The molecular basis for implantation failure in endometriosis - On the road to discovery

Endometriosis is a benign gynecologic disorder associated with pelvic pain and infertility, with the latter being due, in part, to failure of embryonic implantation in the maternal endometrium. Adequacy of the endometrium for fertility has been classically investigated by histologic evaluation of a mid-late luteal phase biopsy and, historically, normal histology has been reassuring. However, recent studies demonstrate histologically normal, but biochemically abnormal, endometrium during the window of implantation in some women with endometriosis. In the pregenomic era, a "one-by-one" approach has been adopted to investigate proteins and genes expressed in the window of implantation, and several genes or gene products have been found to be aberrantly expressed in endometrium of women with endometriosis either during the implantation window or at other times of the cycle. Some of these are related to failure of implantation, while others likely contribute to the establishment and growth of endometriotic lesions. The time has come for a genome-wide approach to evaluate uterine endometrium for embryonic implantation. Knowing the biochemical mechanisms underlying normal implantation and the abnormalities in endometriosis will facilitate development of new diagnostic criteria beyond histologic evaluation and will permit identification and validation of molecular targets for future drug discovery. This monograph reviews (a) some of the evidence of compromised fertility in women with endometriosis and treatments targeted to improve their fertility; (b) the concept of the window of implantation; (c) genes/gene products aberrantly expressed in endometrium during the window of implantation or other times of the cycle in women with endometriosis; and (d) the use of microarray technology to investigate endometrial gene expression in human endometrial stromal cells and preliminary data resulting from a collaborative consortium effort of a genome-wide investigation of gene expression in the window of implantation of women with versus without endometriosis.