Associations of maternal obesity, frozen embryos, and offspring adverse cardiometabolic alterations

Abstract

Objective: To evaluate the long-term cardiometabolic health of offspring conceived by frozen embryo transfer and born to mothers with overweight/obesity.

Design: Retrospective cohort study.

Setting: Center for Reproductive Medicine.

Patient(s): A total of 2,741 offspring born to mothers who underwent in vitro fertilization/intracytoplasmic sperm injection treatment were followed between June 2014 and August 2021. The offspring were singletons aged 4-11 years at follow-up.

Intervention(s): None.

Main outcome measure(s): Age-specific z-scores of cardiometabolic parameters were examined, including adiposity, systolic/diastolic blood pressure, glucose, and lipid profiles, and the metabolic sum score of different cardiometabolic characteristics.

Results: Of 2,741 offsprings, 965 (35.21%) were born to mothers with overweight/obesity, including 396 (41.04%) offspring who were conceived by frozen embryo transfer. After adjusting for paternal and maternal age, paternal body mass index (BMI), offspring age, offspring sex, and offspring postnatal energy intake, offspring born to mothers with overweight/obesity and conceived by frozen embryo transfer showed a significantly higher BMI z-score, systolic blood pressure z-score, metabolic sum score-1, and metabolic sum score-2 compared with those conceived by fresh embryo transfer (BMI z-score: adjusted mean difference, 0.17; 95% confidence interval [CI], 0.04-0.30; systolic blood pressure z-score: adjusted mean difference, 0.16; 95% CI, 0.02-0.29; metabolic sum score-1: adjusted mean difference, 0.54; 95% CI, 0.15-0.94; metabolic sum score-2: adjusted mean difference, 0.45; 95% CI, 0.07-0.83). However, in offspring of mothers with normal weight, offspring conceived by frozen embryo transfer showed a significantly lower low-density lipoprotein-cholesterol z-score compared with those conceived by fresh embryo transfer (adjusted mean difference, -0.12; 95% CI, -0.22 to -0.02). Other cardiometabolic parameters were comparable between offspring with frozen and fresh embryo transfers after adjusting for multivariate confounder variables.

Conclusions: This study found that among offspring from mothers who were overweight/obese, those offspring conceived by frozen embryo transfer were associated with higher systolic blood pressure z-scores and adverse metabolic changes compared with those conceived by fresh embryo transfer. The changes show that the association between frozen embryo transfer and offspring adverse cardiometabolic changes is apparent only among those born to mothers who are overweight/obese.

Keywords: Assisted reproductive technology; blood pressure; frozen embryo transfer; maternal overweight/obesity; offspring metabolic health.