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Endometrial Receptivity and Implantation Are Not Affected by the Presence of Uterine Intramural Leiomyomas: A Clinical and Functional Genomics Analysis

Fundación IVI-Instituto Universitario IVI-University of Valencia (J.A.H., J.A.M.-C., M.M., C.S., A.P.), 46015 Valencia, Spain; Instituto Valenciano de Infertilidad (E.G., P.G., G.G., M.M., C.S., A.P.), 46015 Valencia, Spain; and Hospital Universitario Dr Peset (M.A.H., A.P.), University of Valencia, 46017 Valencia, Spain

Address all correspondence and requests for reprints to: A. Pellicer c/ Guadassuar, 1 Bajo. Valencia 46015, Spain. E-mail: apellicer{at}ivi.es.

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

Objective: The objective of the study was 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 B, 5 cm) 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 in vitro fertilization outcome, a total of 1035 cases from our oocyte donation database were included, comprising patients with one fibroid less than 5 cm (A1, n = 532); two leiomyomas less than 5 cm (A2, n = 128); three or more leiomyomas less than 5 cm (A3, n = 125); one fibroid 5 cm or greater (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 three of the 25 genes related to the window of implantation were dysregulated. 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.