Clinical Trial: Metformine and CC Compared With Placebo and CC for Induction Ovulation in PCOS Patients With Insulin Resistant

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: Is the Co-administration of Metformine and CC as Compared to Placebo and CC Superior to Induce Ovulation in PCOS Patients With a Confirmed insulin-resistant-a Double Blind Randomized Clinical Trial

Brief Summary: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility which affects 12-21% of the population.Several studies performed evaluate the possible benefit of metformin alone or in combination with clomiphene (CC)as first-line treatment for infertility in women with PCOS have reported conflicting results. These conflicting results may be due to the presence or absence of insulin resistance(IR).Metformin decreases IR .However there is not a single randomized clinical trial with metformin in IR PCOS patients. Therefore, the aim of current study is to compare CC with coadministration of metformin and with CC with coadministration of placebo in IR PCOS patients to induce ovulation.

Detailed Summary:

Introduction:

PCOS is the most common cause of anovulatory infertility which affects 12-21% of the population. This percentage may vary according to the criteria used and population studied.Hyperandrogenism, chronic anovulation, and occasionally obesity are the characteristics of this syndrome. Currently, CC is the first-line infertility treatment in women with the PCOS .However, 20-25% of PCOS women fail to ovulate with incremental doses of CC and and do not respond due to resistance to CC .IR and hyperinsulinemia are considered as important factors in the pathogenesis of PCOS .Hence, lean and obese women with PCOS may have IR.Hyperinsulinism has been shown to play a part in ovarian hyperandrogenism and may directly influence and even prevent ovulation.Metformin, an insulin sensitizing agent, reduces levels of luteinizing hormone, hyperinsulinemia and also decreases ovarian production of androgens .For this reason a number of studies have been performed and evaluated the possible beneficial role of metformin in managing women with PCOS. However, the studies performed evaluate the possible benefit of metformin alone or in combination with CC as first-line treatment for infertility in women with PCOS have reported conflicting results .Recently a meta-analysis concluded that metformin was more burdensome than placebo, hence CC alone and not CC plus metformin should be the drug of choice in these patients.A high-quality Cochrane systematic review has reported on randomized controlled trials(RCTs) comparing metformin with CC in women with PCOS and demonstrated that CC had a significantly higher pregnancy and live birth rate in women with a BMI >30 kg/m2 whereas metformin had better results in women with a BMI <30 kg/m2.Lately, a meta-analysis reported that due to conflicting findings and heterogeneity across the included RCTs, there is insufficient evidence to establish
Sponsor: Semnan University of Medical Sciences

Current Primary Outcome: ovulation rate [ Time Frame: every other weeks up to 8 weeks ]

The progesterone levels will be measured every other week in order to document ovulation. A progesterone level > 5 ng/ml (16 nmol per liter) will considered as confirmatory of ovulation during metformine administration .Ovarian follicular response will be monitored by transvaginal sonography every other day from day 10 of the cycle to the 16th day of the cycle.ovulation will be confrmed When at least one follicle reached ≥18 mm in diameter.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Clinical pregnancy rate [ Time Frame: 5 weeks of gestation ]
    Clinical pregnancy will be defined as the detection of at least one gestational sac on transvaginal ultrasound examination starting one week after the missed period
  • Ongoing pregnancy rate [ Time Frame: 12 weeks of gestation ]
    Ongoing pregnancy will be defined as the detection of an alive fetus>12weeks of gestation on transvaginal ultrasound examination.


Original Secondary Outcome: Same as current

Information By: Semnan University of Medical Sciences

Dates:
Date Received: July 11, 2015
Date Started: November 2015
Date Completion: August 2020
Last Updated: October 12, 2016
Last Verified: October 2016