Metformin plus Clomiphene Citrate versus Gonadotropins in Clomiphene Citrate- Resistant Polycystic Ovary Syndrome

Introduction: Clomiphene citrate (CC) is the first-line pharmacological therapy for ovulation induction in polycystic ovary syndrome (PCOS). However, 15%-40% of patients show CC-resistance. Different drugs and drug combinations were in trial to overcome resistance. Aim of the study: comparison between the metformin plus CC and low dose exogenous follicle stimulating hormone (FSH) in CC-resistant PCOS. Subjects and methods: A prospective comparative trial was carried out for a period of 36 months (between June 2019 to June 2022) with ovulation induction period of 3 months. It included 40 patients with CC- resistance. They were divided into 2 groups. The first received metformin plus CC and the second received low dose exogenous FSH for 3 months. The cycles were monitored by transvaginal sonography (TVS), starting on the 11th day of the cycle. The primary outcome was the successful ovulation, and the secondary outcome was the detection of pregnancy sac (clinical pregnancy). Results: Metformin plus CC succeeded to produce a higher rate of ovulation. However, gonadotrophins are more effective as it produced a significantly higher rate in the first cycle (45.0% vs. 15%). However, there were no significant differences at the second and third cycles. The overall ovulation rate was 60% and 80.0% in metformin-CC group compared to gonadotrophin group. The clinical pregnancy rate was 25% and 15% in groups I and II, respectively (p value >0.05). Complications were confined to gonadotrophin group (multiple pregnancy and ovarian hyperstimulation syndrome (each in one patient). Conclusions: Gonadotrophins are more effective than metformin plus CC in the management of CC-resistant PCOS. However, it was associated with lower clinical pregnancy rate and higher complications rate. But the difference was statistically non-significant.