Testing the role of unstimulated in vitro maturation for potential development of immature oocytes in women with oocyte maturation abnormalities

Objective: The aim of this study was to investigate the developmental potential of immature oocytes and evaluate whether unstimulated in vitro maturation (IVM) could serve as a treatment option for women with oocyte maturation abnormalities (OMAs).

Material and methods: This cohort study was conducted between September 2019 and December 2022, and included women who underwent unstimulated, non-human chorionic gonadotropin (hCG) priming IVM. Oocytes were incubated with IVM medium for 26-48 hours and evaluated to compare their maturation profiles with the immature oocytes retrieved from the same patients in their previous in vitro fertilization cycles.

Results: Among the twelve women in the study, eleven (91.6%) underwent whole exome sequencing analysis. Of these, 18 variants were identified in 10 individuals, excluding case 1, who had no previous mutation analysis. Of the mutations identified, 9 (50%) were located in FSHR, 5 (27.8%) in TUBB8, 1 (5.6%) in ZP1, 1 (5.6%) in SLFN14, 1 (5.6%) in AR, and 1 (5.6%) in STEAP3. Apart from one woman with resistant ovary syndrome (ROS), none treated with unstimulated IVM had oocyte maturation. Remarkably, the only patient to achieve oocyte maturation in an unstimulated IVM cycle was case 11, who had ROS and a single FSHR variant.

Conclusion: Unstimulated, non-hCG primed IVM does not appear to be effective in the treatment of OMAs, perhaps with the exception of women with ROS. However, this study led our team to develop novel treatment options based on physiological mechanisms for some subtypes and supraphysiological approach for other subtypes of OMAs.