P-586 Adding letrozole to gonadotropins during ovarian stimulation for IVF results in a similar cumulative live birth rate at lower costs following a failed IVF cycle
Authors: Yamout W , Kadoch I J , Jamal W , Lapensée L , Phillips S , Hemmings R 
Published: June 2023

Study question

Following a failed IVF cycle, does adding letrozole for the first 5 days of a repeated cycle have any advantage versus repeating the same protocol?

Summary answer

Following a failed IVF cycle, letrozole supplementation during ovarian stimulation for IVF results in a similar cumulative live birth rate (CLBR) with 22% less gonadotropins.

What is known already

Letrozole results in an increase of intraovarian androgen concentration, which augments follicular stimulating hormone (FSH) receptor expression on granulosa cells and follicular responsiveness to exogenous gonadotropins. Letrozole co-treatment with gonadotropins during controlled ovarian stimulation (COH) for IVF has been investigated mainly in poor and normo-responders with conflicting clinical outcomes. This is the first and largest study that investigates the effects of adding letrozole for the first five days of COH for IVF, in GnRH antagonist cycles, to a category of patients who had a prior failed stimulated IVF cycle using the same protocol.

Study design, size, duration

This is retrospective monocentric study of 426 patients, with a prior failed stimulated IVF cycle using an antagonist protocol, who underwent a second cycle between 2012 and 2017. In those patients, we studied the clinical outcomes of doing a repeated cycle, using the same protocol with the addition of 5mg of letrozole daily in the first 5 days of the cycle (Group A, N = 213) versus doing a repeated similar cycle without letrozole (Group B, N = 213).

Participants/materials, setting, methods

Groups A and B were matched for age, body mass index, anti-mullerian hormone and infertility diagnosis. Statistical analyses were carried out using student t test, Anova and linear regression models. The primary outcome was the CLBR. Secondary outcomes included the number of mature follicles, the number of mature oocytes (MII), the number of usable embryos, clinical pregnancy rates (CPR), live birth rates (LBR) and the total dose of gonadotropins administered.

Main results and the role of chance

This is the first study that investigates the effects of co-treatment with letrozole during COH for IVF in the category of patients who had a prior failed IVF cycle. Our results show that patients who received letrozole during COH with gonadotropins, versus gonadotropins alone, had a significantly lower number of MII oocytes (7±4.6 vs 8,2±5.0; P &lt; 0.01). However, despite that, they had a similar number of usable embryos (1.8±1.6 vs 1.9±1.7; P = 0.31), CPR (23.5% vs 28.7%; p = 0.22), LBR per embryo transfer (16.9% vs 22.1%; p = 0.17) and CLBR (27.8% vs 25.3%; p = 0.55). A 22% lower dose of gonadotropins (3468±1389IU vs 4442±1657IU; p &lt; 0.001) was needed to achieve similar pregnancy outcomes in the letrozole group versus the control group, resulting in lower treatment costs.

Limitations, reasons for caution

The retrospective nature of this study is its main limitation.

Wider implications of the findings

This study confirms that in women with a prior failed IVF cycle, co-treatment with letrozole results a similar cumulative live birth rate at a significant lower cost.

Trial registration number

NCT05677828