Association between weight loss and reproductive outcomes among women with overweight or obesity: a cohort study using UK real-world data.
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STUDY QUESTION: In women with BMI ≥25 kg/m2, does a 10-25% weight loss versus stable weight increase the chance of pregnancy? SUMMARY ANSWER: In women with overweight or obesity, weight loss was associated with an increase in the chance of pregnancy. WHAT IS KNOWN ALREADY: Weight loss has been shown to improve conception rates among women with overweight or obesity and concomitant polycystic ovary syndrome (PCOS). However, evidence on the effect of weight loss on conception rates among the general population of women with overweight or obesity, irrespective of PCOS status, is lacking. STUDY DESIGN, SIZE, DURATION: A large cohort study of patient data collected from primary-care practices linked to hospital records in England between January 2000 and May 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women were included if they were aged 18-40 years with BMI ≥25 kg/m2. Patient data were extracted from the UK Clinical Practice Research Datalink Aurum database of electronic medical records. The primary outcome was the first pregnancy recorded during a 3-year follow-up period. Key secondary outcomes were the occurrence of miscarriage, gestational diabetes, and pregnancy-induced hypertension, as well as emergency caesarean section, and risk of babies being born large for gestational age (LGA). MAIN RESULTS AND THE ROLE OF CHANCE: The final cohort of 246 670 women comprised 195 666 who kept a stable weight and 51 004 who lost weight. Pregnancy occurred in 22 756/246 670 (9.2%) women. On average, a 10-25% weight loss (median 14%) was associated with a 5.2% increase in the chance of pregnancy over the following 3 years (hazard ratio 1.05; 95% CI 1.02, 1.09; P = 0.003) compared with stable weight. Gestational diabetes was reported for 950/11 825 (8.0%) women, and weight loss reduced the risk of gestational diabetes by 42% (odds ratio [OR] 0.58; 95% CI 0.48, 0.70; P < 0.001). Emergency caesarean section was performed in 1453/11 558 (12.6%) pregnancies. This intervention was significantly reduced in the weight-loss cohort (OR 0.82; 95% CI 0.71, 0.95; P = 0.008). Pregnancy-induced hypertension was reported in a few women (244/11 740 [2.1%]) and one-tenth of women (791/7988 [9.9%]) gave birth to babies who were LGA. Weight loss prior to pregnancy resulted in non-significant reductions in pregnancy-induced hypertension (OR 0.77; 95% CI 0.55, 1.07; P = 0.121) and risk of babies being born LGA (OR 0.86; 95% CI 0.72, 1.04; P = 0.117). Rates of miscarriages, preterm births, live births, or babies born small for gestational age were not impacted by weight loss. LIMITATIONS, REASONS FOR CAUTION: In our study, the intention of pregnancy was unknown. Women who intend to conceive are more likely to attempt weight loss. The inclusion of women who do not intend to conceive may therefore underestimate the true relationship between weight loss and chance of pregnancy. Also, we assessed women aged between 18 and 40 years, but due to the requirement of having two BMI records, the median age at index date across the cohort was 30 years which limits the generalizability of our findings. Furthermore, while an association between weight loss and increased chance of pregnancy was observed, we cannot imply causality as it is unknown whether higher pregnancy rates were caused by weight loss. WIDER IMPLICATIONS OF THE FINDINGS: These findings provide further evidence of the association of weight loss with reproductive outcomes in a broad population of women with overweight or obesity, including those with PCOS. Previous studies have focused mostly on outcomes in women undergoing fertility treatment. Our study was not restricted to those actively trying to conceive and, therefore, the benefit of weight loss may be even greater in women who are actively trying to become pregnant. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Novo Nordisk A/S. A.H.B. declares consultancy fees from Novo Nordisk A/S. M.L.V., V.S., E.W.L., and A.R.G. are employees of and/or hold shares in Novo Nordisk A/S. A.R.G. holds stock in Novo Nordisk. Medical writing support was provided by Carolyn Bowler, PhD, CMPP, of Apollo, OPEN Health Communications, and funded by Novo Nordisk A/S, in accordance with Good Publication Practice (GPP) guidelines (GPP 2022) (ismpp.org). TRIAL REGISTRATION NUMBER: N/A.