Induction of ovulation in women with PCOS using letrozole versus letrozole plus gonadotropin and its effect on spontaneous on going pregnancy rate through multicenter IVF in Beni-Suef city using randomized controlled study

Hamada Ashry Abd-Elwahed; Thoraya Mohamed Aly; Ahmed Ragab Ali; Eman Moustafa Mahmoud Khalil

doi:10.53730/ijhs.v6nS4.11717

Authors

Hamada Ashry Abd-Elwahed Assistant professor of Obstetrics and Gynecology, Faculty of Medicine – Beni-Suef University, Egypt
Thoraya Mohamed Aly Lecturer of Internal Medicine, Faculty of Medicine – Beni-Suef University, Egypt
Ahmed Ragab Ali
ahmedrageb210@yahoo.com
Fayoum general hospital, Fayoum
Eman Moustafa Mahmoud Khalil Lecturer of Obstetrics and Gynecology, Faculty of Medicine – Beni-Suef University, Egypt

Keywords:

gonadotropin, letrozole, ovulation induction, polycystic ovarian syndrome

Abstract

Background: We developed a multicenter randomized observational trial to assess the effectiveness of letrozole monotherapy and the co-therapy of letrozole and gonadotropins on pregnancy outcomes including the ovulation induction, pregnancy rate, estradiol (E₂) levels and endometrial thickness in infertile women with polycystic ovarian syndrome (PCOS).Methods:At three in vitro fertilization (IVF) centers in Egypt, we conducted our study since May 2019 until we have recruited the planned number of patients. Infertile PCOS patients were recruited after they met our criteria. We had two intervention groups based on the treatment regimen.Moreover, baseline parameters, outcomes, and hormonal assessment was conducted throughout the study period. Results: We included 90 patients in this study and were equally randomized into two groups; the letrozole monotherapy (Group A) and the letrozole with gonadotropins (Group B) groups. The mean age was significantly higher in group A [26 (±3.5)] than group B [24.2 (±3.1)] (P= 0.015). Both groups showed resulted in similar pregnancy rates (31.1%) (P= 0.079).Moreover, group B [2.4 (±0.8)] resulted in a significantly higher (P= 0.023) mean number of follicles than group A [2.0 (±0.7)]. On the other hand, no statistical significance was estimated in terms of estradiol levels and endometrial thickness (P= 0.209 and 0.485, respectively).

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References

Akhtar M, Njar VCO, Neville Wright J. Mechanistic studies on aromatase and related CC bond cleaving P-450 enzymes. The Journal of Steroid Biochemistry and Molecular Biology. 1993;44(4):375-87.

Alizzi F. Letrozole with or without gonadotropin as a first-line ovulation induction in anovulatory infertile women due to polycystic ovary syndrome. Asian Journal of Pharmaceutical and Clinical Research. 2018;11:129.

Amer SA, Li TC, Ledger WL. Ovulation induction using laparoscopic ovarian drilling in women with polycystic ovarian syndrome: predictors of success. Hum Reprod. 2004;19(8):1719-24.

Biljan MM, Hemmings R, Brassard N. The Outcome of 150 Babies Following the Treatment With Letrozole or Letrozole and Gonadotropins. Fertil Steril. 2005;84:S95.

Broekmans F, Knauff E, Valkenburg O, Laven J, Eijkemans M, Fauser B. PCOS according to the Rotterdam consensus criteria: change in prevalence among WHO‐II anovulation and association with metabolic factors. BJOG: An International Journal of Obstetrics & Gynaecology. 2006;113(10):1210-7.

Buzdar A, Howell A. Advances in aromatase inhibition: clinical efficacy and tolerability in the treatment of breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2001;7(9):2620-35.

Casper RF, Mitwally MFM. Review: aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab. 2006;91(3):760-71.

Chen Z, Zhang M, Qiao Y, Yang J. Effects of letrozole in combination with low-dose intramuscular injection of human menopausal gonadotropin on ovulation and pregnancy of 156 patients with polycystic ovary syndrome. Pak J Med Sci. 2016;32(6):1434-8.

Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008;23(3):462-77.

Dale O, Tanbo T, Lunde O, Abyholm T. Ovulation induction with low-dose follicle-stimulating hormone in women with the polycystic ovary syndrome. Acta Obstet Gynecol Scand. 1993;72(1):43-6.

Dickey RP, Olar TT, Taylor SN, Curole DN, Rye PH. Sequential clomiphene citrate and human menopausal gonadotrophin for ovulation induction: comparison to clomiphene citrate alone and human menopausal gonadotrophin alone. Human Reproduction. 1993;8(1):56-9.

Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility: Wolters Kluwer Health; 2012.

Geisler J, Haynes B, Anker G, Dowsett M, Lønning PE. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2002;20(3):751-7.

Ghanem ME, Elboghdady LA, Hassan M, Helal AS, Gibreel A, Houssen M, et al. Clomiphene citrate co-treatment with low dose urinary FSH versus urinary FSH for clomiphene resistant PCOS: randomized controlled trial. J Assist Reprod Genet. 2013;30(11):1477-85.

Healey S, Tan SL, Tulandi T, Biljan MM. Effects of letrozole on superovulation with gonadotropins in women undergoing intrauterine insemination. Fertil Steril. 2003;80(6):1325-9.

Health and fertility in World Health Organization group 2 anovulatory women. Human Reproduction Update. 2012;18(5):586-99.

Herman A, Ron-El R, Golan A, Soffer Y, Bukovsky I, Caspi E. Overstimulated cycles under low-dose gonadotrophins in patients with polycystic ovary syndrome: characterization and management. Human Reproduction. 1993;8(1):30-4.

Kamphuis EI, Bhattacharya S, van der Veen F, Mol BW, Templeton A. Are we overusing IVF? Bmj. 2014;348:g252.

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(6):551-66.

Legro RS, Kunselman AR, Brzyski RG, Casson PR, Diamond MP, Schlaff WD, et al. The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome. Contemporary clinical trials. 2012;33(3):470-81.

Lord JM, Flight IHK, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ (Clinical research ed). 2003;327(7421):951-3.

Lu PY, Chen ALJ, Atkinson EJ, Lee SH, Erickson LD, Ory SJ. Minimal stimulation achieves pregnancy rates comparable to human menopausal gonadotropins in the treatment of infertility**Presented at the 50th Annual Meeting of The American Fertility Society, San Antonio, Texas, November 7, 1994. Fertil Steril. 1996;65(3):583-7.

McNeilly AS. The control of FSH secretion. Acta endocrinologica Supplementum. 1988;288:31-40.

Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril. 2001;75(2):305-9.

Mukhtar, A. U. S., Budu, B., Sanusi B, Y., Mappawere, N. A., & Azniah, A. (2022). The effect of reproductive health education with multimedia video learning on the improvement of fluor albus prevention behavior young woman pathologist. International Journal of Health & Medical Sciences, 5(1), 75-79. https://doi.org/10.21744/ijhms.v5n1.1841

Orvieto R, Homburg R. Chronic ultra-low dose follicle-stimulating hormone regimen for patients with polycystic ovary syndrome: one click, one follicle, one pregnancy. Fertil Steril. 2009;91(4 Suppl):1533-5.

Ransom MX, Doughman NC, Garcia AJ. Menotropins alone are superior to a clomiphene citrate and menotropin combination for superovulation induction among clomiphene citrate failures. Fertil Steril. 1996;65(6):1169-74.

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41-7.

Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical epidemiology. 2014;6:1.

Suryasa, I. W., Rodríguez-Gámez, M., & Koldoris, T. (2021). Health and treatment of diabetes mellitus. International Journal of Health Sciences, 5(1), i-v. https://doi.org/10.53730/ijhs.v5n1.2864

Tanbo T, Mellembakken J, Bjercke S, Ring E, Abyholm T, Fedorcsak P. Ovulation induction in polycystic ovary syndrome. Acta Obstet Gynecol Scand. 2018;97(10):1162-7.

Weil SJ, Vendola K, Zhou J, Adesanya OO, Wang J, Okafor J, et al. Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations. J Clin Endocrinol Metab. 1998;83(7):2479-85.

Yu X, Cao Z, Hou W, Hu W, Yan G. Effects of letrozole combined with human menopausal gonadotrophin in ovarian stimulation for intrauterine insemination cycles. Annals of Translational Medicine. 2019;7(23).