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 the benefit of preconception maternal
weight loss on fertility and pregnancy outcomes. We aimed to determine if preconception
weight loss, either with
diet modification or
glucose-like
peptide 1 receptor agonist
liraglutide, improves maternal weight, fertility, and pregnancy outcomes. C57BL/6 female mice were fed either a high-fat diet (HFD) or chow for 8 weeks. HFD-fed dams were administered
liraglutide (0.3 mg/kg, s.c., for 4 weeks) 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 the intervention and at late gestation. Offspring outcomes were assessed.
Liraglutide or diet switch led to
weight reduction, improved
insulin resistance (P< 0.001), and enhanced fertility, particularly in the
liraglutide group (P< 0.005).
Liraglutide-treated mice had significantly higher
gestational weight gain (GWG) 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. 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 GWG without diet intervention in pregnancy.