Preconception weight loss improves fertility and maternal outcomes in obese mice

Women with obesity have higher incidences of infertility, with longer time to conception and increased risk of pregnancy complications compared to women with normal body weight. There is a lack of evidence demonstrating benefit of preconception maternal weight loss on fertility and pregnancy outcomes. We aimed to determine if preconception weight loss, with diet modification or glucose-like peptide 1 receptor agonist liraglutide, improves maternal weight, fertility, and pregnancy outcomes. Methods:C57BL/6 female mice were fed either a high-fat-diet (HFD) or chow for 8 weeks. HFD-fed dams were administered liraglutide (0.3mg/kg,s.c,for4weeks) or switched to chow to induce weight loss. Prior to mating, liraglutide was ceased and mice continued on HFD. Mice in the ‘diet switch’group continued on chow. Pregnancy rates were recorded. Maternal anthropometry and glucose tolerance were measured before and after intervention, and at late gestation. Results: Liraglutide or diet-switch led to weight reduction, improved insulin resistance (P<0.001), and enhanced fertility, particularly the liraglutide group (P<0.005). Liraglutide treated mice had significant gestational weight gain compared to the diet-switch group (P<0.05), with similar weight and glucose tolerance in late gestation to HFD mice. In contrast, diet-switch maintained similar weight and glucose tolerance in late gestation to control mice. Conclusion: Pre-pregnancy weight intervention with liraglutide was effective at restoring fertility. Diet modification also improved fertility and avoided catch-up weight gain in pregnancy. Liraglutide may be a therapeutic strategy for weight loss to prepare for pregnancy. However, our study provides caution about the potential for excessive gestational weight gain without diet intervention in pregnancy.