From Ovulation Induction to IVF: A Short Review of Fertility Treatments for Women with PCOS

Abstract

Background: Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility. Managing infertility in PCOS requires an evidence-based, stepwise approach that balances effectiveness, safety, and patient preferences. Over the last decade, practice-changing trials and modern ART safety strategies have shifted first-line and ART protocols. Objective: To synthesize contemporary evidence across the fertility-treatment continuum in PCOS — from lifestyle and oral ovulation induction to surgical options, gonadotropin stimulation, and assisted reproductive technologies (ART) including in-vitro fertilization (IVF) and in-vitro maturation (IVM) — with attention to comparative effectiveness (ovulation, clinical pregnancy, live birth) and safety (OHSS, multiple pregnancy, perinatal outcomes). Methods: We performed a narrative systematic approach prioritizing high-quality randomized controlled trials (RCTs), Cochrane reviews, recent meta-analyses, and international guidelines through December 2024. Key sources included the 2023 International PCOS Guideline, the NEJM randomized trial comparing letrozole and clomiphene, Cochrane reviews on metformin and laparoscopic ovarian drilling, and ASRM guidance on OHSS prevention and IVM. For each treatment category, we summarize mechanisms, efficacy, key trial evidence, safety considerations, and guideline recommendations. Results: Letrozole (aromatase inhibitor) demonstrates superior ovulation and live-birth rates compared with clomiphene and is now recommended as the first-line oral ovulation induction agent in many patients. Metformin improves ovulation and may be useful where metabolic indications exist, but evidence for consistent live-birth benefit as monotherapy is limited. Gonadotropins are effective second-line agents for ovulation induction but increase monitoring needs and OHSS/multiple pregnancy risk; low-dose step-up regimens reduce but do not eliminate these harms. Laparoscopic ovarian drilling (LOD) can restore ovulation in selected clomiphene-resistant women but carries surgical risks and uncertain live-birth advantage vs medical alternatives. In ART, GnRH antagonist stimulation protocols combined with GnRH-agonist trigger and selective “freeze-all”/deferred embryo transfer markedly reduce OHSS risk while maintaining comparable pregnancy outcomes. IVM offers an OHSS-sparing option with reasonable success in specialized centres, but technique heterogeneity limits generalizability. Pregnancies conceived in women with PCOS continue to show higher risks of gestational diabetes and hypertensive disorders, necessitating integrated preconception metabolic optimization and obstetric surveillance. Conclusions: Contemporary evidence supports letrozole as first-line ovulation induction for many anovulatory patients with PCOS, careful selective use of metformin for metabolic indications, stepwise escalation to gonadotropins or LOD when needed, and ART strategies prioritizing OHSS prevention (antagonist regimens, agonist trigger and freeze-all). IVM is promising for OHSS-risk reduction in specialist settings. Key research gaps include phenotype-specific randomized data, long-term offspring outcomes, and optimized individualized stimulation algorithms.

Keywords: PCOS, infertility, ovulation induction, letrozole, IVF, IVM, OHSS, systematic review.