Association between miscarriage rates in modified natural ovulation cycles and hormone replacement cycles during frozen-thawed embryo transfer in three IVF JAPAN GROUP fertility clinics: a retrospective analysis

Optimal endometrial preparation for frozen-thawed embryo transfer (FET) remains debated owing to conflicting results regarding outcomes in modified natural ovulation cycles (NCs) versus hormone replacement cycles (HRCs). Therefore, we aimed to compare clinical pregnancy and miscarriage rates between modified NCs and HRCs in FETs. We retrospectively analyzed 9,136 clinical pregnancies by FET between January 2020 and February 2025 at three IVF JAPAN GROUP fertility clinics. Of these, 5,230 were HRCs and 3.906 were modified NCs. Clinical pregnancy was defined as the presence of a gestational sac, while miscarriage was defined as pregnancy loss before 9 weeks of gestation. Subgroup and multivariate analyses were performed, adjusting for maternal age, prior miscarriage, embryo developmental stage, and use of preimplantation genetic testing for aneuploidy. Miscarriage rates were lower in the modified NC group compared with the HRC group (19.4% vs. 25.6%; P < 0.001). This reduction was also observed in high-risk subgroups, including women aged ≥ 40 and those with prior miscarriage. Multivariate analysis confirmed the association (adjusted odds ratio: 0.74; 95% confidence interval: 0.66–0.82). This trend was consistent across all facilities, despite differing NC utilization rates, and was independent of chromosomal status. Given that HRC remains the dominant strategy in many countries, our findings indicate that modified NC in FET may provide clinical benefits in early pregnancy outcomes.