High incidence of decidualization failure in infertile women.

Purpose: Decidualization is an important event for embryo implantation and successful pregnancy. Impaired decidualization leads to implantation failure and miscarriage. However, it is unclear how often decidualization failure occurs in infertile women. By analyzing the endometrium at late-secretory phase, we investigated the incidence and pathogenesis of decidualization failure among infertile women. Methods: Endometrial dating was performed on the endometria obtained in the late-secretory phase from 33 infertile women. Endometrial dating of more than 2 days delay was taken as an indication of decidualization failure. The expression of essential transcription factors for decidualization (FOXO1, WT1, and C/EBPß) was examined by immunohistochemistry. Results: Among 32 cases, 20 cases (62.5%) showed decidualization failure. These patients tended to have a history of more frequent miscarriages than those without decidualization failure. The percentage of cells that immunostained positive for the expression of three transcription factors was significantly lower in the patients with decidualization failure than in those without decidualization failure. Serum progesterone levels measured in the mid- and late-secretory phase were not significantly different between the cases with and without decidualization failure. Conclusions: The incidence of decidualization failure is high in infertile women.

Combined histological and DNA methylome profiling approaches may provide insights into the pathophysiology of ovarian endometriomas.

Purpose: To test the theory that invaginated ovarian surface epithelium and endometrial implants on the ovary form ovarian endometriomas. Methods: Adhesion sites of ovarian endometrioma on the peritoneum and consecutive ovarian endometrioma cyst wall, called non-adhesion sites, were histologically examined. DNA methylomes of the adhesion sites, non-adhesion sites, and blueberry spots were compared with those of ovary, endometrium, and peritoneum. Results: The non-adhesion sites showed an ovarian surface epithelium-like structure near the adhesion site, which continued to a columnar epithelium-like structure. Calretinin staining was strong in the ovarian surface epithelium-like structure but weak in the columnar epithelium-like structure. Estrogen receptors were absent in the ovarian surface epithelium-like structure, but present in the columnar epithelium-like structure. The adhesion sites had endometrial gland-like structures that expressed estrogen receptors. Analyses of DNA methylomes classified the non-adhesion sites and ovaries into the same group, suggesting that ovarian endometriomas originate from the ovarian surface epithelium. The adhesion sites, blueberry spots and peritoneum were classified in the same group, suggesting that the adhesion sites and blueberry spots originate from the peritoneum. Conclusions: The present results support the invagination theory. Ovarian endometriomas consist of invaginated ovarian surface epithelium with celomic metaplasia and endometrium implants on the peritoneum.