Risk factors and treatment strategies for live birth in women with high BMI undergoing ART

Women with a high BMI represent a growing and challenging population in assisted reproductive technology, as known impairments to treatment outcomes. However, the specific risk factors contributing to recurrent live birth failure and the potential treatment strategies to overcome initial setbacks in this group remain unclear.

In this large-scale retrospective cohort study (2010-2023), 10,581 women were stratified into overweight (BMI 24-27.99 kg/m ², n = 8,350) and obese (BMI ≥ 28 kg/m ², n = 2,231) groups. Two-tiered analysis used generalized linear mixed models (GLMMs): (1) multilevel multinomial logistic regression to identify risk factors for recurrent failure; and (2) multilevel logistic regression to evaluate treatment strategies following initial failed frozen embryo transfers (FETs).

In the risk factor analysis, women with recurrent failure were older (33-35 years) and had poorer ovarian reserve (AFC ~ 7-9) than those with live birth (~ 31 years, AFC ~ 12-15). Multivariable analysis confirmed advanced maternal age as a key risk factor (aOR = 1.98, 95% CI: 1.85-2.12). Higher hMG dose per mature follicle increased single-failure risk versus < 350 IU: for 350-500 IU, aOR = 1.43, 95% CI: 1.16-1.76 (overweight) and 1.66, 95% CI: 1.14-2.43 (obese); for > 500 IU, aOR = 1.77, 95% CI: 1.45-2.16 (overweight) and 1.58, 95% CI: 1.1-2.25 (obese). Switching to PPOS-versus mild stimulation-was associated with a lower risk of continued failure (aOR = 0.54, 95% CI: 0.40-0.74). Propensity score matching confirmed PPOS positively related with embryological yields; live birth rates were higher but not statistically significant (45.7% vs. 43.7%). Blastocyst transfer (aOR = 0.54, 95% CI: 0.42-0.69) was associated with a lower risk of continued failure.

This study is, to our knowledge, one of the largest studies to systematically distinguish non-modifiable baseline risks (age and AFC) from modifiable ART-related factors (stimulation protocol, hMG dosage, and embryo transfer policy) for recurrent failure in a large population with high-BMI. This distinction provides preliminary insights to implement risk-stratified clinical approaches, especially for lower-risk patients. These approaches include adopting PPOS, optimizing gonadotropin dosage, and cautiously individualizing embryo transfer strategy, which may serve as potential therapeutic alternatives after initial setbacks.