Volume 10, Issue 6 (4-2012)                   IJRM 2012, 10(6): 531-536 | Back to browse issues page


XML Persian Abstract Print

1- Department of Obstetrics and Gynecology, Besat Hospital, Kurdistan University of Medical Sciences, Sanandaj, Iran , f.seyedoshohadaei@muk.ac.ir
2- Department of Obstetrics and Gynecology, Besat Hospital, Kurdistan University of Medical Sciences, Sanandaj, Iran
Abstract:   (7264 Views)
Background: Unovulation is the most common cause of infertility. The first line oral treatment has been clomiphene citrate. Another anti-estrogen used for ovulation induction is tamoxifen. Many unovulatory infertile women are resistance to anti-estrogens and need another treatment. Alternative treatments are aromatas inhibitors.
Objective: This study was designed to compare the effectiveness of clomiphene, tamoxifen and letrozole in ovulation induction outcomes in isolated non PCOS unovulatory patients.
Materials and Methods: 150 unovulatory infertile women who had isolated non- polycystic ovarian syndrome (PCOS), randomized to 3 groups. Group A received clomiphene 50 mg to maximum 150 mg for 5 days, Group B received tamoxifen 10mg to maximum 30 mg for 5 days, Group C received letrozole 2.5 mg for 5 days, to maximum 7.5 mg until ovulation was induced. If ovulation failed to occur with 5 days treatments, drug continued for 7 days. Treatment has been stopped if they became pregnant or if patient didn’t ovulate with maximum dose for 7 days (resistant to treatment) or failed to concept after six months despite ovulation (failure of treatment). Main outcome measures were: number of mature follicles, endometrial thickness, pregnancy rate, multiple pregnancy rate, live birth and miscarriage.
Results: Overall ovulation rate was 60 (73.4%), this rate in group A was 39 (78%), in group B it was 24 (68%) and in group C was 37 (74%). Pregnancy rate in groups A, B and C were, 32 (64%), 20 (40%), and 25 (50%) respectively, and live birth rate was 22 (44%) in A, 17 (34%) in B and 21 (42%) in C. Miscarriage rate with clomiphene was 10 (20%) while this was 3 (6%) in tamoxifen and 4 (8%) in letrozole group (p=0.05). One twin pregnancy was occurred with clomiphene and one with tamoxifen, while all pregnancies with letrozole were singleton.
Conclusion: Because of higher pregnancy rate with clomiphene citrate than tamoxifen and letrozole, Clomiphene citrate is still the first-line therapy for ovulation induction. Surprisingly, pregnancies after tamoxifen and letrozole have lower miscarriage rate than clomiphene.
Full-Text [PDF 700 kb]   (249 Downloads) |   |   Full-Text (HTML)  (141 Views)  
Type of Study: Original Article |

1. Brown J, Farquhar C, Beck J, Boothroyd C, Proctor M, Hughes E. Oral anti-estrogen and medical adjuncts for subfertility associated with anovulation. Cochrane Database Syst Rev 2009; 1: CD002249.
2. Fisher SA, Reid RL, Van Vugt DA, Casper RF. A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women. Fertil Steril 2002; 78: 280-285. [DOI:10.1016/S0015-0282(02)03241-7]
3. Sipe CS, Davis WD, Maifeld M, Van Voorhis BJ. A prospective randomized trial comparing anastrozole and clomiphene citrate in an ovulation induction protocol using gonadotropins. Fertil Steril 2006; 86: 1676-1681. [DOI:10.1016/j.fertnstert.2006.05.048]
4. Ganesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B. 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 2009; 26: 19-24. [DOI:10.1007/s10815-008-9284-4]
5. Bedaiwy MA, Forman R, Mousa NA, Al Inany HG, Casper RF. Cost-effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation. Hum Reprod 2006; 21: 2838-2844. [DOI:10.1093/humrep/del273]
6. Richard JP, Steiner AZ, Terplan M. Comparison of tamoxifen and clomiphene citratefor ovulation induction: a meta-analysis. Hum Reprod 2005; 20: 1511-1515. [DOI:10.1093/humrep/deh840]
7. Messinis IE. Ovulation induction: a mini review. Hum Reprod 2005; 20: 2688-2697. [DOI:10.1093/humrep/dei128]
8. Quintero RB, Urban R, Lathi RB, Westphal LM, Dahan MH. A comparison of letrozole to gonadotropins for ovulation induction, in subjects who failed to conceive with clomiphene citrate. Fertil Steril 2007; 88: 879-885. [DOI:10.1016/j.fertnstert.2006.11.166]
9. Bayar U, Tanriverdi HA, Barut A, Ayoğlu F, Ozcan O, Kaya E. Letrozole vs. clomiphene citrate in patients with ovulatory infertility. Fertil Steril 2006; 85: 1045-1048. [DOI:10.1016/j.fertnstert.2005.09.045]
10. 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]
11. Landeras J, Herrero J, Navarro E, Neyro JL, Salvador C, Tur R, et al. Use of letrozole in assisted reproduction: a systematic review and meta-analysis. Hum Reprod Update 2008; 14: 571-582. [DOI:10.1093/humupd/dmn033]
12. Eijkemans MJ, Imani B, Mulders AG, Habbema JD, Fauser BC. High singleton live birth rate following classical ovulation induction in normogonadotrophic anovulatory infertility. Hum Reprod 2003; 18: 2357-2362. [DOI:10.1093/humrep/deg459]
13. Abu Hashim H, Shokeir T, Badawy A. Letrozole versus combined metformin and clomiphene citrate for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Fertil Steril 2010; 94: 1405-1409. [DOI:10.1016/j.fertnstert.2009.07.985]
14. Hughes E, Collins J, Vandekerckhove P. [Intervention Review] Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea. Cochrane Database Syst Rev 2009; 1: CD000056.
15. Elnashar A, Fouad H, Eldosoky M, Saeid N. Letrozole induction Of ovulation in women with clomiphene citrate-resistant polycystic ovary syndrome may not depend on the period of infertility, the body mass index, or the luteinizing hormone/follicle-stimulating hormone ratio. Fertil Steril 2006; 85: 511-513 [DOI:10.1016/j.fertnstert.2005.08.016]
16. Boostanfar R, Jain JK, Mishell RD, Paulson RJ. A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Fertil Steril 2001: 75: 1024-1026. [DOI:10.1016/S0015-0282(01)01749-6]
17. Mitwally MF, Biljan MM, Casper RF. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol 2005; 192: 381-386. [DOI:10.1016/j.ajog.2004.08.013]
18. Wu Ch. Less miscarriage in pregnancy following Tamoxifen treatment of infertile patients with luteal phase dysfunction as compared to clomiphene treatment. Early Pregnancy 1997; 3: 301-305.
19. Badawy A, Shokeir T, Allama F, Abdelhady H. Pregnancy outcome after ovulation induction with aromatase inhibitors or clomiphene citrate in unexplained infertility. Acta Obstetricia et Gynecologica 2009; 88: 187-191 [DOI:10.1080/00016340802638199]
20. Karaer O, Oruç S, Koyuncu FM. Aromatase inhibitors: possible future applications. Acta Obstet Gynecol Scand 2004; 83: 699-706. [DOI:10.1111/j.0001-6349.2004.00562.x]
21. Mitwally MF, Biljan MM, Casper RF. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol 2005; 192: 381-386. [DOI:10.1016/j.ajog.2004.08.013]