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The effect of metformin treatment to ovarian response in cases with PCOS

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Archives of Gynecology and Obstetrics Aims and scope Submit manuscript



To examine the effect of metformin therapy on ovarian response in clomiphene-resistant PCOS patients.


Randomized prospective study.


Zeynep Kamil Hospital IVF Center.


Thirty-two female PCOS patients with clomiphene citrate resistance.


Test group A received 2×850 mg/day metformin therapy for 8 weeks, followed by gonadotropin induction. Only gonadotropin induction was applied to Control group B.

Main outcome measures.

Total gonadotropin dosage, duration of gonadotropin therapy, estradiol level on HCG-day, number of follicles with ≥16 mm diameter, number of cases with hyperstimulation development, number of cancelled cycles, endometrial thickness on HCG-day, pregnancy outcome, multiple pregnancy rate.


The total gonadotropin doses given to metformin-study group was significantly lower than the control group. In addition, duration of therapy, HCG level, plasma estradiol level on HCG-day in the study group was significantly lower than in the control group.


Metformin therapy has led to a higher pregnancy outcome, as well as to a decrease in hyperstimulation risk, cycle cancellations, and multiple pregnancy rates with a lower gonadotropin dosage.

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  1. Adams J, Franks S, Polson DW, Mason HD (1985) Multifollicular ovaries: clinical endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet 2:1375–1378

  2. Bailey CJ (1992) Biguanides and NIDDM. Diabetes Care 15:755–772

  3. Barbieri RL, Makris A, Ryan KJ (1984) Insulin stimulates androgen accumulation in incubations of human ovarian stroma and theca. Obstet Gynecol 73:80–84

  4. Bailey CJ, Turner RC (1996) Metformin drug therapy. N Engl J Med 334:574–579

  5. Diamanti-Kandarakis E, Kouli C, Tsianateli T, Bergiele A (1998) Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. Eur J Endocrinol 138:269–274

  6. Dor J, Seidman DS, Ben-Shlomo I, Levran D, Karasik A, Mashiach S (1992) The prognostic importance of the number of oocytes retrieved and estradiol levels in poor and normal responders in in vitro fertilization (IVF) treatment. J Assist Reprod Genet 9:228–232

  7. Dunaif A (1992) Insulin resistance and ovarian hyperandrogenism. Endocrinologist 2:248–260

  8. Ficicioglu C, Api M, Ozden S (1996) The number of follicles and ovarian volume in the assessment of response to clomiphene citrate treatment in polycystic ovarian syndrome. Acta Obstet Gynecol Scand 75:31–35

  9. Fox R, Corrigan E, Thomas PA, Hull MGR (1991) The diagnosis of polycystic ovaries in women with oligo-amenorrhoea: predictive power of endocrine tests. Clin Endocrinol 34:127–131

  10. Frank S (1995) Polycystic ovary syndrome. N Engl J Med 333:853

  11. Franks S, Gilling-Smith C, Watson H, Willis D (1999) Insulin action in the normal and polycystic ovary. Endocrinol Metab Clin North Am 28:361–378

  12. Glasier AF (1990) Clomiphene citrate. Baillieres Clin Obstet Gynaecol 3:491–502

  13. Hammond MG (1984) Monitoring technique for improved pregnancy rates during CC ovulation induction. Fertil Steril 42:499–509

  14. Kocak M, Caliskan E, Simsir C, Haberal A (2002) Metformin therapy improves ovulatory rates, cervical scores and pregnancy rate in clomiphene citrate resistant women with PCOS. Fertil Steril 77:310–315

  15. La Marca A, Morgante G, Paglia T, Ciotta L, Cianci A, De Leo V (1999) Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome. Fertil Steril 72:985–989

  16. Leroith D, Werner H, Beitner-Johnson D, Roberts CT Jr (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 16:143–163

  17. Nestler JE, Jakubowicz DJ (1996) Decreases in ovarian cytochrome P450c17a activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 335:617–623

  18. Nestler JE, Jakubowicz DJ (1997) Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17a activity and serum androgens. J Clin Endocrinol Metab 82:4075–4079

  19. Nestler JE, Powers LP, Matt DW (1991) A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 72:83–89

  20. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R (1998) Effects of metformin on spontaneous and clomiphene induced ovulation in the polycystic ovary syndrome. N Engl J Med 338:1876–1880

  21. Pellicer A, Valbuena D, Cano F, Remohi J, Simon C (1996) Lower implantation rates in high responders: evidence for an altered endocrine milieu during the preimplantation period. Fertil Steril 65:1190–1195

  22. Shepard MK, Balmaceda JP, Leija CG (1979) Relationship of weight to successful induction ovulation with CC citrate. Fertil Steril 32:641–645

  23. Stadtmauer LA, Toma SK, Riehl RM, Talbert LM (2001) Metformin treatment of patients with PCOS undergoing IVF improves outcomes and is associated with modulation of insulin-like growth factors. Fertil Steril 75:505–509

  24. Utiger RD (1996) Insulin and the polycystic ovary syndrome. N Engl J Med 335:657–658

  25. Valezquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ (1994) Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia and systolic blood pressure while facilitating normal menses and pregnancy. Metabolism 43:647–654

  26. Vandermolen DT, Ratss VS, Evans WS, Stovall DW, Kauma SW, Nestler J (2001) Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with PCOS, are resistant to clomiphene citrate. Fertil Steril 75:101–105

  27. L. De Vincenzo (1999) Effects of metformin on gonadotropin induced ovulation in women with polycystic ovary syndrome. Fertil Steril 282:285–288

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Correspondence to Cem Ficicioglu.

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Tasdemir, S., Ficicioglu, C., Yalti, S. et al. The effect of metformin treatment to ovarian response in cases with PCOS. Arch Gynecol Obstet 269, 121–124 (2004).

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