Clomiphene stair-step protocol for ovulation induction in women with polycystic ovarian syndrome

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American Journal of BioMedicine  Volume 2, Issue 7, pages 840-854, July 2014


Basima Al Ghazali

Abstract

The objective of this study is to evaluate the efficacy of the clomiphene stair-step protocol to induce ovulation in women with polycystic ovarian syndrome (PCOS) compared to traditional protocol. This single center randomized controlled trial was undertaken. A 140-patients who met all of the inclusion criteria were divided into two main groups and induction of ovulation for both protocols was performed. Follow up of follicular maturation is done by transvaginal ultrasound. The time to ovulation with the stair step protocol was 21-28 days as compared with the traditional protocol which was 42-70 days. The dose dependent ovulation rate was 43% at 100 mg with the stair step protocol compared with 25.3% with the traditional regimen and the ovulation rate at 150 mg was 21.6% with the stair step protocol compared with 14.7% with the traditional protocol while the clomiphene citrate resistance rate was higher with the traditional protocol 38.7% as compared to the stair step method which was 20% which are statistically significant. This randomized controlled trial suggests that clomiphene stair step protocol decreases the time to ovulation and may improve ovulation rates in clomiphene-resistant women.

Keywords: Polycystic ovarian syndrome (PCO); Stair-step and traditional protocol; Transvaginal ultrasonography


References

1. 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: 41-47. [PubMed]

2. Balen AH. Polycystic ovary syndrome and secondary amenorrhoea. Dewhurst’s Textbook of Obstetrics and Gynaecology (7th Edition), editor D.K. Edmonds, Blackwell Scientific Publications, 2007, pp 377-398.

3. Amin M, Abdel-Kareem O, Takekida S, Moriyama T, Abd el-Aal G, Maruo T. Up-date Management of Non Responder to Clomiphene Citrate in Polycystic Ovary Syndrome. Kobe J Med Sci 2003; 49(3-4): 59-73. [PubMed]

4. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril 2008; 89(3): 505-522. [PubMed]

5. Practice Committee of the American Society for Reproductive Medicine. The use of clomiphene citrate in women. Fertil Steril 2006; 86: S187-93. [PubMed]

6. Moll E, van der Veen F, van Wely M. The role of metformin in polycystic ovary syndrome: a systematic review. Hum Reprod Update 2007; 6: 527-37. [PubMed]

7. Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356: 551–566. [PubMed]

8. Nestler JE. Metformin for the treatment of the polycystic ovary syndrome. N Engl J Med 2008; 358: 47-54. [PubMed]

9. Trolice MP. Evaluating the Infertile Patient: An Evidence-Based Review. Reproductive medicine 2011; 36: 25-30. [Abstract/ Full-Text]

10. Heijnen EMEW, Eijkemans MJC, Hughes EG, Laven JSE, Macklon NS, Fauser BCJM. A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update 2006; 12:13–21. [PubMed]

11. Schorge J, Schaffer J, Halvorson LM, Hoffman BL, Bradshaw KD, Cunningham FG.Treatment of the Infertile Couple. Williams.ginecologia. McGraw-Hill Companies, Inc., 2008, pp383-401. [Full-Book]

12. Hurst BS, Hickman JM, Matthews ML, Usadi RS, Marshburn PB. Novel clomiphene "stair-step" protocol reduces time to ovulation in women with polycystic ovarian syndrome. Am J Obstet Gynecol 2009; 200(5): 510.e1-4. [PubMed]

13. Jakimiuk AJ, Weitsman SR, Magoffin DA. 5α-reductase activity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1999; 84(7): 2414-8. [PubMed]

14. Farhi j, Orvieto R, Homburg R. Administration of clomiphene citrare in patients with polycystic ovary syndrome without inducing withdrawal bleeding, achieves comparable treatment characteristics and outcome. Fertil Steril 2010; 93(6): 2077-9. [PubMed]

15. Dickey RP, Taylor SN, Curole DN, Rye PH, Lu PY, Pyrzak R. Relationship of clomiphene dose and patient weight to successful treatment. Human Reproduction 1997; 12(3): 449-453. [PubMed]

16. Dickey RP, Olar TT, Taylor SN, Curole DN, Rye PH. Relationship of follicle number and other factors to fecundability and multiple pregnancy in clomiphene citrate-induced intrauterine insemination cycles. Fertil Steril 1992; 57: 613–619. [PubMed]

17. Richter KS, Bugge KR, Bromer JG, Levy MJ. Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos. Fertil Steril 2007; 87(1): 53-59. [PubMed]

18. Esmailzadeh S, Faramarzi M. Endometrial thickness and pregnancy outcome after intrauterine insemination 2007; 88: 432-437. [PubMed]

19. Ziba Zahiri, Seideh Hajar, Zahra Atrkar. Relationship between endometrial thickness and pattern with pregnancy rate in infertile patients. Journal of research in medical sciences 2007; 12(5): 257-261. [Abstract]

20. Farhi j, Orvieto R, Gavisu O, Homburg R. The association between follicular size on human chorionic gonadotropin day and pregnancy rate in clomiphene citrate treated polycystic ovary syndrome patients. Gynecol Endocrinol 2010; 26(7): 546-8. [PubMed]

21. Ghosh C, Buck G, Priore R, Wacktawski-Wende J, Severino M. Follicular response and pregnancy among infertile women undergoing ovulation induction and intrauterine insemination. Fertil Steril 2003; 80(2): 328-335. [PubMed]

22. van Rumste MM, Custers IM, van der Veen F, van Wely M, Evers JL, Mol BW. The influence of the number of follicles on pregnancy rates in intrauterine insemination with ovarian stimulation: a meta-analysis. Human Reproduction Journal 2008; 14(6): 563-570. [PubMed]

23. Karuppaswamy J, Smedley M, Carter L. Intra-uterine insemination: pregnancy rate in relation to number, size of pre-ovulatory follicles and day of insemination. J indian Med Assoc 2009; 107(3):141-143. [PubMed]

24. Agarwal S, Mittal S. A randomized prospective trial of intrauterine insemination versus timed intercourse in superovulated cycles with clomiphene. Indian J Med Res 2004; 120: 519-522. [PubMed]