Letrozole+ GnRH antagonist stimulation protocol in poor ovarian responders undergoing intracytoplasmic sperm injection cycles: An RCT

Abstract

Background:Gonadotropin-releasing hormone (GnRH) antagonist protocol has been proposed as a potentially proper option for the patients with limited ovarian reserve. Nevertheless, there is no significant difference in terms of clinical pregnancy between the GnRH antagonist and agonist cycles. The use of aromatase inhibitors such as letrozole was suggested by some studies. Objective:The object of this study was to evaluate the efficacy of letrozole co-treatment with GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing intracytoplasmic sperm injection.Materials and Methods:A double-blinded randomized control trial was conducted on 70 infertile women with poor ovarian response based on Bologna criteria in two groups: letrozole+GnRH-antagonist (LA) group and placebo+GnRH-antagonist (PA) group (n=35/each). The LA group involved at letrozole 2.5 mg daily over 5 days and recombinant human follicle stimulating hormone 225 IU/daily. The PA group received placebo over 5 days and recombinant human follicle stimulating hormone at the same starting day and dose, similar to LA group. GnRH-antagonist was introduced once one or more follicle reached ≥14 mm. The main outcome measures were the number of oocytes retrieved, fertilization rate, implantation rate, cycle cancellation rate, and clinical pregnancy rate.Results:There were no significant differences in demographic characteristics between groups. There were no significant differences between groups regarding the number of oocytes retrieved (p=0.81), number of embryos transferred (p=0.82), fertilization rate (p=0.225), implantation rate (p=0.72), total cycle cancelation rate (p=0.08), and clinical pregnancy rate (p=0.12). Conclusion:The use of letrozole in GnRH-antagonist cycles does not improve clinical outcomes in poor responder patients undergoing intracytoplasmic sperm injection.

Androgens and ovarian function: translation from basic discovery research to clinical impact

“…Mitri et al be significantly improved by the supplementation of poor responders with letrozole (Goswami et al 2004, Schoolcraft et al 2008, Yarali et al 2009, Jovanovic et al 2011, Mohsen & El Din 2013, Ebrahimi et al 2017. Furthermore, analysis of pooled data from several studies also fail to show a significant association with increased clinical pregnancy rates (Bosdou et al 2012, Jeve & Bhandari 2016, Kamath et al 2017.…”

The Frequency of Ovarian Hyperstimulation Syndrome and Thromboembolism with Originator Recombinant Human Follitropin Alfa (GONAL-f) for Medically Assisted Reproduction: A Systematic Review

“…The risk of bias was assessed as high, low or unclear/unreported in seven categories (random sequence generation, allocation concealment, blinding of participants, blinding of outcome assessments, incomplete outcome data, selective reporting and other biases). Only five studies were judged to be free of bias in all of the categories [24,25,41,55,65]. Bias was mostly reported for allocation concealment, blinding of participants and blinding of outcome assessment (Fig.…”

Does daily co administration of gonadotropins and letrozole during the ovarian stimulation improve IVF outcome for poor and sub optimal responders?

“…Co-administration of 2.5 mg letrozole for the first 5 days of ovarian stimulation during a high dose FSH/hMG GnRH-antagonist protocol, resulted in a higher number of retrieved oocytes and an increased implantation rate [5]. These encouraging findings, however, were not reproduced by a later, doubleblinded randomized control study, where letrozole was added to a standard GnRH-antagonist protocol, at a dose and timing similar to the previous study presented [6]. Additional retrospective studies demonstrated that cotreatment with 5 mg letrozole resulted in reduction of gonadotropins dosage [13][14][15], while decreasing cancellation rates [13] and increasing pregnancy and live birth rates [14].…”

“…Several studies evaluated the co-administration of Letrozole during ovarian stimulation in patients suffering from diminished ovarian reserve, yielding conflicting results [4][5][6] . In these studies, Letrozole was started either concomitantly with or prior to gonadotropins, and was given for a total of 5 stimulation days.…”