Abstract Study question Does in vitro maturation (IVM) of immature oocytes retrieved from small antral follicles during mild stimulation protocol have an impact on future IVF outcomes? Summary answer Although fertilization, cleavage, and blastocyst rates were lower in IVM oocytes, mature and immature groups are comparable for the implantation and cumulative clinical pregnancy rates What is known already Mild-stimulation protocols are patient-friendly, cost-effective, and have acceptable outcomes, especially among poor responders. IVM obtained attention among fertility specialists for riskless ovarian hyperstimulation syndrome along with acceptable clinical pregnancy and live birth. This study is aimed to investigate IVF outcomes of IVM during mild stimulation protocols. Study design, size, duration This prospective cohort study has enrolled 949 IVF/ICSI cycles carried out with clomiphene-based mild stimulation protocol during 2018-2020 at RMC national IVF center in Mongolia. A total of 2346 oocytes were selected and divided into mature (metaphase II-MII, n = 1272) and immature (metaphase I–MI, and prophase I-GV, n = 1074) groups. Participants/materials, setting, methods 50 mg of clomiphene citrate was provided from day 3 of menstruation. The oocyte retrieval was usually performed after 30-36 hours of triggering the GnRH agonist while using a 21-G needle (Kitazato Corporation). MII oocytes were either freshly fertilized conventional insemination or intracytoplasmic sperm injection approximately after 3 and 5 hours of oocyte retrieval. MI and GV oocytes had reached the metaphase II stage in vitro after 8 to 40h of culture. Main results and the role of chance Fertilization rate was 76.3% (n = 971/1272) in mature group and 62.4% (n = 312/500) in immature group (Chi square=34.8, p < 0.01). Cleavage rate was 98.4% (n = 955/971) vs 95.5%(n = 298/312) (Chi square=8.33, p < 0.01), and blast formation rate was 62.3% (n = 595/955) vs 38.7% (n = 115/298) (Chi square=51.3, p < 0.01) which is significantly lower compared to the mature group. A total of 296 fresh or frozen single embryo transfer procedures were performed at blastocysts. Implantation rate was 58.4% (n = 149/255) in mature group and 58.5% (n = 24/41) in immature group, cumulative clinical pregnancy rate was 33.3% (n = 85/255) vs 41.5% (n = 17/41), live birth rate was 28.2% (n = 72/255) vs 41.5% (n = 17/41), which has no statistical difference between the groups Limitations, reasons for caution The sample size of embryo transfer in the immature group was small in the study, and randomized clinical trials are further required to clarify the difference between outcomes of mature and immature oocytes in mild stimulation Wider implications of the findings Data from the study has confirmed favorable clinical outcomes of in vitro maturation of the immature oocytes during mild stimulation. IVM seems to remain as an alternative option and is recommended for all IVF laboratories rather than neglecting it. Trial registration number Not applicable
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