Becker, A. S., Castilhos, J. P., Shugair, S. A. S., Colombo, T., & Hentschke, M. R. (2026). GLP-1 Receptor Agonists and Fertility: What Is Known So Far? JBRA assisted reproduction. https://doi.org/10.5935/1518-0557.20260028
Becker AS, Castilhos JP, Shugair SAS, Colombo T, Hentschke MR. GLP-1 Receptor Agonists and Fertility: What Is Known So Far? JBRA assisted reproduction. 2026. doi:10.5935/1518-0557.20260028
Becker, Alice Scalzilli, et al. "GLP-1 Receptor Agonists and Fertility: What Is Known So Far?" JBRA assisted reproduction, 2026.
GLP-1 drugs improved menstrual regularity and ovulation in PCOS trials
A narrative review reports that GLP-1 drugs improved menstrual regularity and ovulation in some trials, mostly in overweight or obese women. The women had PMOS (polyendocrine metabolic ovarian syndrome), formerly PCOS. In one trial of 60 women, the ovulation rate was 86% with exenatide plus metformin and 29% with metformin alone.
Key Findings
In a trial of 60 overweight or obese women with PMOS / PCOS and infrequent ovulation, ovulation rates were 86% with exenatide plus metformin, 50% with exenatide and 29% with metformin (p<0.01).
Natural pregnancy rates were higher after exenatide pretreatment than after metformin (43.6% vs 18.7%, p<0.05) in a trial of 176 women with overweight or obesity and PMOS / PCOS.
A cited meta-analysis of randomized trials with 840 patients reported more natural pregnancies and better menstrual regularity with GLP-1 drugs, with no statistically significant difference in overall pregnancy rate.
Human pregnancy data are limited and animal studies reported fetal risks. Advice cited is to stop semaglutide or tirzepatide two months before conception. Pharmacokinetic studies found tirzepatide lowered oral contraceptive blood levels.
In more than 50,000 pregnant women with type 2 diabetes, no increased malformation risk was identified after periconceptional antidiabetic drug exposure, including GLP-1 drugs, versus insulin (adjusted RR 0.95; 95% CI 0.72-1.26).
Interpretation
This narrative review searched three databases through June 2025 and drew on trials, case reports and laboratory work. The five tabulated trials compared GLP-1 drugs with metformin or placebo. The authors link the benefits to weight loss and describe possible direct ovarian effects. They call GLP-1 drugs promising for women with PMOS / PCOS and obesity-related infertility, especially alongside metformin, and advise avoiding them in pregnancy and lactation. The findings support larger studies of GLP-1 drugs in PMOS / PCOS.
RRM Context
Restorative reproductive medicine asks why ovulation is disrupted in PMOS / PCOS, and metabolic health is part of the answer. The trials tracked cycle regularity and ovulation, signs that charting shows. Restorative care includes both partners, and the review reports mixed findings in men.
Our editorial summary of this paper, not the article's abstract.
Abstract
GLP-1 receptor agonists (GLP-1RAs) have gained attention as a potential adjunct in preconception care for women with polycystic ovary syndrome (PCOS) and infertility. This narrative literature review (June 2025) searched PubMed, SciELO, and LILACS using the descriptors "weight loss medication," "GLP-1 receptor agonists," "liraglutide," "semaglutide," "fertility," "PCOS," and "reproductive outcomes," including studies published between 2014 and 2025, yielding 47 relevant articles. Overall, GLP-1RAs show consistent metabolic benefits and emerging evidence of improved reproductive outcomes in PCOS, with clinical trials reporting increased menstrual regularity, ovulation, and pregnancy rates-particularly when combined with metformin. Liraglutide (1.2-3.0 mg/day) and exenatide (10 µg twice daily) have been associated with improved follicular development and endometrial receptivity. Mechanistically, GLP-1 receptors are expressed in reproductive tissues, and these agents may exert anti-inflammatory, antifibrotic, and androgen-lowering effects; liraglutide has also been reported to restore granulosa-oocyte communication via suppression of CXCL10. In one randomized trial, pregnancy rates were higher with liraglutide plus metformin (69.2%) than with metformin alone (35.4%; p<0.05). Ovulation rates up to 86% have been described with exenatide plus metformin, exceeding those observed with monotherapy. Despite these signals of benefit, GLP-1RAs remain contraindicated during pregnancy due to limited human data and fetal risks observed in animal studies; semaglutide and tirzepatide require an 8-10 week washout period prior to conception, and tirzepatide may reduce oral contraceptive effectiveness because of delayed gastric emptying. In summary, GLP-1RAs are a promising strategy for preconception management in women with PCOS and obesity-related infertility, especially in combination with metformin, but they should be avoided during pregnancy and lactation, and individualized counseling is essential to align therapy with reproductive goals.
