A large prospective cohort study found body mass index outside the normal range in both women and men was associated with lower fecundability, subfertility, and increased odds of miscarriage.
The study, published in JAMA Network Open, analyzed data from 3,604 women and their partners in Rotterdam, Netherlands.
Key Findings:
- Higher body mass index (BMI) in women and men was associated with lower fecundability (fecundability ratio [FR] per unit increase: women, 0.98 [95% CI, 0.97-0.99]; men, 0.99 [95% CI, 0.98-1.00]).
- Compared to women of normal weight, those who were overweight (FR, 0.88 [95% CI, 0.80-0.98]) and obesity (FR, 0.72 [95% CI, 0.63-0.82]) had lower fecundability.
- Women who were underweight (odds ratio [OR], 1.88 [95% CI, 1.22-2.88]), overweight (OR, 1.35 [95% CI, 1.11-1.63]), or with obesity (OR, 1.67 [95% CI, 1.30-2.13]) were associated with increased odds of subfertility compared to women of normal weight.
- In men, obesity was associated with increased odds of subfertility (OR, 1.69 [95% CI, 1.24-2.31]).
- Overweight (OR, 1.49 [95% CI, 1.12-1.98]) and obesity (OR, 1.44 [95% CI, 1.00-2.08]) in women were associated with increased odds of miscarriage compared to women of normal weight.
Methods:
The Generation R Next Study, a population-based prospective cohort study, included 3,604 women and their partners from preconception through pregnancy between August 2017 and July 2021. The study population for time-to-pregnancy analyses consisted of 3,033 episodes among women (median age, 31.6 years; median BMI, 23.5) and 2,288 episodes among men (median age, 33.4 years; median BMI, 24.9). For miscarriage analyses, 2,770 pregnancy episodes among women and 2,189 pregnancy episodes among men were included.
Height and weight measurements were taken at enrollment and subsequent preconception or first trimester visits. Prepregnancy weight was obtained via questionnaires if pregnant at enrollment. BMI was categorized as underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9), and obesity (≥30.0).
Time to pregnancy and mode of conception were assessed through questionnaires. Fecundability was defined as the probability of conceiving within 1 month (28 days). Subfertility was defined as time to pregnancy or duration of actively pursuing pregnancy >12 months or use of assisted reproductive technology. Miscarriage was defined as pregnancy loss before 22 weeks of gestation.
Cox proportional hazards regression models were used to examine associations of BMI with fecundability and miscarriage. Logistic regression models assessed associations with subfertility and miscarriage odds. Models were adjusted for age, ethnicity, educational level, smoking, alcohol consumption, parity, and history of miscarriage.
Results:
The median time to pregnancy was 3.7 months (95% range, 0.0-68.3 months). Of the 3,033 episodes, 541 (17.8%) were subfertile, and 314 of 2,770 pregnancy episodes (11.3%) resulted in miscarriage.
Fecundability decreased with increasing BMI in both women and men. Compared to women of normal weight, those who were categorized as overweight or obesity had 12% and 28% lower fecundability, respectively. Overweight and obesity in both partners was associated with subfertility (OR, 1.41 [95% CI, 1.06-1.87]) compared to normal weight in both.
For miscarriage, overweight in women increased the probability per week (hazard ratio, 1.43 [95% CI, 1.10-1.86]) compared to normal weight. Overweight and obesity in women were associated with 49% and 44% increased odds of miscarriage, respectively.
Additional Findings:
The study population consisted of 62.1% Dutch, 8.9% other non-Western, and 29.0% other Western women. For men, the distribution was 66.3% Dutch, 9.2% other non-Western, and 24.6% other Western. Higher education was completed by 71.7% of women and 65.8% of men.
BMI distribution for women was 3.2% underweight, 61.3% normal weight, 23.4% overweight, and 12.0% obese. For men, it was 0.7% underweight, 49.9% normal weight, 38.5% overweight, and 10.9% obese.
Regarding lifestyle factors, 13.3% of women reported smoking during pregnancy, while 64.6% consumed alcohol within 3 months before pregnancy. For men, 17.8% reported smoking, and 88.2% consumed alcohol within 3 months before pregnancy.
Obstetric history showed 65.7% of women were nulliparous, and 20.8% of women and 19.3% of men reported a history of miscarriage.
Time to pregnancy was ≤12 months for 64.1% of women and 74.0% of men. Assisted reproductive technology led to pregnancy in 9.5% of women and 9.4% of men.
The median timing of miscarriage was 8.3 weeks (IQR, 7.1-9.5 weeks) for women, with 92.2% occurring in the first trimester.
Statistical analyses included checking proportional hazards assumptions using Schoenfeld residuals, assessing linearity of associations using Martingale residuals, and assessing influentials using deviance residuals. Multiple imputation by chained equations was used to address missing data, which ranged from 0% to 18.4% for covariates.
Sensitivity analyses excluding assisted reproductive technology users, top 5% of time-to-pregnancy observations, or restricting to first episodes did not materially change effect estimates.
Limitations:
The study had some limitations, including potential selection bias, as excluded participants differed from those included. Missing prepregnancy weight data for some women was substituted with early-pregnancy measurements. Time-to-pregnancy duration may have been affected by retrospectively answered questionnaires. Residual confounding remains possible due to the observational nature of the study.
The authors declared having no competing interests.