Metformin plus Clomiphene Citrate versus Gonadotropins in Clomiphene Citrate- Resistant Polycystic Ovary Syndrome Ovulation induction in CC-resistant PCOS

Abstract

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 11^th 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.