Effects of Letrozole in Prevention of Premature Luteinizing Hormone (LH) Surge in Infertile Women with Clomiphene Citrate Resistant Polycystic Ovary Syndrome (PCOS) Undergoing Intrauterine Insemination
AbstractBackground: Polycystic ovarian syndrome (PCOS) is among the important causes of infertility in young women. Premature luteinizing hormone (LH) surge (PLS) is one of its complications. PLS can reduce the quality of oocytes and therefore decrease the success of intrauterine insemination (IUI). Letrozole, a non-steroidal aromatase inhibitor, prevents LH surge. In this study, we aim to evaluate the effects of letrozole on preventing premature LH surge in clomiphene-resistant patients with PCOS undergoing IUI. Materials and Methods: In this randomized clinical trial, 131 patients who were developed with PCOS were selected for IUI cycle, divided into two groups randomly: control group (n=67) and letrozole group (n=64). Incidence of premature LH surge, pregnancy, abortion and ongoing pregnancy rate, endometrial thickness and number of follicles were measured in both groups. Results: No significant difference was seen between mean ages in the two groups; 11.9% of the control group and 21.9% of the letrozole group became pregnant (P =0.005); furthermore, premature LH surge was seen in 4.7% of the letrozole group and 8.9% of the control group (P =0.003). E2 and Endometrial thickness was higher in letrozole group; however, LH was significantly higher in the control group (P =0.026). Conclusion: Administration of letrozole in clomiphene-resistant patients with PCO undergoing IUI cycle can decrease the incidence of PLS. In addition, it can increase pregnancy rate significantly. Therefore, using letrozole is more reasonable in patients who have not responded to clomiphene or are hypersensitive. [GMJ.2015;4(3):104-11]
Gnoth C, Godehardt E, Frank-Herrmann P, Friol K, Tigges J, Freundl G. Definition and prevalence of subfertility and infertility. Hum Reprod. 2005;20(5):1144-7.
Franks S, Mason H, White D, Willis D. Etiology of anovulation in polycystic ovary syndrome. Steroids. 1998;63(5-6):306-7.
Kini S. Polycystic ovary syndrome: diagnosis and management of related infertility. Obstetrics, Gynaecology & Reproductive Medicine. 2012;22:347-53.
Homburg R, Armar N, Eshel A, Adams J, Jacobs HS. Influence of serum luteinising hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome. BMJ. 1988;297(6655):1024-6.
Perales-Puchalt A, Legro RS. Ovulation induction in women with polycystic ovary syndrome. Steroids. 2013;78(8):767-72.
Balen AH. Hypersecretion of luteinizing hormone in the polycystic ovary syndrome and a novel hormone 'gonadotrophin surge attenuating factor'. J R Soc Med. 1995;88(6):339P-341P.
Sönmezer M, Pelin Cil A, Atabekoğlu C, Ozkavukçu S, Ozmen B. Does premature luteinization or early surge of LH impair cycle outcome? Report of two successful outcomes. J Assist Reprod Genet. 2009;26(2-3):159-63.
Al-Inany H, Azab H, El-Khayat W, Nada A, El-Khattan E, Abou-Setta AM. The effectiveness of clomiphene citrate in LH surge suppression in women undergoing IUI: a randomized controlled trial. Fertil Steril. 2010;94(6):2167-71.
Legro RS, Kunselman AR, Brzyski RG, Casson PR, Diamond MP, Schlaff WD, et al. The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: Rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome. Contemp Clin Trials. 2012;33(3):470-81.
Savaris RF, Groll JM, Young SL, DeMayo FJ, Jeong JW, Hamilton AE, et al. Progesterone Resistance in PCOS Endometrium: A Microarray Analysis in Clomiphene Citrate-Treated and Artificial Menstrual Cycles. J Clin Endocrinol Metab. 2011;96:1737-46.
Kamath M, George K. Letrozole or clomiphene citrate as first line for anovulatory infertility: a debate. Reprod Biol Endocrinol. 2011;9:86.
Chen X. Suggestion and comment for clomiphene citrate preventing luteinizing hormone surge. Fertil Steril. 2011;95(8):e55.
Lin YH, Seow KM, Chen HJ, Hsieh BC, Huang LW, Tzeng CR, et al. Effect of cetrorelix dose on premature LH surge during ovarian stimulation. Reprod Biomed Online. 2008;16(6):772-7.
Sohrabvand F, Ansari Sh, Bagheri M. Efficacy of combined metformin-letrozol in comprasion with metformin-clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease. Hum Reprod. 2006;21(6):1432-5.
Cortínez A, De Carvalho I, Vantman D, Gabler F, Iñiguez G, Vega M. Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients. Fertil Steril. 2005;83(1):110-5.
Fouda U, Sayed A. Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trial. Reprod Biol Endocrinol. 2011;9:84.
Mitwally MFM, Casper R. Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility. Hum Reprod. 2003;18(8):1588-97.
Polyzos NP, Tzioras S, Badawy AM, Valachis A, Dritsas C, Mauri D. Aromatase inhibitors for female infertility: a systematic review of the literature. Reprod Biomed Online. 2009;19(4):456-71.
Rahmani E, Ahmadi S, Motamed N, Maneshi HO. Dosage Optimization for Letrozole Treatment in Clomiphene-Resistant Patients with Polycystic Ovary Syndrome: A Prospective Interventional Study. Obstet Gynecol Int. 2012;2012:758508.
Cunha-Filho JS, Kadoch J, Righini C, Fanchin R, Frydman R, Olivennes F. Premature LH and progesterone rise in intrauterine insemination cycles: analysis of related factors. Reprod Biomed Online. 2003;7(2):194-9.
Siddiqui M, Chowdhury T. Letrozole for Induction of Ovulation in PCOS Patients: Resistant to Clomiphene Citrate. South Asian Federation of Obstetrics and Gynecology. 2010;2:99-103.
Al-Inany H, Azab H, El-Khayat W, Nada A, El-Khattan E, Abou-Setta AM. The effectiveness of Clomiphene Citrate in LH surge suppression in women undergoing IUI:A randomized controlled trial. Fertil Steril. 2010;94(6):2167-71.
Allegra A, Marino A, Coffaro F, Scaglione P, Sammartano F, Rizza G, et al. GnRH antagonist induce inhibition of the premature LU surge increases pregnancy rates in IUI stimulated cycle. A prospective randomized trial. Hum Reprod. 2007;22(1):101-8.
Casper RF, Mitwally MF. Use of the Aromatase Inhibitor Letrozole for Ovulation Induction in Women With Polycystic Ovarian Syndrome. Clin Obstet Gynecol. 2011;54(4):685-95.
Begum M, Ferdous J, Begum A, Quadir E. Comparison of efficacy of aromatase inhibitor and clomiphene citrate in induction of ovulation in polycystic ovarian syndrome. Fertil Steril. 2009;92(3):853-7.
Abd EI. Efficacy of combined metformin-letrozole in comparison with bilateral ovarian drilling in clomiphene-resistant infertile women with polycystic ovarian syndrome. Arch Gynecol Obstet. 2013;288(1):119-23.
Branigan E, Estes M. Minimal stimulation IVF using clomiphene citrate and oral contraceptive pill pretreatment for LH suppression. Fertil Steril. 2000r;73(3):587-90.
Antaki R, Dean NL, Lapensée L, Racicot MH, Ménard S, Kadoch IJ. An algorithm combining ultrasound monitoring and urinary luteinizing hormone testing: a novel approach for intrauterine insemination timing. J Obstet Gynaecol Can. 2011;33(12):1248-52.
Ziegler Dd. The dawning of the non-cancer uses of aromatase inhibitors in gynaecology. Hum Reprod. 2003;18(8):1598-602.
Bedaiwy MA, Abdelaleem MA, Hussein M, Mousa N, Brunengraber LN, Casper RF. Hormonal, follicular and endometrial dynamics in letrozole-treated versus natural cycles in patients undergoing controlled ovarian stimulation. Reprod Biol Endocrinol. 2011;9:83.
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