Preconception GLP-1 Receptor Agonist Therapy and Reproductive Outcomes in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis

Review title: Preconception GLP-1 Receptor Agonist Therapy and Reproductive Outcomes in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis Type and method of review: Systematic review, with meta-analysis where appropriate Stage of review at time of this submission: Review ongoing — the protocol has been finalised and the peer-reviewed search prepared; formal screening not yet started. Review question: In Women of reproductive age with polycystic ovary syndrome (Rotterdam, NIH, or AE-PCOS criteria) planning pregnancy or undergoing fertility treatment, what is the effect of Preconception GLP-1 receptor agonists (liraglutide, semaglutide, exenatide, dulaglutide, tirzepatide), alone or with metformin and/or lifestyle modification compared with Placebo, no treatment, lifestyle modification alone, metformin alone, or other standard care on Live birth rate (primary); clinical pregnancy, spontaneous pregnancy, ovulation, menstrual regularity, miscarriage, weight/BMI change, and adverse events (secondary)? Searches: The following sources will be searched: PubMed / MEDLINE, Embase, Cochrane CENTRAL, Scopus, Web of Science Core Collection, ClinicalTrials.gov, WHO ICTRP. Additional records may be imported from other databases. No date or language restrictions are applied unless otherwise stated. The search strategy underwent peer review (PRESS) before execution. Condition or domain being studied: Women of reproductive age with polycystic ovary syndrome (Rotterdam, NIH, or AE-PCOS criteria) planning pregnancy or undergoing fertility treatment Participants / population: Women of reproductive age with polycystic ovary syndrome (Rotterdam, NIH, or AE-PCOS criteria) planning pregnancy or undergoing fertility treatment Intervention(s), exposure(s): Preconception GLP-1 receptor agonists (liraglutide, semaglutide, exenatide, dulaglutide, tirzepatide), alone or with metformin and/or lifestyle modification Comparator(s) / control: Placebo, no treatment, lifestyle modification alone, metformin alone, or other standard care Types of study to be included: Inclusion criteria: Women of reproductive age diagnosed with PCOS using Rotterdam, NIH, or AE-PCOS criteria; GLP-1 receptor agonist given before conception or before fertility treatment; Has a comparator group (placebo, no treatment, lifestyle, metformin, or standard care); Reports at least one reproductive outcome (live birth, pregnancy, ovulation, menstrual regularity, or miscarriage); Randomised controlled trial or prospective/retrospective cohort study. Exclusion criteria: Animal or laboratory study; Review, editorial, letter, case report, or conference abstract without full data; Population without PCOS, or mixed population without separate PCOS data; GLP-1 receptor agonist started only during pregnancy (no preconception exposure); No reproductive outcome reported Main outcome(s): Live birth rate (primary); clinical pregnancy, spontaneous pregnancy, ovulation, menstrual regularity, miscarriage, weight/BMI change, and adverse events (secondary) Data extraction (selection and coding): Two reviewers will independently screen titles/abstracts and full texts, blinded to each other’s decisions, and extract data in duplicate using a standardised, piloted form. Disagreements will be resolved by discussion or a third reviewer. Risk of bias (quality) assessment: The risk of bias of each included study will be assessed independently by two reviewers using a study-design-appropriate tool. Disagreements will be resolved by consensus. Risk of bias in the review itself will be appraised with ROBIS. Strategy for data synthesis: Results will be synthesised narratively. Where studies are sufficiently homogeneous, effect estimates will be pooled in a meta-analysis using a fixed- or random-effects model as indicated by heterogeneity (I²). The certainty of the evidence will be rated using GRADE.