The effect of aromatase inhibitor letrozole incorporated in gonadotrophin-releasing hormone antagonist multiple dose protocol in poor responders undergoingin vitrofertilization

Abstract

ObjectiveTo evaluate whether letrozole incorporated in a gonadotrophin-releasing hormone (GnRH) antagonist multiple dose protocol (MDP) improved controlled ovarian stimulation (COS) and in vitro fertilization (IVF) results in poor responders who underwent IVF treatment.MethodsIn this retrospective cohort study, a total of 103 consecutive IVF cycles that were performed during either the letrozole/GnRH antagonist MDP cycles (letrozole group, n=46) or the standard GnRH antagonist MDP cycles (control group, n=57) were included in 103 poor responders. COS results and IVF outcomes were compared between the two groups.ResultsTotal dose and days of recombinant human follicle stimulating hormone (rhFSH) administered were significantly fewer in the letrozole group than in the control group. Duration of GnRH antagonist administered was also shorter in the letrozole group. The number of oocytes retrieved was significantly higher in the letrozole group. However, clinical pregnancy rate per cycle initiated, clinical pregnancy rate per embryo transfer, embryo implantation rate and miscarriage rate were similar in the two groups.ConclusionThe letrozole incorporated in GnRH antagonist MDP may be more effective because it results comparable pregnancy outcomes with shorter duration and smaller dose of rhFSH, when compared with the standard GnRH antagonist MDP.

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

“…In contrast to studies which used DHEA pre-treatment, studies which assessed the efficacy of testosterone pre-treatment vary widely in the dose used (2.5-25 mg/day) and the duration of exposure (4-5 days -4 weeks), making comparison between studies difficult. Kim et al conducted a pilot controlled study with the aim to investigate the effect of transdermal testosterone gel in POR patients exposed for 2, 3 or 4 weeks prior to their IVF cycle (Kim et al 2014). Interestingly, while testosterone pre-treatment for 2 weeks failed to show any significant effects, patients treated for 3 and 4 weeks exhibited a significantly improved ovarian response to hyperstimulation, but only patients exposed for 4 weeks displayed a significant increase in clinical pregnancy and live birth rates (Kim et al 2014).…”

“…Kim et al conducted a pilot controlled study with the aim to investigate the effect of transdermal testosterone gel in POR patients exposed for 2, 3 or 4 weeks prior to their IVF cycle (Kim et al 2014). Interestingly, while testosterone pre-treatment for 2 weeks failed to show any significant effects, patients treated for 3 and 4 weeks exhibited a significantly improved ovarian response to hyperstimulation, but only patients exposed for 4 weeks displayed a significant increase in clinical pregnancy and live birth rates (Kim et al 2014). Systematic reviews and meta-analysis have reported that POR patients may benefit from the use of testosterone pre-treatment transdermal.…”

Letrozole as an adjunct treatment in antagonist cycles that previously failed in poor responders

“…When the cycle characteristics are examined, the results of the use of letrozole in the early follicular phase and in previous studies are slightly more conflicting [17,18,21,[25][26][27] [25,26,17]. The number of metaphase II oocytes was significantly higher, consistent with the total number of oocytes retrieved.…”

“…The administration of ART cycles for these patient populations is one of the largest difficulties for the clinician. Although there is not a strong relationship between pregnancy results and the use of letrozole in the first days of the follicular phase of OS in poor responder patients, various positive effects on the cycles have been found [16][17][18][19][20][21][25][26][27]. In a randomized study conducted by Ozmen et al [21], ovarian stimulation with FSH plus letrozole along with GnRH antagonist in poor responder patients significantly reduces the necessary doses of gonadotrophin and the cost of gonadotrophin stimulation.…”

“…In a randomized study conducted by Ozmen et al [21], ovarian stimulation with FSH plus letrozole along with GnRH antagonist in poor responder patients significantly reduces the necessary doses of gonadotrophin and the cost of gonadotrophin stimulation. More recently, Lee et al [26], analyzed a total of 103 consecutive IVF cycles in poor responder patients performed with either FSH plus letrozole along with GnRH antagonist or with only FSH along with GnRH antagonist. They reported that the total doses of gonadotrophin and days of gonadotrophin administration were significantly lower in the letrozole group.…”