Abstract
Objectives
To compare the hormonal-metabolic profiles and reproductive outcomes between women receiving metformin plus letrozole and women undergoing bilateral ovarian drilling in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS).
Methods
In this randomized study, 146 patients were randomly allocated into group 1 (n = 73) who received metformin plus letrozole, and group 2 (n = 73) who underwent bilateral ovarian drilling. Comparison was done between the basal and after treatment biochemical values for each group, in addition reproductive outcomes after treatment were compared between both groups.
Results
There was significant reduction in testosterone (p ≤ 0.001), fasting insulin (p ≤ 0.001), and fasting glucose/fasting insulin ratio (p = 0.029) in metformin plus letrozole group, while there was significant reduction in FSH, LH and LH/FSH ratio in bilateral drilling group (p ≤ 0.001, 0.001 and 0.001). No significant difference in cycle regularity (p = 0.82), ovulation (p = 0.24), pregnancy rate (p = 0.32) and abortion rate (p = 0.51) between both groups.
Conclusion
Both metformin plus letrozole and bilateral ovarian drilling are similarly effective as second-line strategies for the treatment of women with PCOS who do not conceive with CC.
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References
Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA et al (2007) Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 356(8):551–556
Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Sattar N (2002) Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab 87:569–574
Homburg R (2005) Clomiphene citrate—end of an era? A mini-review. Hum Reprod 20(8):2043–2051
Palomba S, Falbo A, Zullo F (2009) Management strategies for ovulation induction in women with polycystic ovary syndrome and known Clomiphene citrate resistance. Curr Opin Obstet Gynecol 21(6):465–473
Palomba S, Zullo F, Diamanti-Kandarakis E, Orio F Jr (2006) Treatment of infertility in PCOS: surgery and laser diathermy. In: Nestler JE, Diamanti-Kandarakis E, Pasquali R, Panidis D (eds) Insulin resistance and polycystic ovary syndrome, evaluation and treatment. The Human Press Inc p, London, pp 67–81
Farquhar C, Lilford RJ, Marjoribanks J, Vandekerckhove P (2007) Laparoscopic “drilling” by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Systematic Review 20:CD001122
Glueck CJ, Morrison JA, Friedman LA, Goldenberg N, Stroop DM et al (2006) Obesity, free testosterone, and cardiovascular risk factors in adolescents with polycystic ovary syndrome and regularly cycling adolescents. Metabolism 55:508–514
Hahn S, Quadbeck B, Elsenbruch S, Gartner R, Finke R, Mann K et al (2004) Metformin, an efficacious drug in the treatment of polycystic ovary syndrome. Dtsch Med Wochenschr 129:1059–1064
Lord JM, Flight IH, Norman RJ (2003) Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome. Cochrane Database of Syst Rev 3 CD003053
Palomba S, Orio F, Falbo A, Manguso F, Russo T, Cascella T et al (2005) Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in non obese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab 90:4068–4074
Casper RF (2007) Aromatase inhibitors in ovarian stimulation. J Steroid Biochem Mol Biol 106 (1–5):71–5, Epub May 24
Okman KT, Kucuk M, Altaner S (2003) Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat. Fertil Steril 80(6):1330–1332
Fauser B, Tarlatzis B, Chang J, Azziz R, Rotterdam the, ESHRE/ASRM-sponsored PCOS consensus workshop group) (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47
Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E (2009) Clomiphene and anti-oestrogens for ovulation induction in PCOS,” Cochrane Database of Systematic Reviews, no. 4, Article ID CD002249
Ganesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B (2009) Comparison of letrozole with continuous gonadotropins and clomiphene gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial. J Assist Reprod Genet 26(1):19–24
Dhanalakshmi G, Sumathi P, Pasupathi P, Kumar KS (2011) Lipid profile and Homocysteine level changes in metformin and metformin letrozole therapy with south Indian PCOS women. Int J Cur Biomed Phar Res 1(3):102–108
Ashrafinia M, Hosseini R, Moini A, Eslami B, Asgari Z (2009) Comparison of metformin treatment and laparoscopic ovarian diathermy in patients with polycystic ovary syndrome. Int J Gynecol Obstet 107:236–239
Api M, Gorgen H, Cetin A (2005) Laparoscopic ovarian drilling in polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 119:76–81
Hamed HO, Hasan AF, Ahmed OG, Ahmed MA (2010) Metformin versus laparoscopic ovarian drilling in clomiphene and insulin-resistant women with polycystic ovary syndrome. Int J Gynecol Obstet 108:143–147
Abu Hashim H, El Lakany N, Sherief L (2011) Combined metformin and clomiphene citrate versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. J Obstet Gynaecol Res 37(6):169–177
Abdellah MS (2011) Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome. Int J Gynecol Obstet 113:218–221
Abu Hashim H, Maged AM, Badawy A (2010) Letrozole versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Arch Gynecol Obstet 282(5):567–571
Sohrabvand F, Ansari S, Bagheri M (2006) Efficacy of combined metformin–letrozole in comparison with metformin–clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease. Hum Reprod 21(6):1432–1435
Naether OGJ, Fischer R, Weise HC (1993) Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease. Fertil Steril 60:88–94
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Abd Elgafor, I. Efficacy of combined metformin–letrozole in comparison with bilateral ovarian drilling in clomiphene-resistant infertile women with polycystic ovarian syndrome. Arch Gynecol Obstet 288, 119–123 (2013). https://doi.org/10.1007/s00404-013-2714-2
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DOI: https://doi.org/10.1007/s00404-013-2714-2