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Gynecol Endocrinol. 2011 Mar;27(3):190-6. doi: 10.3109/09513590.2010.488771. Epub 2010 Jun 23.

Combined metformin and clomiphene citrate versus highly purified FSH for ovulation induction in clomiphene-resistant PCOS women: a randomised controlled trial.

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Department of Obstetrics and Gynecology, Mansoura University, Mansoura, Egypt.



To compare the effect of combined metformin-clomiphene citrate (CC) with highly purified urinary FSH (HP-uFSH) for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS).


One-hundred fifty-three anovulatory women with CC-resistant PCOS were selected in this randomised controlled trial. Patients received combined metformin-CC (n=75, 205 cycles) or HP-uFSH (n=78, 186 cycles) for three cycles. Outcome measures were; Ovulation rate, number of growing and mature follicles, serum E2, serum P, endometrial thickness, pregnancy and miscarriage rates.


The ovulation rate per cycle was significantly higher in the HP-uFSH group (83.8% vs. 62%, p=0.01). The number of follicles ≥ 12 mm ≥ 14 mm and ≥ 18 mm on the hCG day was significantly greater in the HP-uFSH group (p=0.01, p=0.02 and p=0.03, respectively). Pregnancy occurred in 23/205 cycles (11.2%) in combined metformin-CC group and 40/186 cycles (21.5%) in the HP-uFSH group; the difference was statistically significant (p=0.02). Two patients in the HP-uFSH group suffered mild OHSS.


Combined metformin-CC resulted in modest ovulation and pregnancy rates without side effects. It is logical to offer this first for CC-resistant PCOS women before resorting to more expensive alternatives especially in developing communities where economic aspects of therapy are important.

[Indexed for MEDLINE]

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