Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Comparison of Tamoxifen and Clomiphene Citrate for Ovulation Induction in Women with Polycystic Ovarian Syndrome: A Prospective Study

Authors
1 Department of Reproductive Medicine, Mahatma Gandhi University of Medical Science and Technology, Rajasthan, India
2 Manipal Hospital Jaipur, Rajasthan, India
Abstract
Background: The purpose of this study was to compare the efficacy of tamoxifen and clomiphene citrate in induction of ovulation in women with PCOS and anovulation. Methods: In this prospective cohort study, 104 women with PCOS and primary infertility were enrolled after fulfilling the inclusion and exclusion criteria. The patients were allocated in two groups; group A (n=54) received tamoxifen 40 mg once daily (Days 3-7) and group B (n=50) received clomiphene citrate 100 mg once daily (Days 3-7). Serial ultrasounds were done till the administration of human chorionic gonadotropin (hCG). The ovulation and pregnancy rates in both groups were compared. The number of dominant follicles, estradiol levels, and endometrial thickness were also studied. Comparison was done using chi-square and student’s t-test and a p-value of less than 0.05 was considered statistically significant. Results: The number of dominant follicles and serum estradiol levels were significantly higher in group B (p<0.05), whereas the endometrial thickness was significantly more in group A (p<0.05). The ovulation rates were similar in both groups (66.6% vs. 70%, p=0.715). Pregnancy rate per treatment cycle and per ovulatory cycle was marginally higher in group A (14.81% and 22.22%, respectively), as compared to group B (14% and 20%, respectively), but the difference was not statistically significant (p>0.05). Conclusion: Tamoxifen and clomiphene citrate are both equally effective in induction of ovulation and achieving a pregnancy in women with PCOS.
Keywords

  1. Hamilton-Fairley D, Kiddy D, Watson H, Paterson C, Franks S. Association of moderate obesity with poor pregnancy outcome in women with polycystic ovary syndrome. Br J Obstet Gynaecol. 1999;99(2):128-31.
  2. Berek JS. Novak's textbook of gynecology. 13th ed. US: Williams & Wilkins; 2002. 1432 p.
  3. NICE guidelines. Fertility problems: assessment and treatment (CG156); 2013. 51 p.
  4. Greenblatt RB, Barfield WE, Jungck EC, Ray AW. Induction of ovulation with MRL/41, preliminary report. JAMA. 1961;178:101-4.
  5. Wolf LJ. Ovulation induction. Clin Obstet Gynecol. 2000;43(4):902-15.
  6. Gorlitsky GA, Kase NG, Speroff L. Ovulation and pregnancy rates with clomiphene citrate. Obstet Gynecol. 1978;51(3):265-9.
  7. Gysler M, March CM, Mishell DR Jr, Bailey EJ. A decade’s experience with an individualized clomiphene treatment regimen including its effect on the postcoital test. Fertil Steril. 1982;37(2):161-7.
  8. Eden JA, Place J, Carter GD, Jones J, Alaghband-Zadeh J, Pawson ME. The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume. Fertil Steril. 1989;73(2):187-90.
  9. Williamson JG, Ellis JD. The induction of ovulation by tamoxifen. J Obstet Gynecol Br Commonw. 1973;80(9):844-7.
  10. Borenstein R, Shoham Z, Yemini M, Barash A, Fienstein M, Rozenman D. Tamoxifen treatment in women with failure of clomiphene citrate therapy. Aust N Z J Obstet Gynaecol. 1989;29(2):173-5.
  11. Gulekli B, Ozaksit G, Turhan NO, Senoz S, Oral H, Gokman O. Tamoxifen: an alternative approach in clomiphene resistant polycystic ovarian syndrome patients. J Pak Med Assoc. 1993;43(5):89-90.
  12. Nicholas S, Macklon. Optimizing protocols for ovulation induction. Female infertility therapy. London: Martin Dunitz; 2000. p. 75-83.
  13. Fox R, Corrigan E, Thomas PA, Hull MGR. The diagnosis of polycystic ovarian in women with menstrual disorder. Fertil Steril. 2000;66:761-4.
  14. Roumen FJ, Doesburg HW, Rolland R. Treatment of infertile women with a deficient postcoital test with two antiestrogens: clomiphene and tamoxifen. Fertil Steril. 1984;41(2):237-43.
  15. Rotterdam ESHRE/ASRM‐Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long‐term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41-7.
  16. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010. 271 p.
  17. Boostanfar R, Jain JK, Mishell DR Jr, Paulson RJ. A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Fertil Steril. 2001;75(5):1024-6.
  18. Nardo LG. Management of anovulatory infertility associated with polycystic ovary syndrome: tamoxifen citrate an effective alternative compound to clomiphene citrate. Gynecol Endocrinol. 2004;19(50:235-8.
  19. Seyedoshohadaei F, Zandvakily F, Shahgeibi S. Comparison of the effectiveness of clomiphene citrate, tamoxifen and letrozole in ovulation induction in infertility due to isolated unovulation. Iran J Reprod Med. 2012;10(6):531-6.
  20. Badawy A, Gibreal A. Clomiphene citrate versus tamoxifen for ovulation induction in women with PCOS: a prospective randomized trial. Eur J Obstet Gynecol Reprod Biol. 2011;159(1):151-4.
  21. Chunfeng Sun, Musen Wang. Comparative study on the curative effect of clomifene and tamoxifen in infertile patients with polycystic ovary syndrome. China Health Stand Manage. 2016;13:121-3.
  22. Daqing Xiang, Ling Chen, Ling Zeng. Clinical efficacy of clomiphene and tamoxifen on infertility patients with polycystic ovary syndrome. Iran J Reprod Med. 2016;2:284-7.
  23. Narayanan M, Jahaan U, Gupta N. Comparative evaluation of different cost effective ovulation induction drugs and their effect on follicular growth, endometrial thickness and pregnancy outcome. Int J Reprod Contracept Obstet Gynecol. 2019;8(11):4549-53.
  24. Steiner AZ, Terplan M, Paulson RJ. Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Hum Reprod. 2005;20(6):1511-5.
  25. Jie L, Li D, Yang C, Haiying Z. Tamoxifen versus clomiphene citrate for ovulation induction in infertile women. Eur J Obstet Gynecol Reprod Biol. 2018;228:57-64.
  26. Sattar MM, El-Halaby AE, El-Shamy ES, Taha SN. Effect of clomiphene citrate, tamoxifen, and letrozole on endometrial thickness in cycles of ovulation induction: a randomized controlled trial. Menoufia Med J. 2020;33(2):405.
  27. Huang Xuekun Shang, Huiling Zhang, Siyou. Different stimulate ovulation drugs influence of early pregnancy outcome in patients with polycystic ovary syndrome. Pract Med J. 2011;27:3760-2.
  28. Yu Li, Dong-zi Yang. Letrozole, tamoxifen or clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome after pretreatment: a prospective randomized trial. Chin J Pract Gynecol Obstetr. 2011;27:606-8.
  29. Lu Ye. Letrozole, tamoxifen and clomiphene citrate compared the clinical effect of treatment of polycystic ovary syndrome. Chin Foreign Med Res. 2012;10:11-2.
  30. Lixia Zhang, Li Yu. Three kinds of drugs in the treatment of polycystic ovary syndrome with infertility clinical comparative study. Stud Chin Foreign Med. 2015;32:57-9.
  31. Roumen FJ. [Decreased quality of cervix mucus under the influence of clomiphene: a meta- analysis]. Ned Tijdschr Geneeskd. 1997;41(49):2401-5. Dutich.
  32. Gadalla MA, Huang S, Wang R, Norman RJ, Abdullah SA, El Saman AM, et al. Effect of clomiphene citrate on endometrial thickness, ovulation, pregnancy and live birth in anovulatory women: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018;51(1):64-76.
  33. Qiu-yan Luo. The clinical effect of letrozole, tamoxifen and clomiphene in treatment of patients with polycystic ovary syndrome infertility. Clin Med Res Pract. 2016;1:39-40.
  34. Brown J, Farquhar C. Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome. Cochrane Database Syst Rev. 2016;12(12):CD002249.
  35. Cook LS, Weiss NS, Schwartz SM, White E, McKnight B, Moore DE, et al. Population-based study of tamoxifen therapy and subsequent ovarian, endometrial and breast cancers. J Natl Cancer Inst. 1995;87(18):1359-64.