Obesity is associated with an increased risk of early pregnancy loss after euploid frozen embryo transfer

Abstract

Objective: To determine whether obesity is associated with an increased risk of pregnancy loss in patients undergoing autologous euploid frozen embryo transfer (FET). Design: Retrospective cohort study. Subjects: Patients with recorded body mass index (BMI) from nine clinical sites during January 2019 to December 2024, undergoing their first, autologous, single, euploid FET were included. Other preimplantation genetic testing indications were excluded. Exposure: Patients were stratified into two groups: patients with obesity (BMI ≥30.0 kg/m2) and nonobese patients (BMI <30.0 kg/m2). Main Outcome Measures: Primary outcome was biochemical pregnancy loss (beta human chorionic gonadotropin [β-hCG] >5 mIU/mL without ultrasound evidence of pregnancy until β-hCG <5 mIU/mL) or clinical pregnancy loss (ultrasound evidence of at least an intrauterine gestational sac, which did not progress to live birth). Secondary outcomes included implantation, ectopic, clinical and ongoing pregnancy (8–9 weeks gestational age with cardiac activity), and live birth (neonate >24 weeks gestational age). Results: A total of 14,990 patients were included: 11,179 nonobese and 3,811 with obesity. Compared with nonobese, patients with obesity were older. Parity, antimüllerian hormone (AMH) levels, and blastulation day were similar between groups. After adjustment, patients with obesity had a 19% increased risk of pregnancy loss (adjusted relative risk [aRR]: 1.19, 95% confidence interval [CI] 1.14–1.24) compared with nonobese. When stratified by BMI categories, class I (BMI 30.0–34.9 kg/m2), II (BMI 35.0–39.9 kg/m2), and III (BMI ≥40.0 kg/m2) obesities had 12%, 22%, and 41% increased risk of pregnancy loss, respectively, whereas the underweight (BMI <18.0 kg/m2) and overweight (BMI 25.0–29.9 kg/m2) groups performed similarly to the normal-weight group (BMI 18.5–24.9 kg/m2). The predicted probability of pregnancy loss was lowest at a BMI of 25.3 kg/m2. Although there was no difference in implantation (aRR: 0.98, 95% CI 0.86–1.37), patients with obesity had lower chances of clinical (aRR: 0.96, 95% CI 0.94–0.99) and ongoing pregnancy (aRR: 0.94, 95% CI 0.92–0.96) and live birth (aRR: 0.92, 95% CI 0.91–0.94). Risk of pregnancy loss was attenuated in parous patients with obesity (aRR: 0.90, 95% CI 0.79–1.02). Conclusion: When accounting for embryonic aneuploidy in the setting of euploid-only transfers, patients with obesity had a 19% increased risk of early pregnancy loss compared with nonobese patients, with risk rising across BMIs and BMI categories.