Xu M, Fazleabas AT, Shikanov A, Jackson E, Barrett SL, Hirshefeld-Cytron J, Kiesewetter SE, Shea LD, Woodruff TK.
Female cancer patients who seek fertility preservation but cannot undergo ovarian stimulation and embryo preservation may consider: 1) retrieval of immature oocytes followed by in vitro maturation (IVM); 2) ovarian tissue cryopreservation followed by transplantation or in vitro follicle culture (IVFC). Conventional IVM is carried out during the follicular phase of menstrual cycle. There is limited evidence demonstrating that immature oocyte retrieved during the luteal phase can mature in vitro and be fertilized to produce viable embryos. While in vitro follicle culture is successful in rodents, its application in nonhuman primates has made limited progress. The objective of this study was to investigate the competence of immature luteal-phase oocytes from baboon and to determine the effect of FSH on baboon preantral follicle culture and oocyte maturation in vitro. Oocytes from small antral follicle COCs with multiple cumulus layers (42%) were more likely to resume meiosis and progress to MII than oocytes with a single layer of cumulus cells, or less (23% vs. 3%, respectively). Twenty-four percent of mature oocytes were successfully fertilized by ICSI, and 25% of these developed to morula stage embryos. Preantral follicles were encapsulated in fibrin-alginate-matrigel (FAM) matrices, and cultured to small antral stage in a FSH-independent manner. FSH negatively impacted follicle health by disrupting the integrity of oocyte and cumulus cells contact. Follicles grown in the absence of FSH produced MII oocytes with normal spindle structure. In conclusions, baboon luteal-phase COCs and oocytes from cultured preantral follicles can be matured in vitro. Oocyte meiotic competence correlated positively with the number of cumulus cell layers. This study clarifies the parameters of the follicle culture system in nonhuman primates and provides foundational data for future clinical development as a fertility preservation option for women with cancer.