Published date: Jul 27 2021

Journal Title: International Journal of Reproductive BioMedicine

Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 19, Issue No. 6

Pages: 537–544

DOI: 10.18502/ijrm.v19i6.9375

Sholeh ShahgheibiDepartment of Obstetrics and Gynecology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

Fariba SeyedoshohadaeiDepartment of Obstetrics and Gynecology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

Danial KhezriStudent Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran

Solmaz Ghasemighasemisolmaz123@gmail.comBesat Hospital, Kurdistan University of Medical Sciences, Sanandaj, Iran

Background: Various strategies have been proposed for polycystic ovary syndrome (PCOS) treatment.

Objective: To investigate and compare the number and size of ovarian follicles, endometrial thickness, and ovulation rate by traditional protocol (TP) and stair-step protocol (SSP).

Materials and Methods: Sixty infertile PCOS women were allocated into two groups (SSP = 30 and control TP = 30) between May and October 2019 in the Besat Hospital, Sanandaj, Iran. In the SSP group, the infertile women were treated with 50 mg/daily clomiphene citrate (CC) for five days, while the nonresponsive women were prescribed 100 mg daily CC for five days in the same cycle. The maximum dose (150 mg) was administered until ovulation occurred. In the control group, in non-ovulatory cases, the dose was increased in the next cycle. Ultrasound was used to detect ovulation.

Results: Endometrial thickness changes with various doses of CC were significantly different in the TP. The comparison of both protocols showed a significant difference in endometrial thickness only at 50 mg CC. The number of follicles in the left ovary was significantly different in both protocols at 150-mg CC. The size of ovarian follicles in the left ovary was significantly different between the two protocols at 100-mg CC. The ovulation rate was significantly different in the SSP at 100- and 150-mg doses of CC. Moreover, 86% of ovulation occurred at 100-mg CC in the SSP, while this rate was 73% in the TP.

Conclusion: The most appropriate dose for ovulation in patients with PCOS is 100 mg CC.

Key words: Polycystic ovary syndrome, Clomiphene, Infertility, Ovulation induction.

[1] Pundir J, Psaroudakis D, Savnur P, Bhide P, Sabatini L, Teede H, et al. Inositol treatment of anovulation in women with polycystic ovary syndrome: A metaanalysis of randomised trials. BJOG 2018; 125: 299–308.

[2] Cappelli V, Musacchio MC, Bulfoni A, Morgante G, De Leo V. Natural molecules for the therapy of hyperandrogenism and metabolic disorders in PCOS. Eur Rev Med Pharmacol Sci 2017; 21: 15–29.

[3] Patel S. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J Steroid Biochem Mol Biol 2018; 182: 27–36.

[4] Milewicz A. Reimbursement of metformin for polycystic ovary syndrome. Endokrynol Pol 2013; 64: 409–414.

[5] Abu Hashim H, Bazeed M, Abd Elaal I. Minimal stimulation or clomiphene citrate as first-line therapy in women with polycystic ovary syndrome: A randomized controlled trial. Gynecol Endocrinol 2012; 28: 87–90.

[6] Mejia RB, Summers KM, Kresowik JD, Van Voorhis BJ. A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome. Fertil Steril 2019; 111: 571–578.

[7] Deveci CD, Demir B, Sengul O, Dilbaz B, Goktolga U. Clomiphene citrate ‘stair-step’ protocol vs. traditional protocol in patients with polycystic ovary syndrome: A randomized controlled trial. Arch Gynecol Obstet 2015; 291: 179–184.

[8] Wada M, Kasai T, Nagai S, Fujie M, Miyake M, Suzuki K, et al. Effect of repeated administration of clomiphene citrate at two different times on the endometrium in patients undergoing intrauterine insemination. Reprod Med Biol 2004; 3: 153–157.

[9] Yamamoto M, Feigenbaum SL, Crites Y, Escobar GJ, Yang J, Ferrara A, et al. Risk of preterm delivery in non-diabetic women with polycystic ovarian syndrome. J Perinatol 2012; 32: 770–776.

[10] Jones T, Ho JR, Gualtieri M, Bruno-Gaston J, Chung K, Paulson RJ, et al. Clomiphene stair-step protocol for women with polycystic ovary syndrome. Obstet Gynecol 2018; 131: 91–95.

[11] Al Ghazali B. Clomiphene stair-step protocol for ovulation induction in women with polycystic ovarian syndrome. Am J Biomed 2014; 2: 840–854.

[12] Agrawal K, Gainder S, Dhaliwal LK, Suri V. Ovulation induction using clomiphene citrate using stair-step regimen versus traditional regimen in polycystic ovary syndrome women - A randomized control trial. J Hum Reprod Sci 2017; 10: 261–264.

[13] 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: 510.e1–510.e4.

[14] Haritha S, Rajagopalan G. Follicular growth, endometrial thickness, and serum estradiol levels in spontaneous and clomiphene citrate-induced cycles. Int J Gynaecol Obstet 2003; 81: 287–292.

[15] Homburg R. Clomiphene citrate-end of an era? A mini-review. Hum Reprod 2005; 20: 2043–2051.

[16] Nakai A, Yokota A, Koshino T, Araki T. Assessment of endometrial perfusion with Doppler ultrasound in spontaneous and stimulated menstrual cycles. J Nippon Med Sch 2002; 69: 328–332.

[17] Mousa AA, Mohammed MA, Saad WA. Clomiphene citrate stair step protocol with phytoestrogen vs. traditional protocol in patient with polycystic ovary syndrome. N Y Sci J 2017; 10: 206–212.

[18] Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: An analysis of 400 135 treatment cycles. Hum Reprod 2011; 26: 1768–1774.

[19] Dura C, Demir B, Dilbaz B, Goktolga U. Clomiphene ‘Stair-step’ protocol vs traditional protocol in patients with polycystic ovary syndrome (PCOS): A prospective trial. Fertil Steril 2011; 96: S90–S96.

[20] Rebar R. Stepping up to a shorter time to ovulation in women with PCOS 2018. Available from: https://www.jwatch.org/na45791/2018/01/02/ stepping-shorter-time-ovulation-women-with-pcos.

[21] Xi W, Yang Y, Mao H, Zhao X, Liu M, Fu S. Circulating anti-mullerian hormone as predictor of ovarian response to clomiphene citrate in women with polycystic ovary syndrome. J Ovarian Res 2016; 9: 3–9.

[22] Horowitz E, Weissman A. The stair-step approach in treatment of anovulatory PCOS patients. Ther Adv Reprod Health 2020; 14: 2633494120908818.