THE OPTIMAL FOLLICLE SIZE AT OVULATORY TRIGGER IN OVARIAN STIMULATION CYCLES WITH LETROZOLE CO-ADMINISTRATION

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Letrozole co-administration during ovarian stimulation minimizes exposure to supraphysiologic estrogen levels for patients with estrogen-sensitive malignancies or those at increased risk for venous thromboembolism. Initial studies describing the use of letrozole as an IVF adjunct noted an improvement in oocyte maturity rates when the ovulatory trigger was administered at larger follicle sizes. We sought to determine the optimal follicle size at the time of ovulatory trigger to maximize oocyte maturity rates in women undergoing IVF with letrozole co-administration. We performed a single-center retrospective study of women undergoing ovarian stimulation with letrozole co-administration from 2010 to 2019. Cycles were divided into seven groups based on the size of the lead and 2nd largest follicles on the day of ovulatory trigger (≥24 mm, 22-23.9 mm, 20-21.9 mm, 17-19.9 mm). The reference group was comprised of cycles in which the lead follicle was ≥20 mm and the 2nd largest follicle was 17-19.9 mm. The primary outcomes were the number of MII oocytes retrieved and the proportion of MII oocytes. Comparisons between groups were made using the Student’s t-test. 309 patients were identified for analysis. The most common indications for letrozole co-administration were breast cancer (n=219, 71.6%), BRCA mutation (n=17, 5.6%), history of venous thromboembolism (n=13, 4.4%), and endometrial hyperplasia/cancer (n=12, 3.9%). The number of oocytes retrieved was highest when both the lead and 2nd largest follicle were 22-23.9 mm (19.9, p < 0.01) and lowest in the reference group (12.0). The proportion of MII oocytes was lowest in the reference group (67.1%) when compared to all groups where both the lead and 2nd largest follicle were ≥20 mm. The highest proportion of MII oocytes occurred when the lead follicle was ≥24 mm and the 2nd largest follicle was 22-23.9 mm (77.0%, p=0.03), and when the lead follicle was ≥24 mm and the 2nd largest follicle was 20-21.9 mm (79.4%, p=0.07). In ovarian stimulation cycles where letrozole is co-administered, pushing lead follicles to advanced sizes (≥20 mm) before ovulatory trigger increases the proportion of MII oocytes. Oocyte maturity rates were highest when the lead follicle was ≥24 mm and the 2nd largest follicle was 20-23.9 mm.