A comparison between a combination of letrozole and clomiphene citrate versus gonadotropins for ovulation induction in infertile patients with clomiphene citrateresistant polycystic ovary syndrome — a retrospective study
Abstract
Objectives: The aim of this study was to compare a combination treatment with CC plus letrozole versus gonadotropins
in CC-resistant polycystic ovary syndrome (PCOS) patients with regard to ovulation and clinical pregnancy rate.
Material and methods: One hundred sixteen CC-resistant infertile PCOS patients were evaluated retrospectively. The patients
were divided into two groups. Group 1 (n = 73) received CC plus letrozole, and Group 2 (n = 43) received gonadotropins.
Results: The ovulation rate in Group 1 was 65/73 (89%), the pregnancy rate was 13/73 (18%), the twin foetuses rate was
1/73 (1.3%) and the miscarriage rate was 2/73 (2.7%). In Group 2, the ovulation rate was 41/43 (95%), and the pregnancy
rate was 8/43 (19%) the rate of the twin foetuses was 1/43 (2.3%) and the miscarriage rate was 1/43 (2.3%). There was no
statistically significant difference in the ovulation (p = 0.25), pregnancy (p = 0.91), twin foetuses (p = 0.89) and miscarriage
p = 0.89) rates between two groups.
Conclusions: This new drug combination suggests that it may be a lower cost, lower risk alternative treatment that increases
the rate of ovulation. Larger randomized clinical trials are needed to provide information on live birth rates of this
combination.
Keywords: polycystic ovary syndromegonadotropinsclomiphene resistanceletrozoleovulation induction
References
- Heard MJ, Pierce A, Carson SA, et al. Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome. Fertil Steril. 2002; 77(4): 669–673.
- Randall JM, Templeton A. Cervical mucus score and in vitro sperm mucus interaction in spontaneous and clomiphene citrate cycles. Fertil Steril. 1991; 56(3): 465–468.
- Nakamura Y, Ono M, Yoshida Y, et al. Effects of clomiphene citrate on the endometrial thickness and echogenic pattern of the endometrium. Fertil Steril. 1997; 67(2): 256–260.
- Holzer H, Casper R, Tulandi T. A new era in ovulation induction. Fertil Steril. 2006; 85(2): 277–284.
- Mitwally M, Casper R. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril. 2001; 75(2): 305–309.
- Mitwally MF, Biljan MM, Casper RF. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol. 2005; 192(2): 381–386.
- Al-Omari WR, Sulaiman WR, Al-Hadithi N. Comparison of two aromatase inhibitors in women with clomiphene-resistant polycystic ovary syndrome. Int J Gynaecol Obstet. 2004; 85(3): 289–291.
- Fritz M, Speroff L. Clinical Gyneocology endocrinology and infertility. 8th ed. L. Lippincott Williams & Wilkins, Philadelphia 2011: 1305–1313.
- Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81(1): 19–25.
- Beck JI, Boothroyd C, Proctor M, et al. Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation. Cochrane Database Syst Rev. 2005(1): CD002249.
- World Health Organization. Laboratory manual of the WHO for the examination of human semen and sperm-cervical mucus interaction. Annali dell’Istituto superiore di sanita. ; 2001.
- Farhi J, Orvieto R, Gavish Oz, et al. 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): 546–548.
- Ganesh A, Goswami SK, Chattopadhyay R, et al. 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(1): 19–24.
- Jee BC, Ku SY, Suh CS, et al. Use of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles: a pilot study. Fertil Steril. 2006; 85(6): 1774–1777.
- Quintero RB, Urban R, Lathi RB, et al. A comparison of letrozole to gonadotropins for ovulation induction, in subjects who failed to conceive with clomiphene citrate. Fertil Steril. 2007; 88(4): 879–885.
- Hajishafiha M, Dehghan M, Kiarang N, et al. Combined letrozole and clomiphene versus letrozole and clomiphene alone in infertile patients with polycystic ovary syndrome. Drug Des Devel Ther. 2013; 7: 1427–1431.
- Mejia RB, Summers KM, Kresowik JD, et al. 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(3): 571–578.e1.
- Fauser BC, Devroey P, Macklon NS. Multiple birth resulting from ovarian stimulation for subfertility treatment. Lancet. 2005; 365(9473): 1807–1816.
- Ozdemir U, Ozaksit G, Cakir Gungor AN, et al. Letrozole usage adjuvant to gonadotropins for ovulation induction for patients with clomiphene citrate failure. Arch Gynecol Obstet. 2013; 288(2): 445–448.
- Diamond MP, Legro RS, Coutifaris C, et al. National Institute of Child Health and Human Development (NICHD) Reproductive Medicine Network. Assessment of multiple intrauterine gestations from ovarian stimulation (AMIGOS) trial: baseline characteristics. Fertil Steril. 2015; 103(4): 962–973.e4.
