Context: Uterine leiomyomas are the most frequent benign tumors during reproductive age. Whether intramural leiomyomas cause infertility and should be removed is controversial as no study has addressed the underlying mechanism of infertility.

Objective: To test the effect of intramural leiomyomas on endometrial function by comparing gene during the window of implantation, and implantation in an oocyte donation program, in which the quality of the embryos replaced is similar, and the endocrine environment of the endometrium is standardized by exogenous steroids.

Design: Human endometria of women with single intramural leiomyomas (Group A<5 cm and Group B5cm) and controls (Group C) were collected on day LH+7 and processed for histology and gene expression analysis, using different methods and validated by quantitative RT-PCR. To compare IVF outcome, a total of 1,035 cases from our oocyte donation database were included, comprising patients with 1 fibroid<5cm (A1, n=532); 2 leiomyomas<5cm (A2, n=128); 3 leiomyomas<5cm (A3, n=125); 1 fibroid 5cm (B, n=22); and two control groups: C1 (n=93) women with previous myomectomy; and C2 (n=135) women without uterine pathology treated on the same dates as C1.

Results: There was a strong positive and negative correlation in the expression profile of 69 genes according to the leiomyomas's size, but only 3 of the 25 genes related to the window of implantation were dys-regulated. Term pregnancy rates after oocyte donation were 36.9, 34.1, 39.0, 36.4, 39.2 and 42.6% (p=0.769) among the established groups. Similarly, no correlation between implantation and miscarriage with leiomyoma number and size was found.

Conclusions: This study provides evidence that intramural leiomyomas not affecting the endometrial cavity alters the expression pattern of some endometrial genes, but the genes involved in implantation are not affected. This is confirmed by leiomyomas having no effect on oocyte donation outcome when the size and number of leiomyomas are analyzed.