Ovulation Rate after Metformin and Clomiphene vs Clomiphene Alone in Polycystic Ovary Syndrome (PCOS): A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Background: Polycystic ovary syndrome (PCOS) affects 5%-15% of women of reproductive age and has a negative impact on their fertility. The primary outcome of this study is ovulation rate when standard (immediate release) metformin (MF) is added to clomiphene citrate (CC) in oligoovulatory and anovulatory women with PCOS. Methods: This is a randomized, double-blind, placebo-controlled trial. Twenty-seven women with PCOS (according to the Rotterdam consensus), desiring pregnancy and without another cause of subfertility were recruited from a public hospital outpatient gynecology clinic. Up to six cycles of CC (25-150 mg) plus either MF 500 mg tds (CC+MF) or placebo (CC+Pl) were offered. Student’s t-test, Chi-squared test, and Fisher’s exact test were used for analysis. Results: Thirteen women with up to six cycles each were included in the final analysis. The rate of ovulation and ovulation rate per cycle was similar between women in the CC+MF and CC+Pl groups RR 1.09 (95% CI 0.80-1.49) and RR 0.88 (95% CI 0.63-1.22), respectively as was chemical pregnancy rate RR 1.77 (95% CI 0.58-5.38). The live birth rate was higher in CC+MF RR 6.83 (95% CI 0.83-56.27) and miscarriage rate was lower RR 0.21 (95% CI 0.002-1.07). The number needed to treat for live birth was 10. Conclusion: Use of standard MF, 500 mg tds, when given with CC results in an increase in live birth rate, and a decrease in miscarriage rate.

A Deep Dive into Polycystic Ovary Syndrome: A Multidisciplinary Approach

“…[47] It was observed that the usage of standard metformin (500 mgtds) along with the Clomiphene citrate increased in the live birth and the decrease in miscarriage rates. [48] According to a study, its use during pregnancy can help in maintaining androgen levels as well as insulin levels in the normal range. The female children born to such women have reduced AMH levels, whereas male children have reduced androgen levels and are heavier.…”

Mini review: The FDA‐approved prescription drugs that induce ovulation in women with ovulatory problems

“…Also, the combination of metformin and gonadotropins can promote the rate of monoovulations and reduce the duration of administration and dosage of gonadotropins and the risk of canceled cycles (Elnashar, 2011). Common side effects of metformin include diarrhea, nausea asthenia, flatulence, weakness, myalgia, hypoglycemia, and abdominal pain (Heathcote et al, 2020; Sharpe et al, 2019).…”