Impact of Pretreatment With a Gonadotropin-Releasing Hormone Agonist and Letrozole on In Vitro Fertilization Outcomes in Normal Responders With Ovarian Endometrioma

Qingqing Sun, Yijuan Cao, Juan Gu, Yang Y
In: Clinical and Experimental Obstetrics & Gynecology · 2026 · vol. 53(10) · doi:10.31083/ceog50028 · W7225139556
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Abstract

Background: The optimal pretreatment strategy for patients with ovarian endometrioma (OEM) undergoing in vitro fertilization (IVF) remains controversial, particularly among those with a normal ovarian response. Letrozole (LE) has been proposed to modulate the ovarian hormonal environment and improve ovarian stimulation outcomes. However, its clinical value in this patient population has not been fully established. We assessed the clinical value of pretreatment with LE in combination with a gonadotropin-releasing hormone agonist (GnRHa) in patients with OEM and normal ovarian response undergoing IVF. Methods: In this retrospective study, 71 patients with OEM and normal ovarian response who underwent IVF-embryo transfer (IVF-ET) were initially enrolled and assigned to the GnRHa + LE group (n = 36) or the GnRHa group (n = 35). After one patient was excluded from each group, 35 patients in the GnRHa + LE group and 34 patients in the GnRHa group were included in the final transfer-cycle analysis. During controlled ovarian stimulation, patients received pretreatment with GnRHa (3.75 mg) either alone or in combination with LE (2.5 mg) and were accordingly allocated to the GnRHa group or the GnRHa + LE group. Between-group differences were evaluated regarding baseline characteristics, ovarian stimulation profiles, and reproductive outcomes. Results: The total gonadotropin dose was significantly lower in the GnRHa + LE group and was accompanied by reduced serum estradiol levels on the trigger day (p < 0.01). This group also demonstrated increased numbers of retrieved and metaphase II oocytes (all p < 0.01), as well as improved fertilization rates (p = 0.02) and day-3 high-quality embryo rates (p < 0.05). Stimulation duration, cleavage rate, progesterone levels, embryo transfer number, endometrial thickness, and fresh embryo transfer cancellation rates did not differ significantly between groups (all p > 0.05). The clinical pregnancy rate was significantly higher in the GnRHa + LE group (p = 0.04). The implantation rate was significantly higher in the GnRHa + LE group than in the GnRHa group (p = 0.04), whereas the early miscarriage rate was comparable between the two groups (p = 0.82). Reduction in maximal ovarian-endometriotic-cyst diameter was significantly greater in the GnRHa + LE group (p = 0.04). Conclusions: Combined pretreatment with LE and GnRHa may enhance ovarian response efficiency and improve IVF-ET outcomes among women with OEM who exhibit a normal ovarian response.

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