Effect of adding letrozole to gonadotropin on in vitro fertilization outcomes: An RCT

RCT OA: gold CC-BY-NC-4.0
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This randomized trial found that adding letrozole to gonadotropin in normal responders reduced total gonadotropin consumption and estradiol levels but did not improve fertilization or pregnancy rates compared to conventional protocols.

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This randomized clinical trial evaluated the impact of adding letrozole to gonadotropin stimulation in 100 women with normal ovarian response undergoing in vitro fertilization. The study found that while the addition of letrozole significantly reduced total gonadotropin consumption and estradiol levels, it did not improve chemical or clinical pregnancy rates compared to the control group receiving gonadotropin alone. Although endometrial thickness was lower in the letrozole group, the intervention successfully lowered estrogen exposure without increasing the risk of ovarian hyperstimulation syndrome. Relevance to endometriosis: listed as one indication for GnRH antagonists, though the paper's main focus is uterine fibroids.

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Abstract

BACKGROUND: Aromatase inhibitors prevent the aromatization of androgens into estrogens, which reduces the negative feedback of estrogen on the hypothalamic-pituitary axis. It is clear that increasing the secretion of follicle-stimulating hormones results in an increased follicular growth. OBJECTIVE: This study aimed to evaluate the effect of adding letrozole to gonadotropin on in vitro fertilization outcomes in normal responders. MATERIALS AND METHODS: In this randomized clinical trial, 100 normal responder women candidate for controlled ovarian stimulation were randomly enrolled in two groups (n = 50/each). In the case group letrozole was added to gonadotropin in the antagonist protocol. The control group received the conventional antagonist protocol. The main outcome was clinical and chemical pregnancy; and the second outcomes were the number of mature oocytes, the fertilization rate, estradiol level, and the total dose of gonadotropins. RESULTS: Basic clinical and demographic features were comparable between the groups. Estradiol level on the day of human-chorionic-gonadotropin administration and the total gonadotropin consumption were significantly higher in the control group than the case group (p = 0.045). In addition, the number of MII oocytes was higher (but not significantl) in the case group than the control group (p = 0.09). Moreover, the endometrial thickness was significantly lower in the case group. There were no significant differences in fertilization rate and chemical and clinical pregnancy rates between the two groups. CONCLUSION: Although adding letrozole to gonadotropin in normal responders reduces the total dose of gonadotropin, it does not improve the pregnancy outcomes.
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Section

Adding letrozole to gonadotropin in women with normal ovarian response reduces the overall gonadotropin dose; however, it does not improve pregnancy outcomes.

Coi Statement

The authors declare that they have no conflict of interests.

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europepmc
last seen: 2026-10-11T09:27:45.537177+00:00
pubmed
last seen: 2026-10-08T21:27:42.253718+00:00
unpaywall
last seen: 2026-05-21T05:10:58.409756+00:00
License: CC-BY-NC-4.0