DOI: https://dx.doi.org/10.18203/2320-1770.ijrcog20222786
Published: 2022-10-28

Low dose-extended letrozole versus double dose-short letrozole protocol for ovulation induction in polycystic ovary syndrome

Shirin Jahan, Farzana Deeba, Shakeela Ishrat, Jesmine Banu, Chalontika Rani, Sumaiya Akter, Sohely Nazneen, Nishat Jahan

Abstract


Background: Letrozole, an aromatase inhibitor has been regarded as the first line drug for ovulation induction in anovulatory PCOS patients because of its monofollicular growth and there is no chance of hyperstimulation by letrozole. Traditional protocol of letrozole includes administration of letrozole for 5 days in first half of follicular phase which induces ovulation in 61.7% cases. Few recent studies have shown that extended letrozole protocol causes more follicles to grow and induces more ovulation than the traditional protocol. The aim was to compare the effects of low dose-extended letrozole protocol and double dose-short letrozole protocol for ovulation induction in infertile PCOS patients.

Methods: A randomized controlled trial (RCT) was conducted in the department of reproductive endocrinology and Infertility at Bangabandhu Sheikh Mujib Medical University (BSMMU) on seventy infertile polycystic ovary syndrome patients. Low dose-extended letrozole group or experimental group received tablet letrozole 2.5 mg daily for 10 days and double dose-short letrozole group or control group received tab. Letrozole 5 mg daily for 5 days starting from the 2nd day of menstrual cycle or withdrawal bleeding. The ovarian response was assessed by folliculometry on day 12 of menstrual cycle by transvaginal sonography for measurement of total number of growing follicles, biggest follicle size and endometrial thickness. Mid luteal serum progesterone was measured on day 21-23 to confirm ovulation.

Results: The mean number of growing follicle was 1.44±0.95 versus 0.99±0.65 in low dose-extended letrozole group and double dose-short letrozole group respectively generating p value of 0.001. The mean size of the dominant follicle at day 12 was greater in low dose-extended letrozole group than the other displaying 17.69±3.63 mm and 16.6±3.49 mm respectively but the difference was not statistically significant. The number of ovulating patients was greater in low dose-extended letrozole group (76.5% versus 71.9%), but without significant statistical difference. Pregnancy rate was insignificantly greater in low dose-extended letrozole group (23.5% versus 18.8%) as well.

Conclusions: Low dose-extended letrozole protocol produces more multifollicular growth and larger size dominant follicle with a trend to raise the ovulation rate and pregnancy rate, though insignificantly.


Keywords


Letrozole, Ovulation induction, Polycystic ovary syndrome

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References


Taylor HS, Pal L, Seli E. Female Infertility. In: Speroff”s Clinical Gynecologic Endocrinology and Infertility. 9th ed. Wolters Kluwer, Philadelphia: Lippincottt Williams and Wilkins; 2020:990-991.

Dumont A, Robin G, Catteau-Jonard S, Dewailly D. Role of anti-müllerian hormone in pathophysiology, diagnosis and treatment of polycystic ovary syndrome: a review. Reprod Biol Endocrinol. 2015;13(1):1-10.

Committee Opinion No. 738. American College of Obstetricians and Gynecologists. Aromatase inhibitors in gynecologic practice. Obstet Gynecol. 2018;131(6):194-9.

March W. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010;25(2):544-51.

Legro RS, Strauss III JF. Molecular progress in infertility: polycystic ovary syndrome. Fertil Steril. 2002;78(3):569-76

Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med. 2010;8(1):1-10.

De Zegher F, Ibanez L. Early Origins of polycystic ovary syndrome: hypotheses may change without notice. J Clin Endocrinol Metab. 2009;94(10):3682-5.

Priya M, Nanthini A, Bini K. Polycystic ovary syndrome: An updated review. Int J Health Allied Sci. 2019;8(4):229.

Victor VM, Rocha M, Banuls C, Sanchez-Serrano M, Sola E, Gomez M, et al. Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance. J Clin Endocrinol Metab. 2009;94(9):3505-12.

Berger JJ, Bates Jr GW. Optimal management of subfertility in polycystic ovary syndrome. Int J Women Health. 2014;6:613.

Wang R, Mol BW. The Rotterdam criteria for polycystic ovary syndrome: evidence-based criteria? Hum Reprod. 2017;32(2):261-4.

Costello MF, Misso ML, Wong J, Hart R, Rombauts L, Melder A, et al. The treatment of infertility in polycystic ovary syndrome: a brief update. A N Z J Obstet Gynaecol. 2012;52(4):400-3.

Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018;33(9):1602-18.

Garg N, Vanitha VG. A Comparative study of letrozole versus clomiphene citrate as first line for anovulatory infertility- an institutional experience. Asian Res J Gynaecol Obstet. 2019;2(1):1-8.

Fouda UM, Sayed AM. Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: a randomized controlled trial. Reprod Biol Endocrinol. 2011;9(1):1-7.

Kahyaoğlu S, Yılmaz B, Işık AZ. Pharmacokinetic, pharmacodynamic, and clinical aspects of ovulation induction agents: A review of the literature. J Turk German Gynecol Assoc. 2017;18(1):48.

Miller WR, Bartlett J, Brodie AM, Brueggemeier RW, Di Salle E, Lønning PE, et al. Aromatase inhibitors: are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter? Oncologist. 2008;13(8):829-37.

El-Aziz M, Fouad MS, Ouf TF. Short letrozole therapy vs extended (long) letrozole therapy for induction of ovulation in women with polycystic ovary syndrome. Egypt J Hosp Med. 2019 74(8):1884-90.

Fouda UM, Sayed AM. Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET. Gynecol Endocrinol. 2011;27(12):1018-22.

Baruah J, Roy KK, Rahman SM, Kumar S, Sharma JB, Karmakar D. Endometrial effects of letrozole and clomiphene citrate in women with polycystic ovary syndrome using spiral artery Doppler. Arch Gynecol Obstet. 2009;279(3):311-4.

Bao SH, Le Sheng S, Peng YF, De Lin Q. Effects of letrozole and clomiphene citrate on the expression of HOXA10 and integrin αvβ3 in uterine epithelium of rats. Fertil Steril. 2009;91(1):244-8.

Cortínez A, De Carvalho I, Vantman D, Gabler F, Iñiguez G, Vega M. Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients. Fertil Steril. 2005;83(1):110-5.

Badawy A, Mosbah A, Tharwat A, Eid M. Extended letrozole therapy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a novel protocol. Fertil Steril. 2009;92(1):236-9.

Hassanein MS, Hegab MH, Attia AM, Zayed MA. Extended letrozole therapy for ovulation induction in clomiphene resistant women with polycystic ovary syndrome. Egypt J Hosp Med. 2018;73(7):7032-6.

Yadav P, Agarwal M, Agarwal V, Verma U, Agarwal R. To study the efficacy on fertility outcome by short term letrozole versus extended letrozole regimen in clomiphene citrate resistant PCOS Women. J Med Sci Clin Res. 2018; 6(6): 340-5.

Salama KM, Sakr BE, Azab SA. Short letrozole therapy versus extended (long) letrozole therapy for induction of ovulation in women with polycystic ovary syndrome. Randomised study. Benha J Appl Sci. 2021;6(2):243-53.

Gardner DK, Weissman A, Howles CM, Shoham Z. Initial investigation of infertile couple. Volume 2: Clinical Perspectives. In: Textbook of Assisted Reproductive Techniques. 5th edn. CRC Pres: Taylor and Francis Group; 2018:476.