Integrins as markers of uterine receptivity in women with primary unexplained infertility

Lessey BA, Castelbaum AJ, Sawin SW, Sun J

doi:10.1016/s0015-0282(16)57422-6

Fertility and Sterility, 63(3), 535-542, 1995

Integrins as markers of uterine receptivity in women with primary unexplained infertility

Sawin SW , A J Castelbaum , Bruce A Lessey

Author affiliations

University of South Carolina ROR

DOI10.1016/s0015-0282(16)57422-6 PMID7851583

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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 Measure

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.

Topics

diagnostics/endometrial-assessment/receptivity-testing infertility/uterine-factor/endometrial-receptivity menstrual-cycle/cycle-biomarkers/hormonal-markers

integrin markers uterine receptivity unexplained infertility, beta 3 integrin expression endometrial biopsy implantation, endometrial integrin deficiency unexplained infertility women, Lessey integrin uterine receptivity implantation window, alpha 1 alpha 4 beta 3 integrin endometrium, defective uterine receptivity implantation window markers, endometrial biopsy immunohistochemistry integrin expression, out of phase endometrium histologic lag implantation failure, cell adhesion molecules endometrial receptivity infertility, window of implantation days 20 to 24 integrin staining

PMID 7851583 7851583 DOI 10.1016/s0015-0282(16)57422-6 10.1016/s0015-0282(16)57422-6 Lessey et al. 1995, Lessey 1995

Cite this article

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

Keywords

Adult, Biomarkers/analysis, Biopsy, Endometrium/cytology/pathology, Female, Fertility, Humans, Immunoenzyme Techniques, Immunohistochemistry, Infertility, Female/pathology, Integrin Alpha1, Integrin Alpha4, Integrin Beta3, Integrins/analysis, Observer Variation, Prospective Studies, Reference Values, Single-Blind Method, Uterus/physiology/physiopathology, Biomarkers, Integrin Alpha1, Integrin Beta3, Integrins, Integrin Alpha4

Hormonal Agents · Estrogen Preparations

Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium

Takasaki A et al., 2009 Fertil Steril

To examine whether thin endometria can be improved by increasing uterine radial artery (uRA) blood flow. A prospective observational study. University hospital and city general hospital. PATIENT(S): Sixty-one patients with a thin endometrium (endometrial thickness [EM] <8 mm) and high radial artery-resistance index of uRA (RA-RI >or=0.81). INTERVENTION(S): Vitamin E (600 mg/day, n = 25), l-arginine (6 g/day, n = 9), or sildenafil citrate (100 mg/day, intravaginally, n = 12) was given. MAIN OUTCOME MEASURE(S): EM and RA-RI were assessed by transvaginal color-pulsed Doppler ultrasound. RESULT(S): Vitamin E improved RA-RI in 18 (72%) out of 25 patients and EM in 13 (52%) out of 25 patients. L-arginine improved RA-RI in eight (89%) out of nine patients and EM in six (67%) patients. Sildenafil citrate improved RA-RI and EM in 11 (92%) out of 12 patients. In the control group (n = 10), who received no medication to increase uRA-blood flow, only one (10%) patient improved in RA-RI and EM. The effect of vitamin E was histologically examined in the endometrium (n = 5). Vitamin E improved the glandular epithelial growth, development of blood vessels, and vascular endothelial growth factor protein expression in the endometrium. CONCLUSION(S): Vitamin E, l-arginine, or sildenafil citrate treatment improves RA-RI and EM and may be useful for the patients with a thin endometrium.

Endometrial Assessment · Receptivity Testing

Endometrial progesterone receptors and markers of uterine receptivity in the window of implantation

Lessey BA et al., 1996 Fertil Steril

To compare the expression of endometrial P receptors (PR) levels with markers of endometrial receptivity during the window of implantation. Prospective, controlled study to examine endometrial PR and three cycle-specific integrins in endometrial biopsies obtained during the window of implantation. An academic teaching hospital. 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). Immunohistochemical staining intensity of each antigen using the semi-quantitative grading system (HSCORE), compared using analysis of variance with Scheffe's correction. 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. 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.

Uterine Factor · Endometrial Receptivity

Unexplained recurrent pregnancy loss and unexplained infertility: twins in disguise

Fox CW et al., 2020 Human Reproduction Open

Endometrial BCL6 protein levels are significantly elevated in women with unexplained recurrent pregnancy loss and unexplained infertility compared with fertile controls, with 79% of subfertile women displaying elevated BCL6. Among those with abnormal BCL6 who underwent laparoscopy, most were found to have endometriosis, suggesting a continuum of progesterone resistance and inflammatory/endometriosis-related endometrial dysfunction.

Endometrial Assessment · Receptivity Testing

Expression of progesterone receptors is significantly impaired in the endometrium of infertile women during the implantation window: a prospective observational study

Petousis S et al., 2016 J Matern Fetal Neonatal Med

To compare the expression of progesterone receptors (A + B) and type-B progesterone receptors in the epithelial and stromal cells of fertile and infertile women. Women were divided into two groups, the group of fertile controls (group 1) and the group of infertile women (group 2) and were set on regular ultrasound imaging in order to detect ovulation. An endometrial biopsy was obtained on the seventh or eighth post-ovulatory day. Immunohistochemistry was performed to measure percentage of positive nuclei, intensity of staining and h-score for progesterone receptors (PgR) (A + B) as well as type-B progesterone receptors in epithelial and stromal cells. Secondary outcomes included endometrial tissue dating, the rate of tissues being out-of-phase and endometrial thickness. Endometrial issue was obtained from 15 fertile and 30 infertile women. Expression of PgR (A + B) and PgR type-B was significantly lower in the epithelial cells of infertile women. PgR (A + B) h-score was 220.0 ± 18.5 for fertile versus 147.3 ± 18.0 for infertile women (p = 0.02). PgR type-B h-score in epithelial cells was 166.8 ± 30.7 for fertile versus 90.8 ± 20.6 for infertile (p = 0.04). No significant difference was observed in stromal cells. Expression levels of PgR (A + B) as well as type-B receptors are significantly lower in the epithelial cells of infertile women during implantation window.

Integrins as markers of uterine receptivity in women with primary unexplained infertility

Abstract

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