 This study was designed to understand the role of the endometrium, the lining of the womb in patients who suffer from weakened pregnancy loss. So, weakened pregnancy loss or weakened miscages affect 1-5% of all women during the reproductive age. It's a severe and debilitating disorder. And previously we have shown that the lining of the womb, the stroma cells within the lining of the womb, become able to sense an embryo or a pulmonary implantation. To do that, the stroma cells have to differentiate in these specialized decidable cells. And that process is defective in patients who have frequent miscages, which basically disable the ability of the endometrium to select out high quality versus low quality endometrium. What is so surprising is that the behavior of these cells from an individual patient is recapitulated in culture. And this suggests that the cells were programmed and have memories. And so the purpose of this study was to try to understand the nature of this memory in these primary cultures. So we obtained the genome-wide methylation data for a number of patients and spent a lot of money. And we analyzed this data set in our lab. And at first it seemed that there was absolutely no differential methylation between the patients and the controls. And it was quite a disappointment. We were wondering what to do with the data and initially it looked like the whole data was a waste. But then, luckily, instead of discarding the data, we deepened the analysis. We went beyond standard tools. We explored the data further. And we found that there was hidden from this side of normal tools, which are based on CPG methylation. There was a big pervasive signature that was characterizing the difference between patient and controls on the genomic signature that involved CA rich motifs. Yeah, so CA methylation is largely absent in somatic cells. But it is a feature of stem cells, including embryonic stem cells. So the methylation analysis pointed that there may be a deficiency in stem cell population in the endometrium of patients who suffer miscages. So we set out to characterize and to quantify the abundance of clonogenic cells in the endometrium of controlled patients and miscaged patients, analyzing approximately 60 biopsies. And what we found was that there was a strong correlation between deficiency in stem cells and the number of previous miscages in these patients. In addition, we also found evidence that samsar deficiency in the endometrium is associated with heightened senescence, accelerated aging of these cells. And that explained the primary defects in patients with suffering weakened miscages. So this study is important for several reasons. First of all, it really points towards a strategy where we can identify patients who are at risk of miscages before they even become pregnant. Secondly, it really also suggests that cell-based therapies may be an effective way of preventing miscages in these women. So it really opens up a very new and novel treatment strategy which we hope to develop in studies to come.