Preconception Leptin and Fecundability, Pregnancy, and Live Birth Among Women With a History of Pregnancy Loss

Abstract

Context With the increase of obesity, it is imperative to understand the neuroendocrine mechanisms, including the neuroendocrine hormone leptin, by which obese or overweight women are at increased risk for subfertility and infertility. Objective The objective was to examine associations between preconception serum leptin concentrations, fecundability, pregnancy, and live birth. Design Secondary analysis of a prospective cohort among women with prior pregnancy losses. Setting The study was conducted at four US medical centers (2006 to 2012). Intervention Not available. Materials and Methods Preconception serum leptin concentrations were measured at baseline, and women were followed for up to six menstrual cycles, and throughout pregnancy if they conceived. Discrete Cox proportional hazard regression models were used to assess fecundability odds ratios (FORs) and log-binomial regression to estimate risk ratios (RRs) for pregnancy and live birth. Models were adjusted for age, physical activity, treatment arm, and adiposity, either by measured waist-to-hip ratio or body mass index (BMI). Results High leptin concentrations were associated with decreased fecundability (FOR 0.72, 95% CI 0.58, 0.90), reduced risk of pregnancy (RR 0.87, 95% CI 0.78, 0.96) and live birth (RR 0.76, 95% CI 0.65, 0.89) comparing the upper to the lower tertile. However, adjustment for BMI in lieu of waist-to-hip ratio nullified observed associations. Conclusions In women with a history of pregnancy loss, relations between higher preconception leptin and fecundability were attenuated after adjustment for BMI, although not after adjustment for other markers of adiposity. Leptin may serve as a complementary marker of adiposity for assessment of obesity and reproductive outcomes.

Periconceptional biomarkers for maternal obesity: a systematic review

“…Leptin The present review demonstrated that levels of leptin are elevated in obese women and correlate positively with BMI at both systemic and local levels throughout the periconceptional period [35,40,42,45,50,51,62,65,66,68,71,74,[76][77][78]. The results are consistent with other studies, confirming the effect of obesity on increasing leptin levels [91,92].…”

“…Preconception: Higher levels of follicular fluid and serum leptin were observed in obese and overweight/obese women compared to women of normal weight in two studies [42,50]. Additionally, BMI was positively correlated with follicular fluid leptin levels in three studies (i.e., higher levels of leptin with increasing BMI) [40,45,51].…”

“…Figure 4 illustrates the relationship between biomarkers of these three pathways and clinical outcomes. Obese women are at increased risk of subfertility which can be related to lower progesterone and increased leptin levels [40,177]. Leptin can modulate reproductive function by affecting ovarian folliculogenesis and ovulation, and by perturbing the hypothalamic-pituitary-gonadal axis, such as by lowering progesterone and gonadotropin-releasing hormone levels [178,179].…”

Mutltifaceted biological roles of leptin

“…conceptionnelle semble réduire la fécondité, les chances de grossesse et le nombre de naissances vivantes[80]. La leptine a également été dosée dans le liquide folliculaire de patientes ayant recours à la fécondation in vitro et son augmentation était associée à la diminution des naissances vivantes[81].…”