Meryem KURU PEKCAN, Nilüfer AKGÜN, Hasan ULUBASOGLU, Refik Ersin EROĞLU, Yasemin TASCİ

The Cost-effectiveness of Clomiphene Citrate Against Gonadotropin Therapy in Women with Unexplained Infertility

Aim: Clomiphene citrate (CC) is the most frequently used agent for ovarian stimulation (OS). Gonadotropin (GND) treatment can be encouraged as a next step in women who are not able to become pregnant with CC. We aimed to determine the efficacy and costeffectiveness of CC and GND in patients with unexplained infertility undergoing OS and intrauterine insemination. Material and Method: The cost-effectiveness and success of CC and GND were retrospectively evaluated in 358 infertile women, of whom 247 received CC and 11 received GND treatment. The total CC/GND dose, endometrial thickness, semen parameters, duration of OS, follicle size, and pregnancy outcome were recorded. The medical costs of both strategies were analyzed, including the costs of medication and cycle monitoring. The cost of insemination was not evaluated since it was applied in both groups. The Shapiro-Wilk test, Student’s t-test and Mann-Whitney U test were used for statistical analyses. Results: There were no statistically significant differences between the groups in terms of cycle characteristics, semen analysis, total drug dose used, duration of OS, and dominant follicle size (p>0.05 for all). The pregnancy rate was 23.5% among the 264 (73.7%) patients with primary infertility and 17% among the 94 (26.3%) patients with secondary infertility. No significant difference was observed between the CC and GND groups with regard to the achieved pregnancy rate (21.1% vs. 23.4%, p=0.615). No side effect was observed. The cost of treatment for a couple with unexplained infertility was 1,716.42 TL for GND and 30.67 TL for CC. Conclusion: The treatment success of OS with CC and GND seems to be similar in patients with unexplained infertility. Therefore, considering the cost-effectiveness and side effects of GND medication, the first choice should be CC in these patients.

Keywords:

clinical pregnancy, clomiphene citrate, gonadotropin, ovulation induction; unexplained infertility,

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1. Tomlinson MJ, Amissah-Arthur JB, Thompson KA, Kasraie JL, Bentick B. Prognostic indicators for intrauterine insemination (IUI): statistical model for IUI success. Hum Reprod. 1996;11:1892–6.
2. Dankert T, Kremer JA, Cohlen BJ, Hamilton CJ, Pasker-de Jong PC, Straatman H, et al. A randomized clinical trial of Clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility. Hum Reprod. 2007;22:792–7.
3. Barroso G, Menocal G, Felix H, Rojas-Ruiz JC, Arslan M, Oehninger S. Comparison of the efficacy of the aromatase inhibitor letrozole and Clomiphenee citrate as adjuvants to recombinant folliclestimulating hormone in controlled ovarian hyperstimulation: a prospective, randomized, blinded clinical trial. Fertil Steril. 2006;86:1428–31.
4. 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;78:280–5.
5. Kaplan PF, Patel M, Austin DJ, Freund R. Assessing the risk of multiple gestation in gonadotropin intrauterine insemination cycles. Am J Obstet Gynecol. 2002;186:1244–7.
6. World Health Organization. Laboratory manual for the examination of human semen and semen- cervical mucus interaction, 4th ed. Cambridge: Cambridge University Press; 1999.
7. Gleicher N, Oleske DM, Tur-Kaspa I, Vidali A, Karande V. Reducing the risk of high-order multiple pregnancy after ovarian stimulation with gonadotropins. N Engl J Med. 2000;343:2–7.
8. Tur R, Barri PN, Coroleu B, Buxaderas R, Martínez F, Balasch J. Risk factors for high-order multiple implantation after ovarian stimulation with gonadotrophins: evidence from a large series of 1878 consecutive pregnancies in a single centre. Hum Reprod. 2001;16:2124–9.
9. Dhaliwal LK, Sialy RK, Gopalan S, Majumdar S. Minimal stimulation protocol for use with intrauterine insemination in the treatment of infertility. J Obstet Gynaecol Res. 2002;28:295–9.
10. Karen Peeraer, J. Luyten, C. Tomassetti, S. Verschueren, C. Spiessens, A. Tanghe, et al. Cost-effectiveness of ovarian stimulation with gonadotrophin and clomiphene citrate in an intrauterine insemination programme for subfertile couples. Reproductive BioMedicine Online. 2018; 36(3):302–10.
11. Balasch J, Ballescá JL, Pimentel C, Creus M, Fábregues F, Vanrell JA. Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles. Hum Reprod. 1994;9(10):1863–6.
12. Kolibianakis EM, Zikopoulos KA, Fatemi HM, Osmanagaoglu K, Evenpoel J, Van Steirteghem A, et al. Endometrial thickness cannot predict ongoing pregnancy achievement in cycles stimulated with clomiphene citrate for intrauterine insemination. Reprod Biomed Online. 2004;8(1):115–8.
13. Tsai HD, Chang CC, Hesieh YY, Lee CC, Lo HY. Artificial insemination. Role of endometrial thickness and pattern, of vascular impedence of the spiral and uterine arteries, and of the dominant follicle. J Reprod Med. 2000; 45(3):195–200.
14. Badawy A, Khiary M, Ragab A, Hassan M, Sherif L. Laparoscopy-or not-for management of unexplained infertility. J Obstet Gynaecol. 2010;30(7):712–5.
15. Diamond MP, Legro RS, Coutifaris C, Alvero R, Robinson RD, Casson P, et al. Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility. N Engl J Med. 2015;373:1230.
16. Marcoux S, Maheux R, Bérubé S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med. 1997; 337:217.
17. Sunderam S, Kissin DM, Crawford SB, Suzanne G Folger, Denise J Jamieson, Lee Warner, et al. Assisted Reproductive Technology Surveillance-United States, 2012. MMWR Surveill Summ. 2015;64:1.
18. Practice Committee of American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy: an American Society for Reproductive Medicine Practice Committee opinion. Fertil Steril. 2012;97:825.
19. Reindollar RH, Regan MM, Neumann PJ, Levine BS, Thornton KL, Alper MM, et al. A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial. Fertil Steril. 2010;94:888.
20. Danhof NA, van Wely M, Repping S, Koks C, Verhoeve HR, de Bruin JP, et al. Follicle stimulating hormone (FSH) versus Clomiphene Citrate (CC) in intrauterine insemination for unexplained subfertility: A randomized controlled trial. Hum Reprod. 2018;33:1866–74.
21. Bordewijk EM, Weiss NS, Nahuis MJ, Bayram N, van Hooff MHA, Boks DES, et al; M-ovin study group. Gonadotrophins versus clomiphene citrate with or without IUI in women with normogonadotropic anovulation and clomiphene failure:a costeffectiveness analysis. Hum Reprod. 2019;34(2):276–84.