Information for Physicians

Infertility affects approximately 5.3 million couples. It is estimated that 15% to 20% of females undergoing evaluation for infertility have no cause identified for their failure to conceive. Uncertainty about the underlying reasons for infertility often leads to empirical treatment strategies that can create significant psychological and financial burdens. It appears that a cohort of women with unexplained infertility may have alterations in uterine function that can now be detected by immunohistochemical staining of the Beta-3 (ß3) integrin subunit as a marker protein. Integrins, a family of cell-surface receptors, are believed to play a key role in the adhesion and motility of cells. The appearance of ß3 integrin on the epithelial lining of the uterus correlates well to the timing of implantation of the human embryo.1 The expression of ß3 integrin during this window of implantation makes this integrin of unique importance in the assessment of the endometrium.

Patterns of Integrin Expression: There are three typical patterns of integrin expression. A normal pattern is exhibited when the endometrium is “in phase" and ß3 integrin is present. Lack of expression of ß3 integrin has been found in two forms of infertility: luteal phase defect and occult defects, which are not normally detectable using routine pathologic diagnosis. Women lacking ß3 integrin with an “out of phase" endometrium usually fall into the category of luteal phase defect.1 Women with unexplained infertility identified as having one "out of phase" endometrial biopsy (>3 days disagreement between chronological and histologic criteria) are advised, following treatment, to undergo a repeat biopsy to confirm the diagnosis.

Women with “in phase" endometrium and lack of ß3 integrin are classified as those with occult defects, which have been described in unexplained infertility,1 minimal to mild endometriosis,4 and hydrosalpinx.3

An assessment of endometrial receptivity increases the chances of a successful pregnancy. For example, in women with endometriosis, treatment of this condition with surgery or medical management has improved the pregnancy rates from 10% to 40% and 68%, respectively.4 In women with hydrosalpinges, removal or repair of the damaged fallopian tube(s) results in return of the ß3 integrin and an improvement in pregnancy rates.3 Women who were missing the endometrial ß3 integrin achieved pregnancy with more than a 65% success rate when treated for ninety days with the GnRH analog, Lupron Depot. In contrast, treatment of laser ablation only achieved a 40% success rate and the time to pregnancy was greatly delayed.4

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1 Lessey BA, Castlebaum AJ, Sawin SW, Sun J. Integrins as markers of uterine receptivity in women with primary unexplained infertility. Fertil Steril 1995; 63:535-42.

2 Lessey BA, Castlebaum AJ, Sawin SW, Buck CA, Schinnar R, Bilker W, Strom BL. Abberant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab 1994; 79:643-9.

3 Meyer, Castlebaum AJ, Somkuti S, Sagoskin AW, Doyle M, Harris JE, Lessey BA. Hydrosalpignes adversely affect markers of endometrial receptivity. Human Rep 1997; 12:1393-8.

4Lessey, BA, Castelbaum AJ, Harris J, Sun J, Young SL, Wolf L. Improvement in pregnancy rates with GnRH agonist in women with infertility, minimal or mild endometriosisand aberrant vß3 expression. Amer Soc Reprod Med Annual Mtg 1996;O165:S82.