The Role of Endometrial Aquaporin-2 in Implantation in Infertile Couples Undergoing IVF-ICSI Cycles

Abstract

In this pilot study, fifty couples with infertility, meeting the inclusion criteria, who were planned to undergo ICSI treatments at the Assisted Reproduction Technology Unit (ARTU), of Ain Shams University Maternity Hospital, were recruited during the one-year study period. Endometrial biopsies were obtained from the consenting ladies, using endometrial suction curettes, during the estimated implantation window prior to starting the controlled ovarian hyperstimulation (COH) protocols. The implantation window was calculated as 7 days following the LH surge, detected by urine ovulation detection kits. The biopsied samples were then subject to histopathological and immune-histochemical examination for AQP-2 expression, that was semi-quantitatively scored on a scale of 4 (0-3). The ladies were followed up for the data of the COH, as well as embryology data, and implantation and pregnancy rates. The results of the study have shown that endometrial AQP-2 expression was not significantly correlated to the following patients’ characteristics; women’s age or BMI, the duration of infertility, or pre-COH hormonal profile. However, statistical analysis has shown that there was a significant difference in AQP-2 expression between the non-pregnant and the pregnant (both biochemical and clinical)groups, who showed higher levels of AQP-2 expression. This was despite the fact that these groups were matched as to the baseline patient characteristics and all other variables of the COH and embryo numbers and qualities. A strong correlation between the AQP-2 expression and the implantation rates was observed, which was statistically highly significant. The data were further analysed to evaluate the predictive value of AQP-2 expression in assessment of the outcome of ICSI cycles. The results have demonstrated that, even after adjustment for potential confounding factors, the odds ratios (OR) for biochemical and clinical pregnancies with positive AQP-2 expression were 7.03 and 10.73, respectively, which were statistically significant. Furthermore, data analysis was extended to assess the value of different AQP-2 expression scores as independent predictors of pregnancy. Multiple logistic regression analysis and Receiver Operating Characteristic (ROC) curves have shown that an endometrial AQP-2 score of 2 during the implantation window, held the best statistical parameters for prediction of both biochemical and clinical pregnancy rates. With an AQP-2 score of 2, used to predict biochemical and clinical pregnancy rates, the sensitivity is 58.06% (95% CI 39.1-75.5) and 92.86% (95% CI 66.1 - 99.8), the specificityis 84.21% (95% CI 60.4 – 96.6) and 77.78% (95% CI 60.8 - 89.9), the positive predictive valueis 85.7% (95% CI 63.7 – 97.0) and 61.9% (95% CI 29.0 - 96.3), and finally the negative predictive value is 55.2% (95% CI 35.3 – 73.9) and 96.6% (95% CI 81.8 - 99.9), respectively.