GLP-1 receptor agonists (GLP-1RAs) address key metabolic drivers of Polycystic Ovary Syndrome (PCOS), yet their integration into fertility management remains challenging because reproductive efficacy is variably reported, preconception washout is required, and standardized clinical pathways are lacking.
MAIN BODY: We present a structured, fertility-centered, hypothesis-generating narrative synthesis of the metabolic-reproductive-pregnancy continuum in PCOS, integrating evidence from randomized trials, observational studies, reviews, and clinical guidance. Heterogeneous findings are organized by intervention/comparator, follow-up window, and key effect modifiers, including baseline obesity/insulin-resistance phenotype, concomitant metformin, and lifestyle co-interventions. The clinical framework is derived from this narrative synthesis rather than from quantitative reproductive meta-analysis. As a methodological proof-of-concept only, we additionally performed a Bayesian network meta-analysis restricted to body-weight change within a prespecified 12-16-weeks window in the largest connected treatment network. Because ovulation, clinical pregnancy, time to pregnancy, and live birth were inconsistently defined and sparsely reported across trials, no confirmatory quantitative synthesis or treatment ranking was undertaken for these reproductive outcomes. We therefore distinguish evidence domains explicitly, with relatively robust support for short-term metabolic benefit but substantially greater uncertainty for reproductive translation and periconception safety.
Conclusion
The narrative evidence supports positioning GLP-1RAs as time-limited, preconception metabolic-optimization tools, not as confirmed fertility-enhancing therapies per se. Their use in PCOS fertility care should be individualized through shared decision-making, with explicit discussion of the difference between established metabolic benefit and hypothesis-generating reproductive benefit, together with drug-specific washout planning and strategies to minimize post-discontinuation rebound. Future trials should standardize reproductive endpoints and systematically capture periconception exposure to enable confirmatory synthesis and individualized benefit-risk estimation.
Becker AS et al., 2026·JBRA assisted reproduction·
Open Access
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.
Metabolic and Endocrine Agents · GLP-1 Receptor Agonists
Carmina E et al., 2026·Journal of clinical medicine
Irregular menses and chronic anovulation are key components of Polyendocrine Metabolic Ovarian Syndrome (PMOS), but available treatments generally only mask the clinical problem, which presents itself again when the drugs are stopped. Because reduction of body weight in these patients is often associated with improvement of menstrual cycles, we evaluated the effects of treatment with semaglutide, a GLP-1 agonist that has emerged as an effective treatment for obesity. A total of 96 women with PMOS and body mass index (BMI) > 25 kg/m2 completed a six-month treatment protocol with semaglutide using an individualized dose-escalation regimen. Body weight, fasting glucose, insulin levels, insulin resistance (HOMA-IR), and ovulatory function were assessed before and after treatment. After six months of treatment, mean body weight decreased significantly (-11.3 ± 5%, p < 0.01). Before treatment, 83% of PMOS patients presented with oligomenorrhea and anovulatory cycles. Following treatment, ovulatory cycles were observed in 52.5% of previously anovulatory women. The results were particularly good in overweight patients, with almost 95% of these PMOS patients achieving menstrual cycle normalization and ovulation, but also in patients with mild obesity. Results were less favorable in PMOS patients with moderate or severe obesity, but 25% of these patients achieved menstrual ovulatory cycle normalization when treated with semaglutide. This study represents an important therapeutic advancement, suggesting that women with PMOS and excessive body weight should be considered for treatment with GLP-1 receptor agonists before proceeding to therapies specifically aimed at inducing normal cycles and ovulation.
Restorative Care and Assisted Reproduction · Outcome Comparisons
Restorative Reproductive Medicine (RRM) aims to restore fertility by diagnosing and treating the underlying causes of infertility. RRM is frequently promoted as an alternative to assisted reproductive technology (ART), despite uncertainty regarding its comparative effectiveness and safety. Where delayed childbearing and infertility are becoming more common, reliance on optimization of natural physiology alone may delay effective treatment and compromise reproductive outcomes. A systematic review of the current evidence comparing RRM to either ART or unassisted conception is, therefore, essential to inform clinical practice, guideline development, and shared decision-making for patients experiencing infertility. To assess the effectiveness and safety of RRM approaches, evaluated as a whole, rather than as individual components, compared with ART and medically unassisted conception in couples experiencing infertility. A systematic literature search of MEDLINE, Embase, CENTRAL and the Journal of Restorative Reproductive Medicine from inception to 28 November 2025. We included randomized control trials (RCTs) or nonrandomized comparative studies evaluating reproductive and safety outcomes of RRM as a unified treatment, compared with either ART or expectant management (attempted medically unassisted conception). Two reviewers independently screened titles, abstracts and full texts with disagreements resolved by a third reviewer. We retrieved 724 records, of which 16 studies underwent full-text review. No RCTs or comparative observational studies were identified. All 16 full-text studies were excluded for an ineligible study design (no control group); most were cohort studies in which all participants underwent RRM. Ten studies reported reproductive outcomes; nine of these made claims regarding the benefits or effectiveness of RRM. None of these claims were supported by the study designs used, as the lack of a comparison group precludes reliable estimation of treatment effects. Consequently, these studies cannot provide valid estimates of RRM success rates, nor permit any meaningful inference about its effectiveness relative to unassisted conception or ART. Large-scale RCTs or prospective cohort studies reporting effectiveness and safety outcomes are required to inform evidence-based fertility guidelines. There are no comparative studies to support reliable estimates of the safety and effectiveness of RRM compared with ART or medically unassisted conception for couples experiencing infertility.
This systematic review and meta-analysis examined the relationship between menstrual cycle phases and the incidence of muscle injuries in female team sport athletes, following PRISMA 2020 and PERSiST guidelines. A comprehensive search was conducted in PubMed, Scopus, and SPORTDiscus from inception to mid-January 2024. Studies were included if they examined female team sport athletes of reproductive age with regular menstrual cycles and compared the occurrence of muscle injuries across at least two menstrual phases. Studies involving hormonal contraceptive use, medications affecting the menstrual cycle or musculoskeletal system, or menstrual dysfunction were excluded. Three studies met the inclusion criteria, involving 318 participants. Meta-analysis yielded a pooled Risk Ratio of 1.18 (95% CI: 0.75 to 1.86, p = 0.46) for injury risk between the luteal and follicular phases, suggesting no statistically significant association. However, the certainty of the cumulative evidence was rated as very low due to methodological limitations, including inconsistent phase classifications and reliance on imprecise methods for identifying menstrual phases. Consequently, no practical or clinical recommendations can be made at this time. Future research employing standardised, physiologically accurate methods for classifying and detecting menstrual cycle phases is necessary to better understand the potential links between hormonal fluctuations and injury risk. Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-36763-0.