Lessey, B. A., Castelbaum, A. J., Sawin, S. W., & Sun, J. (1995). Integrins as markers of uterine receptivity in women with primary unexplained infertility. Fertility and Sterility, 63(3), 535-542. https://doi.org/10.1016/s0015-0282(16)57422-6
Lessey BA, Castelbaum AJ, Sawin SW, Sun J. Integrins as markers of uterine receptivity in women with primary unexplained infertility. Fertil Steril. 1995;63(3):535-542. doi:10.1016/s0015-0282(16)57422-6
Lessey, Bruce A., et al. "Integrins as markers of uterine receptivity in women with primary unexplained infertility." Fertility and Sterility, vol. 63, no. 3, 1995, pp. 535-542.
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Most women with unexplained infertility lacked a uterine marker
The beta 3 integrin was absent in about 65 out of 100 women with unexplained infertility. A 1995 controlled study of 87 such women and 32 mothers found this in biopsies from days 20 to 24 of the cycle.
Key Findings
The beta 3 integrin subunit was not expressed in 57 of 87 (65%) women with unexplained infertility. Every control biopsy showed normal beta 3 staining.
The alpha 1 subunit was present in all 87 women. The alpha 4 subunit was missing in 10 of 87 (11%), which did not differ significantly from controls.
Type I defects (delayed lining lacking beta 3) occurred in 23 of 87 (26%). Type II defects (lining on schedule, still lacking beta 3) occurred in 34 of 87 (39%).
Minimal or mild endometriosis was present in 56 of 87 (64%) women with unexplained infertility.
All 16 treated women returned to normal histology. The 5 whose beta 3 did not return all had minimal or mild endometriosis. Pregnancy came only after both corrected.
Interpretation
The study is a prospective controlled study at two university centers. Biopsies were taken on cycle days 20 to 24 and timed by the urinary LH surge in the cases. All 87 women had completed a standard evaluation that included laparoscopy. The controls had given birth before, and the cases had not. The authors call the group a selected population. The authors propose that a delayed lining and a missing beta 3 integrin are two distinct forms of reduced uterine receptivity.
RRM Context
Unexplained infertility means the standard workup found no cause. These women had finished that workup, yet biopsies showed a missing uterine protein in most of them. The authors link it to endometriosis and to lining delay that earlier luteal phase testing had not found. Restorative reproductive medicine treats unexplained infertility as undiagnosed infertility, and this paper points to one possible cause.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To assess uterine receptivity in women with unexplained infertility using integrin cell adhesion molecules as markers.
Design
Prospective, controlled study design.
Patients
Eighty-seven nulliparous women with unexplained infertility and 32 fertile and infertile parous controls.
Main Outcome Measures
Immunohistochemical staining for alpha 1, alpha 4, and beta 3 integrin subunits in endometrial biopsies obtained during the window of implantation (days 20 to 24), using the semiquantitative HSCORE by two observers in a blinded fashion.
Results
All endometrial biopsies from parous controls contained positive immunostaining for the alpha 1, and beta 3 integrin subunits in glandular epithelium. Some samples from parous controls were missing the alpha 4 subunit. In contrast, compared with parous controls, biopsies from women with unexplained infertility had reduced significantly beta 3 expression, with similar expression of alpha 1 and alpha 4. Two distinct defects in integrin expression were identified: "out-of-phase" samples that lacked beta 3 because of histologic lag (type I defects) and "in-phase" endometrium that still failed to express this integrin (type II defects). These subclassifications accounted for 26% and 39% of the total unexplained infertility group, respectively.
Conclusions
Abnormal endometrial integrin expression was a frequent finding in women with unexplained infertility. These data suggest that defective uterine receptivity may be an unrecognized cause of infertility in this population of women.
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