Volume 10, Issue 1 (7-2012)                   IJRM 2012, 10(1): 33-40 | Back to browse issues page

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Azargoon A, Alavy Toussy J, Fakhr Darbanan F. Pregnancies following the use of sequential treatment of metformin and incremental doses of letrozole in clomiphen-resistant women with polycystic ovary syndrome. IJRM 2012; 10 (1) :33-40
URL: http://ijrm.ir/article-1-252-en.html
Pregnancies following the use of sequential treatment of metformin and incremental doses of letrozole in clomiphen-resistant women with polycystic ovary syndrome
Azam Azargoon * 1, Jafar Alavy Toussy2 , Fakhry Fakhr Darbanan3
1- Department of Gynecology and Obstetrics, Semnan University of Medical Sciences, Semnan, Iran , azarmona2003@yahoo.com
2- Department of Pathology, Semnan University of Medical Sciences, Semnan, Iran
3- Department of Gynecology and Obstetrics, Semnan University of Medical Sciences, Semnan, Iran
Abstract:   (6735 Views)
Background: Clomiphen citrate (CC) is the first line therapy for women with infertility and poly cystic ovary syndrome( PCOS). However, 20-25% of women are resistant to CC and do not ovulate.
Objective: The objective of this study was to evaluate the efficacy of sequential treatment of metformin and incremental doses of letrozole in induction of ovulation in cases of CC-resistant PCOS patients.
Materials and Methods: In this prospective before-after study, we enrolled 106 anovulatory PCOS women who failed to ovulate with CC alone from Amir-Almomenin University Hospital in Semnan, Iran. After an initial 6-8 weeks of metformin treatment, they received 2.5 mg letrozole daily on days 3-7 after menes. If they did not ovulate with 2.5 mg letrozole, the doses were increased to 5 to 7.5 mg daily in subsequent cycles. The main outcomes were ovulatory rate, pregnancy rate and cumulative pregnancy rate.
Results: 13.33% of patients conceived with metformin alone. Ovulation occurred in 83 out of remaining 91 patients (91.2%). 78.02% of patients responded to lower doses of letrozole. Cumulative pregnancy rate was 60/ 105 (57.14%).
Conclusion: We suggest that treatment in CC-resistant PCOS patients should begin at first with lower doses of letrozole and could increase to the higher dose depending on the patient response before considering more aggressive therapeutic alternatives such as gonadotropins.
Keywords: CC-resistant, Induction ovulation, Letrozole, Metformin, PCOS.
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Type of Study: Original Article |
References
1. Neveu N, Granger L, St-Michel P, Lavoie HB. Comparison of clomiphene citrate, metformin, or the combination of both for first- line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome. Fertil Steril 2007; 87: 113-120. [DOI:10.1016/j.fertnstert.2006.05.069]
2. Abdulrahim A. Rouzi, Mohammed Salleh M. Ardawi. A randomized controlled trial of the efficacy of rosiglitazone and clomiphene citrate versus metformin and clomiphene citrate in women with clomiphene citrate-resistant polycystic ovary syndrome. Fertil Steril 2006; 85: 428-435. [DOI:10.1016/j.fertnstert.2005.07.1312]
3. Elnashar A, Fouad H, Eldosoky M, Abelgafar N. Letrozole induction of ovulation in clomiphene citrate resistant polycystic ovary syndrome: responders and non-responders. Mid East Fertil Soc J 2004; 9: 157-162.
4. Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril 2001; 75: 305-309. [DOI:10.1016/S0015-0282(00)01705-2]
5. George SS, George K, Irwin C, Job V, Selvakumar R, Jeyaseelan V, et al. Sequential treatment of metformin and clomiphene citrate in clomiphene-resistant women with polycystic ovary syndrome: a randomized, controlled trial. Hum Reprod 2003; 18: 299-304. [DOI:10.1093/humrep/deg105]
6. Sohrabvand F, Ansari Sh, Bagheri M. Efficacy of combined metformin-letrozole in comparison with metformin-clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease. Hum Reprod 2006; 21: 1432-1435. [DOI:10.1093/humrep/del020]
7. Al-Omari WR, Sulaiman WR, Al-Hadithi N. Comparison of two aromatase inhibitors in women with clomiphene-resistant polycystic ovary syndrome. Int J Gynaecol Obstet 2004; 85: 289-291. [DOI:10.1016/j.ijgo.2003.11.010]
8. Sönmez AS, Yasar L, Savan K, Koç S, Ozcan J, Toklar A, et al. Comparison of the effects of acarbose and metformin use on ovulation rates in clomiphene citrate-resistant polycystic ovary syndrome. Hum Reprod 2005; 20: 175-179. [DOI:10.1093/humrep/deh580]
9. Al-Fadhli R, Sylvestre C, Buckett W, Tan SL, Tulandi T. A randomized trial of superovulation with two different doses of letrozole. Fertil Steril 2006; 85: 161-164. [DOI:10.1016/j.fertnstert.2005.07.1283]
10. Vandermolen DT, Ratts VS, Evans WS, Stovall DW, Kaumma SW, Nestler JE. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Fertil Steril 2001; 75: 310-315. [DOI:10.1016/S0015-0282(00)01675-7]
11. Speroff L, Fritz MA. Induction ovulation In :Cilinical gynecologic endocrinology and infertility. 7th Ed. Philadelphi: Lippincott,Williams and Wilkins; 2005: 499-1180.
12. Bart CJM, Fauser MD. Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome.The Rotterdam ESHREASRM-sponsored pcos consensus workshop group. Fertil Steril 2004; 81: 19-25. [DOI:10.1016/j.fertnstert.2003.10.004]
13. Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994; 43 :647-654. [DOI:10.1016/0026-0495(94)90209-7]
14. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998; 338: 1876-1880. [DOI:10.1056/NEJM199806253382603]
15. Kocak M, Carliskan E, Simsir C, Haberal A. Metformin therapy improves ovulatory rates,cervical scores,and pregnancy rates in clomiphene citrate resistant women with polycystic ovary syndrome. Fertil Steril 2002; 77: 101-106. [DOI:10.1016/S0015-0282(01)02941-7]
16. Sturrock NDC, Lannon B, Fay TN. Metformin doesn't enhance ovulation induction in the clomiphene resistant polycystic ovary syndrome in clinical practice. Br J Clin Pharmacol 2002; 53: 469-473. [DOI:10.1046/j.1365-2125.2002.01575.x]
17. Sibert THI, Kruger THF, Steyn DW, Nasarka S. Is the addition of metformin efficacious in the treatment of clomiphene citrate resistant women with polycystic ovary syndrome? A structural literature review. Fertil Steril 2006; 86: 1432-1437. [DOI:10.1016/j.fertnstert.2006.06.014]
18. Heard MJ, Pierce A, Carson SA, Buster JE. Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome. Fertil Steril 2002; 77: 669-673. [DOI:10.1016/S0015-0282(01)03266-6]
19. Gilbert C, Valois M, Koren G. Pregnancy. Outcome after first-trimester exposure to metformin:a meta analysis. Fertil Steril 2006; 86: 658-662. [DOI:10.1016/j.fertnstert.2006.02.098]
20. Metawie MH. Comparative study of aromatase inhibitor, Letrozole, with clomiphene citrate for induction of ovulation. Mid East Fertil Soc J 2001; 6: 7-9.
21. Al-Fozan H, Al-Khadouri M, Tan SL, Tulandi T. A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation. Fertil Steril 2004; 82: 1561-1563. [DOI:10.1016/j.fertnstert.2004.04.070]
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