Rates and risk factors of oocyte immaturity: toward personalized selection for rescue in vitro maturation

Purpose: To identify treatment-related factors influencing low oocyte maturation rates in standard ovarian stimulation (OS) cycles and patients' candidates for clinical studies on rescue-IVM. Methods: Retrospective study including retrievals with ≥ 1 cumulus-oocyte-complex (COC; years: 2008-2022). The weighted-mean immaturityrate (19%) was defined in the whole dataset (N = 16,155). Variables associated with immaturity rates and warning limit (defined as weighted average + 2SD) were appraised among first retrievals with ≥ 5 COCs (N = 7962). Of the patients undergoing a first oocyte pick-up, 667 completed three retrieval cycles, enabling evaluation of the true prevalence of patients exceeding the immaturity rate warning threshold over multiple cycles. Results: Factors influencing immaturity rate included OS duration, trigger type (GnRH-agonist versus urinary-hCG), ovulation trigger to oocytes' denudation interval and ratio COC to follicle > 14 mm at ovulation trigger. In first retrievals with ≥ 5 COCs, the immaturity rate warning limit was 51%, occurring in 3.6% of initial retrievals, 3.8% of second retrievals, and 2.1% of third retrievals. In three consecutive retrievals, the conservative prevalence of patients exceeding this threshold once, twice, and three times was 4.4%, 0.3%, and 0.03%, respectively. Assuming all patients would have conducted three retrievals, these rates were estimated as 7.8%, 1.5%, and 0.3%. In the 667 patients who conducted three retrievals, observed rates were 7.6%, 0.9%, and 0.4%, confirming the reliability of the estimates. Conclusions: Ovarian stimulation and laboratory factors impact oocyte maturation rate. An oocyte immaturity rate exceeding 51%, in patients retrieving ≥ 5 oocytes, may represent a strong inclusion criterion for future clinical studies on rescue-IVM.