Detecting DNA methylation dysregulation of the endometrial window of implantation from cervical secretions

The window of implantation is a critical period during which the endometrium becomes receptive to embryo implantation. Despite advancements in techniques and selecting good embryos, implantation failure remains a bottle neck in IVF treatment, resulting in pregnancy rates of less than 60% and wasting of good quality embryos. This underscores the importance of assessing endometrial quality before embryo transfer. It is clear that the endometrium plays an essential role in the establishment of successful implantation and in supporting pregnancy. This process is regulated by steroid hormones and involves the proliferation and differentiation of a new population of endometrial progenitor/stem cells, which are accompanied in changes in endometrial DNA methylome in each new menstrual cycle. During the window of implantation, which is a self-limited period in the mid secretory phase of the menstrual cycle, the endometrium becomes optimally receptive to support embryo implantation. This suggests that invasive assessment of the endometrium using biopsy sampling in cycles without embryo transfer may not provide useful information about the endometrial receptivity required for successful embryo implantation and pregnancy. There is currently a lack of accurate non-invasive methods for assessing endometrial quality and predicting pregnancy outcomes ahead of embryo transfer. This presents a significant challenge for IVF treatment, where accurate assessment of the endometrium's receptive status is necessary for increasing success rates and reducing the number of wasted embryos.
DNA methylation has been evident to be involved in endometrial biology and pathologies. Studies have demonstrated that altered endometrial DNA methylation is associated with implantation failure or recurrent pregnancy loss. Additionally, DNA methylation markers from cervicovaginal materials have been widely studied and used as proxies in noninvasive investigating endometrial conditions, including cancer. Thus, it is anticipated that DNA methylation changes in cervical secretions during the WOI can reflect endometrial receptivity in each individual menstrual cycle.
In my thesis, I tested the hypothesis that noninvasively detected DNA methylation in cervical secretions during the WOI are associated with endometrial receptivity, as determined by ongoing pregnancy status in embryo transfer cycles. Furthermore, I demonstrated that such DNA methylation changes have potential to predict embryo transfer outcomes. The findings from this work not only provide proof-of -concept evidence to further investigate noninvasive DNA methylation biomarkers in cervical secretions for predicting pregnancy ahead of embryo transfer in IVF treatment, but also contribute to a better understanding of endometrial biology.