Weight-Lowering Drugs and Natural Female Fertility-A Systematic Review and Meta-Analysis

Overweight and obesity are global health concerns linked to impaired female fertility. Weight-lowering drugs are an alternative for achieving weight loss; however, their effect on natural female fertility is unclear. A systematic review and meta-analysis were conducted to summarise the literature on the effects of weight-lowering drugs on ovulation, conception, pregnancy and live birth rates. Inclusion criteria comprised interventional and observational studies involving women with overweight or obesity receiving weight-lowering drugs, compared with non-users, lifestyle modifications or other medications. MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov were searched, yielding 2731 records. After screening, seven clinical trials were included (n = 575), six of which were randomised. Sample sizes ranged from 40 to 120 women aged 25.9-29.7 years. Six trials evaluated orlistat, while one assessed semaglutide. In four trials, orlistat was associated with a higher ovulation rate than lifestyle modifications. A meta-analysis of ovulation rates comparing orlistat and metformin showed no significant difference (RR = 0.78, 95% CI: 0.41-1.49; p = 0.45). Two studies reported pregnancy rates: one found a higher rate with orlistat compared to lifestyle modifications (23.3% vs. 6.7%, p = 0.044), and another showed that adding semaglutide to metformin increased the pregnancy rate compared to metformin alone (35% vs. 15%, p < 0.05). Future studies should address current limitations and evaluate the effects of newer weight-lowering drugs on natural pregnancy and live birth rates in adequately powered studies.