Absence of biochemical or morphologic markers of endometrial glandular development in a mock cycle predicts pregnancy failure in a subsequent donor oocyte transfer cycle. 1HJ Kliman, 1JS Arruda, 1RF Feinberg, 2DL Keefe. 1Department of Obstetrics and Gynecology, Yale University, New Haven, CT, 2Department of Obstetrics and Gynecology, Brown University, Providence, RI.
Objectives: We have previously shown that MAG mucin expression abnormalities in endometrial biopsies are correlated with reproductive outcome in patients with long-standing infertility. In this study we attempted to determine if MAG expression and histologic evaluation of day 16 and 25 endometrial biopsies predicted pregnancy outcome in a subsequent donor oocyte transfer cycle.
Design: MAG mucin immunohistochemistry was performed on mock cycle day 16 and 25 endometrial biopsies. The patterns of MAG epithelial staining were compared to standard histologic dating criteria for each cycle day. MAG and histologic findings were correlated with pregnancy outcomes in subsequent donor oocyte transfer cycles.
Materials and Methods: Day 16 and 25 endometrial biopsies were collected from 54 blood group A patients. Biopsies were fixed in formalin, paraffin embedded and immunohistochemically stained for MAG (AJP, 146:166-181, 1995), ABO blood group antigens, MUC1 (+ control), and NMA (- control). Less than 10% epithelial MAG reactivity was considered negative. Hematoxylin and eosin sections were used for endometrial dating of the stroma and glands according to the criteria of Hendrickson and Kempson. The degree of glandular-stromal dyssynchrony in the d25 biopsy was assessed. Of the original 54 patients, 21 patients had embryo transfers with pregnancy outcomes.
Results: Three patterns of MAG immunostaining were identified: 1) Normal: MAG was positive in the follicular phase, but negative after d20; 2) Prolonged or delayed (Type I defect): MAG was expressed in both follicular and luteal phases or only during the luteal phase; 3) Absent (Type II defect): MAG was absent at all times. Of the 4 patients with normal MAG expression, 3 became pregnant, while 1 did not. Of the 11 patients with Type I MAG defect, 2 became pregnant, while 9 did not. None of the 6 patients with Type II MAG defect became pregnant. Two histologic groups were identified: 0-50% or >50% glandular-stromal dyssynchrony in the d25 biopsy. Of the sixteen patients with 0-50% dyssynchrony, half became pregnant, while half did not. On the other hand, none of the 5 patients with >50% glandular-stromal dyssynchrony became pregnant.
Conclusions: Severe defects in endometrial glandular development (Type II MAG defect or severe (>50%) glandular-stromal dyssynchrony) in mock cycles were predictive of pregnancy failure in a subsequent donor oocyte transfer. Type I MAG defect was associated with an 18% success rate, while normal MAG expression showed a 75% success rate. Less than or equal to 50% glandular-stromal dyssynchrony was not predictive for pregnancy outcome.
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