The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome

Saudi Med J. 2002 Jun;23(6):663-6.


Objective: To study the effect of metformin in combination with clomiphene citrate, as compared with placebo plus clomiphene citrate, on the ovulation and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.

Methods: This study was carried out at King Hussein Medical Center, Amman, Jordan, during the period January 2001 through to July 2001. Twenty-eight clomiphene citrate-resistant polycystic ovary syndrome women were evaluated prospectively for 6 treatment cycles by receiving metformin, 850mg twice daily throughout the cycle along with 50 mg clomiphene citrate, starting on day 5-9 of the same cycle (N=16), or by taking placebo with clomiphene citrate (N=12). During cycles 2-6, clomiphene citrate was added with increments of 50mg (up to 200 mg/day) for both groups. Progesterone level on day 21 and 28 >5ng/dl was indicative of ovulation.

Results: A statistically significant increase in the rates of ovulation (68.6% versus 25%, p<0.05) and pregnancy (56.3% versus 16.6%, p<0.05) were observed in the metformin-clomiphene citrate group as compared with the placebo-clomiphene citrate controls. Insignificant increase in the rate of ovarian hyperstimulation was noted in the placebo-clomiphene citrate group.

Conclusion: Metformin-clomiphene citrate regimen in resistant-clomiphene citrate polycystic ovary syndrome women significantly increases the ovulation and pregnancy rates, and decreases the occurrence of ovarian hyperstimulation syndrome.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Clomiphene / therapeutic use*
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Fertility Agents, Female / therapeutic use*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Metformin / therapeutic use*
  • Ovulation Induction
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy


  • Fertility Agents, Female
  • Hypoglycemic Agents
  • Clomiphene
  • Metformin