registration statement, as permitted by the SEC. You should refer to the registration statement including the exhibits, for further information about us and the securities we may offer pursuant to this prospectus. Statements inof which this prospectus regarding the provisions of certain documents filed with, or incorporated by reference in, the registration statement are not necessarily complete and each statement is qualified in all respects by that reference. Copies of all or any part of the registration statement, including the documents incorporated by reference or the exhibits, may be obtained upon payment of the prescribed rates at the offices of the SEC listed above ina part. See "Where You Can Find More Information." The documents we are incorporating by reference are:

•

our Annual Report on Form 10-K for the fiscal year ended December 31, 2016 that we filed with the SEC on March 2, 2017;



•

the portions of our definitive proxy statement on Schedule 14A filed on April 18, 2016 that are deemed "filed" with the SEC under the Exchange Act;



•

our Current Reports on Form 8-K that we filed with the SEC on January 10, 2017 (except for the information furnished under Items 2.02 or 7.01 and the exhibits furnished thereto);



•

the description of our common stock contained in our Registration Statement on Form 8-A filed on April 25, 2013, including any amendment or report filed for the purpose of updating such description; and



•

all reports and other documents subsequently filed by us pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act after the date of this prospectus and prior to the termination or completion of the offering of securities under this prospectus shall be deemed to be incorporated by reference in this prospectus and to be a part hereof from the date of filing such reports and other documents.

        The SEC file number for each of the documents listed above is 001-35890.

        In addition, all reports and other documents filed by us pursuant to the Exchange Act after the date of Amendment No. 1 to the registration statement and prior to effectiveness of the registration statement shall be deemed to be incorporated by reference into this prospectus.

        Any statement contained in this prospectus or in a document incorporated or deemed to be incorporated by reference into this prospectus will be deemed to be modified or superseded for purposes of this prospectus to the extent that a statement contained in this prospectus or any other subsequently filed document that is deemed to be incorporated by reference into this prospectus modifies or supersedes the statement. Any statement so modified or superseded will not be deemed, except as so modified or superseded, to constitute a part of this prospectus.

        You may request, orally or in writing, a copy of any or all of the documents incorporated herein by reference. These documents will be provided to you at no cost, by contacting:

OvaScience, Inc.
9 Fourth Avenue
Waltham, Massachusetts

Table of Contents

Attention: Investor Relations
Telephone: (617) 500-2802

        You may also access these documents on our website,http://www.ovascience.com. The information contained on, or that can be accessed through, our website is not a part of this prospectus. We have included our website address in this prospectus solely as an inactive textual reference.

        You should rely only on information contained in, or incorporated by reference into, this prospectus and any prospectus supplement. We have not authorized anyone to provide you with information different from that contained in this prospectus or incorporated by reference in this prospectus. We are not making offers to sell the securities in any jurisdiction in which such an offer or solicitation is not authorized or in which the person making such offer or solicitation is not qualified to do so or to anyone to whom it is unlawful to make such offer or solicitation.

Table of Contents

OVASCIENCE, INC.

$175,000,000

Common Stock
Preferred Stock
Debt Securities
Warrants
Rights Purchase
Contract Units

PROSPECTUS

                        , 2017

Table of Contents

THE INFORMATION IN THIS PROSPECTUS IS NOT COMPLETE AND MAY BE CHANGED. WE MAY NOT SELL THESE SECURITIES UNTIL THE REGISTRATION STATEMENT FILED WITH THE SECURITIES AND EXCHANGE COMMISSION IS EFFECTIVE. THIS PROSPECTUS IS NOT AN OFFER TO SELL THESE SECURITIES AND IS NOT SOLICITING AN OFFER TO BUY THESE SECURITIES IN ANY STATE WHERE THE OFFER OR SALE IS NOT PERMITTED.

SUBJECT TO COMPLETION, DATED MARCH 2, 2017

PROSPECTUS

$50,000,000

OvaScience, Inc.

Common Stock

        We have entered into a Sales Agreement, or sales agreement, with Cowen and Company, LLC, or Cowen, relating to the sale of shares of our common stock offered by this prospectus. In accordance with the terms of the sales agreement, we may offer and sell shares of our common stock, $0.001 par value per share, having an aggregate offering price of up to $50,000,000 from time to time through Cowen, acting as our agent.

        Sales of our common stock, if any, under this prospectus will be made by any method permitted that is deemed an "at the market offering" as defined in Rule 415 under the Securities Act of 1933, as amended, or the Securities Act, including sales made directly on or through The NASDAQ Global Market, the existing trading market for our common stock, and/or any other method permitted by law. Cowen is not required to sell any specific amount, but will act as our sales agent using commercially reasonable efforts consistent with its normal trading and sales practices. There is no arrangement for funds to be received in any escrow, trust or similar arrangement.

        Cowen will be entitled to compensation at a commission rate of up to 3.0% of the gross sales price per share sold under the sales agreement. See "Plan of Distribution" beginning on page SA-13 for additional information regarding the compensation to be paid to Cowen. In connection with the sale of the common stock on our behalf, Cowen may be deemed to be an "underwriter" within the meaning of the Securities Act and the compensation of Cowen may be deemed to be underwriting commissions or discounts. We have also agreed to provide indemnification and contribution to Cowen with respect to certain liabilities, including liabilities under the Securities Act.

        Our common stock is listed on The NASDAQ Global Market under the symbol "OVAS." On February 27, 2017, the last reported sale price of our common stock was $1.50 per share.

Investing in our securities involves a high degree of risk. Before deciding whether to invest in our securities, you should consider carefully the risks that we have described on page SA-4 of this prospectus under the caption "Risk Factors" and in the documents incorporated by reference in this prospectus.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of this prospectus. Any representation to the contrary is a criminal offense.

Cowen and Company

The date of this prospectus is                        , 2017

Table of Contents

ABOUT THIS PROSPECTUS

        This prospectus is part of a registration statement that we filed with the Securities and Exchange Commission, or SEC, utilizing a "shelf" registration process. Under this shelf registration process, we may from time to time sell shares of our common stock having an aggregate offering price of up to $50,000,000 under this prospectus at prices and on terms to be determined by market conditions at the time of the offering.

        Before buying any of the common stock that we are offering, we urge you to carefully read this prospectus and all of the information incorporated by reference herein and therein, as well as the additional information described under the headings "Where You Can Find MoreAdditional Information" and "Incorporation of Documents"Information Incorporated by Reference." These documents contain important information that you should consider when making your investment decision.

        To the extent there is a conflict between the information contained in this prospectus, on the one hand, and the information contained in any document incorporated by reference in this prospectus, on the other hand, you should rely on the information in this prospectus. If any statement in one of these documents is inconsistent with a statement in another document having a later date—for example, a document incorporated by reference in this prospectus—the statement in the document having the later date modifies or supersedes the earlier statement.

        You should rely only on the information contained in or incorporated by reference in this prospectus and any related free writing prospectus filed by us with the SEC. We have not, and Cowen has not, authorized anyone to provide you with different information. If anyone provides you with different or inconsistent information, you should not rely on it. This prospectus does not constitute an offer to sell or the solicitation of an offer to buy any securities other than the securities described in this prospectus or an offer to sell or the solicitation of an offer to buy such securities in any circumstances in which such offer or solicitation is unlawful. You should assume that the information appearing in this prospectus, the documents incorporated by reference and any related free writing prospectus is accurate only as of their respective dates. Our business, financial condition, results of operations and prospects may have changed materially since those dates.

        We further note that theThe representations, warranties and covenants made by us in any agreement that is filed as an exhibit to any document that is incorporated by reference in the accompanying prospectussuch agreements were made solely for the benefit of the parties to such agreement,agreements, including, in some cases, for the purpose of allocating risk among the parties to such agreements,thereto, and should not be deemed to be a representation, warranty or covenant to you. Moreover, such representations, warranties or covenants were accurate onlymade as of the date when made.an earlier date. Accordingly, such representations, warranties and covenants should not be relied on as accurately representing the current state of our affairs.

        Unless the context otherwise requires, "OvaScience," "OVAS," "the Company," "we," "us," "our" and similar terms refer to OvaScience, Inc. and our subsidiaries.

SA-1

Table of Contents

SA-2

Table of Contents

SA-3

Table of Contents

RISK FACTORS

An investment in our common stock involves a high degree of risk. Before deciding whether to invest in our common stock, you should consider carefully the risks described below and discussed under the sections captioned "Risk Factors" contained in our most recent Annual Report on Form 10-K, as well as in any of our subsequent Quarterly Reports on Form 10-Q and Exhibit 99.3 to our Current Report on Form 8-K filed on May 25, 2016, which are incorporated by reference herein in their entirety, together with other information in this prospectus, the information and documents incorporated by reference in this prospectus, and in any free writing prospectus that we have authorized for use in connection with this offering. If any of these risks actually occurs, our business, financial condition, results of operations or cash flow could be seriously harmed. This could cause the trading price of our common stock to decline, resulting in a loss of all or part of your investment.

Our business, financial condition or results of operations could be materially adversely affected by any of these risks. The trading price of our securities could decline due to any of these risks, and you may lose part or all of your investment. This prospectus and the incorporated documents also contain forward-looking statements that involve risks and uncertainties. Our actual results could differ materially from those anticipated in these forward-looking statements as a result of certain factors, including the risks mentioned below. Forward-looking statements included in this prospectus are based on information available to us on the date hereof, and all forward-looking statements in documents incorporated by reference are based on information available to us as of the date of such documents. We disclaim any intent to update any forward-looking statements.

Risks Related to This Offering

Our management will have broad discretion over the use of the net proceeds from this offering, and you may not agree with how we use the proceeds and the proceeds may not be invested successfully.

        Our management will have broad discretion as to the use of the net proceeds from this offering and could use them for purposes other than those contemplated at the time of this offering. Accordingly, you are relying on the judgment of our management with regard to the use of these net proceeds, and you will not have the opportunity, as part of your investment decision, to assess whether the proceeds will be used appropriately. It is possible that the proceeds will be invested in a way that does not yield a favorable, or any, return for OvaScience.

You may experience future dilution as a result of future equity offerings.

        In order to raise additional capital, we may in the future offer additional shares of our common stock or other securities convertible into or exchangeable for our common stock. We cannot assure you that we will be able to sell shares or other securities in any other offering at a price per share that is equal to or greater than the price per share paid by investors in this offering, and investors purchasing shares or other securities in the future could have rights superior to existing stockholders. The price per share at which we sell additional shares of our common stock or other securities convertible into or exchangeable for our common stock in future transactions may be higher or lower than the price per share in this offering.

SA-4

Table of Contents

SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

        This prospectus and the documents incorporated by reference in this prospectus include forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. Words such as, but not limited to, "believe," "expect," "anticipate," "estimate," "intend," "may," "plan," "potential," "predict," "project," "targets," "likely," "will," "would," "could," "should," "continue," and similar expressions or phrases, or the negative of those expressions or phrases, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Although we believe that we have a reasonable basis for each forward-looking statementStatements contained in this prospectus as to the contents of any contract or other document are not necessarily complete, and in each instance we refer you to the copy of the contract or other document filed or incorporated by reference in this prospectus, we caution you that these statements are based on our projections of the future that are subject to known and unknown risks and uncertainties and other factors that may cause our actual results, level of activity, performance or achievements expressed or implied by these forward-looking statements, to differ. The sections in our periodic reports, including our Annual Report on Form 10-K for the fiscal year ended December 31, 2016, entitled "Business," "Risk Factors," and "Management's Discussion and Analysis of Financial Condition and Results of Operations," as well as other sections in this prospectus and the documents or reports incorporated by reference in this prospectus, discuss some of the factors that could contribute to these differences. These forward-looking statements include, among other things, statements about:

•

the risks implicit in the development process of preparing bovine and human eggs for fertilization;



•

regulatory risks associated with obtaining authorization to fertilize human EggPC^SM cells for research;



•

the possibility that internationalin vitro fertilization ("IVF") clinics that we work with may determine not to provide or continue providing the AUGMENT treatment or OvaPrime treatment, or to delay providing such treatments, or to limit the population of patients receiving the treatments based on clinical efficacy, safety or commercial, logistic, economic, available data, regulatory or other reasons;



•

challenges associated with enrolling and completing clinical trials, the science underlying our treatments (including the AUGMENT, OvaPrime and OvaTure treatments), which is unproven;



•

scientific and regulatory challenges associated with characterizing and fertilizing an EggPC cell-derived egg;



•

our ability to obtain regulatory approval or licenses where necessary for our treatments;



•

our ability to develop our treatments on the timelines we expect, if at all;



•

our ability to commercialize our treatments on the timelines we expect, if at all;



•

our expectation that the AUGMENT treatment and OvaPrime treatment are exempt from premarket review and approval applicable to drugs, biologics, medicinal products and medical devices under applicable regulations in those countries where we have introduced or plan to introduce the AUGMENT treatment or the OvaPrime treatment;



•

our plans to develop further clinical evidence for the AUGMENT treatment and the OvaPrime treatment;



•

our anticipated timing of announcing results from studies or trials;

SA-5

Table of Contents

•

the science underlying our treatment and treatments in development (including the AUGMENT, OvaPrime and OvaTure treatments), which is unproven;



•

our ability to obtain regulatory approval or licenses where necessary for our potential treatments;



•

the size and growth of the market for our fertility treatments and our ability to serve those markets;



•

the rate and degree of market acceptance of any future fertility treatments that we develop;



•

our ability to adjust our operations to manage our organizational changes and comply with applicable securities laws and regulations;



•

our ability to obtain additional financing;



•

the accuracy of our estimates regarding expenses, future revenues, capital requirements and the need for additional financing; and



•

our ability to attract and retain key scientific or management personnel.

We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. We have included important cautionary statements in this prospectus or in the documents incorporated by reference in this prospectus, particularly in the "Risk Factors" section, that we believe could cause actual results or events to differ materially from the forward-looking statements that we make. For a summary of such factors, please refer to the section entitled "Risk Factors" in this prospectus, as updated and supplemented by the discussion of risks and uncertainties under "Risk Factors" contained in any supplements to this prospectus and in our most recent annual report on Form 10-K, as revised or supplemented by our subsequent quarterly reports on Form 10-Q or our current reports on Form 8-K, as well as any amendments thereto, as filed with the SEC and which are incorporated herein by reference. The information contained in this document is believed to be current as of the date of this document. We do not intend to update any of the forward-looking statements after the date of this document to conform these statements to actual results or to changes in our expectations, except as required by law.

        In light of these assumptions, risks and uncertainties, the results and events discussed in the forward-looking statements contained in this prospectus or in any document incorporated herein by reference might not occur. Investors are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this prospectus or the date of the document incorporated by reference in this prospectus. We are not under any obligation, and we expressly disclaim any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise. All subsequent forward-looking statements attributable to us or to any person acting on our behalf are expressly qualified in their entirety by the cautionary statements contained or referred to in this section.

SA-6

Table of Contents

USE OF PROCEEDS

        We may issue and sell shares of our common stock having aggregate sale proceeds of up to $50,000,000 from time to time. Because there is no minimum offering amount required to be sold in connection with this offering, the actual total public offering amount, commissions and proceeds to us, if any, are not determinable at this time. We intend to use any net proceeds from the sale of securities under this prospectus to fund activities relating to the development and commercialization of our fertility treatments, and for other general corporate purposes, including, but not limited to, working capital, capital expenditures, investments, acquisitions, should we choose to pursue any, and collaborations. The amounts and timing of our actual expenditures will depend on numerous factors, including the progress of our clinical trials and other development efforts and other factors described under "Risk Factors" in this prospectus and the documents incorporated by reference herein, as well as the amount of cash used in our operations. As a result, our management will have broad discretion to allocate the net proceeds, if any, we receive in connection with securities offered pursuant to this prospectus for any purpose.

DIVIDEND POLICY

        We have never paid cash dividends on any of our capital stock and we currently intend to retain our future earnings, if any, to fund the development and growth of our business. We do not intend to pay cash dividends to holders of our common stock in the foreseeable future.

SA-7

Table of Contents

DESCRIPTION OF CAPITAL STOCK

        We are authorized to issue 100,000,000 shares of common stock, par value $0.001 per share, and 5,000,000 shares of preferred stock, par value $0.001 per share. As of February 27, 2017, we had 35,641,505 shares of common stock outstanding and approximately 80 stockholders of record.

        The following summary of certain provisions of our capital stock does not purport to be complete. You should refer to the section of this prospectus entitled "Certain Provisions of Delaware Law and of the Company's Restated Certificate of Incorporation and Bylaws" and our restated certificate of incorporation and our amended and restated bylaws, both of which are included as exhibits to the registration statement of which this prospectus is a part. The summary below is also qualified by provisions of applicable law.

Common Stock

General

        Holders of our common stock are entitled to one vote for each share held on all matters submitted to a vote of stockholders and do not have cumulative voting rights. An election of directors by our stockholders shall be determined by a plurality of the votes cast by the stockholders entitled to vote on the election. Holders of common stock are entitled to receive proportionately any dividends as may be declared by our board of directors, subject to any preferential dividend rights of any series of preferred stock that we may designate and issue in the future. All shares of common stock outstanding as of the date of this prospectus and, upon issuance and sale, all shares of common stock that we may offer pursuant to this prospectus, will be fully paid and nonassessable.

        In the event of our liquidation or dissolution, the holders of common stock are entitled to receive proportionately our net assets available for distribution to stockholders after the payment of all debts and other liabilities and subject to the prior rights of any outstanding preferred stock. Holders of common stock have no preemptive, subscription, redemption or conversion rights. There are no redemption or sinking fund provisions applicable to the common stock. Our outstanding shares of common stock are validly issued, fully paid and nonassessable. The rights, preferences and privileges of holders of common stock are subject to and may be adversely affected by the rights of the holders of shares of any series of preferred stock that we may designate and issue in the future.

Transfer Agent and Registrar

        The transfer agent and registrar for our common stock is Computershare Trust Company, N.A., with offices at 250 Royall Street, Canton, Massachusetts 02021.

Stock Exchange Listing

        Our common stock is listed on The NASDAQ Global Market under the symbol "OVAS."

Preferred Stock

        Our board of directors may, without further action by our stockholders, from time to time, direct the issuance of shares of preferred stock in series and may, at the time of issuance, determine the rights, preferences and limitations of each series, including voting rights, dividend rights and redemption and liquidation preferences. Satisfaction of any dividend preferences of outstanding shares of preferred stock would reduce the amount of funds available for the payment of dividends on shares of our common stock. Holders of shares of preferred stock may be entitled to receive a preference payment in the event of any liquidation, dissolution or winding-up of our company before any payment is made to the holders of shares of our common stock. In some circumstances, the issuance of shares of preferred stock may render more difficult or tend to discourage a merger, tender offer or proxy contest, the assumption of control by a holder of a large block of our securities or the removal of incumbent management. Upon the affirmative vote of our board of directors, without stockholder approval, we may issue shares of preferred stock with voting and conversion rights which could adversely affect the holders of shares of our common stock.

SA-8

Table of Contents

CERTAIN PROVISIONS OF DELAWARE LAW AND OF THE COMPANY'S CERTIFICATE OF INCORPORATION AND BYLAWS

Anti-Takeover Provisions

Delaware Law

        We are subject to Section 203 of the Delaware General Corporation Law. Subject to certain exceptions, Section 203 prevents a publicly held Delaware corporation from engaging in a "business combination" with any "interested stockholder" for three years following the date that the person became an interested stockholder, unless the interested stockholder attained such status with the approval of our board of directors or unless the business combination is approved in a prescribed manner. A "business combination" includes, among other things, a merger or consolidation involving us and the "interested stockholder" and the sale of more than 10% of our assets. In general, an "interested stockholder" is any entity or person beneficially owning 15% or more of our outstanding voting stock and any entity or person affiliated with or controlling or controlled by such entity or person.

Staggered Board

        Our restated certificate of incorporation and by-laws divide our board of directors into three classes with staggered three year terms. In addition, our restated certificate of incorporation and by-laws provide that directors may be removed only for cause and only by the affirmative vote of the holders of 75% of our shares of capital stock present in person or by proxy and entitled to vote. Under our restated certificate of incorporation and by-laws, any vacancy on our board of directors, including a vacancy resulting from an enlargement of our board of directors, may be filled only by vote of a majority of our directors then in office. Furthermore, our restated certificate of incorporation provides that the authorized number of directors may be changed only by the resolution of our board of directors, subject to the rights of any holders of preferred stock to elect directors. The classification of our board of directors and the limitations on the ability of our stockholders to remove directors, change the authorized number of directors and fill vacancies could make it more difficult for a third party to acquire, or discourage a third party from seeking to acquire, control of our company.

Authorized but Unissued Shares

        The authorized but unissued shares of common stock and preferred stock are available for future issuance without stockholder approval, subject to any limitations imposed by the listing standards of any exchange on which our shares are listed. These additional shares may be used for a variety of corporate finance transactions, acquisitions and employee benefit plans. The existence of authorized but unissued and unreserved common stock and preferred stock could make more difficult or discourage an attempt to obtain control of us by means of a proxy contest, tender offer, merger or otherwise.

Special Meeting of Stockholders; Advance Notice Requirements for Stockholder Proposals and Director Nominations; Stockholder Action

        Our restated certificate of incorporation and by-laws provide that, except as otherwise required by law, special meetings of the stockholders can only be called by our chairman of the board, our chief executive officer or our board of directors. In addition, our by-laws establish an advance notice procedure for stockholder proposals to be brought before an annual meeting of stockholders, including proposed nominations of candidates for election to our board of directors. Stockholders at an annual meeting may only consider proposals or nominations specified in the notice of the meeting or brought before the meeting by or at the direction of our board of directors, or by a stockholder of record on the record date for the meeting who is entitled to vote at the meeting and who has delivered timely written notice in proper form to our secretary of the stockholder's intention to bring such business

SA-9

Table of Contents

before the meeting. These provisions could have the effect of delaying until the next stockholder meeting stockholder actions that are favored by the holders of a majority of our outstanding voting securities. In addition, our restated certificate of incorporation and by-laws require that stockholder actions must be effected at a duly called stockholders meeting and prohibit actions by our stockholders by written consent.

Super Majority Voting

        The General Corporation Law of the State of Delaware provides generally that the affirmative vote of a majority of the shares entitled to vote on any matter is required to amend a corporation's certificate of incorporation or by-laws, unless a corporation's certificate of incorporation or by-laws, as the case may be, require a greater percentage. Our by-laws may be amended or repealed by a majority vote of our board of directors or the affirmative vote of the holders of at least 75% of the votes that all our stockholders would be entitled to cast in any election of directors. In addition, the affirmative vote of the holders of at least 75% of the votes that all our stockholders would be entitled to cast in any election of directors is required to amend or repeal or to adopt any provisions inconsistent with certain of the provisions of our restated certificate of incorporation.

Limitation of Liability and Indemnification

        Our restated certificate of incorporation and our amended and restated bylaws provide that each person who was or is made a party or is threatened to be made a party to or is otherwise involved (including, without limitation, as a witness) in any action, suit or proceeding, whether civil, criminal, administrative or investigative, by reason of the fact that he or she is or was one of our directors or officers or is or was serving at our request as a director, officer, or trustee of another corporation, or of a partnership, joint venture, trust or other enterprise, including service with respect to an employee benefit plan, whether the basis of such proceeding is alleged action in an official capacity as a director, officer or trustee or in any other capacity while serving as a director, officer or trustee, shall be indemnified and held harmless by us to the fullest extent authorized by the Delaware General Corporation Law against all expense, liability and loss (including attorneys' fees, judgments, fines, ERISA excise taxes or penalties and amounts paid in settlement) reasonably incurred or suffered by such.

        Section 145 of the Delaware General Corporation Law permits a corporation to indemnify any director or officer of the corporation against expenses (including attorneys' fees), judgments, fines and amounts paid in settlement actually and reasonably incurred in connection with any action, suit or proceeding brought by reason of the fact that such person is or was a director or officer of the corporation, if such person acted in good faith and in a manner that he or she reasonably believed to be in, or not opposed to, the best interests of the corporation, and, with respect to any criminal action or proceeding, if he or she had no reasonable cause to believe his or her conduct was unlawful. In a derivative action (i.e., one brought by or on behalf of the corporation), indemnification may be provided only for expenses actually and reasonably incurred by any director or officer in connection with the defense or settlement of such an action or suit if such person acted in good faith and in a manner that he or she reasonably believed to be in, or not opposed to, the best interests of the corporation, except that no indemnification shall be provided if such person shall have been adjudged to be liable to the corporation, unless and only to the extent that the Delaware Chancery Court or the court in which the action or suit was brought shall determine that such person is fairly and reasonably entitled to indemnity for such expenses despite such adjudication of liability.

SA-10

Table of Contents

        Pursuant to Section 102(b)(7) of the Delaware General Corporation Law, Article Ninth of our restated certificate of incorporation eliminates the liability of a director to us or our stockholders for monetary damages for such a breach of fiduciary duty as a director, except for liabilities arising:

•

from any breach of the director's duty of loyalty to us or our stockholders;



•

from acts or omissions not in good faith or which involve intentional misconduct or a knowing violation of law;



•

under Section 174 of the Delaware General Corporation Law; and



•

from any transaction from which the director derived an improper personal benefit.

        We have entered into indemnification agreements with our directors and certain officers, in addition to the indemnification provided in our restated certificate of incorporation and our amended and restated bylaws, and intend to enter into indemnification agreements with any new directors and executive officers in the future. We have purchased and intend to maintain insurance on behalf of any person who is or was a director or officer against any loss arising from any claim asserted against him or her and incurred by him or her in any such capacity, subject to certain exclusions.

        The foregoing discussion of our restated certificate of incorporation, amended and restated bylaws, indemnification agreements, indemnity agreement, and Delaware law is not intended to be exhaustive and is qualified in its entirety by such restated certificate of incorporation, amended and restated bylaws, indemnification agreements, indemnity agreement, or law.

        Insofar as indemnification for liabilities arising under the Securities Act may be permitted to our directors, officers and controlling persons pursuant to the foregoing provisions, or otherwise, we have been advised that in the opinion of the SEC such indemnification is against public policy as expressed in the Securities Act and is, therefore, unenforceable.

SA-11

Table of Contents

PLAN OF DISTRIBUTION

        We have entered into a sales agreement with Cowen under which we may issue and sell shares of our common stock of up to $50,000,000 from time to time through Cowen acting as sales agent, subject to certain limitations, including the number of shares registered under the registration statement to which the offering relates. The sales, if any, of shares made under the sales agreement will be made by any method that is deemed an "at the market" offering as defined in Rule 415 under the Securities Act, including sales made directly on or through The NASDAQ Global Market, the existing trading market for our common stock, and/or any other method permitted by law. We may instruct Cowen not to sell common stock if the sales cannot be effected at or above the price designated by us from time to time. We or Cowen may suspend the offering of common stock upon notice and subject to other conditions.

        Each time we wish to issue and sell common stock under the sales agreement, we will notify Cowen of the number of shares to be sold, the dates on which such sales are anticipated to be made, any minimum price below which sales may not be made and other sales parameters as we deem appropriate. Once we have so instructed Cowen, unless Cowen declines to accept the terms of the notice, Cowen has agreed to use its commercially reasonable efforts consistent with its normal trading and sales practices to sell such shares up to the amount specified on such terms. The obligations of Cowen under the sales agreement to sell our common stock are subject to a number of conditions that we must meet.

        We will pay Cowen commissions for its services in acting as sales agent in the sale of shares of common stock. Cowen will be paid a commission in an amount of up to 3.0% of the gross sales price per share sold. Because there is no minimum offering amount required as a condition to close this offering, the actual total public offering amount, commissions and proceeds to us, if any, are not determinate at this time. In addition, we have agreed to reimburse Cowen for fees and disbursements related to its legal counsel in an amount not to exceed $50,000, and for certain other expenses. We estimate that total expenses for the offering, excluding compensation paid to Cowen under the terms of the sales agreement, will be approximately $200,000.

        Settlement for sales of common stock will generally occur on the third trading day following the date on which any sales are made, or on some other date that is agreed upon by us and Cowen in connection with a particular transaction, in return for payment of the net proceeds to us. Sales of shares of our common stock as contemplated in this prospectus will be settled through the facilities of The Depository Trust Company or by such other means as we and Cowen may agree upon. There is no arrangement for funds to be received in an escrow, trust or similar arrangement.

        In connection with the sale of the common stock on our behalf, Cowen may, and will with respect to sales effected in an "at the market" offering, be deemed to be an "underwriter" within the meaning of the Securities Act and the compensation of Cowen may be deemed to be underwriting commissions or discounts. We have agreed to provide indemnification and contribution to Cowen against certain civil liabilities, including liabilities under the Securities Act.

        The offering of our common stock pursuant to the sales agreement will terminate upon the earlier of (i) the sale of all of our common stock provided for in this prospectus or (ii) termination of the sales agreement as provided therein.

        This summary of the material provisions of the sales agreement does not purport to be a complete statement of its terms and conditions. A copy of the sales agreement is filed as an exhibit to the registration statement of which this prospectus is a part.

        To the extent required by Regulation M, Cowen will not engage in any market making activities involvingor as an exhibit to our common stock while the offering is ongoing under this prospectus.

        Cowen and its affiliates may in the future provide various investment banking and other financial services for us and our affiliates, for which services they may in the future receive customary fees.

SA-12

Table of Contents

LEGAL MATTERS

        Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C., Boston, Massachusetts, will pass upon the validity of the issuance of the securities to be offered by this prospectus. Cowen and Company, LLC is being represented by Goodwin Procter, LLP, New York, New York in connection with this offering.

EXPERTS

        Ernst & Young LLP, independent registered public accounting firm, has audited our consolidated financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2016, and the effectiveness of our internal control over financial reporting as of December 31, 2016, as set forth in their reports, which are incorporated by reference in this prospectus and the registration statement. Our financial statements are incorporated by reference in reliance on Ernst & Young LLP's report, given on their authority as experts in accounting and auditing.

WHERE YOU CAN FIND MORE INFORMATION

        We are subject to the reporting requirements of the Securities Exchange Act of 1934, as amended, and file annual, quarterly and current reports, proxy statements and other information with the SEC. You may read and copy these reports, proxy statements and other information at the SEC's public reference facilities at 100 F Street, N.E., Room 1580, Washington, D.C. 20549. You can request copies of these documents by writing to the SEC and paying a fee for the copying cost. Please call the SEC at 1-800-SEC-0330 for more information about the operation of the public reference facilities. SEC filings, are also available at the SEC's web site athttp://www.sec.gov.

        This prospectus is only part of a registrationeach such statement on Form S-3 that we have filed with the SEC under the Securities Act of 1933, as amended, and therefore omits certain information contained in the registration statement. We have also filed exhibits and schedules with the registration statement that are excluded from this prospectus, and you should refer to the applicable exhibit or schedule for a complete description of any statement referring to any contract or other document. You may inspect a copy of the registration statement, including the exhibits and schedules, without charge, at the public reference room or obtain a copy from the SEC upon payment of the fees prescribed by the SEC.

        We also maintain a website atwww.ovascience.com through which you can access our SEC filings. The information set forth on our website is not part of this prospectus.

INCORPORATION OF DOCUMENTS BY REFERENCE

        The SEC allows us to "incorporate by reference" information that we file with them. Incorporation by reference allows us to disclose important information to you by referring you to those other documents. The information incorporated by reference is an important part of this prospectus, and information that we file later with the SEC will automatically update and supersede this information. We filed a registration statement on Form S-3 under the Securities Act of 1933, as amended, with the SEC with respect to the securities we may offer pursuant to this prospectus. This prospectus omits certain information contained in the registration statement, as permitted by the SEC. You should refer to the registration statement, including the exhibits, for further information about us and the securities we may offer pursuant to this prospectus. Statements in this prospectus regarding the provisions of certain documents filed with, or incorporated by reference in, the registration statement are not necessarily complete and each statement isbeing qualified in all respects by thatsuch reference. Copies of all or any part of the registration statement, including the documents incorporated by reference or the

SA-13

Table of Contents

exhibits, may be obtained upon payment of the prescribed rates at the offices of the SEC listed above in "Where You Can Find More Information." The documents we are incorporating by reference are:

•

our Annual Report on Form 10-K for the fiscal year ended December 31, 2016 that we filed with the SEC on March 2, 2017;





•

the portions of our definitive proxy statement on Schedule 14A filed on April 18, 2016 that are deemed "filed" with the SEC under the Exchange Act;



•

our Current Reports on Form 8-K that we filed with the SEC on January 10, 2017 (except for the information furnished under Items 2.02 or 7.01 and the exhibits furnished thereto);



•

the description of our common stock contained in our Registration Statement on Form 8-A filed on April 25, 2013, including any amendment or report filed for the purpose of updating such description; and



•

all reports and other documents subsequently filed by us pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act after the date of this prospectus and prior to the termination or completion of the offering of securities under this prospectus shall be deemed to be incorporated by reference in this prospectus and to be a part hereof from the date of filing such reports and other documents.

        The SEC file number for each of the documents listed above is 001-35890.

        In addition, all reports and other documents filed by us pursuant to the Exchange Act after the date of Amendment No. 1 to the registration statement and prior to effectiveness of the registration statement shall be deemed to be incorporated by reference into this prospectus.

        Any statement contained in this prospectus or in a document incorporated or deemed to be incorporated by reference into this prospectus will be deemed to be modified or superseded for purposes of this prospectus to the extent that a statement contained in this prospectus or any other subsequently filed document that is deemed to be incorporated by reference into this prospectus modifies or supersedes the statement. Any statement so modified or superseded will not be deemed, except as so modified or superseded, to constitute a part of this prospectus.

        You may request, orally or in writing, a copy of any or all of the documents incorporated herein by reference. These documents will be provided to you at no cost, by contacting:

OvaScience, Inc.
9 Fourth Avenue
Waltham, Massachusetts 02451
Attention: Investor Relations
Telephone: (617) 500-2802

        You may also access these documents on our website,http://www.ovascience.com. The information contained on, or that can be accessed through, our website is not a part of this prospectus. We have included our website address in this prospectus solely as an inactive textual reference.

        You should rely only on information contained in, or incorporated by reference into, this prospectus. We have not authorized anyone to provide you with information different from that contained in this prospectus or incorporated by reference in this prospectus. We are not making offers to sell the securities in any jurisdiction in which such an offer or solicitation is not authorized or in which the person making such offer or solicitation is not qualified to do so or to anyone to whom it is unlawful to make such offer or solicitation.

SA-14

Table of Contents

OVASCIENCE, INC.

$50,000,0001,886,574 Shares

Common Stock

PROSPECTUS

Cowen and Company

                        , 2017

Table of Contents

PART II

INFORMATION NOT REQUIRED IN PROSPECTUS

ItemITEM 14.    Other Expenses of Issuance and DistributionOTHER EXPENSES OF ISSUANCE AND DISTRIBUTION

        The following table sets forth an itemization of the variousfees and expenses all of which we will pay,incurred and to be incurred in connection with the issuance and distributionregistration of the securities being registered. Allregistered hereby, all of the amounts shown are estimated exceptwhich will be borne by us. Except for the SEC Registration Fee.registration fee, all amounts are estimates.

ItemITEM 15.    Indemnification of Directors and OfficersINDEMNIFICATION OF OFFICERS AND DIRECTORS

Delaware Law

        Section 102        Subsection (a) of the General Corporation Law of the State of Delaware permits a corporation to eliminate the personal liability of directors of a corporation to the corporation or its stockholders for monetary damages for a breach of fiduciary duty as a director, except where the director breached his duty of loyalty, failed to act in good faith, engaged in intentional misconduct or knowingly violated a law, authorized the payment of a dividend or approved a stock repurchase in violation of Delaware corporate law or obtained an improper personal benefit.

Section 145 of the General Corporation Law of the State of Delaware provides that("DGCL"), empowers a corporation hasto indemnify any person who was or is a party or who is threatened to be made a party to any threatened, pending or completed action, suit or proceeding, whether civil, criminal, administrative or investigative (other than an action by or in the power to indemnifyright of the corporation) by reason of the fact that the person is or was a director, officer, employee or agent of the corporation, or a personis or was serving at the request of the corporation foras a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise, in related capacities against expenses including(including attorneys' fees,fees), judgments, fines and amounts paid in settlement actually and reasonably incurred by the person in connection with ansuch action, suit or proceeding if the person acted in good faith and in a manner the person reasonably believed to which hebe in or not opposed to the best interests of the corporation, and, with respect to any criminal action or proceeding, had no reasonable cause to believe the person's conduct was unlawful.

        Subsection (b) of Section 145 empowers a corporation to indemnify any person who was or is a party or is threatened to be made a party to any threatened, endingpending or completed action or suit by or proceedingin the right of the corporation to procure a judgment in its favor by reason of the fact that the person acted in any of the capacities set forth above, against expenses (including attorneys' fees) actually and reasonably incurred by the person in connection with the defense or settlement of such position,action or suit if suchthe person acted in good faith and in a manner hethe person reasonably believed to be in or not opposed to the best interests of the corporation, and, in any criminal action or proceeding, had no reasonable cause to believe his conduct was unlawful, except that in the case of actions brought by or in the right of the corporation, no indemnification shall be made within respect toof any claim, issue or matter as to which such person shall have been adjudged to be liable to the corporation unless and only to the extent that the Court of Chancery or other adjudicatingthe court determinesin which such action or suit was brought shall determine upon application that, despite the adjudication of liability but in view of all of the circumstances of the case, such person is fairly and reasonably entitled to indemnity for such expenses which the Court of Chancery or such other court shall deem proper.

Restated Certificate of Incorporation

        Our restated certificate of incorporation limits the personal liability of directors for breach of fiduciary duty        Section 145 further provides that to the maximum extent permitteda director or officer of a corporation has been successful on the merits or otherwise in the defense of any action, suit or proceeding referred to in subsections (a) and (b) of Section 145, or in defense of any claim, issue or matter therein, such person shall be indemnified against expenses (including attorneys' fees) actually and reasonably incurred by such person in connection therewith; that indemnification provided for by Section 145 shall not be deemed exclusive of any other rights to which the Delaware General Corporation Lawindemnified party may be entitled; and provides that nothe indemnification provided for by Section 145 shall, unless otherwise provided when authorized or ratified, continue as to a person who has ceased to be a director, will have personal liabilityofficer, employee or agent and shall inure to us or to our stockholders for monetary damagesthe benefit of such person's heirs, executors and administrators. Section 145 also empowers the

II-1

Table of Contents

corporation to purchase and maintain insurance on behalf of any person who is or was a director, officer, employee or agent of the corporation, or is or was serving at the request of the corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise against any liability asserted against such person and incurred by such person in any such capacity, or arising out of his status as such, whether or not the corporation would have the power to indemnify such person against such liabilities under Section 145.

        Section 102(b)(7) of the DGCL provides that a corporation's certificate of incorporation may contain a provision eliminating or limiting the personal liability of a director to the corporation or its stockholders for monetary damages for breach of fiduciary duty or other duty as a director. However, these provisions dodirector, provided that such provision shall not eliminate or limit the liability of any of our directors for:

•

a director (i) for any breach of the director's duty of loyalty to usthe corporation or our stockholders;



•

its stockholders, (ii) for acts or omissions not in good faith or thatwhich involve intentional misconduct or a knowing violation of law;



•

for voting forlaw, (iii) under Section 174 of the DGCL or assenting to unlawful payments of dividends, stock repurchases or other distributions; or



•

(iv) for any transaction from which the director derived an improper personal benefit.

        In addition, ourOvaScience's restated certificate of incorporation provides that we willOvaScience shall indemnify and advance expenses to each person who was or is a party or threatened to be made a party to any threatened, pending or completed action, suit or proceeding, other than an action bywhether criminal, civil, administrative or in the right of us,investigative, by reason of the fact that he or she is or was, or has agreed to become, a director or officer of OvaScience, or is or was serving, or has agreed to serve, at ourthe request as a director, officer, partner, employee or trustee of or in a similar capacity with, another corporation, partnership, joint venture, trust or other enterprise (all such persons being referred to as an "Indemnitee"), or by reason of any action alleged to have been taken or omitted in such capacity, against all expenses, including attorneys' fees, judgments, fines and amounts paid in settlement actually and reasonably incurred in connection with such action, suit or proceeding and any appeal therefrom, if such Indemnitee acted in good faith and in a manner he or she reasonably believed to be in, or not opposed to, our best interests, and, with respect to any criminal action or proceeding, he or she had no reasonable cause to believe his or her conduct was unlawful.

        Our restated certificate of incorporation also provides that we will indemnify any Indemnitee who was or is a party to an action or suit by or in the right of us to procure a judgment in our favor by reason of the fact that the Indemnitee is or was, or has agreed to become, a director or officer, or is or was serving, or has agreed to serve, at our requestOvaScience, as a director, officer, partner, employee or trustee of, or in a similar capacity with, another corporation, partnership, joint venture, trust or other enterprise, or by reason of any action alleged to have been taken or omitted in such capacity, against all expenses including(including attorneys' fees,fees), liabilities, losses, judgments, fines, and to the extent permitted by law, amounts paid in settlement actually and reasonably incurred in connection with such action, suit or proceeding and any appeal therefrom, iftherefrom.

        OvaScience has indemnification agreements with its directors, in addition to the Indemniteeindemnification provided for in its restated certificate of incorporation, and intends to enter into indemnification agreements with any new directors in the future.

        OvaScience has purchased and intends to maintain insurance on behalf of any person who is or was a director or officer of OvaScience against any loss arising from any claim asserted against him or her and incurred by him or her in any such capacity, subject to certain exclusions.

        Pursuant to the terms of the Merger Agreement and subject to applicable law, from the Effective Time through the sixth anniversary of the date on which the Effective Time occurs, OvaScience shall indemnify and hold harmless each person who is now, or has been at any time prior to the date thereof, or who becomes prior to the Effective Time, a director or officer of OvaScience or Millendo, respectively, against all Costs incurred in connection with any claim, action, suit, proceeding or investigation, whether civil, criminal, administrative or investigative, arising out of or pertaining to the fact that such person is or was a director or officer of OvaScience or Millendo, whether asserted or claimed prior to, at or after the Effective Time, in each case, to the fullest extent permitted under the DGCL for directors or officers of Delaware corporations, provided that such officer or director acted in good faith and in a manner he or she reasonablysuch party reasonable believed to be in or not opposed to ourthe best interests, exceptinterest of OvaScience or the Surviving Corporation, as applicable, and, with respect to any criminal proceeding, such officer or director had no reasonable cause to believe such conducted was unlawful; provided, further, that, if applicable law so provides, no indemnification against such Costs shall be made within respect toof any claim, issue or matter in such proceeding as to which such personthe director or officer shall have been adjudged to be liable to us,OvaScience or the Surviving Corporation unless a court determines that, despite such adjudication but in view of all of the circumstances, he or she is entitled to indemnification of such expenses. Notwithstanding the foregoing,and to the extent that any Indemnitee has been successful, on the merits or otherwise, he or sheCourt of Chancery of the State of Delaware shall determine that such indemnification may be made. Subject to applicable law, each such director and officer will be indemnified by us against allentitled to advancement of expenses including attorneys' fees, actually and reasonably incurred in connection therewith. Expenses must be advanced to an Indemnitee under certain circumstances.

Indemnification Agreements

        We have entered into indemnification agreements withthe defense of any such claim, action, suit, proceeding or investigation from each of ourOvaScience and the Surviving Corporation, jointly and severally, upon receipt by OvaScience or

II-2

Table of Contents

the Surviving Corporation from such director or officer of a request therefor; provided that any such person to whom expenses are advanced provides an undertaking to OvaScience or the Surviving Corporation, as applicable, to the extent then required by the DGCL, to repay such advances if it is ultimately determined that such person is not entitled to indemnification. Such statement or statements shall reasonably evidence the expenses incurred by the directors and officers. These

        Further, pursuant to the Merger Agreement, the provisions of the OvaScience restated certificate of incorporation and the OvaScience by-laws with respect to indemnification, agreements may require us, among other things, to indemnify ouradvancement of expenses and exculpation of present and former directors and officers of OvaScience shall not be amended, modified or repealed for some expenses, including attorneys' fees, judgments, finesa period of six years from the Effective Time in a manner that would adversely affect the rights thereunder of individuals who, at or prior to the Effective Time, were officers or directors of OvaScience, unless such modification is required by applicable law.

        From and settlement amounts incurred byafter the Effective Time, (i) the Surviving Corporation shall fulfill and honor in all respects the obligations of Millendo to each person who is or has served as a director or officer inof Millendo as of immediately prior to the Closing pursuant to any actionindemnification provisions under the Millendo certificate of incorporation or proceedingMillendo bylaws and pursuant to any indemnification agreements between Millendo and such directors and officers, with respect to claims arising out of hismatters occurring at or her serviceprior to the Effective Time and (ii) OvaScience shall fulfill and honor in all respects the obligations of OvaScience to each person who is or has served as onea director or officer of ourOvaScience as of immediately prior to the Closing pursuant to any indemnification provisions under the OvaScience Charter or OvaScience Bylaws and pursuant to any indemnification agreements between OvaScience and such directors and officers that were in effect prior to the date of the Merger Agreement, with respect to claims arising out of matters occurring at or prior to the Effective Time.

        The Merger Agreement also provides that OvaScience shall maintain directors' and officers' liability insurance policies commencing at the closing time of the Merger, on commercially available terms and conditions with coverage limits customary for U.S. public companies similar situated to OvaScience. In addition, OvaScience shall purchase, prior to the Effective Time, a six-year prepaid "D&O tail policy" for the non-cancellable extension of the directors' and officers' liability coverage of OvaScience's existing directors' and officers' insurance policies and OvaScience's existing fiduciary liability insurance policies, in each case, for a claims reporting or discovery period of at least six years from and after the Effective Time.

        From and after the Effective Time, OvaScience shall pay all expenses, including reasonable attorneys' fees, that are incurred by indemnified persons in connection with their successful enforcement of the rights provided to such persons in the Merger Agreement. The director and officer indemnification provisions of the Merger Agreement are intended to be in addition to the rights otherwise available to the current and former officers and directors of OvaScience and Millendo by law, charter, statute, bylaw or agreement, and shall operate for the benefit of, and shall be enforceable by, each of such indemnified persons, their heirs and their representatives.

        In the event OvaScience or the Surviving Corporation or any of our subsidiariestheir respective successors or assigns (i) consolidates with or merges into any other companyperson and shall not be the continuing or enterprisesurviving corporation or entity of such consolidation or merger, or (ii) transfers all or substantially all of its properties and assets to whichany person, then, and in each such case, proper provision shall be made so that the person provides services at our request.successors and assigns of OvaScience or the Surviving Corporation, as the case may be, shall succeed to the indemnification obligations set forth in the Merger Agreement. OvaScience shall cause the Surviving Corporation to perform all of the director and officer indemnification obligations of the Surviving Corporation under the Merger Agreement.

        We maintain a general liability insurance policy that covers certain liabilities of directors and officers of our corporation arising out of claims based on acts or omissions in their capacities as directors or officers.

II-2II-3

Table of Contents

ItemITEM 16.    ExhibitsEXHIBITS AND FINANCIAL STATEMENT SCHEDULES

        TheA list of exhibits filed herewith is contained in the exhibit index that immediately precedes the signatures to this registration statement are listed in the Exhibit Index to this registration statement, which Exhibit Indexand is hereby incorporated herein by reference.

ItemITEM 17.    UndertakingsUNDERTAKINGS

        (a)        The undersigned registrant hereby undertakes:

        (1)   To file, during any period in which offers or sales are being made, a post-effective amendment to this registration statement:

(i)

To include any prospectus required by sectionSection 10(a)(3) of the Securities Act of 1933;





(ii)

To reflect in the prospectus any facts or events arising after the effective date of the registration statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in the registration statement. Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the Securities and Exchange Commission pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price represent no more than a 20% change in the maximum aggregate offering price set forth in the "Calculation of Registration Fee" table in the effective registration statement; and





(iii)

To include any material information with respect to the plan of distribution not previously disclosed in the registration statement or any material change to such information in the registration statement;provided,

Provided however,, that paragraphs (a)(1)(i), (a)(1)(ii) and (a)(1)(iii) of this section do not apply if the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the Commission by the registrant pursuant to section 13 or section 15(d) of the Securities Exchange Act of 1934 that are incorporated by reference in the registration statement, or is contained in a form of prospectus filed pursuant to Rule 424(b) that is part of the registration statement.

        (2)   That, for the purpose of determining any liability under the Securities Act of 1933, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initialbona fide offering thereof.

        (3)   To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at the termination of the offering.

        (4)   That, for the purpose of determining liability under the Securities Act of 1933 to any purchaser:

(i)

If the registrant is relying on Rule 430B:



(A)

Each prospectus filed by the registrant pursuant to Rule 424(b)(3) shall be deemed to be part of the registration statement as of the date the filed prospectus was deemed part of and included in the registration statement; and

         (ii)  



(B)

Each prospectus required to be filed pursuant to Rule 424(b)(2), (b)(5), or (b)(7) as part of a registration statement in reliance on Rule 430B relating to an offering made pursuant to Rule 415(a)(1)(i), (vii), or (x) for the purpose of providing the

II-4

Table of Contents

information required by sectionSection 10(a) of the Securities Act of 1933 shall be deemed to be part of and included in the registration statement as of the earlier of the date such form of prospectus is first used after effectiveness or the date of the first contract of sale of securities in the

II-3

---

Table of Contents

offering described in the prospectus. As provided in Rule 430B, for liability purposes of the issuer and any person that is at that date an underwriter, such date shall be deemed to be a new effective date of the registration statement relating to the securities in the registration statement to which that prospectus relates, and the offering of such securities at that time shall be deemed to be the initialbona fide offering thereof.Provided,,however,, that no statement made in a registration statement or prospectus that is part of the registration statement or made in a document incorporated or deemed incorporated by reference into the registration statement or prospectus that is part of the registration statement will, as to a purchaser with a time of contract of sale prior to such effective date, supersede or modify any statement that was made in the registration statement or prospectus that was part of the registration statement or made in any such document immediately prior to such effective date.date; or

        (5)   That, for the purpose of determining liability of

(ii)

If the registrant under the Securities Act of 1933is subject to any purchaser in the initial distribution of the securities, in a primary offering of securities of the undersigned registrant pursuant to this registration statement, regardless of the underwriting method used to sell the securities to the purchaser, if the securities are offered or sold to such purchaser by means of any of the following communications, the undersigned registrant will be a seller to the purchaser and will be considered to offer or sell such securities to such purchaser:

          (i)  Any preliminaryRule 430C, each prospectus or prospectus of the undersigned registrant relating to the offering required to be filed pursuant to Rule 424;

         (ii)  Any free writing prospectus relating to the offering prepared by or on behalf of the undersigned registrant or used or referred to by the undersigned registrant;

        (iii)  The portion of any other free writing prospectus relating to the offering containing material information about the undersigned registrant or its securities provided by or on behalf of the undersigned registrant; and

        (iv)  Any other communication that is an offer in the offering made by the undersigned registrant to the purchaser.

        (b)   That, for purposes of determining any liability under the Securities Act:

          (i)  the information omitted from the form of prospectus filed424(b) as part of thea registration statement relating to an offering, other than registration statements relying on Rule 430B or other than prospectuses filed in reliance uponon Rule 430A, and contained in the form of prospectus filed by the registrant pursuant to Rule 424(b)(1) or (4) or 497(h) under the Securities Act shall be deemed to be part of and included in the registration statement as of the timedate it was declared effective; and

         (ii)  each post-effective amendmentis first used after effectiveness. Provided, however, that containsno statement made in a form of prospectus shall be deemed to be a new registration statement relatingor prospectus that is part of the registration statement or made in a document incorporated or deemed incorporated by reference into the registration statement or prospectus that is part of the registration statement will, as to a purchaser with a time of contract of sale prior to such first use, supersede or modify any statement that was made in the securities offered therein, andregistration statement or prospectus that was part of the offeringregistration statement or made in any such document immediately prior to such date of such securities at that time shall be deemed to be the initialbona fide offering thereof.

first use.

        (c)        The undersigned registrant hereby undertakes that, for purposes of determining any liability under the Securities Act of 1933, each filing of the registrant's annual report pursuant to section 13(a) or section 15(d) of the Securities Exchange Act of 1934 (and, where applicable, each filing of an employee benefit plan's annual report pursuant to section 15(d) of the Securities Exchange Act of 1934) that is incorporated by reference in the registration statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initialbona fide offering thereof.

        (d)        Insofar as indemnification for liabilities arising under the Securities Act of 1933 may be permitted to directors, officers and controlling persons of the registrant pursuant to the foregoing provisions, or otherwise, the registrant has been advised that in the opinion of the Securities and Exchange Commission such indemnification is against public policy as expressed in the Securities Act and is, therefore, unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the registrant of expenses incurred

II-4

---

Table of Contents

or paid by a director, officer or controlling person of the registrant in the successful defense of any action, suit or proceeding) is asserted by sucha director, officer or controlling person in connection with the securities being registered, the registrant will, unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act of 1933 and will be governed by the final adjudication of such issue.

        (e)   The undersigned registrant hereby undertakes to file an application for the purpose of determining the eligibility of the trustee to act under subsection (a) of Section 310 of the Trust Indenture Act ("Act") in accordance with the rules and regulations prescribed by the Commission under section 305(b)(2) of the Act.

II-5

---

Table of Contents


EXHIBIT INDEX


        The following exhibits are filed as part of this Registration Statement:

Exhibit No.			Description
	2.1		Agreement and Plan of Merger and Reorganization, dated as of August 8, 2018, by and among OvaScience, Inc., Orion Merger Sub, Inc. and Millendo Therapeutics, Inc. (incorporated by reference from Annex A to Amendment No. 1 to the Registration Statement on Form S-4, as filed with the Securities and Exchange Commission on November 1, 2018, File No. 333-227547).
	2.2		First Amendment to Agreement and Plan of Merger and Reorganization, dated as of August 8, 2018, by and among OvaScience,  Inc., Orion Merger Sub, Inc. and Millendo Therapeutics, Inc. (incorporated by reference from Annex A to Amendment No. 1 to the Registration Statement on Form S-4, as filed with the Securities and Exchange Commission on November 1, 2018, File No. 333-227547).
	2.3		Second Amendment to Agreement and Plan of Merger and Reorganization, dated as of August 8, 2018, by and among OvaScience,  Inc., Orion Merger Sub, Inc. and Millendo Therapeutics, Inc. (incorporated by reference from Annex A to Amendment No. 1 to the Registration Statement on Form S-4, as filed with the Securities and Exchange Commission on November 1, 2018, File No. 333-227547).
	4.1		Restated Certificate of Incorporation of OvaScience, Inc. (incorporated by reference from the Current Report on Form 8-K filed by the Registrant on April 30, 2013, File No. 001-35890).
	4.2		Third Amended and Restated Bylaws, as amended, of OvaScience, Inc. (incorporated by reference from the Current Report on Form 8-K filed by the Registrant on August 9, 2018, File No. 001-35890).
	4.3		Specimen Stock Certificate evidencing shares of Common Stock of OvaScience, Inc. (incorporated by reference to the Registration Statement on Form S-1 filed by the registrant on August 29, 2012, File No. 333-183602).
	4.4		Registration Rights Agreement, dated November 1, 2018, by and among OvaScience, Inc. and the persons listed on Schedule A thereto (incorporated by reference from Exhibit 10.46 to Amendment No. 1 to the Registration Statement on Form S-4, as filed with the Securities and Exchange Commission on November 1, 2018, File No. 333-227547).
	4.5		Stock Purchase Agreement, dated November 1, 2018, by and among OvaScience, Inc., the purchasers set forth on Schedule I thereto and Millendo Therapeutics, Inc. (incorporated by reference from Exhibit 10.45 to Amendment No. 1 to the Registration Statement on Form S-4, as filed with the Securities and Exchange Commission on November 1, 2018, File No. 333-227547).
	4.6		Second Amended and Restated Investor Rights Agreement by and among Millendo Therapeutics, Inc. and certain of its stockholders, dated December 19, 2017 (incorporated by reference from Exhibit 4.6 to the Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on November 6, 2018, File No. 333-228209).
	4.7		First Amendment to Second Amended and Restated Investor Rights Agreement, dated October 24, 2018 (incorporated by reference from Exhibit 4.7 to the Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on November 6, 2018, File No. 333-228209).

II-6

---

Table of Contents

Exhibit No.			Description
	4.8		Shareholders and Option Agreement, by and between Millendo Therapeutics, Inc. and Otonnale SAS, dated December 19, 2017 (incorporated by reference from Exhibit 4.8 to the Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on November 6, 2018, File No. 333-228209).
	4.9		First Amendment to Shareholders and Option Agreement, dated September 28, 2018 (incorporated by reference from Exhibit 4.9 to the Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on November 6, 2018, File No. 333-228209).
	4.10	*	First Amendment to Stock Purchase Agreement, dated November 28, 2018, by and among OvaScience, Inc., the purchasers set forth on Schedule I thereto and Millendo Therapeutics, Inc.
	5.1		Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. regarding the validity of the securities (incorporated by reference from Exhibit 5.1 to the Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on November 6, 2018, File No. 333-228209).
	10.1		Lease Agreement, by and between Millendo Therapeutics, Inc. and 301 N. Main Street, L.L.C., dated December 31, 2015 (incorporated by reference from Exhibit 10.1 to the Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on November 6, 2018, File No. 333-228209).
	10.2		Lease Extension and Modification Agreement, by and between Millendo Therapeutics, Inc. and 301 N. Main Street, L.L.C., dated November 30, 2017 (incorporated by reference from Exhibit 10.2 to the Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on November 6, 2018, File No. 333-228209).
	10.3		Lease Extension and Modification Agreement, by and between Millendo Therapeutics, Inc. and 301 N. Main Street, L.L.C., dated October 22, 2018 (incorporated by reference from Exhibit 10.3 to the Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on November 6, 2018, File No. 333-228209).
	10.4	#	Amendment No. 1 to the Atterocor, Inc. (n/k/a Millendo Therapeutics, Inc.) 2012 Stock Plan, dated December 17, 2015 (incorporated by reference from Exhibit 10.4 to the Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on November 6, 2018, File No. 333-228209).
	10.5	#	Millendo Therapeutics, Inc. Amendment to 2012 Stock Plan, dated June 21, 2018 (incorporated by reference from Exhibit 10.5 to the Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on November 6, 2018, File No. 333-228209).
	23.1	*	Consent of Ernst & Young LLP, Independent Registered Public Accounting Firm to OvaScience, Inc.
	23.2	*	Consent of Ernst & Young LLP, Independent Auditors to Millendo Therapeutics, Inc.
	23.3	*	Consent of RSM Rhône-Alpes, Independent Auditors to Millendo Therapeutics SAS

II-7

---

Table of Contents

Exhibit No.			Description
	23.4		Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. (included in Exhibit 5.1)
	24.1		Power of Attorney (included on the signature page of this Registration Statement filed on November 6, 2018)

---

*

Filed herewith.



#

Indicates a management contract or compensatory plan, contract or arrangement.

II-8

---

Table of Contents

SIGNATURES


        Pursuant to the requirements of the Securities Act of 1933, as amended, the registrantRegistrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-3 and has duly caused this Amendment No. 1 to the registration statementRegistration Statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Waltham, Commonwealth of Massachusetts, on March 2, 2017.the 28th day of November, 2018.

		OvaScience, Inc.
		By:		/s/ MICHELLE DIPPCHRISTOPHER A. KROEGER, M.D., M.B.A. Michelle Dipp,Christopher A. Kroeger, M.D., Ph.D.M.B.A. President and Chief Executive Chair of the Board of Directors and acting PresidentOfficer


SIGNATURES AND POWER OF ATTORNEY


        Pursuant to the requirements of the Securities Act of 1933, as amended, this registration statementRegistration Statement on Form S-3 has been signed below by the following persons in the capacities and on the dates indicated.

SignatureName		Title		Date
/s/ MICHELLE DIPPCHRISTOPHER A. KROEGER, M.D., M.B.A. Michelle Dipp,Christopher A. Kroeger, M.D., Ph.D.M.B.A.		President and Chief Executive Chairman of the Board of Directors and acting PresidentOfficer (Principal executive officer)Executive Officer)		March 2, 2017November 28, 2018
/s/ CHRISTOPHE COUTURIERJONATHAN GILLIS Christophe CouturierJonathan Gillis		ChiefSenior Vice President, Finance (Principal Financial Officer and Treasurer (Principal financial and accounting officerOfficer)		March 2, 2017November 28, 2018
* Richard Aldrich		Director		March 2, 2017
* Jeffrey D. Capello				Director		March 2, 2017November 28, 2018
* Richard Aldrich		Director		November 28, 2018
* Mary Fisher		Director		March 2, 2017November 28, 2018
* John P. Howe, III, M.D.		Director		March 2, 2017November 28, 2018

II-6

---

Table of Contents

Signature				Title		Date
* Marc Kozin				Director		March 2, 2017
* Thomas Malley				Director		March 2, 2017November 28, 2018
* John Sexton, Ph.D.		Director		March 2, 2017November 28, 2018
*By:		/s/ CHRISTOPHE COUTURIER Christophe Couturier Attorney-in-fact

II-7II-9

---

Table of Contents


EXHIBIT INDEX


Exhibit Number			Exhibit Description		Filed Herewith		Incorporated by Reference herein from Form or Schedule		Filing Date		SEC File/ Reg. Number
	1.1	*	Form of Underwriting Agreement.
	1.2		Sales Agreement, dated as of November 3, 2016, by and between the Registrant and Cowen and Company, LLC				S-3 (Exhibit 1.2)		11/3/2016		333-214413
	4.1		Restated Certificate of Incorporation of the Registrant				8-K (Exhibit 3.1)		04/30/2013		001-35890
	4.2		Second Amended and Restated By-laws of the Registrant				8-K (Exhibit 3.2)		04/30/2013		001-35890
	4.3		Specimen Stock Certificate evidencing the shares of Common Stock				S-1 (Exhibit 4.1)		08/29/2012		333-183602
	4.4	*	Form of Certificate of Amendment or Designation with respect to Preferred Stock
	4.5	*	Form of Senior Debt Security
	4.6	*	Form of Subordinated Debt Security
	4.7		Form of Senior Indenture				S-1 (Exhibit 4.7)		11/3/2016		333-214413
	4.8		Form of Subordinated Indenture				S-1 (Exhibit 4.8)		11/3/2016		333-214413
	4.9	*	Form of Warrant Agreement and Warrant Certificate
	4.10	*	Form of Rights Agreement and Right Certificate
	4.11	*	Form of Purchase Contract
	4.12	*	Form of Unit Agreement and Unit
	5.1	†	Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. with respect to the legality of the securities being registered		X
	12.1	*	Computation of Ratio of Earnings to Fixed Charges
	23.1		Consent of Ernst & Young LLP		X
	23.2		Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. (included in the opinion filed as Exhibit 5.1)		X

---

Table of Contents

Exhibit Number			Exhibit Description		Filed Herewith		Incorporated by Reference herein from Form or Schedule		Filing Date		SEC File/ Reg. Number
	24.1		Powers of Attorney.				Included on signature page to initial Registration Statement		11/3/2016		333-214413
	25.1	*	The Statement of Eligibility on Form T-1 under the Trust Indenture Act of 1939, as amended, of the Trustee under the Senior Indenture will be incorporated herein by reference from a subsequent filing in accordance with Section 305(b)(2) of the Trust Indenture Act of 1939.
	25.2	*	The Statement of Eligibility on Form T-1 under the Trust Indenture Act of 1939, as amended, of the Trustee under the Subordinated Indenture will be incorporated herein by reference from a subsequent filing in accordance with Section 305(b)(2) of the Trust Indenture Act of 1939.

---

*

To be subsequently filed, if applicable, by an amendment to this registration statement or by a Current Report on Form 8-K



†

Replaces previously filed exhibit

---