# Letrozole Cotreatment Reduces Unexpectedly Poor Responses in Ovarian Stimulation With Follitropin Delta: A Strategy to Prevent High Anti-Müllerian Hormone (AMH) but Poor Response

## TL;DR

Adding letrozole to follitropin delta during ovarian stimulation may reduce poor responses and lower medication needs in IVF treatments.

## Contribution

This study shows letrozole cotreatment reduces unexpected poor responses in ovarian stimulation with follitropin delta.

## Key findings

- Cotreatment with letrozole reduced poor responses from 18.4% to 2.8% in follitropin delta cycles.
- Letrozole shortened ovarian stimulation duration by 1.7 days and reduced total follitropin delta dosage.
- Poor responses were less frequent at lower follitropin delta doses when combined with letrozole.

## Abstract

Background: Follitropin delta is a novel recombinant follicle-stimulating hormone preparation used for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The dosage is determined using an original algorithm designed to achieve a target retrieval of 8-14 oocytes based on body weight and anti-Müllerian hormone (AMH) levels. However, unexpected poor responses, characterized by low oocyte retrieval numbers, occasionally occur in patients with high AMH levels who are otherwise expected to respond well. This study investigated whether cotreatment with letrozole reduces such poor responses.

Methods: A retrospective cohort study including 153 controlled ovarian stimulation (COS) cycles for IVF/ICSI using follitropin delta was performed at Haruki Ladies Clinic in Japan from October 2021 to March 2023. In total, 42 cycles were performed in the letrozole cotreatment group, and 111 cycles were performed in the group treated with follitropin delta alone. According to the concept of follitropin delta, seven or fewer oocytes retrieved were defined as a poor response.

Results: An unexpectedly poor response was observed at 6.0-6.9 µg daily doses of follitropin delta. The poor response was less frequent in the cotreatment group: one of 36 cycles (2.8%) in the cotreatment group and nine of 49 cycles (18.4%) in the follitropin delta alone group (p < 0.05). At daily doses of 7.0-11.9 μg, poor response was not often observed in both groups (0% vs. 3.6%). At 12.0 μg of daily dose, poor response frequently occurred in both groups. The duration of ovarian stimulation was decreased by cotreatment with letrozole (10.4 days vs. 8.7 days, p < 0.01). Letrozole cotreatment also reduced the total dosage of follitropin delta (65.2 µg vs. 53.3 µg, p < 0.01).

Conclusions: Cotreatment with letrozole may reduce unanticipated suboptimal responses in patients expected to have good responses. Additionally, it may shorten the duration of ovarian stimulation and decrease the total dosage of follitropin delta required.