Testing the role of unstimulated ın vitro maturation in the developmental potential of immature oocytes in women with oocyte maturation abnormalities.

Objective: This study aims to investigate the developmental potential of immature oocytes and questions whether unstimulated in vitro maturation (IVM) can be used as a treatment in women with oocyte maturation abnormalities.

Material and methods: This cohort study was conducted between September 2019 and December 2022, and it included 12 women who underwent unstimulated, non-hCG priming IVM.Oocytes were incubated in in vitro maturation medium for 26-48 hours and evaluated to compare their maturation profiles with the immature oocytes retrieved from the same patients in their previous IVF cycles.

Results: Among the twelve women in the study, eleven (91.6%) underwent whole exome sequencing (WES) analysis. Of these, ten women presented a total of 18 mutations, excluding Case 1, which had no previous mutation analysis. Of the mutations identified, 9 (50%) were located in the FSHR gene, 5 (27.8%) in the TUBB8 gene, 1 (5.6%) in the ZP1 gene, 1 (5.6%) in the SLFN14 gene, 1 (5.6%) in the AR gene, and 1 (5.6%) in the STEAP3 gene. Apart from one woman with resistant ovary syndrome,none of the women treated with unstimulated in vitro maturation 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 mutation.

Conclusion: Unstimulated non hCG primed IVM has no value in the treatment of OMAS, except in cases with resistant ovary syndrome. 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 oocyte maturation abnormalities.