The PPOS protocol mitigates the detrimental effects of high BMI on embryo and clinical pregnancy outcomes.

Background: The impact of high body mass index (BMI) on embryo and pregnancy outcomes in women using the PPOS (progestin-primed ovarian stimulation) protocol during their first frozen embryo transfer (FET) cycles is not clear. This study is to investigate the impact of BMI on oocyte, embryo, and pregnancy outcomes in patients who underwent the PPOS protocol.

Methods: This retrospective study included the first FET cycle of 22,392 patients following the PPOS protocol. The impact of BMI on oocyte and pregnancy outcomes was assessed across different BMI groups, using direct acyclic graph to determine covariates, followed by the application of multiple linear and logistic regressions to further validate this influence.

Results: The high BMI groups exhibited a higher number of oocytes; however, no significant differences were observed in good-quality embryos, clinical pregnancy rate, and implantation rate. Nevertheless, the high BMI groups demonstrated a significantly elevated miscarriage rate (9.9% vs. 12.2% vs. 15.7% vs. 18.3%, P < 0.001), particularly in late miscarriages, resulting in lower live birth rates (LBR, 41.1% vs. 40.2% vs. 37.3% vs. 36.2%, P = 0.001). These findings were further confirmed through multiple liner and logistic regression analyses. Additionally, several maternal factors showed significant associations with adjusted odds ratios for early miscarriage. However, women with a BMI ≥ 24 who underwent hormone replacement cycle or hMG late stimulation protocol for endometrial preparation experienced an increased risk of late miscarriage.

Conclusions: By utilizing the PPOS protocol, women with a high BMI exhibit comparable outcomes in terms of embryo and clinical pregnancies. However, an elevated BMI is associated with an increased risk of miscarriage, leading to a lower LBR. Adopting appropriate endometrial preparation protocols such as natural cycles and letrozole stimulation cycles may potentially offer benefits in reducing miscarriages.