Adult ; Endometriosis ; complications ; metabolism ; Endometrium ; metabolism ; Female ; Humans ; Infertility, Female ; etiology ; metabolism ; Leptin ; metabolism

Primary ovarian insuffiency (POI), which accounts for female infertility, is characterized by amenorrhea before the age of 40 and high serum level of follicular stimulating hormone (>40 U/L) at two measurements taken at least one month apart. The disorder is believed to have a strong genetic component. A large number of candidate genes have been proposed, though few of them were extensively studied. With the rapid evolvement of genome sequencing technology, recent research raised the possibility that the genes involved in essential steps of meiosis such as chromosome synapsis and recombination play an important role in the pathogenesis of POI. Clarifying the genetic pathogenesis of POI not only can enhance understanding of the molecular mechanism of reproductive functions and infertility, but also provide accurate information for genetic counseling for such patients.
Female ; Follicle Stimulating Hormone ; metabolism ; Humans ; Infertility, Female ; genetics ; Meiosis ; Primary Ovarian Insufficiency ; genetics ; metabolism

OBJECTIVEOvarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis.

DATA SOURCESWe searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-γ), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms.

STUDY SELECTIONArticles were obtained and reviewed to analyze the pathogenic mechanism of ovarian fibrosis and related ovarian diseases.

RESULTSMany cytokines, such as MMPs, TIMPs, TGF-β1, CTGF, PPAR-γ, VEGF, and ET-1, are involved in ovarian fibrogenesis. Ovarian fibrogenesis is associated with various ovarian diseases, including ovarian chocolate cyst, PCOS, and premature ovarian failure. One finding of particular interest is that fibrogenesis in peripheral tissues around an ovarian chocolate cyst commonly causes ovarian function diminution, and therefore, this medical problem should arouse widespread concern in clinicians worldwide.

CONCLUSIONSPatients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases.

Animals ; Cytokines ; metabolism ; Female ; Fibrosis ; complications ; diagnosis ; etiology ; metabolism ; Humans ; Infertility, Female ; etiology ; Ovary ; pathology

Endometriosis is a common disease of reproductive age women and infertility is one of its clinical manifestations. Infertility of patients with severe endometriosis may be attributed to the anatomy alteration of pelvis.However, the infertility of patients with minimal to mild endometriosis whose pelvic anatomy remains intact is still hard to explain. It is considered that the infertility of patients with ninimal to mild endometriosis is associated with the alteration of the pelvic microenvironment. Several kinds of cytokines and proteins are involved in this process. They may disturb steps necessary to achieve successful pregnancy, such as ovulation,gamete transport, fertilization, embryo transport and implantation. Any disturbance to one of the steps mentioned above may lead to pregnant loss.
Cytokines ; metabolism ; Endometriosis ; complications ; metabolism ; pathology ; Female ; Humans ; Infertility, Female ; etiology ; metabolism ; Nitric Oxide Synthase ; metabolism ; Pregnancy

OBJECTIVE: To analyze the difference in the gene expression, amino acid and carnitine levels in the cervical secretions between the endometria of pre-receptive and receptive stages, with an aim to provide clues for identifying new molecular markers for endometrial receptivity. METHODS: Fifty nine infertile women treated at the Department of Reproductive Medicine of Linyi People's Hospital from January 6, 2020 to January 31, 2022 were selected as as the study subjects, which were matched with 3 pairs (6 cases) of infertile women preparing for embryo transfer based on factors such as age, body mass index, and length of infertility. Endometrial tissue samples were collected for gene transcription and expression analysis. Twenty five women who had become pregnant through assisted reproductive technology were selected as the control group, and 28 non-pregnant women receiving ovulation monitoring at the Outpatient Department were enrolled as the case group. Status of endometrial receptivity was determined by ultrasonography. In the former group, endometrial tissues were sampled for sequencing, and GO and KEGG database enrichment analysis of differentially expressed genes was carried out. In the latter group, cervical secretions were collected, and amino acid and carnitine levels were measured by mass spectrometry. Statistical analysis was carried out using rank sum test, t test and chi-square test with SPSS v25.0 software. RESULTS: No difference was found in the clinical data of the patients with regard to age, body mass index, infertility years, AMH, FSH, LH, E2, and type of infertility. Compared with the receptive endometrial tissues, there were 100 significantly up-regulated genes and 191 significantly down-regulated genes in the pre-receptive endometrial tissue, with the most significantly altered ones being HLA-DRB5 and MMP10. The biological processes, molecular functions and pathways enriched by more differentially expressed genes in GO and KEGG were mainly immune regulation, cell adhesion and tryptophan metabolism. Analysis of secretion metabolism also revealed a significant difference in the levels of amino acids and carnitine metabolites between the two groups (P < 0.05), in particular those of Alanine, Valine, 3-hydroxybutyrylcarnitine (C4OH) + malonylcarnitine (C3DC)/captoylcarnitine (C10). CONCLUSION A significant difference has been discovered in the levels of gene transcription and protein expression in the endometrial tissues from the pre-receptive and receptive stages. The levels of amino acids and carnitine, such as Alanine, Valine, 3-hydroxybutyryl carnitine (C4OH)+malonyl carnitine (C3DC)/caproyl carnitine (C10), may be associated with the receptive status of the endometrium, though this need to be verified with larger samples.
Pregnancy ; Humans ; Female ; Infertility, Female/genetics* ; Endometrium/metabolism* ; Amino Acids/metabolism* ; Gene Expression ; Carnitine ; Alanine/metabolism* ; Valine/metabolism*

Animals ; Cdc20 Proteins/metabolism* ; Cell Line ; Embryo, Mammalian/embryology* ; Embryonic Development ; Female ; Infertility, Female/metabolism* ; Mice ; Mutation ; Oocytes/metabolism*

Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women's reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.
Female ; Humans ; Atrophy/metabolism* ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Infertility/metabolism* ; Ovarian Follicle ; Ovulation

OBJECTIVETo assess the diagnostic value of sperm DNA fragmentation (SDF) for male infertility.

METHODSTwo hundred and ninety-nine males attending infertility clinic were classified into 157 primary infertile cases and 142 fertile controls. Semen analysis was performed as recommended by the World Health Organization (WHO). SDF was assessed by sperm chromatin dispersion (SCD) assay, and the results were expressed as DNA fragmentation index (DFI).

RESULTSThe DFI was significantly higher in infertile males than that in fertile controls [(17.1± 9.3)% vs. (14.2± 9.0)%](P< 0.01). No significant difference was detected in the age of male and female partners, seminal volume, sperm count, motility and morphology between infertile males and fertile controls (P> 0.05). The area under the receiver operating characteristic curve (AUC) was 0.861 [95% confidence interval (CI)= 0.814-0.907] for 15.1% of SDF. The threshold level of 15.1% was derived as cut-off value to discriminate infertile men from fertile controls. By this threshold, specificity was 88.2% and sensitivity was 81.8%. The 299 men were divided into group A (n= 120) with DFI≥ 15.1% and group B (n= 179) with DFI< 15.1% based on the cut-off value. The percentage of infertile men in group A was significantly higher than that in group B (79.2% vs. 34.6%) (P< 0.01). The odds ratio (OR) for infertility in the two groups was 7.2 (95%CI= 4.2-12.3).

CONCLUSIONSperms with high-level of DNA fragmentation can impair male fertility. DFI can be used as a good diagnostic marker for male infertility.

Adolescent ; Adult ; DNA ; metabolism ; DNA Fragmentation ; Female ; Humans ; Infertility, Male ; diagnosis ; genetics ; Male ; Spermatozoa ; metabolism ; Young Adult

OBJECTIVETo investigate the role of nitric oxide (NO) in the pathogenesis of early endometriosis-associated infertility.

METHODSThe volume of peritoneal fluids was recorded and the concentration of NO in peritoneal fluid and serum was measured with a fluorescence method using 4, 5-diaminofluorescein (DAF-2) as an indicator, in 60 patients with early endometriosis-associated infertility ( endometriosis group), 60 patients with tubal infertility (tubal infertility group) and 20 patients without infertility (control group). The IVF-ET outcomes between patients with endometriosis and tubal infertility were compared.

RESULTThe volume of peritoneal fluids from endometriosis group patients increased significantly compared with that in tubal infertility group patients and control groups. The concentration of NO in peritoneal fluid of the control group,the tubal infertility group and the endometriosis group was 9.98, 13.76 and 20.72, respectively (P<0.017). Furthermore the concentration of NO in serum of the patients of control group,tubal infertility group and endometriosis group was 12.25, 13.00, 13.60, respectively; there were no significant differences among these three groups. There were no significant differences in implantation rate, pregnancy rate and abortion rate of IVF-ET between endometriosis group patients and tubal infertility group patients. However, the fertilization rate was significantly lower in endometriosis group patients than that in tubal infertility group patients.

CONCLUSIONChanges of nitric oxide in peritoneal fluids may play an important role in the pathogenesis of early endometriosis-associated infertility and IVF-ET may serve as an alternative method for this type of infertility.

Adult ; Ascitic Fluid ; metabolism ; Biomarkers ; blood ; Embryo Transfer ; Endometriosis ; blood ; complications ; metabolism ; pathology ; Female ; Fertilization in Vitro ; Humans ; Infertility, Female ; blood ; etiology ; metabolism ; Nitric Oxide ; blood ; metabolism

Chinese medicine (CM) has been used in clinical treatment for thousands of years in China, Japan, Korea, and other countries. CM is at present attracting many attentions around the world for reproductive health care and disease prevention, including treatment of female infertility. This review focuses on the CM treatment for female infertility patients, and supplies a summary on the efficacy, safety, and mechanism of some Chinese herbal medicines, herbal medicine-derived active compounds, and acupuncture. A large number of researches have reported that CM could alleviate or even cure female infertility by regulating hormone, improving reproductive outcome of in vivo fertilization, affecting embryonic implantation, curing polycystic ovarian syndrome, endometriosis, pelvic inflammatory disease, relieving mental stress, and regulating immune system. Meanwhile, a few studies claimed that there was little adverse reaction of CM in randomized controlled trials. However, up to present there is a lack of adequate evidences with molecular mechanistic researches and randomized controlled trials to prove the CM as an effective and safe treatment for infertility. Thus, utility of CM as a complementary medicine will be a feasible method to improve the outcome of female infertility treatment.
Complementary Therapies ; Embryo Implantation ; Female ; Fertilization in Vitro ; Hormones ; metabolism ; Humans ; Infertility, Female ; immunology ; therapy ; Medicine, Chinese Traditional