Pathogenesis Of Endometriosis-associated Infertility Research Articles

Increased Expression of YAP Inhibited the Autophagy Level by Upregulating mTOR Signal in the Eutopic ESCs of Endometriosis.

We first reported that the Hippo-YAP signaling pathway plays a critical role in the pathogenesis of endometriosis (EMS). Autophagy is also related to the invasion ability of endometrial cells and is involved in the pathogenesis of EMS through multi-levels. However, the precise regulatory mechanism of YAP on autophagy in the eutopic endometrial stromal cells (ESCs) is still unclear. Primary eutopic ESCs of EMS patients (n = 12) and control patients without EMS (n = 9) were isolated and cultured to investigate the expressions of YAP and mTOR, the role of YAP in autophagy, and the effect of the YAP-autophagy signal on the decidualization of the eutopic ESCs. Endometriosis-related sequencing data (GSE51981) in the GEO database were used to find the genes significantly correlated with YAP. We found 155 genes with significant differences in the interaction with YAP in EMS from the dataset, and the autophagy pathway was significantly enriched. Following on from our previous studies of YAP knockdown, overexpression of YAP resulted in an increased expression of mTOR and decreased ratio of LC3-II/LC3-I and autophagy markers, in the eutopic ESCs; transmission electron microscope observation also showed fewer autophagosomes compared with the control cells. Furthermore, ESCs of the Rapamycin-treated group showed significant decidual-like changes with significantly increased decidual prolactin level at 72 h after in vitro decidualization. These results demonstrate that the increased YAP inhibited the level of autophagy by upregulating the mTOR signal in the eutopic ESCs of endometriosis. The YAP-autophagy signal plays an important role in the pathogenesis of endometriosis-associated infertility.

Early Pregnancy Outcomes in Fresh Versus Deferred Embryo Transfer Cycles for Endometriosis-Associated Infertility: A Retrospective Cohort Study.

Given the estrogen-dependence associated with endometriosis, hyper-stimulation associated with assisted reproduction treatment may exacerbate the disease process and adversely affect endometrial receptivity and subsequent implantation. In this way, a freeze-all deferred embryo transfer (ET) approach may benefit patients with endometriosis, although controversy exists regarding the mechanism of endometriosis-associated infertility and benefits of deferred ET on endometrial receptivity. Hence, the purpose of this study was to compare in vitro fertilization (IVF) outcomes in women with endometriosis, diagnosed by histology, undergoing fresh versus deferred-ET after elective cryopreservation. Of the 728 women included, no significant differences were observed in baseline patient characteristics and response to gonadotrophin stimulation between fresh and deferred ET groups. Furthermore, no significant differences in implantation rate (49.7 vs. 49.9%, p = 0.73), clinical pregnancy rate (40.9 vs. 39.9%, p = 0.49), and miscarriage rate (9.4 vs. 9.9%, p = 0.63) were observed between fresh and deferred ET groups, respectively. Hence, contrary to previous studies, our results suggest that a deferred ET “freeze-all” IVF strategy does not improve early pregnancy outcomes among women with endometriosis. However, prospective studies are required to validate these findings and further insight into the etiology and pathogenesis of endometriosis-associated infertility are necessary to optimize IVF protocols in this population.

ENDOMETRIC FACTOR OF ENDOMETRIOSIS-ASSOCIATED INFERTILITY

BACKGROUND Despite numerous studies and a not decreasing amount of endometriosis and associated infertility, the study of endometriosis- associated infertility does not lose its relevance, and the characteristics of the endometrium is appeared to be central and predictive factors that determine the success of overcoming infertility. OBJECTIVE To reflect the molecular genetic features of the state of the endometrium with endometriosis associated with infertility, expand the understanding of its pathogenesis, substantiate theoretical aspects of the use of hormonal preimplantation preparation of the endometrium in endometriosis-associated infertility. MATERIALS AND METHODS To write this review, we searched for domestic and foreign publications in Russian and international search systems (eLIBRARY, PubMed, MedLine, Crossref, etc.) over the past 1–16 years. RESULTS The model of changes in endometrial receptivity is examined the mechanisms of resistance to progesterone and overproduction of estrogens as key endometrial factors in the pathogenesis of endometriosis-associated infertility and theoretical justification for the use of hormonal therapy for the preimplantation preparation of compromised endometrium is given. CONCLUSION Despite the large number of publications, there is no consensus and the same approaches to determining the receptivity of the endometrium and its role in implantation disorders in endometriosis, as well as clear ideas about the pathogenesis of endometriosis-associated infertility. A personalized approach in the management of patients with endometriosis-associated infertility will lead to a common denominator of many factors affecting reproduction and determine their potential role in both the diagnosis and treatment of a particular patient.

Potential Involvement of Iron Overload in the Pathogenesis of Endometriosis-Associated Infertility

Endometriosis is defined as the appearance of intimal tissue, including both endometrial glands and stroma...

Circulating Antisperm Antibody is not Related to the Pathogenesis of Infertility in Women with Endometriosis

Objective To investigate the role of circulating antisperm antibody (ASA) in the pathogenesis of endometriosis-associated infertility. Methods Serum samples were collected from 75 infertile women with minimal or mild endometriosis. Indirect immunobead test reporting on the percentage of motile sperm with adherent immunobeads was used to detect the circulating ASA levels. Results No infertile cases enrolled in the present study developed significant ASA level in the serum samples. That is to say, no one could achieve the diagnosis of ASA-mediated infertility according to the World Health Organization criteria (50% or more of the motile sperm with immunobead binding). There were only 5 cases (6.7%) who had 20%-40% of the motile sperm that were found to have adherent particles of ASA-IgG. All the cases were found to be completely absent of ASA-IgA. Conclusions Endometriosis seems to have little impact on the production of circulating ASA. Clearly, ASA is not the key factor implicated in the pathogenesis of endometriosis-associated infertility. The presence of a low titer of ASA in a small proportion of the infertile women with endometriosis may exist by chance and, at least in part, explain the impaired fecundity in those patients.

The Peritoneal Leptin, MCP-1 and TNF-α in the Pathogenesis of Endometriosis-Associated Infertility

To explore the roles of leptin, monocyte chemotactic protein (MCP)-1, and tumour necrosis factor (TNF)-α in the peritoneal fluid (PF) in the pathogenesis of endometriosis-associated infertility. Leptin, MCP-1, and TNF-α levels in the PF from 28 infertile women with endometriosis (study group), 23 women with fallopian-associated infertility (controls), and 24 women with myoma (controls) were determined by performing enzyme-linked immunosorbent assay (ELISA). Leptin and TNF-α levels in the PF showed no significant difference among three groups. The MCP-1 level in patients with endometriosis was higher than those in fallopian-associated infertility group and myoma group (P < 0.01). There was a positive correlation between leptin and MCP-1 levels in the PF of patients with endometriosis (P < 0.05). Peritoneal leptin and MCP-1 play important roles in the pathogenesis of infertility in the early stage of endometriosis.

Downregulative Effects of Nitric Oxide on Oocyte Fertilization and Embryo Development: Possible Roles of Nitric Oxide in the Pathogenesis of Endometriosis-associated Infertility

Aims: To investigate the effects of elevated nitric oxide (NO) levels in peritoneal fluids (PF) on oocyte fertilization and pre-implantation embryo development, and the relation of those effects to endometriosis-associated infertility. Methods: PF from women undergoing laparoscopy for infertility of minor endometriosis, tubal blockage and operation for tubal ligation was aspired at the pouch of the cul-de-sac during surgery. Oocytes and embryos of adult ICR mice were cultured in vitro with or without endometriotic PF. The fertilization rate of oocyte and the cleavage rate of 2-cell embryos were examined. Also, the clinical indexes of IVF-ET of women with minor endometriosis and tubal infertility were analyzed. Results: Oocyte fertilization rate of endometriotic women with IVF-ET treatment was significantly lower than that of tubal block women. The dose-related adverse effects of endometriotic PF and SNP (NO donor) in culture medium on oocyte fertilization and embryos development were confirmed. Conclusion: Increased NO levels in PF play an important role in mediating the effects of endometriotic PF on oocyte fertilization and embryo development. IVF might serve as an alternative treatment for endometriosis-associated infertility.