Donor side effects experienced under minimal controlled ovarian stimulation (COS) with in vitro maturation (IVM) versus conventional COS for in vitro fertilization (IVF) treatment

Objective: To evaluate how minimal controlled ovarian stimulation (COS) for in vitro maturation (IVM) affects subjects' oocyte retrieval experiences compared to conventional COS, considering side effects Design: Retrospective Survey Study Setting: Clinical in vitro fertilization (IVF) treatment centers in Spain and the United States. Subjects: Data were collected from subjects undergoing minimal COS (n=110; 600-800 IU FSH) for IVM and conventional COS for egg donation (n=48; 2000-3000 IU FSH) from April 2022 to November 2023. In the same period, a pairwise comparison of subjects (n=13) undergoing both minimal COS for IVM and conventional COS for oocyte cryopreservation was conducted. Intervention/Exposure: Minimal and conventional controlled ovarian stimulation. Main Outcome Measures: The most common side effects suffered during ovarian stimulation and after OPU, satisfaction level, and the likelihood of recommending or repeating minimal or conventional COS. Statistical analysis included Mann Whitney, Wilcoxon, Chi-square, and McNemar tests, with a significance level set at p<0.05. Results: During minimal COS, most subjects did not experience breast swelling (86%), pelvic or abdominal pain (76%), nausea or vomiting (96%), and bleeding (96%). After oocyte pick-up, the majority (75%) reported no pelvic or abdominal pain. The most common side effect was abdominal swelling (52%). Compared to conventional COS cycles, minimal COS subjects reported significantly less post-retrieval pain, with 33% experiencing no pain (vs. 6%; p=0.0011) and with a reduced severe level of pain (5% vs.19%; p=0.0097), leading to fewer subjects requiring pain medication (25% vs. 54%; p=0.0003). Additionally, 85% of women were very satisfied with minimal stimulation and would recommend or repeat the treatment. In the comparison in which each donor underwent both minimal and conventional COS treatments, women indicated more side effects with the conventional stimulation, presenting a significantly overall higher level of pain (p=0.0078). Conclusion: Reducing the hormonal dose for ovarian stimulation has a beneficial effect on subjects, suggesting the combination of minimal COS with IVM techniques is a well-tolerated alternative for women who cannot or do not wish to undergo conventional controlled ovarian hyperstimulation.