Metabolic health status and fecundability in a Singapore preconception cohort study

Abstract

Background: Obesity compromises metabolic health and female fertility, yet not all obese women are similar in metabolic status. The extent to which fecundability is influenced by the metabolic health status of women who are overweight or obese before conception is unknown.

Objective: This study aimed to: (1) determine the metabolic health status, and (2) examine the association between metabolic health status and fecundability of overweight and obese women trying to conceive in the Singapore PREconception Study of long-Term maternal and child Outcomes cohort study.

Study design: We conducted a prospective preconception cohort study of Asian women (Chinese, Malay, and Indian) aged 18 to 45 years trying to conceive who were treated from 2015 to 2017 in KK Women's and Children's Hospital in Singapore (n=834). We defined women to have metabolically unhealthy status if they: (1) met 3 or more modified Joint Interim Statement metabolic syndrome criteria; or (2) had homeostasis model assessment-insulin resistance index ≥2.5. Body mass index was categorized as normal (18.5-22.9 kg/m²), overweight (23-27.4 kg/m²), or obese (≥27.5 kg/m²) on the basis of cutoff points for Asian populations. Fecundability was measured by time to pregnancy in menstrual cycles within a year of enrolment. Discrete-time proportional hazards models were used to estimate fecundability odds ratios, with adjustment for confounders and accounting for left truncation and right censoring.

Results: Of 232 overweight women, 28 (12.1%) and 25 (10.8%) were metabolically unhealthy by metabolic syndrome ≥3 criteria and homeostasis model assessment-insulin resistance ≥2.5, respectively. Of 175 obese women, 54 (30.9%) and 93 (53.1%) were metabolically unhealthy by metabolic syndrome ≥3 criteria and homeostasis model assessment-insulin resistance ≥2.5, respectively. Compared with metabolically healthy normal-weight women, lower fecundability was observed in metabolically unhealthy overweight women on the basis of metabolic syndrome criteria (fecundability odds ratios, 0.38 [95% confidence interval, 0.15-0.92]) and homeostasis model assessment-insulin resistance (fecundability odds ratios, 0.68 [95% confidence interval, 0.33-1.39]), with metabolic syndrome criteria showing a stronger association. Metabolically unhealthy obese women showed lower fecundability than the healthy normal-weight reference group by both metabolic syndrome (fecundability odds ratios, 0.35; 95% confidence interval, 0.17-0.72) and homeostasis model assessment-insulin resistance criteria (fecundability odds ratios, 0.43; 95% confidence interval, 0.26-0.71). Reduced fecundability was not observed in overweight or obese women who showed healthy metabolic profiles by either definition.

Conclusion: Overweight or obesity was not synonymous with having metabolic syndrome or insulin resistance. In our preconception cohort, metabolically unhealthy overweight and obese women showed reduced fecundability, unlike their counterparts who were metabolically healthy. These findings suggest that metabolic health status, rather than simply being overweight and obese per se, plays an important role in fecundability.

Keywords: conception; fertility; insulin resistance; lipids; metabolic syndrome; obesity; overweight; pregnancy planning; time to pregnancy.

Figure 1

Forest plots showing fecundability odds ratios according to metabolic health status of normal weight (18.5-22.9 kg/m²), overweight (23-27.4 kg/m²) and obese women (≥27.5 kg/m²) trying to conceive. Body mass index categories were based on cut-offs for Asian populations. Metabolic health status was defined by (a) metabolic syndrome ≤2 (MHS) vs. ≥3 (MUS) criteria; and (b) HOMA-IR <2.5 (MHS) vs. ≥2.5 (MUS). The dots and capped lines represent point estimates and 95% confidence intervals, respectively, of fecundability odds ratios. The reference group comprised normal weight women with MHS. Data were analyzed using discrete-time proportional hazards models, adjusting for age, ethnicity, education, physical activity, smoking exposure and alcohol intake. HOMA-IR, homeostasis model assessment-insulin resistance; MHS, metabolically healthy status; MUS, metabolically unhealthy status.