Effect of GnRH agonist and letrozole treatment in women with recurrent implantation failure

Abstract

Objective: To compare the influence of dual suppression with the use of GnRH agonist plus aromatase inhibitor compared with suppression with the use of GnRH agonist alone or no suppression at all in patients with idiopathic recurrent implantation failure (RIF). Design: Retrospective cohort study. Setting: University-affiliated reproductive center. Patient(s): A total of 523 infertile women who failed two blastocyst transfers underwent a third frozen blastocyst transfer. Women with known endometriosis were excluded. Intervention(s): A total of 204 subjects were not pretreated, 143 received 2 months of GnRH agonist (3.75 mg intramuscular leuprolide acetate monthly) only, and 176 received GnRH agonist and aromatase inhibitor (5 mg oral letrozole daily for 60 days). Demographic and stimulation information was collected and cycle outcomes reported. Main Outcome Measure(s): Clinical pregnancy rates. Result(s): Age, antral follicle count, basal FSH levels, duration of infertility, previous pregnancies, and full-term deliveries were similar (P>.05). Clinical pregnancy rates were higher among women who received GnRH agonist plus letrozole compared with women who received GnRH agonist only or women without pretreatment (63%, 42%, and 40%, respectively; P< .0001). Live birth rates were higher among women who received GnRH agonist plus letrozole compared with the other groups (56%, 36%, and 34%; P< .0001). No differences in pregnancy outcomes were noted between patients who did not receive pretreatment and those in the GnRH agonist only group. Conclusion(s):In patients with RIF, treatment with a GnRH agonist plus letrozole may improve live birth rates in subsequent cycles. We hypothesize that this improvement is due to alterations in the endometrium receptivity or treatment of undiagnosed endometriosis. (Fertil Steril Ò 2019;112:98-104. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

Diagnostic and therapeutic options in recurrent implantation failure

“…A retrospective study demonstrated an increase in integrin expression as well as ongoing pregnancy rate in patients who were initially integrin negative and treated with letrozole compared to those who were integrin negative and did not receive the intervention 80 . These results were validated in a more recent retrospective cohort study utilizing both a GnRH agonist and letrozole, with improved live birth rates in RIF patients receiving letrozole (superior to GnRH alone) 81 . While RCTs are needed to further support the use of this intervention, existing basic and clinical evidence combined with low cost and no evidence of harm support a consideration of letrozole in RIF patients.…”

Pretreatment with a gonadotropin-releasing hormone agonist and an aromatase inhibitor may improve outcomes in in vitro fertilization cycles of women with stage I–II endometriosis

“…Furthermore, AI may improve IVF success rates in endometriosis patients via enhanced endometrial receptivity (1,16,26). Endometriosis tissues have a low expression of beta-integrin, which is needed for the maintenance of pregnancy (27).…”

Determining Diagnostic Criteria of Unexplained Recurrent Implantation Failure: A Retrospective Study of Two vs Three or More Implantation Failure

“…With the advancement of ART, about 70% of transferred embryos have been identified as high-quality embryos recently ( 8 ), it seems that the failure of embryo implantation failure is more closely related to endometrial receptivity. A recent literature showed that patients with unexplained RIF, GnRH agonist combined with letrozole could significantly improve endometrial receptivity, thus increasing the clinical pregnancy rate and live birth rate ( 9 ). Infertile patients seeking assisted pregnancy treatment had experienced recurrent embryo implantation failures, which means higher physical and mental pressure and economic cost.…”