Lessey, B. A., Yeh, I., Castelbaum, A. J., Fritz, M. A., Ilesanmi, A. O., Korzeniowski, P., Sun, J., & Chwalisz, K. (1996). Endometrial progesterone receptors and markers of uterine receptivity in the window of implantation. Fertility and Sterility, 65(3), 477-483. https://doi.org/10.1016/s0015-0282(16)58140-0
Lessey BA, Yeh I, Castelbaum AJ, Fritz MA, Ilesanmi AO, Korzeniowski P, Sun J, Chwalisz K. Endometrial progesterone receptors and markers of uterine receptivity in the window of implantation. Fertil Steril. 1996;65(3):477-483. doi:10.1016/s0015-0282(16)58140-0
Lessey, Bruce A., et al. "Endometrial progesterone receptors and markers of uterine receptivity in the window of implantation." Fertility and Sterility, vol. 65, no. 3, 1996, pp. 477-483.
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Luteal phase defect biopsies show high progesterone receptors
Biopsies from women with luteal phase defect showed more progesterone receptors in the lining than four comparison groups. In this controlled study, researchers stained biopsies from five groups of women with regular cycles. Eighty biopsies came from women with luteal phase defect. The biopsies came from the implantation window.
Study at a glance, prospective, controlled study of five groups of women with regular cycles: Luteal phase defect biopsies showed more progesterone receptors in the lining. Source: Lessey BA et al., 1996, PMID 8774273.
Key Findings
Among 80 biopsies with a lining delayed by 3 days or more, glandular epithelial progesterone receptor staining was significantly higher (P < 0.001) than in the other four groups.
Sixteen biopsies came from cycles where medical treatment had corrected luteal phase defect. They showed normal histology, normal integrin expression and loss of epithelial receptors, like controls.
The alpha v beta 3 integrin, a receptivity marker, was significantly reduced in the delayed group and, by definition, in the 21 biopsies from women with mild or minimal endometriosis.
Those 21 biopsies had abnormal alpha v beta 3 but epithelial receptor levels that matched controls.
Two further integrins, alpha 1 beta 1 and alpha 4 beta 1, showed no difference among the groups.
Interpretation
This controlled study found that women with higher receptor levels also had a delayed lining and a missing integrin marker. Medical treatment that fixed the luteal phase defect also brought the lining, the integrin, and the receptor levels back to normal, like the control groups. The authors think signals such as cytokines or growth factors may control the integrin in endometriosis. The findings support larger studies of these markers in women with implantation problems.
RRM Context
Restorative reproductive medicine evaluates the luteal phase and the uterine lining as one part of the same cycle. This paper's markers add to that picture. A delayed lining was linked to high receptor levels and a missing integrin. The authors point to earlier work that found the same missing integrin in women with unexplained infertility, even when the lining looked normal on standard dating.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To compare the expression of endometrial P receptors (PR) levels with markers of endometrial receptivity during the window of implantation.
Design
Prospective, controlled study to examine endometrial PR and three cycle-specific integrins in endometrial biopsies obtained during the window of implantation.
Setting
An academic teaching hospital.
Patients
One hundred seventy-five endometrial biopsies from regularly cycling women with luteal phase defect (LPD; group 1; n = 80), medically treated LPD (group 2; n = 16), minimal and mild endometriosis with aberrant alpha v beta 3 expression (group 3; n = 21), fertile controls (group 4; n = 26), and infertile controls (group 5; n = 32).
Main Outcome Measures
Immunohistochemical staining intensity of each antigen using the semi-quantitative grading system (HSCORE), compared using analysis of variance with Scheffe's correction.
Results
Among the five groups studied, nuclear PR expression was significantly elevated in glandular epithelial cells from tissue samples with histologic delay > or = 3 days consistent with luteal phase deficiency (LPD; group 1). Failure of PR down-regulation was associated with aberrant alpha v beta 3 integrin expression. Medical correction of LPD was associated with return of normal endometrial histology, normal integrin expression, and the loss of epithelial PR, similar to controls. The other two cycle-dependent integrin markers, alpha 1 beta 1 and alpha 4 beta 1, were not different between groups. In women with aberrant alpha v beta 3 and "in phase" endometrium, epithelial PR expression was not different from controls.
Conclusions
The establishment of normal endometrial receptivity appears to be tightly associated with the down-regulation of epithelial PR. Histologic delay, consistent with LPD, is associated with a failure of PR down-regulation and the lack of normal markers of endometrial receptivity. Occult uterine receptivity defects (aberrant beta 3 expression in otherwise normal histology) are regulated differently, suggesting alternate mechanisms also exist which influence endometrial receptivity.
