Predictive models for starting dose of gonadotropin in controlled ovarian hyperstimulation: review and progress update.

Controlled ovarian hyperstimulation (COH) is an essential for in vitro fertilization-embryo transfer (IVF-ET) and an important aspect of assisted reproductive technology (ART). Individual starting doses of gonadotropin (Gn) is a critical decision in the process of COH. It has a crucial impact on the number of retrieved oocytes, the cancelling rate of ART cycles, and complications such as ovarian hyperstimulation syndrome (OHSS), as well as pregnancy outcomes. How to make clinical team more standardized and accurate in determining the starting dose of Gn is an important issue in reproductive medicine. In the past 20 years, research teams worldwide have explored prediction models for Gn starting doses. With the integration of artificial intelligence (AI) and deep learning, it is hoped that there will be more suitable predictive model for Gn starting dose in the future.

Identification and Immune Characteristics Study of Pyroptosis­Related Genes in Endometriosis.

Endometriosis (EMT) is a prevalent gynecological disorder characterized by pain and infertility associated with the menstrual cycle. Pyroptosis, an emerging cell death mechanism, has been implicated in the pathogenesis of diverse diseases, highlighting its pivotal role in disease progression. Therefore, our study aimed to investigate the impact of pyroptosis in EMT using a comprehensive bioinformatics approach. We initially obtained two datasets from the Gene Expression Omnibus database and performed differential expression analysis to identify pyroptosis-related genes (PRGs) that were differentially expressed between EMT and non-EMT samples. Subsequently, several machine learning algorithms, namely least absolute shrinkage selection operator regression, support vector machine-recursive feature elimination, and random forest algorithms were used to identify a hub gene to construct an effective diagnostic model for EMT. Receiver operating characteristic curve analysis, nomogram, calibration curve, and decision curve analysis were applied to validate the performance of the model. Based on the selected hub gene, differential expression analysis between high- and low-expression groups was conducted to explore the functions and signaling pathways related to it. Additionally, the correlation between the hub gene and immune cells was investigated to gain insights into the immune microenvironment of EMT. Finally, a pyroptosis-related competing endogenous RNA network was constructed to elucidate the regulatory interactions of the hub gene. Our study revealed the potential contribution of a specific PRG to the pathogenesis of EMT, providing a novel perspective for clinical diagnosis and treatment of EMT.

Individualized conservative therapeutic strategies for adenomyosis with the aim of preserving fertility.

Adenomyosis is a diffuse or localized organic disease caused by benign invasion of endometrial glands and stroma into the myometrium. It is a common disease that seriously affects reproductive health of women in childbearing age. Due to the unknown etiology and pathophysiological mechanism, and the lack of unified diagnostic criteria and effective treatment methods, total or subtotal hysterectomy has become a radical treatment for adenomyosis, which will lead to the complete loss of fertility. With the continuous exploration of the treatment to adenomyotic patients who have infertility or fertility intentions, new drugs, surgical methods and treating concepts appears. Adopt individualized conservative therapeutic strategies for patients with different conditions, preserve the uterus as much as possible and protect the patient's fertility, which will play an important role on the follow-up assisted reproductive treatment and long-term management of adenomyosis.

Integrated analysis identified novel miRNAs and mRNA in endometriosis.

OBJECTIVES: Endometriosis is a common gynecological disease that seriously affects women's health and quality of life. However, the pathogenesis of endometriosis remains uncertain. This study aims to find the key microRNAs (miRNAs) and mRNAs and further to elucidate the pathogenesis of endometriosis. MATERIAL AND METHODS: Differentially expressed mRNAs (DEmRNAs) and the differentially expressed miRNAs (DEmiRNAs) were obtained by Gene Expression Omnibus (GEO) datasets integration analysis. Functional enrichment analysis of DEmRNAs and DEmRNAs targeted by DEmiRNAs was enforced using GeneCodis3. The DEmiRNA-DEmRNA interaction network was built using Cytoscape. The expression of candidate DEmRNA and DEmiRNA was verified using quantitative real time-polymerase chain reaction (QRT-PCR) and online datasets followed by diagnostic and immune cell infiltration analysis. RESULTS: A total of 835 (327 down-regulated and 508 up-regulated) DEmRNAs and 39 (24 down-regulated and 15 up-regulated) DEmiRNAs were identified between ectopic endometria (EC) group and eutopic endometria (EU) group. DEmRNAs targeted by DEmiRNAs were markedly enriched in cell adhesion molecules, pathways in cancer, leukocyte transendothelial migration, cytokine-cytokine receptor interaction and MAPK signaling pathway. The DEmiRNA-DEmRNA interaction network of up-regulated miRNAs was consisted of 15 miRNAs and 188 corresponding mRNAs. For down-regulated miRNAs, the DEmiRNA-DEmRNA interaction network was consisted of 24 miRNAs and 305 corresponding mRNAs. QRT-PCR validation results of IRF6, PTGER3, NTRK2, hsa-miR-449a and hsa-miR-873-5p were in line with the GEO analysis result. RF6, PTGER3 and NTRK2 had a potential diagnostic value for endometriosis. In addition, the infiltration of macrophages M2 and NK cells activated was the most significantly increased and reduced in ectopic endometrial, respectively. CONCLUSIONS: These identified DEmRNAs and DEmiRNAs may be may be associated with the pathogenesis of endometriosis. The integrated analysis of miRNA and mRNA expression profiles may provide a new perspective for understanding the mechanisms of endometriosis and developing new treatments.

Identification of critical miRNAs and mRNAs associated with polycystic ovary syndrome.

AIM: Polycystic ovary syndrome (PCOS) is a complicated endocrine and metabolic abnormality diseases common in women of child-bearing age. This study aims to screen out critical miRNAs and mRNAs associated with PCOS, which may be conducive to offer novel insights and treatment for the diseases. METHODS: Three mRNA datasets and one miRNA dataset derived from granulosa cells of patients with PCOS and normal controls were downloaded to obtain the differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs). Then, DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. Quantitative real time polymerase chain reaction (qRT-PCR) validation of the expression of the selected DEmRNAs and DEmiRNAs were performed. RESULTS: A total of 1643 DEmRNAs, 88 DEmiRNAs, 2406 DEmiRNA (down)-DEmRNA (up), and 2179 DEmiRNA (up)-DEmRNA (down) pairs were obtained. The functional annotation of DEmiRNA-target DEmRNAs revealed that C-type lectin receptor signaling pathway, Steroid biosynthesis and Galactose metabolism were significantly enriched KEGG pathways. CONCLUSION: These findings may provide make contribution to understanding PCOS pathogenesis, diagnosis, or treatment.

The role of nesfatin-1 expression in letrozole-induced polycystic ovaries in the rat.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder, generally exhibiting the characteristic features of hyperandrogenemia, insulin resistance (IR) and obesity. Nesfatin-1 is derived from the precursor nucleobindin2 (NUCB2), and plays an active role in energy balance, glucose metabolism and most likely gonadal function. In order to explore the role of nesfatin-1, we employed a rat model that uses letrozole to induce PCOS. The PCOS rats exhibited increased body weight, irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. The expression of both nesfatin-1 mRNA and protein in the ovarian tissues of PCOS group decreased significantly compared to the control group (p < 0.05). Nesfatin-1 expression in peripheral blood also decreased in the PCOS group, in contrast with the control group. Furthermore, we found that nesfatin-1 had a positive correlation with FSH, E2 and P, whereas it had a negative correlation with LH, and total T (p < 0.05). When taken together, these data indicated that the decrease in nesfatin-1 may contribute to the mechanism governing PCOS, and might provide a new potential target for therapies aimed at treating PCOS.

IL-10 regulate decidual Tregs apoptosis contributing to the abnormal pregnancy with Toxoplasma gondii infection.

This study aims to investigate whether IL-10 regulate decidual Treg cells apoptosis to reverse the abnormal pregnancy outcomes with Toxoplasma gondii (T. gondii) infection. Recombinant mouse IL-10 (rIL-10) treatment and IL-10 deficiency (IL-10(-/-)) abnormal pregnancy animal models with T. gondii infection were established. Apoptosis related molecules cleaved Caspase-3 and Caspase-8 in decidual Treg cells were examined using flow cytometry. The levels of cleaved Caspase-3 and Caspase-8 in decidual Treg cells were up-regulated with T. gondii infection. Compared to infected group, the expressions of cleaved Caspase-3 and Caspase-8 in decidual Treg cells were down-regulated in rIL-10-treated group, while up-regulated in infected IL-10(-/-) group. In addition, pregnant outcomes were improved in rIL-10-treated group, while worse in IL-10(-/-) group compared to infected group. These findings revealed that IL-10 reduced the decidual Treg cells apoptosis contributing to improving adverse pregnant outcomes following T. gondii infection.

sHLA-G involved in the apoptosis of decidual natural killer cells following Toxoplasma gondii infection.

This study aims to assess whether soluble HLA-G (sHLA-G) is involved in apoptosis of decidual natural killer (dNK) cells following Toxoplasma gondii infection. dNK cells or NK-92 cells were infected with T. gondii and co-cultured with trophoblast cells or BeWo cells. Infected co-cultured cells were treated without or with sHLA-G neutralizing antibody. Uninfected co-cultured cells were used as controls. Apoptosis of dNK cells were analyzed by flow cytometry and confocal microscope. Real-time PCR and Western blot were used to determine caspase 3 and caspase 8 expression. sHLA-G in supernatant were measured by enzyme-linked immunosorbent assay (ELISA). In infection groups, sHLA-G was increased, while dNK apoptosis proteins caspase 3 and caspase 8 were up-regulated, but significantly decreased in the presence of sHLA-G neutralizing antibody compared to controls. Under the situation of T. gondii-infected dNK cells co-cultured with trophoblast cells, the up-regulation of sHLA-G could induce dNK cells apoptosis which ultimately may contribute to the abnormal pregnancy outcomes with T. gondii infection.