The Ovarian Contraceptive Discovery Initiative
A significant barrier to discovering novel contraceptive agents that target ovulation and fertilization-associated processes is a lack of robust systems for exploring the biology of these processes in a sophisticated manner, particularly with respect to target validation and translational potential.
The Ovarian Contraceptive Discovery Initiative supports the development and deployment of an integrated platform for the systematic study of ovarian biology with the purpose of delivering a robust and optimized series of follicle- and oocyte-focused contraceptive targets, pathways, and screening tools. This comprehensive and enduring biological platform is part of the Bill & Melinda Gates Foundation's broader efforts in female contraceptive discovery.
Institute Structure
The Ovarian Contraceptive Discovery Initiative is multi-PI and institutional endeavor. Francesca Duncan, PhD is the overall program PI, and she leads the Project Management & Technology Dissemination Core. Under this framework are four projects led by PIs: Shuo Xiao, PhD (Rutgers University), Francesca E. Duncan, PhD (Northwestern University), Amander Clark, PhD (UCLA), Britt Goods, PhD (Dartmouth College), and Alex Shalek, PhD (Ragon Institute, Massachusetts General Hospital). In addition to these projects, Sami Farhi, PhD from the Broad Institute has led a pilot on spatial transcriptomics of ovulation. Central to the Ovarian Contraceptive Discovery Initiative is interaction with the following institutional and community following partners: Bill & Melinda Gates Foundation and, Rutgers University, Northwestern University and the Northwestern Center for Reproductive Science, UCLA, Ragon Institute, Micrographia Bio, Exscientia, ReFRAME Calibr at Scripps Research, Schrödinger, Caltech, ApconiX, UIC, and Genomic Prediction.
Project Management & Technology Dissemination Core
Program PI
Francesca E. Duncan, PhD
Northwestern University, Associate Professor
Scientific Lead
Jeff Pea, PhD
Northwestern University
Administrative Lead
Lauren Ataman-Millhouse, MA
Northwestern University
Scientific Adviser
John Proudfoot, PhDMedicinal Chemistry
Projects
Project 1
Organotypic Screening Tools and Targets in the Mouse Follicle
PI: Shuo Xiao, PhD, Rutgers University
Project 2
Harnessing the biology of oocyte maturation-specific pathways to identify novel targets for contraceptive development
PI: Francesca Duncan, PhD, Northwestern University
Project 3
Building mouse and human ovarian follicles de novo from induced pluripotent stem cells
PI: Amander Clark, PhD, University of California, Los Angeles
Project 4
Transcriptional changes driving follicle autonomous activation and ovulation for contraceptive discovery
PIs: Alex Shalek, PhD, Ragon Institute, & Britt Goods, PhD, Dartmouth College
News
July 2024
- OCDI members attended the 2024 Annual Meeting of the Society for the Study of Reproduction (SSR) held in Dublin, Ireland from July 15th-19th! The team was well-represented with poster presentations, talks, and awards!
- Dr. Shuo Xiao, recipient of the SSR Virendra, B. Mahesh New Investigator Award, presented his talk "From a small follicle to a big story" at SSR 2024 as well as his talk "Ovary-on-achip to understand transmitted signals from the follicle" at the Ovarian Workshop Pre-conference
- Dr. Jeff Pea presented his talk titled "Identification of new targets for non-hormonal contraceptive drug development using a phenotypic assay of murine oocyte meiotic maturation" at SSR 2024
- Dr. Sissy Wamaitha presented her work titled "Defining the cell and molecular origins of the primate ovarian reserve" at SSR 2024
- Dr. Hoi Chang Lee presented his poster "A phenotypic screening assay of mouse egg activation identifies novel inhibitors targeting Wee2 for non-hormonal contraceptive applications"
- Emily Zaniker was the recipient of the Anita Payne Scholarship to support the cost of travel and participation in the Frontiers in Reproduction (FIR) program
June 2024
- A new OCDI publication: Huang R, Kratka CE, Pea J, McCann C, Nelson J, Bryan JP, Zhou LT, Russo DD, Zaniker EJ, Gandhi AH, Shalek AK, Cleary B, Farhi SL, Duncan FE, Goods BA. Single-cell and spatiotemporal profile of ovulation in the mouse ovary. bioRxiv [Preprint]. 2024 Jun 5:2024.05.20.594719. doi: 10.1101/2024.05.20.594719. PMID: 38826447; PMCID: PMC11142086.
May 2024
- OCDI members attended the 2024 Bill & Melinda Gates Foundation Non-Hormonal Contraceptive (NHC) Discovery Spring Convening at Bayer Pharmaceuticals in Berlin, Germany!
- Dr. Francesca Duncan gave an invited talk titled "The Ovarian Contraceptive Discovery Initiative"
- Dr. Shuo Xiao presented his poster titled "An ex vivo ovulation platform to identify non-hormonal female contraceptives"
- Dr. Jeff Pea presented his poster titled "Identification of targets that block oocyte meiotic maturation for non-hormonal contraceptive drug development"
- Caroline Kratka presented her poster titled "A spatiotemporal profile of ovulation at single cell resolution reveals novel time-dependent cell states with distinct gene expression that can inform non-hormonal contraceptive discovery"
- Zhanel Nugmanova presented her poster titled "Establishing a consensus definition of human ovarian tissue and cell-type specificity to identify novel gene targets for contraceptive discovery using single-cell RNA sequencing datasets"
- Qiu-Ya Wu presented her poster titled "Engineering Human Ovarian Assembloids to Advance Contraceptive Discovery"
April 2024
- A new OCDI publication: Zhu Y, Kratka CR, Pea J, Lee HC, Kratka CE, Xu J, Marin D, Treff NR, Duncan FE. The severity of meiotic aneuploidy is associated with altered morphokinetic variables of mouse oocyte maturation. Human Reproduction Open. 2024 Apr 23;2024(2):hoae023. doi: 10.1093/hropen/hoae023. PMID: 38764910; PMCID: PMC11099657.
March 2024
- OCDI team members met at the Northwestern University campus in Chicago, Illinois for the 2024 Program Site Visit. The team was also joined by external investigators within the Non-Hormonal Contraceptive (NHC) ecosystem at the Bill & Melinda Gates Foundation to support ongoing discussions on strategic target prioritization.
February 2024
- Dr. Goods was invited to share her ongoing research with the OCDI at the 2024 SSR Rising Stars Webinar. Her talk was titled "Using single-cell transcriptomics to understand ovulation and drive contraceptive discovery".
November 2023
- OCDI members attended the 2023 National Contraception Meeting in Houston, Texas.
- Dr. Shuo Xiao presented his talk "An Ex Vivo Mammalian Ovulation Model to Identify Non-hormonal Contraceptive Candidates"
- Dr. Hoi Chang Lee presented his poster "Using a phenotypic screening assay of mouse egg activation to test novel Wee2 inhibitors for non-hormonal contraceptive applications"
- Dr. Jeff Pea presented his poster "The Ovarian Contraceptive Discovery Initiative: A Collaborative, Multi-Disciplinary Infrastructure Focused on Developing Female Non-Hormonal Contraceptives"
- Dr. Jiyang Zhang presented her poster "Ex Vivo Ovulation Screening of a Protease Inhibitor Library to Identify Non-hormonal Contraceptive Candidates"
- Victoria Zhu presented her poster "A phenotypic drug screening pipeline of mouse oocyte maturation for the identification of compounds targeting meiotic progression"
- Zhanel Nugmanova presented her poster "Establishing a Consensus Definition of Human Ovarian Tissue and Cell-Type Specificity to Identify Novel Gene Targets for Contraceptive Discovery Using Single-Cell RNA Sequencing Datasets"
- A new OCDI publication: Sosa E, Mumu SK, Alvarado CC, Wu QY, Roberson I, Espinoza A, Hsu FM, Saito K, Hunt TJ, Faith JE, Lowe MG, DiRusso JA, Clark AT. Reconstituted ovaries self-assemble without an ovarian surface epithelium. Stem Cell Reports. 2023 Nov 14;18(11):2190-2202. doi: 10.1016/j.stemcr.2023.10.001. PMID: 37890483.
October 2023
- A new OCDI publication: Babayev E, Suebthawinkul C, Gokyer D, Parkes WS, Rivas F, Pavone ME, Hall AR, Pritchard MT, Duncan FE. Cumulus expansion is impaired with advanced reproductive age due to loss of matrix integrity and reduced hyaluronan. Aging Cell. 2023 Oct 18:e14004. doi: 10.1111/acel.14004. Epub ahead of print. PMID: 37850336
- A new OCDI publication: Campo H, Zha D, Pattarawat P, Colina J, Zhang D, Murphy A, Yoon J, Russo A, Rogers HB, Lee HC, Zhang J, Trotter K, Wagner S, Ingram A, Pavone ME, Dunne SF, Boots CE, Urbanek M, Xiao S, Burdette JE, Woodruff TK, Kim JJ. A new tissue-agnostic microfluidic device to model physiology and disease: the lattice platform. Lab on a Chip. 2023 Oct 17. doi: 10.1039/d3lc00378g. Epub ahead of print. PMID: 37846545.
- OCDI members attended and presented at the 2023 American Society for Reproductive Medicine (ASRM) Annual Meeting in New Orleans, Louisiana.
- Dr. Francesca Duncan gave an invited talk title "It's the nest, not just the egg: uncovering the role of the intra-ovarian environment in ovarian aging" as part of a post-graduate ovarian aging course
- Emily Zaniker, recipient of the In-Training Award for Research, presented her talk "Harnessing functional and molecular asymmetry during ex vivo ovulation for non-hormonal contraceptive discovery"
- Caroline Kratka presented her talk "Identification of novel cell populations in the mouse ovary throughout an in vivo time course of ovulation".
- Catherine Kratka, who works at Genomic Prediction in collaboration with the OCDI, presented her poster presentation "Meiotic aneuploidy severity is associated with altered morphokinetics of oocyte maturation"
- The OCDI team (Dr. Francesca Duncan, Dr. Shuo Xiao, Dr. Jeff Pea, Dr. Sissy Wamaitha) traveled to Dakar, Senegal to participate in the 2023 Bill & Melinda Gates Foundation Grand Challenges meeting.
- Dr. Sissy Wamaitha presented her talk "Development and characterization of mouse and human ovarian follicle organoid systems"
- Dr. Jeff Pea presented his poster "The Ovarian Contraceptive Discovery Initiative: A Collaborative, Multi-Disciplinary Infrastructure Focused on Developing Female Non-Hormonal Contraceptives"
- Dr. Shuo Xiao presented his poster "A high-throughput ex vivo ovulation screening platform to identify non-hormonal female contraceptive candidates"
August 2023
- A new OCDI publication: Wamaitha SE, Nie X, Pandolfi EC, Wang X, Yang Y, Stukenborg JB, Cairns BR, Guo J, Clark AT. Single-cell analysis of the developing human ovary defines distinct insights into ovarian somatic and germline progenitors. Developmental Cell. 2023 Aug 8:S1534-5807(23)00361-1. doi: 10.1016/j.devcel.2023.07.014. Epub ahead of print. PMID: 37582368.
July 2023
- The OCDI team met to attend the Annual Program meeting as well as the 2023 Annual Meeting of the Society for the Study of Reproduction (SSR) held in Ottawa, Canada from July 10th-14th! All of the project members were well-represented with poster presentations, talks, and awards!
- Dr. Duncan was invited to present her talk titled "Exceptional longevity of mammalian ovarian and oocyte macromolecules throughout the reproductive lifespan" at SSR 2023
- Astha Adroja, recipient of the Lalor Foundation Merit Award and finalist in the Trainee Research Award Pre-doctoral Competition, presented her talk "Targeting proprotein convertases and follicle rupture to identify non-hormonal contraceptive candidates" at SSR 2023
- Rachel Huang presented her talk titled "Mapping ovulation with spatiotemporal and single-cell resolution" at SSR 2023
- Caroline Kratka, recipient of the SSR Trainee Travel Award, presented her talk "Pharmacological inhibition of proprotein convertases prevents cumulus expansion due to extracellular matrix stability" at SSR 2023
- Dr. Hoi Chang Lee gave a flash talk and presented his poster titled "Establishing timelapse parameters of egg activation to screen Wee2 inhibitors for non-hormonal contraceptive applications" at SSR 2023
- Emily Zaniker, recipient of the SSR Trainee Travel Award, gave a flash talk and presented her poster titled "Harnessing functional and molecular asymmetry during ex vivo ovulation for non-hormonal contraceptive discovery" at SSR 2023
- Sissy Wamaitha presented her poster titled "Single cell analysis of the developing human ovary reveals distinct insights into ovarian somatic and germline progenitors" at SSR 2023
- Isaias Roberson presented his poster titled "Characterizing the induction of PGCLCs use for in vitro gametogenesis" at SSR 2023
May 2023
- A new OCDI publication:
Zaniker EJ, Babayev E, Duncan FE. Common mechanisms of physiological and pathological rupture events in biology: novel insights into mammalian ovulation and beyond. Biological Reviews Cambridge Philosophical Society. 2023 May 8. doi: 10.1111/brv.12970. Epub ahead of print. PMID: 37157877
April 2023
- A new OCDI publication:
Suebthawinkul C, Babayev E, Lee HC, Duncan FE. Morphokinetic parameters of mouse oocyte meiotic maturation and cumulus expansion are not affected by reproductive age or ploidy status, Journal of Assisted Reproduction and Genetics, 2023; 10.1007/s10815-023-02779-y - Dr. Duncan highlighted ongoing research through the OCDI at the UC Davis Reproductive Biology Supergroup seminar series on April 12, 2023 entitled: "Recapitulating folliculogenesis and oogenesis ex vivo: from novel biology to translational application."
- Dr. Clark provided her perspective on in vitro gametogenesis in a recent article on the future of fertility in the New Yorker.
https://www.newyorker.com/magazine/2023/04/24/the-future-of-fertility - The OCDI team attended the Bill & Melinda Gates Foundation Non-Hormonal Contraceptive (NHC) Discovery Convening and the 2023 Tri-Institutional Symposium for Reproductive Biology & Infertility on April 26th-28th!
- Dr. Francesca Duncan co-presented a talk with collaborators at Schröindger titled "Discovery and evaluation of highly selective Wee2 inhibitors" at the NHC Discovery Convening
- Dr. Amander Clark gave a talk titled "Building mouse and human ovarian follicular organoids de novo from iPSCs" at the NHC Discovery Convening
- Dr. Britt Goods gave a talk titled "Application of systems biology to illuminate ovarian biology – a data and bioinformatics perspective" at the NHC Discovery Convening
- Dr. Francesca Duncan gave the Stuart Moss Memorial Lecture titled "Transforming ovarian aging into reproductive longevity" at the 2023 Tri-Repro Symposium
- Dr. Jiyang Zhang gave a talk titled "Targeting proprotein convertases and ovulation to develop non-hormonal contraceptives" at the 2023 Tri-Repro Symposium
- Rachel Huang gave a talk titled "Mapping ovulation with spatiotemporal and single-cell resolution" at the 2023 Tri-Repro Symposium
- Dr. Jeff Pea presented a poster titled "Well-established nuisance compounds in the drug screening pipeline elicit distinct phenotypes during mouse in vitro oocyte maturation" at the 2023 Tri-Repro Symposium
- Dr. Pawat Pattarwat presented a poster titled "A high-throughput ovulation screening platform to identify non-hormonal contraceptive candidates" at the 2023 Tri-Repro Symposium
- Caroline Kratka presented a poster titled "Pharmacologic inhibition of proprotein convertases prevents cumulus expansion due to extracellular matrix instability" at the 2023 Tri-Repro Symposium
January 2023
- A new OCDI publication:
Jiyang Zhang, Brittany A Goods, Pawat Pattarawat, Yingzheng Wang, Tessa Haining, Qiang Zhang, Alex K Shalek, Francesca E Duncan, Teresa K Woodruff, Shuo Xiao, An ex vivo ovulation system enables the discovery of novel ovulatory pathways and non-hormonal contraceptive candidates, Biology of Reproduction, 2023; ioad009, https://doi.org/10.1093/biolre/ioad009
December 2022
- On December 5, 2022, members from all projects of the OCDI met at Rutgers University for a site visit to Dr. Shuo Xiao’s laboratory. During the visit, members of the team visited Dr. Xiao’s facilities, learned more about the technologies used in the lab, and then participated in a day-long discussion about the OCDI research initiatives.
October 2022
- Grand Challenges Meeting
Dr. Duncan traveled to Brussels, Belgium to participate in the 2022 Grand Challenges meeting where she presented on behalf of the Ovarian Contraceptive Discovery Initiative which is funded through the Bill and Melinda Gates Foundation. She was joined by co-PIs Dr. Shuo Xiao and Dr. Amander Clark.
Her talks were:
"Ovarian Contraceptive Discovery Initiative - tools for illuminating ovarian biology." Nonhormonal Contraceptive Discovery Program Meeting. October 22-23, 2022.
"Complex biological systems for novel contraceptive discovery." Gates Grand Challenges Annual Meeting, October 25, 2022.
September 2022
- A new OCDI publication:
Converse A, Zaniker EJ, Amargant F, Duncan FE. Recapitulating folliculogenesis and oogenesis outside the body: encapsulated in vitro follicle growth. Biol Reprod. 2022 Sep 22:ioac176. doi: 10.1093/biolre/ioac176. Epub ahead of print. PMID: 36136744.
August 2022
- A new OCDI publication:
Chen YY, Russo DD, Drake RS, Duncan FE, Shalek AK, Goods BA, Woodruff TK Single-cell transcriptomics of staged oocytes and somatic cells reveal novel regulators of follicle activation. Reproduction 2022 Aug 01;164(2):55-70. doi:10.1530/REP-22-0053
July 2022
- OCDI members attended and presented at the SSR 55th Annual Meeting in Spokane, WA during July 25-29, 2022!
- Dr. Amander Clark gave a talk titled, "Regenerating the Human Germline from Skin Punch Biopsies"
- Dr. Elnur Babayev presented a poster as a finalist for the post-doctoral competition titled, "Cumulus Cell Expansion and Extracellular Matrix Integrity are Impaired with Advanced Reproductive Age". Congratulations Elnur on receiving third place in the post-doctoral competition!
- Daniela Russo presented TWO posters: (1) "Validation of single follicle transcriptomic data to characterize primordial to primary follicle activation" and (2) "Identifying novel contraceptive drug targets using single-cell RNA sequencing"
- Dr. Jiyang Zhang gave a talk titled, "A 3D in vitro follicle growth system preserves molecular signatures of gonadotropin-dependent folliculogensis and enables the identification of ovarian toxicants"
- Emily Zaniker presented a poster as a finalist for the pre-doctoral competition titled, "Spatial Asymmetry in the Molecular Determinants of Ovarian Follicle Rupture". Congratulations Emily on receiving second place in the pre-doctoral competition!
- A new OCDI publication:
Suebthawinkul C, Babayev E, Zhou LT, Lee HC, Duncan FE Quantitative morphokinetic parameters identify novel dynamics of oocyte meiotic maturation and cumulus expansion. Biol Reprod 2022 Jul 08;. pii:ioac139
June 2022
- Emily Zaniker from project 2 presented a poster titled, "Investigating spatial asymmetry in the molecular determinants of ovarian follicle rupture for non-hormonal contraceptive discovery" at the 2022 GLC ASPET 35th Annual Meeting on Friday June 17, 2022 at Lake Forest College, Lake Forest, IL.
- Many congratulations to Emily for being awarded 1st place in the graduate level poster competition!
May 2022
- Members from project 2 had a great time presenting at the 2022 CRS Summit: Frontiers in Reproductive Science and Medicine!
- Chana Suebthawinkul presented an oral talk titled, "Mouse strains with natural variations in mean lifespan exhibit differences in oocyte morphological parameters and morphokinetic dynamics of meiotic maturation. Congratulations to Chana on receiving a prize for her talk!
- Hoi Chang Lee presented a poster titled, "Morphokinetic parameters of mouse egg activation and embryo development by ionomycin and SrCl2 use EmbryoScope+".
- Caroline Kratka presented a poster titled, "Pharmacologic inhibition of proprotein convertases alters the behavior of cumulus cells during mouse in vitro maturation".
- Tracy Zhou presented a poster titled, "Towards germ cell-specific in vivo genome editing: generating transgenic mice that express oocyte-specific Cas9".
- Emily Zaniker presented a poster titled, "Investigating spatial asymmetry in the molecular determinants of ovarian follicle rupture for non-hormonal contraceptive discovery".
- Daniela Russo from project 4 presented a poster titled, "Identifying novel contraceptive targets using single-cell RNA sequencing" at the Probing Human Disease Using Single-Cell Technologies Conference; May 13-16, 2022; Cancun, Mexico. Many congratulations to Daniela for also winning a poster prize as well!
April 2022
- Daniela Russo from project 4 presented a talk titled, "Validation of single follicle transcriptomic data to characterize primordial to secondary follicle development" at the NIH Contraceptive Research and Development Meeting on April 7, 2022
February 2022
- Dr. Shuo Xiao presented a talk titled, "A Small Follicle Tells a Big Story" for SSR's The Rising Stars in Reproductive Biology Webinar Series on February 16th, 2022.
December 2021
- The OCDI team presented multiple posters and oral presentations at the SSR 54th Annual Meeting in St. Louis, MO during December 15-18, 2021!
- Dr. Shuo Xiao presented a poster as well as an oral presentation
- Jiyang Zhang presented a poster titled, "Mouse Ovarian Follicles from Encapsulated In Vitro Follicle Growth (eIVFG) Preserve Molecular Signatures of Mammalian Ovulation"
- Tracy Zhou gave the following oral presentation titled, "3D-printed agarose molds compatible with microphysiologic integration enable in vitro maturation of mouse oocytes in size specific indentations"
- Dr. Chana Suebthawinkul presented a poster titled, "Morphokinetic parameters of meiotic maturation and cumulus expansion are similar between euploid and aneuploid eggs from reproductively young mice"
- Emily Zaniker presented a poster titled, "Transcriptomic Profiling of the Spatial Determinants of Follicle Rupture During In Vitro Ovulation"
November 2021
- Dr. Britt Goods of project 4 presented at the Grand Challenges Annual Meeting for the Bill and Melinda Gates Foundation during the "Optimizing Drug Discovery & Translation" session.
July 2021
- The OCDI team presented at the 2021 SSR Solving Challenges in Contraceptive Discovery and Innovation Series!
- Below is a summary of our representation at SSR and a few snapshots of OCDI members.
- Francesca E. Duncan, PhD (Project 2 PI), Shuo Xiao, PhD (Project 4 PI), and Amander Clark, PhD (Project 3 PI) participated in the Global Health Integrated Organoid Convening July 13-14, 2021.
- A new publication: "A novel platform utilizing Drosophila ovulation for non-hormonal contraceptive screening"
- This publication involved multiple members of the Ovarian Contraceptive Discovery Initiative from project 1.
- Read the article here!
June 2021
- We presented our work titled, "Ex vivo ovulation as a path towards non-hormonal ovarian contraceptive discovery” as a part of the Gates Foundation Discovery Scientific Series, June 3rd, 2021 (virtual).
May 2021
- Dr. Duncan gave the following talk, "Ovarian Contraceptive Discovery Initiative: Enabling Reproductive Intentions" at the Spring 2021 Nonhormonal Contraceptive Discovery Program that took place on May 19-20, 2021 (virtual).
April 2021
- OCDI members from Project 3, Dr. Francesca E. Duncan, and Dr. Shuo Xiao participated in the Engineering Organoids and Organs Cell Symposia Express and the COC/follicle isolation and culture meeting on April 26, 2021 (virtual).
January 2021
- A new publication: "Dental resins used in 3D printing technologies release ovo-toxic leachates"
- This publication involved multiple members of the Ovarian Contraceptive Discovery Initiative and was partially funded by the Bill & Melinda Gates Foundation
- Read the press release and journal article!
- Check out the press release from our UCLA collaborators!
November 2020
- We participated in the virtual Fall 2020 Contraceptive Discovery Program meeting for the Bill & Melinda Gates Foundation Contraceptive Grantees on November 17, 2020!
- Read more about our launch in Northwestern's Press Release!
October 2020
- Congratulations to Britt Goods on receiving a poster award for SSR's virtual symposia!
- We are absolutely thrilled to launch this program on contraceptive research and
discovery!! The Ovarian Contraceptive Discovery Initiative Kick Off Meeting took place
October 22, 2020 - We participated in the Society for the Study of Reproduction's virtual symposia titled, "Solving Challenges in Contraceptive Discovery and Innovation"!
- Dr. Duncan co-chaired the session on October 14, 2020 titled, "Non-Hormonal Female Contraceptive Strategies"
- Dr. Xiao presented the following talk, "3D In Vitro Follicle Culture as an Effective Model for Contraceptive Discovery" on October 14, 2020
- Jiyang Zhang presented the following talk, "Mouse Ovarian Follicles from Encapsulated In Vitro Follicle Growth (eIVFG) Preserve Ovulation Molecular Signatures In Vivo"