Metabolic Syndrome and time to pregnancy: a retrospective study of nulliparous women

Objectives To determine 1) the association between metabolic syndrome (MetS), time to pregnancy (TTP), and infertility 2) associations between individual and increasing number of MetS components, TTP, and infertility; 3) whether these relationships differ by obesity (BMI, <30kg/m2 vs. ≥30kg/m2). Design Retrospective cohort study. Setting Multi‐centre (Australia, United Kingdom, New Zealand, Ireland). Population 5519 low‐risk nulliparous pregnant women. Methods Data on retrospectively reported TTP (number of months to conceive) and a blood sample to assess metabolic health were collected between 14‐16 weeks’ gestation. MetS was defined according to the International Diabetes Federation criteria. Accelerated failure time models with log normal distribution were conducted to estimate time ratios (TR) and 95% CIs. Differences in MetS on infertility (TTP >12 months) was compared using a generalized linear model (Poisson distribution) with robust variance estimates (RR; 95% CIs). All analyses (entire cohort and split by BMI) were controlled for a range of maternal and paternal confounders. Main Outcome Measures TTP and infertility. Results Of the 5519 women included, 12.4% (n=684) had MetS. Compared to women without MetS, women with MetS had a longer TTP (adjusted TR 1.30; 95% CI: 1.15‐1.46), which was similar in the obese and non‐obese women. Marginal estimates for median TTP in women with MetS vs. without MetS was 3.1 (3.0‐3.3) months vs. 4.1 (3.6‐4.5) months, respectively. Women with MetS were at a 62% greater risk for infertility and were at a greater risk for infertility whether they were obese (adjusted RR 1.62; 1.15‐2.29) or not (adjusted RR 1.73; 1.33‐2.23). Reduced HDL‐C and raised TG were the main individual components associated with risk for infertility. Conclusions MetS is associated with longer TTP and infertility, independent of obesity. Additional studies, pre‐pregnancy, are required to support our findings and to determine the applicability of which combinations of metabolic abnormalities pose greatest risk to delayed fertility, or whether individual components are amenable to modification.