Intraovarian Platelet-rich Plasma Administration Induced Spontaneous Ovulation in an Anovulatory Woman With PCOS

Evidence That Semaglutide Represents an Important Tool for Treatment of Irregular Menses and Chronic Anovulation in Women with Polyendocrine Metabolic Ovarian Syndrome

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.

Stair-step versus traditional clomiphene citrate protocols in polycystic ovary syndrome: a systematic review and meta-analysis

Reimão Miller KA et al., 2026 · Reproductive biomedicine online

This review explores whether the clomiphene citrate stair-step protocol (SSP) for ovulation induction in patients with polycystic ovary syndrome (PCOS) outperforms the traditional protocol. The following databases were searched: PubMed, Cochrane Library, ClinicalTrials.gov, EMBASE and Google Scholar from inception to 15 June 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and with PROSPERO registration (CRD420251050294). Of 847 screened records, five randomized controlled trials were included (n = 520: n = 255; traditional protocol: n = 265). Analyses were conducted in Review Manager 5.4 using random-effects models. Risk ratios, mean differences and 95% confidence intervals were calculated. Heterogeneity was assessed with I², risk of bias with RoB2, certainty with GRADE and robustness with leave-one-out sensitivity analysis. The SSP increased ovulation rates compared with the traditional protocol (RR 1.28, 95% CI 1.10 to 1.49; five randomized controlled trials [RCTs], n = 520, I² = 0%). Clinical pregnancy also favoured SSP (RR 1.46, 95% CI 1.04 to 2.05; four RCTs, n = 460; I² = 0%), although this result was largely driven by one study. The SSP shortened treatment duration (mean difference -32.59 days, 95% CI -38.66 to -26.52 days; three RCTs, n = 320, I² = 83%). Endometrial thickness was similar (mean difference 0.32 mm, 95% CI -0.95 to 1.59 mm; four RCTs, n = 460, I² = 91%). SSP improves ovulation rate and shortens treatment without affecting endometrial thickness and may increase clinical pregnancy rates.

Identification of predictors of the ovarian response to clomiphene citrate in infertile women with polycystic ovary syndrome: A post-hoc analysis of a randomized controlled trial

Liu Y et al., 2026 · Frontiers in endocrinology

Clomiphene citrate (CC) is the first-line medication for inducing ovulation in women with polycystic ovary syndrome (PCOS). However, approximately 20% of patients with PCOS are resistant to CC. This study aims to identify reliable baseline predictors of CC resistance in infertile women with PCOS. A post-hoc analysis of a large, multicenter randomized controlled trial (PCOSAct trial) conducted in China. The current analysis comprised the 471 participants who were randomized to the active CC arm and completed the requisite follow-up. To identify potential candidate variables, we employed multivariable logistic and LASSO regression analyses. Within the framework of a multivariable logistic regression model, we also estimated the independent associations between the identified candidate variables and resistance to CC. Additionally, we plotted the Receiver Operating Characteristic (ROC) curve and utilized the DeLong method to compare the statistical differences in the area under the curve (AUC). Finally, we constructed a restricted cubic spline (RCS) logistic regression model to illustrate the dose-response relationship between continuous predictor variables and CC resistance. CC resistance was identified in 32 (6.8%) participants. Body Mass Index (BMI), Total Testosterone (TT), and Anti-Müllerian Hormone (AMH) were useful predictors of ovarian response to CC. The "T+BMI" dual-factor model demonstrated high discriminative power (AUC = 0.801) and was statistically comparable to the three-factor model including AMH (AUC = 0.818; P = 0.347). TT was the strongest individual predictor (OR = 2.73 per 1-unit), while BMI was the most significant modifiable risk factor (OR = 2.49 per 1-SD). A simplified "T + BMI" assessment provides comparable prognostic utility without the need for AMH testing. For patients at high risk of CC resistance, we recommend upfront use of aromatase inhibitors or low-dose gonadotropins. This strategy avoids ineffective treatment cycles and enables personalized ovulation induction. The study was registered on ClinicalTrials.gov under the identification number NCT01573858 on July 6, 2012.

Letrozole replaces clomiphene as first-line for PCOS ovulation induction

Metabolic optimization + letrozole -> clomiphene -> OWR