Fresh embryo transfer versus freeze-only after in vitro maturation with a pre-maturation step in women with high antral follicle count: a randomized controlled pilot study

Purpose In vitro maturation (NM) is an alternative to in vitro fertilization (NF) for women at high risk of developing ovarian hyperstimulation syndrome (OHSS). This study determined the effectiveness and safety of a freeze-only strategy versus fresh embryo transfer (ET) after IVM with a pre-maturation step (CAPA-IVM) in women with a high antral follicle count (AFC). Methods This randomized, controlled pilot study (NCT04297553) was conducted between March and November 2020. Forty women aged 18-37 years with a high AFC (>= 24 follicles in both ovaries) undergoing one cycle of CAPA-IVM were randomized to a freeze-only strategy with subsequent frozen ET (n = 20) or to fresh ET (n = 20). The primary endpoint was ongoing pregnancy resulting in live birth after the first ET of the started treatment cycle. Results The ongoing pregnancy rate in the freeze-only group (65%) was significantly higher than that in the fresh ET group (25%;p = 0.03), as was the live birth rate (60% versus 20%;p = 0.02). Clinical pregnancy rate was numerically, but not significantly, higher after frozen versus fresh ET (70% versus 35%;p = 0.06), while the number of day 3 or good quality embryos, endometrial thickness on the day of oocyte pick-up, implantation rate, and positive pregnancy test rate did not differ significantly between groups. No cases of OHSS were observed, and miscarriage and multiple pregnancy rates were similar in the two groups. Conclusions These findings suggest that the effectiveness of CAPA-IVM could be improved considerably by using a freeze-only strategy followed by frozen ET in subsequent cycles.