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Mitochondria play diverse roles in mammalian physiology. The architecture, activity, and physiological functions of mitochondria in oocytes are largely different from those in somatic cells, but the mitochondrial proteins related to oocyte quality and reproductive longevity remain largely unknown. Here, using whole-exome sequencing data from 1,024 women (characterized by oocyte maturation arrest and degenerated or morphologically abnormal oocytes) and 2,868 healthy controls, we performed a population and gene-based burden test for mitochondrial genes and identified a candidate gene, cytochrome c oxidase assembly protein 15 (COX15). We report that biallelic COX15 pathogenic variants cause human oocyte ferroptosis and female infertility in a recessive inheritance pattern. COX15 variants impaired mitochondrial respiration in Saccharomyces cerevisiae and led to reduced protein levels in HeLa cells. Oocyte-specific deletion of Cox15 led to impaired Fe2+ and reactive oxygen species homeostasis that caused mitochondrial dysfunction and ultimately sensitized oocytes to ferroptosis. In addition, ferrostatin-1 (an inhibitor of ferroptosis) could rescue the oocyte ferroptosis phenotype in vitro and ex vivo. Our findings not only provide a genetic diagnostic marker for oocyte development defects but also expand the spectrum of mitochondrial disorders to female infertility and contribute to unique insights into the role of ferroptosis in human oocyte defects. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can novel genetic factors contributing to early embryonic arrest in infertile patients be identified, along with the underlying mechanisms of the pathogenic variant? SUMMARY ANSWER We identified a heterozygous variant in the SPRY4 (sprouty RTK signaling antagonist 4) in infertile patients and conducted in vitro and in vivo studies to investigate the effects of the variant/deletion, highlighting its critical role in female reproductive health. WHAT IS KNOWN ALREADY SPRY4 acts as a negative regulator of receptor tyrosine kinases (RTKs) and functions as a tumor suppressor. Its abnormal expression can lead to recurrent miscarriage by affecting trophoblast function. In mice, Spry4 knockout (KO) leads to craniofacial anomalies and growth defects. A human study links the SPRY4 variant to a male patient with isolated hypogonadotropic hypogonadism (IHH), hypothetically impacting gonadotropin-releasing hormone (GnRH) neurons, and causing reproductive dysfunctions. SPRY4 is thus potentially integral in regulating endocrine homeostasis and reproductive function. To date, no study has reported SPRY4 variants associated with female fertility, and a causal relationship has not been established with functional evidence. STUDY DESIGN, SIZE, DURATION Whole-exome sequencing (WES) was performed in 392 infertile women who suffered from primary infertility of unknown reason, and the heterozygous SPRY4 variant were identified in one independent family. The infertile patients presenting were recruited from July 2017 to November 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS Women diagnosed with primary infertility were recruited from the Reproduction Center of Zhongshan Hospital, Fudan University. Genomic DNA was extracted from peripheral blood for WES analysis. The SPRY4 variant were identified through WES, in silico analysis, and variant screening. All variants were confirmed by Sanger sequencing. The effects of the variants were investigated in human embryonic kidney (HEK) 293T (HEK293T) cells via western blotting, and in mouse oocytes and embryos through complementary RNA (cRNA) injection, RNA sequencing, fluorescence, absorbance, and RT-qPCR assays. Gene function was further examined in Spry4 KO mice via histology, western blotting, ELISA, and RT-qPCR assays. MAIN RESULTS AND THE ROLE OF CHANCE We identified a missense heterozygous pathogenic variant in SPRY4 (GRCh38, GenBank: NM_030964.5 , c.157C>T p.(Arg53Trp), rs200531302) that reduces SPRY4 protein levels in HEK293T cells and disrupts the redox system and mitochondrial function in mouse oocyte, and perturbs developmental potential in mouse embryos. These phenotypes could be partially reversed by the exogenous addition of Nrf1 cRNA. Additionally, Spry4−/ − mice exhibit ovarian oxidative stress and decreased ovarian function. LIMITATIONS, REASONS FOR CAUTION Due to the limited WES data and population, we identified only one family with a SPRY4 mutation. The deeper mechanism and therapeutic strategy should be further investigated through mutant mice and recovery experiment. WIDER IMPLICATIONS OF THE FINDINGS Our study has identified a pathogenic variant in SPRY4 associated with early embryonic arrest in humans. These findings enhance our understanding of the role of SPRY4 in early embryonic development and present a new genetic marker for female infertility. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (82071643 and 82171655) and Natural Science Foundation of Shanghai (22ZR1456200). None of the authors have any competing interests. TRIAL REGISTRATION NUMBER N/A [ABSTRACT FROM AUTHOR]

• In this study, the medicinal herbs with inductive effects on female reproductive system and their potential mechanisms of action are reviewed. • The clinical trials on the effects of herbal extracts on female reproduction system are also reviewed. • The need for conducting more scientific studies on the herbal extracts and standardization for development new supplements is discussed. Infertility is one of the significant global issues that affects approximately 15–17 % of couples worldwide, with around 50 % of cases being attributed to female infertility factors. The exploration of herbal extracts and their effects on female infertility has been limited, particularly regarding the underlying mechanisms beyond hormonal and oxidative stress influences. In this study, the herbal medicines with potential effects such as antioxidative properties, enhancement of insulin sensitivity, and modulation of the hypothalamic–pituitary–gonadal axis have been reviewed. Several herbal extracts were found to exhibit significant antioxidant properties and demonstrate phytoestrogenic effects on reproductive factors and hormonal levels. Antioxidants are essential in mitigating oxidative stress by neutralizing free radicals, which in turn helps to lower insulin resistance, total cholesterol, fat accumulation, and the proliferation of cancerous cells. Furthermore, this review highlights that certain parts of specific plants are rich in polyphenolic compounds, including isoflavones and flavonoids, along with other advantageous substances that support women's reproductive health. These compounds not only modulate female endocrine systems but also alleviate menopausal symptoms and effectively address a range of reproductive disorders, such as polycystic ovary syndrome (PCOS), premature ovarian failure (POF), endometriosis, hyperprolactinemia, and hypothalamic dysfunction. Turning to the other side, the plants and herbal extracts with suppressive effects on female fertility have been reviewed. These findings indicated that herbal extracts could be exploited to develop natural products as supplements for supporting the female reproductive system. [ABSTRACT FROM AUTHOR]

Purpose: To investigate live birth rate (LBR) and cumulative live birth rate (CLBR) to achieve the first newborn per blastocyst transferred and oocyte retrieved in the first complete IVF cycle of autologous and donated oocytes and identify the possible success factors. Methods: This was a retrospective cohort study of a private IVF center. There were 1867 cycles, 1241 of which were fresh transfers and 626, their subsequent thawing transfers. Results: We found significant variables by binary logistic regression. For LBR, female infertility and the day of blastocyst transferred were relevant; however, for CLBR, the numbers of blastocysts available for future transfers, oocyte age, and maternal age were more critical. Oocyte age is a negative factor that begins to affect CLBR gradually beyond 36 years; from that age, there are significant worse results in polycystic ovary syndrome and poor responder patients. Conclusion: The LBR and CLBR were optimized for oocyte recipients when eight oocytes were retrieved (63.6%; 87.9%); at most, fourteen oocytes should be assigned to avoid freezing surplus blastocysts. Thirteen autologous oocytes (69.2%; 92.3%) were ideal for optimization. CLBR optimized after three blastocysts in donor oocytes (81.8%) and four for autologous oocyte patients (80.9%). Our outcomes are valuable for doctors and infertile couples, and they give us information on what we can expect from a first complete IVF cycle. [ABSTRACT FROM AUTHOR]

Errors during female meiosis lead to embryonic aneuploidy and miscarriage and occur with increasing frequency during aging. The underlying molecular changes that drive female meiotic instability remain a subject of debate. Developing oocytes undergo a tremendous increase in cytoplasmic volume over several months of follicle development and rely on long-lived mRNAs and ribosomes accumulated during this growth phase for subsequent meiotic maturation. In this point of view article, we discuss how the unique reliance on stores of long-lived mRNAs and ribosomes may represent an Achilles' heel for oocyte function and how alterations that reduce the translational capacity of oocytes could be a factor significantly contributing to female infertility. Understanding these mechanisms could lead to new therapeutic strategies to improve fertility outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Female infertility is a global issue that impacts on public health seriously and many mental disorders are observed in infertility groups. Methods: To investigate the casual relationship between those, genome-wide association studies summary data of anxiety disorder (n=9,897), broad depression (n=322,580), major depressive disorder (n=480,359 and n=500,199), bipolar disorder (n=51,710), insomnia (n= 462,341), and female infertility (n=126,342) were extracted from the existing datasets and was analyzed through the two-sample mendelian randomization study. The following heterogeneity and sensitivity test were applied to ensure the robustness of results. Results: Based on inverse variance weighted results, major depressive disorder was associated with female infertility (P = 0.0001, odds ratio 1.396, 95 % confidence interval 1.175-1.658). No causal relationship was identified between the other four mental disorders and infertility. was found. Additionally, reverse mendelian randomization did not indicate a causal relationship among these disorders. Discussion: The early identification and management of anxiety symptoms in women of reproductive age, in conjunction with the effective treatment of major depressive disorder, may be crucial for preserving female fertility. [ABSTRACT FROM AUTHOR]

Objectives: Thyroid dysfunction is commonly associated with the risk of infertility in both females and males. However, recent randomized controlled trials have demonstrated that thyroid function levels in females are not significantly related to infertility, and evidence on the association between male thyroid function and infertility is limited. We aim to investigate the association between thyroid function levels and infertility in both females and males. Method: A two-sample Mendelian randomization study was conducted using four methods, with the inverse variance weighted method (IVW) as the primary approach. Data on thyroid function as the exposure were obtained from the ThyroidOmics Consortium and UK Biobank, including over 700,000 individuals from a large meta-analysis of genome-wide association studies for thyroid function and dysfunction. The outcome data for infertility in both sex encompassed more than 70,000 individuals from the FinnGen Consortium. All participants were adults of European ancestry. The MR Egger regression intercept and Cochran's Q test were employed to evaluate directional pleiotropy and heterogeneity. Results: The results indicated no causal effect of thyroid-stimulating hormone (TSH) and free tetraiodothyronine (fT4) on female and male infertility. Furthermore, no causal association between hypo- and hyperthyroidism and infertility were identified. Notably, we observed a causal relationship between high TSH and endometriosis-related infertility (OR=0.82, 95% CI: 0.74-0.91, P = 1.49E-04). Conclusions: This study did not find evidence for casual relationship between thyroid function levels and risk of infertility. The findings suggest that overall thyroid function levels may not be a significant predictor of infertility risk. [ABSTRACT FROM AUTHOR]

Endometritis is mostly caused by childbirth or postpartum uterine infection. It is one of the important reasons leading to female infertility. Caffeic acid (CA) and its derivatives are widely found in some foods and traditional Chinese medicine, and have biological activities such as antioxidant, free radical scavenging, anti‐inflammatory, and anti‐infection. In this study, we aimed to explore the effect of CA on Staphylococcus aureus‐induced endometritis. The contents of TNF‐α and IL‐1β were detected by ELISA in S. aureus‐induced endometritis model. Western blot assay was used to detect the expression of AMPKα/mTOR/HIF‐1α pathway related proteins and GPX4 expression. In addition, the concentrations of MDA, GSH, and iron were tested by the assay kits. Compared with the model group, CA treatment significantly alleviated S. aureus‐induced uterine injury, MPO activity, the contents of inflammatory factors TNF‐α and IL‐1β, and NF‐κB activation. Meanwhile, CA significantly inhibited S. aureus‐induced ferroptosis, as confirmed by decreased MDA and iron concentration and up‐regulated GPX4 expression and GSH level. Furthermore, CA attenuated S. aureus‐induced HIF‐1α and phosphorylated mTOR expression and increased phosphorylated AMPK expression. In conclusion, CA inhibits inflammation and ferroptosis by regulating AMPKα/mTOR/HIF‐1α signalling pathway to alleviate S. aureus‐induced endometritis in mice. [ABSTRACT FROM AUTHOR]

ABSTRACT Empty follicle syndrome (EFS) is a disorder characterised by the unsuccessful retrieval of oocytes from matured follicles following ovarian stimulation for in vitro fertilisation (IVF). Genetic factors significantly contribute to this pathology. To date, an increasing number of genetic mutations associated with GEFS have been documented, however, some cases still remain unexplained by these previously reported mutations. Here, we identified a novel homozygous missense ZP1 variant (c.1096 C > T, p.Arg366Trp) in a female patient with GEFS from a consanguineous family who failed to retrieve any oocytes during two cycles of IVF treatment. We conducted a molecular dynamics simulation analysis on the mutant ZP1 model, revealing that the mutant ZP1 protein has an altered 3D structure, lower fluctuation, higher compactness and higher instability than wild‐type ZP1. Immunostaining, immunoblotting and co‐immunoprecipitation results showed that the homozygous missense mutation in ZP1 impaired protein secretion and weakened interactions between ZP1 and other ZP proteins, which may affect the ZP assembly. This study contributes to a more comprehensive understanding of the genetic aetiopathogenesis of GEFS. [ABSTRACT FROM AUTHOR]

Purpose: As a cause of primary female infertility, oocyte maturation arrest (OMA) is characterized by failure to obtain mature oocytes due to abnormal meiosis. We aimed to identify pathogenic variants in two sisters with OMA phenotype from a non-consanguineous family. Methods: Whole-exome sequencing and Sanger sequencing were conducted to identify and validate the disease-causing gene variant. Additionally, we performed a minigene assay, quantitative reverse transcription PCR, and Western blotting to assess the effects of the variant. Results: We identified a novel homozygous splicing variant (c.1021-11T>C) in TRIP13, which followed a recessive inheritance pattern. Minigene assay showed that the variant could disrupt the integrity of TRIP13 mRNA, as evidenced by the production of an alternative transcript with intron10 intermediate retention of 79 bp. Compared to normal controls, the expression of TRIP13 mRNA and abundance of TRIP13 protein were also significantly decreased in Epstein-Barr virus-immortalized lymphoblastoid cells derived from affected individuals. Conclusion: Our findings confirm the contribution of genetic factors to OMA and expand the mutation spectrum of TRIP13 in female infertility. [ABSTRACT FROM AUTHOR]

Endometriosis and hyperprolactinaemia are conditions that might lead to infertility as a consequence. The aim of this article was to present the current knowledge about possible relationships between prolactin/hyperprolactinaemia and endometriosis-related infertility. Experimental studies on local prolactin acting as cytokine and relationship of prolactin and endometriotic tissue, as well as clinical studies on hyperprolactinaemia and endometriosis-related infertility suggest the possible role of prolactin in endometriosis-related infertility, but final proof is still missing and the exact pathogenesis of infertility in such cases is still under investigation. Novel strategies in the treatment of endometriosis-related infertility, based on its connection with prolactin such as the use of prolactin receptor antibodies and prolactin receptor antagonists, are under investigation, but adequate clinical studies have yet to be undertaken. [ABSTRACT FROM AUTHOR]

Objective: Adenomyosis is associated with female infertility worldwide. With improvements in imaging methods, such as pelvic magnetic resonance imaging, the diagnosis and treatment of adenomyosis have changed. This study aimed to evaluate the overall prevalence, incidence, and treatment trends of adenomyosis in South Korea using data from the Korean National Health Insurance Service Database (NHIS). Methods: Data were collected from the Korean NHIS, a population‐based complete enumeration database. A total of 678 641 women aged 11–55 years diagnosed with adenomyosis (N80.0 ICD‐10 code) from the database from 2002 to 2016 were enrolled. After applying a one‐year look‐back method, 629 592 patients were analyzed to estimate the prevalence, incidence, and treatment trends of adenomyosis. Results: The overall prevalence during the study period was 3.86 per 1000 people. The prevalence of adenomyosis has increased from 1.42 per 1000 individuals in 2002 to 7.50 per 1000 individuals in 2016. The crude annual incidence rate of adenomyosis was 1.62 per 1000 people in 2003, which increased to 4.12 per 1000 people in 2016. In addition, the proportion of uterus‐preserving surgeries in adenomyosis treatments has increased from 7.51% to 21.29% over 15 years. Conclusion: The prevalence and incidence of adenomyosis in South Korea increased between 2002 and 2016. Furthermore, the proportion of uterus‐preserving surgeries and progestin prescriptions for adenomyosis treatment has increased. We expect that our findings will raise awareness of the necessity for fertility preservation through earlier diagnosis and proper management of patients with adenomyosis. Synopsis: The prevalence and incidence of adenomyosis in South Korea increased between 2002 and 2016. The proportion of uterus‐preserving adenomyosis treatments has increased over the last 15 years. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the pregnancy process, especially the Familial Mediterranean fever (FMF) disease course and attack types during pregnancy, and to examine the relationship between disease-related factors and female infertility in FMF patients. The study, which was planned in a multicenter national network, included 643 female patients. 435 female patients who had regular sexual intercourse were questioned in terms of infertility. Pregnancy and delivery history, FMF disease severity and course during pregnancy were evaluated. The relationship between demographic and clinical findings, disease severity, genetic analysis results and infertility was investigated. 401 patients had at least 1 pregnancy and 34 patients were diagnosed with infertility. 154 patients had an attack during pregnancy. 61.6% of them reported that attacks during pregnancy were similar to those when they were not pregnant. The most common attack symptoms were fever, fatigue and abdominal pain-peritonitis (96%, 87%, and 83%, respectively) in the pregnancy period. The disease-onset age, disease activity score, gene mutation analyses, and regular colchicine use (> 90%) were similar between the fertile and infertile groups, while the frequency of previous appendectomy and alcohol consumption rates were higher in individuals with infertility. Our results indicated no significant change in the frequency and severity of attacks during pregnancy. The low rate of infertility (7.8%) in our patients was noted. It has been suggested that the risk of FMF-related infertility may not be as high as thought in patients who are followed up regularly and received colchicine. [ABSTRACT FROM AUTHOR]

Introduction: Obesity has previously been correlated with an elevated risk of reproductive system diseases in women. The waist-hip ratio (WHR) has been shown to be correlated with visceral fat, making it one of the most commonly used indicators of abdominal obesity. However, little is known about the relationship between WHR and infertility. Therefore, the aim of this study was to evaluate the effect of the WHR on infertility in women of childbearing age. Methods: The study used cross-sectional data from women aged 20–45 who participated in the National Health and Nutrition Examination Survey (NHANES), which was conducted between 2017 and 2020. We collected details of their waist circumference, hip circumference, fertility status, and several other essential variables. We used multivariate logistic regression analysis and subgroup analyses to assess the association between WHR and infertility. Results: There were 976 participants, with 12.0% (117/976) who experienced infertility. After adjusting for potential confounding factors, our multivariate logistic regression analysis revealed that every 0.1 unit increase in WHR resulted in a more than 35% higher risk of infertility (odds ratio [OR; 95% confidence interval [CI]: 1.35 [1.01∼1.81], p = 0.043). Compared to the group with WHR <0.85, the risk of infertility increased in the group with WHR ≥0.85, with an adjusted OR of 1.74 (95% CI: 1.06∼2.85). When WHR was treated as a continuous variable, it was observed that each 0.1 unit increase in WHR was associated with a relatively high risk in the secondary infertility population after adjusting all covariates, with an OR of 1.66 (95% CI: 1.14∼2.40, p = 0.01). When WHR was analyzed as a categorical variable, the group with WHR ≥0.85 exhibited a significantly higher risk of secondary infertility than the group with WHR <0.85, with the OR of 2.75 (95% CI: 1.35–5.59, p = 0.01) after adjusting for all covariates. Furthermore, the interaction analysis indicated that there was a significant interaction between age status on WHR and the risk of infertility. Conclusion: WHR showed a positive correlation with the risk of infertility. This study highlights the importance of effectively managing abdominal fat and promoting the maintenance of optimal WHR levels to mitigate the progression of infertility, particularly for younger women. [ABSTRACT FROM AUTHOR]

Background/Objective: This study aimed to investigate the causal relationship between urate level and female infertility using Mendelian randomization (MR) analysis. Methods: To identify instrumental variables, we selected independent genetic loci associated with serum urate levels in individuals of European ancestry, utilizing data from large-scale genome-wide association studies (GWAS). The GWAS dataset included information on serum urate levels from 288,649 CKDGen participants. Female infertility data, including different etiologic classifications, consisted of 13,142 female infertility patients and 107,564 controls. We employed four MR methods, namely inverse variance weighted (IVW), MR-Egger, weighted median, and weighted model, to investigate the causal relationship between urate levels and female infertility. The Cochran Q-test was used to assess heterogeneity among single nucleotide polymorphisms (SNPs), and the MR-Egger intercept test was employed to evaluate the presence of horizontal pleiotropy. Additionally, a "leave-one-out" sensitivity analysis was conducted to examine the influence of individual SNPs on the MR study. Results: The IVW analysis demonstrated that elevated serum urate levels increased the risk of female infertility (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07–1.33). Furthermore, serum urate levels were found to be associated with infertility due to cervical, vaginal, or other unknown causes (OR = 1.16, 95% CI: 1.06–1.26), also confirmed by other methods. Heterogeneity among instrumental variables was assessed using Cochran's Q-test (p < 0.05), so a random-effects IVW approach was employed in the effects model. The MR-Egger intercept test indicated no presence of horizontal pleiotropy. A "leave-one-out" sensitivity analysis was conducted, demonstrating that no individual SNP had a substantial impact on the overall findings. Conclusions: In the European population, the urate level is significantly and causally associated with an increased risk of female infertility. [ABSTRACT FROM AUTHOR]

Repro57 mice, induced with N-ethyl-N-nitrosourea and harboring a mutation in the Rnf212 gene, exhibit infertility in both homozygous mutant males and females. Rnf212 plays a crucial role in recombination and crossover designation. In male repro57 homozygous mutants, spermatocytes often degenerate during late prophase, and mature spermatozoa are absent in the seminiferous epithelium, indicating arrested spermatogenesis as the cause of infertility. Despite reports of infertility in Rnf212-knockout female mice, the specific mechanisms underlying infertility in female repro57 homozygous mutants remain elusive. This study investigates the chromosomal and kinetochore patterns of mature oocytes and their developmental potential following in vitro fertilization in female repro57 homozygous mutant mice. While all wild-type oocytes progress to metaphase II and exhibit euploidy, all repro57 homozygous mutant mouse oocytes display aneuploidy. Additionally, kinetochore distances in repro57 homozygous mutant oocytes exceed those observed in wild-type counterparts. Although no significant differences are noted in fertilization and early embryo development rates between wild-type and repro57 homozygous mutant mice, embryos derived from repro57 homozygous mutants exhibit significantly lower morula and blastocyst rates, accompanied by frequent cytokinesis failure and vacuole formation. These findings suggest that the premature segregation of sister chromatids in repro57 homozygous mutant mice adversely impacts the later stages of embryo development. [ABSTRACT FROM AUTHOR]

The composite dietary antioxidant index (CDAI) serves as a valuable instrument for evaluating the intake of dietary antioxidants. This research aims to clarify the connection between CDAI and the risk of female infertility by analyzing data from the National Health and Nutrition Examination Survey from 2013 to 2018. Participants underwent two 24-h dietary recall interviews to calculate CDAI. Female infertility was determined through two questionnaires. Logistic regression model, restricted cubic spline and subgroup analysis were employed to examine the association between CDAI and female infertility. The study encompassed 2162 participants. Participants with female infertility had lower CDAI levels compared to those without. Following adjustment for confounding variables, a negative association between CDAI levels and female infertility was observed (Q4 vs. Q1, OR [95% CI] 0.392 [0.193, 0.795], P = 0.016). RCS demonstrated a statistically significant linear negative relationship between CDAI and female infertility. Subgroup analysis showed no significant interaction. This study illustrates a negative link between the CDAI and female infertility, indicating that higher consumption of dietary antioxidants may be associated with a reduced risk of female infertility. Additional rigorously designed prospective studies are necessary to validate these results. [ABSTRACT FROM AUTHOR]

Background: Glehnia littoralis F. Schmidt ex Miq., an endangered plant species with significant medicinal, edible, and ecological value, is now a central concern for conservation and sustainable utilization. Investigating the physiological and ecological mechanisms leading to its endangerment and elucidating its genetic background constitutes the foundation for conducting in-depth research on G. littoralis. Results: Our observations have revealed a significant degree of floral sterility in wild populations of G. littoralis. The inflorescences of G. littoralis are classified into three types: completely fertile, completely sterile, and partially fertile compound umbels. Moreover, the flowers of G. littoralis can be categorized into fertile and sterile types. Sterile flowers exhibited abnormalities in the stigma, ovary, and ovules. This study is the first to discover that the presence or absence of a giant cell at the funiculus during the initiation of ovule primordium determines whether the flower can develop normally, providing cytological evidence for female sterility in G. littoralis. Conversely, both fertile and sterile flowers produced normally developed pollen. Field observations have suggested that robust plants bear more fertile umbels, while weaker ones have fewer or even no fertile umbels, indicating a close relationship between flower fertility and plant nutritional status. Our model correctly predicted that the eastern coastal regions of China, as well as prospective areas in Neimenggu and Sichuan, are suitable environments for its cultivation. Additionally, Using flow cytometry and genome survey, we estimated the genome size of G. littoralis to be 3.06 Gb and the heterozygosity to be 4.58%. Conclusion: The observations and findings presented in this study were expected to provide valuable insights for further conserving its genetic resources and sustainable utilization of G. littoralis. [ABSTRACT FROM AUTHOR]

Background: Obesity stands as an essential factor contributing to infertility in women. Early identification of obese individuals leads to favorable results for female infertility. The objective of this research is to assess the association between the age-adjusted visceral adiposity index (AVAI) and female infertility. Methods: This study was conducted using NHANES data from 2013 to 2018, in which 1,231 women aged 20–45 were selected. Infertility was defined by survey questions. AVAI was calculated using anthropometric and serum data. Covariates included demographics and lifestyle factors. Statistical analysis with R, adjusting for covariates, and assessing nonlinearity and cutoff effects. Results: The study of 1,231 women from the NHANES database revealed that 11.94% were diagnosed with infertility. Individuals with higher AVAI scores showed increased age, WC, BMI, and reduced HDL levels, with a positive correlation between AVAI and female infertility (OR = 1.42, 95%CI: 1.26–1.60). AVAI quartiles showed a pronounced relationship with female infertility risk, with the highest quartile showing the greatest risk(OR = 9.35,95% CI: 2.96–29.55). Nonlinear and threshold effects in the relationship between AVAI and female infertility were identified, with an inflection point at -9.70. Subgroup analyses indicated significant interactions between AVAI and educational status and BMI, particularly in women with a BMI below 25 kg/m2, where a high AVAI level was closely related to increased infertility risk(OR = 1.92, 95%CI: 1.44–2.58). Conclusion: The study identifies a strong association between elevated AVAI scores and female infertility risk, especially in women with a BMI under 25 kg/m2. This suggests that AVAI could be a valuable predictor in female fertility assessments. [ABSTRACT FROM AUTHOR]

CRISPR base editors can introduce point mutations into DNA precisely, and cytosine base editors (CBEs) catalyze C to T transitions. While CBEs have been thoroughly explored in cell culture and organisms such as mice, little is known about DNA base editing in insects. In this study, we evaluated germline editing rates of three different CBEs expressed under actin (ubiquitous) or nanos (germline) promoters utilizing Drosophila melanogaster. The original Rattus norvegicus-derived cytosine deaminase APOBEC1 (rAPO-1) displayed high base editing rates (~99%) with undetectable indel formation. Additionally, we show that base editors can be used for generating male sterility and female lethality. Overall, this study highlights the importance of promoter choice and sex-specific transmission for efficient base editing in flies while providing new insights for future genetic biocontrol designs in insects. Testing three types of cytosine base editors in fruit flies demonstrates the potential usage of these base editors in genetic biocontrol strategies, with the rAPO-1 achieving high editing efficiency (~99%) with no detectable INDEL mutations. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides in cells and is closely related to various diseases. Female infertility is a global health concern, which is associated with a variety of factors. The etiology remains unknown in many women with infertility. With further investigation into the pathogenesis of infertility, a growing number of studies have demonstrated the close connections between infertility and ferroptosis. Through a literature review, it is found that ferroptosis is closely involved in endometriosis- and polycystic ovarian syndrome (PCOS)-associated infertility and tubal factor infertility. Iron overload increases the resistance to ferroptosis, and ferroptosis in some cells accelerates endometrial lesion growth. Moreover, iron overload may be hazardous to oocytes. This review may shed some light on the diagnosis and treatment of female infertility. [ABSTRACT FROM AUTHOR]

Background: The use of antioxidant-rich foods to treat female infertility has received significant attention in recent years. The aim of this study was to investigate the potential correlation between the composite dietary antioxidant index (CDAI) and female infertility. Methods: The participants in the cross-sectional data were women between the ages of 20 and 45 who had complete CDAI-related data and infertility information, which were taken from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2020. The independent association between CDAI and infertility was investigated using multivariate logistic regression analysis. Trends between the two variables were examined using smoothed curve fitting, and subgroup analysis and interaction tests were conducted. Results: The prevalence of infertility was 12.57% of the 3,259 participants included in the study; individuals in higher CDAI quartiles tended to have a lower percentage of infertility. The risk of infertility was 44% lower among individuals in the highest quartile of the CDAI compared to those in the lowest quartile (OR = 0.56, 95%CI: 0.36–0.85, P = 0.0072), and the test for trend was also significant (P for trend = 0.0235). Smoothed curve fitting showed a negative non-linear relationship between CDAI and infertility. Subgroup analysis and interaction tests showed that there was an interaction of BMI in the relationship between CDAI and infertility risk (P for interaction = 0.0497) and that education, PIR, marital status, smoking status, hypertension, diabetes, age at menarche, ever having been treated for pelvic infection, ever having used female hormones, and ever been pregnant had no significant dependence on this negative association (all P for interaction > 0.05). Conclusion: There was a negative non-linear correlation between CDAI and infertility among reproductive-aged women in the US. The risk of infertility may be reduced by increasing the intake of antioxidant-rich foods. [ABSTRACT FROM AUTHOR]

Pannexin1 (PANX1) is a highly glycosylated membrane channel-forming protein, which has been found to implicate in multiple physiological and pathophysiological functions. Variants in the PANX1 gene have been reported to be associated with oocyte death and recurrent in vitro fertilization failure. In this study, we identified a novel heterozygous PANX1 variant (NM_015368.4 c.410 C > T (p.Ser137Leu)) associated with the phenotype of oocyte death in a non-consanguineous family, followed by an autosomal dominant (AD) mode. We explored the molecular mechanism of the novel variant and the variant c.976_978del (p.Asn326del) that we reported previously. Both of the variants altered the PANX1 glycosylation pattern in cultured cells, led to aberrant PANX1 channel activation, affected ATP release and membrane electrophysiological properties, which resulted in mouse and human oocyte death in vitro. For the first time, we presented the direct evidence of the effect of the PANX1 variants on human oocyte development. Our findings expand the variant spectrum of PANX1 genes associated with oocyte death and provide new support for the genetic diagnosis of female infertility. [ABSTRACT FROM AUTHOR]

In social life and global health, infertility is common. History of abdominal surgery, body mass index (BMI), endometriosis, menstrual history, and polycystic ovarian syndrome (PCOS) have not been fully explained as female infertility factors. This study examined infertility causes at ASHA in vitro fertilization Primasatya Husada Citra (PHC) Hospital Surabaya. This quantitative study was cross-sectional. In May-July 2023, 82 childbearing-age women with infertility issues visited the hospital and completed questionnaires. Description and analysis were performed using the Wilcoxon rank test to evaluate menstrual history, BMI, PCOS, endometriosis, and abdominal surgery history in relation to infertility. Infertility was statistically associated with abdominal surgery history (P=0.008), BMI (P=0.000), endometriosis diagnosis (P=0.000), and PCOS (P=0.000). Women with abdominal surgery, endometriosis, and PCOS had significant infertility. Women's infertility can be caused by ovulation disorders, tubal and pelvic disorders, or uterine disorders, but one-third of cases are unexplained. Infertility treatment may benefit from addressing abdominal surgery history, BMI, endometriosis, and PCOS. Early intervention and targeted care based on these determinants may improve fertility outcomes and reduce unexplained infertility. [ABSTRACT FROM AUTHOR]

Adult-onset cases of idiopathic hypogonadotropic hypogonadism (IHH) are characterized by partial or normal puberty development until adolescence and by the impairment of the hypothalamic–pituitary–gonadal (HPG) axis in adulthood. WDR11 and DCC genes are known to be involved in axonal development, particularly of hypothalamic GnRH neurons, and ciliogenesis. We report a female case of adult-onset hypogonadism and cerebellar ataxia, in which we identified two gene mutations. A panel of 48 genes was set up to search for variants in the causative genes of CHH. The variants found were analyzed following the American College of Medical Genetics and Genomics (ACMG) criteria to define their pathogenicity. We identified a missense heterozygous variant in the WDR11 gene NM_018117.12:c.2306T>G (p.Met769Arg) and a mutation in a second gene DCC resulting in amino acid substitutions NM_005215.4:c.3533C>T (p.Ser1178Phe). These variants were classified as being of uncertain clinical significance. We assume that there is a link between the variants found and the impairment of the gonadotrophic and neurological phenotype of the patient. Therefore, we propose the genetic test to identify the best therapeutic approach to identify infertility in female patients with IHH; we believe it is necessary to test WDR11 and DCC genes in larger populations with the same condition to introduce it in future protocols of assessment. [ABSTRACT FROM AUTHOR]

Icariin (ICA), one of the main active components of Herba Epimedii, is a natural prenylated flavonol glycoside that possesses a wide range of pharmacological effects, including antioxidant, antiosteoporotic, anti-aging, neuroprotective, immunomodulatory, antitumor, and aphrodisiac effects, and prevents numerous health disorders, such as cardiovascular diseases, osteoporosis, cancer, sexual dysfunction, menstrual disorders, neurodegenerative diseases, asthma, chronic inflammation, and diabetes. In the reproductive system, it has been observed that ICA may play a role in preserving fertility by regulating different signalling pathways, such as PI3K/AKT, which improves ovarian function, and ERα/Nrf2, which enhances testicular function and prevents ROS generation. In contrast, regulating the NF/kB signalling pathway causes anti-inflammatory effects, reducing spontaneous abortions. In this study, we review and examine the relevant literature on the therapeutic potential of ICA in reproduction, highlight the various mechanisms of action and limitations for the therapeutic applications of ICA, and summarise and highlight the existing preclinical research on its effects on male and female reproduction. [ABSTRACT FROM AUTHOR]

Objective: Infertility has emerged as a significant global public health concern, with a multitude of complex underlying causes. Epidemiological evidence indicates that immunological factors are significant contributors to the aetiology of infertility. However, previous studies on the relationship between immune inflammation and infertility have yielded inconclusive results. Methods: Mendelian randomisation (MR) is an emerging statistical method that employs exposure‐related genetic variation as an instrumental variable (IV) to infer causal relationships between immune cells and infertility by modelling the principle of random assignment in Mendelian genetics. In this study, MR was employed to assess the causal relationship between 731 immune cell signatures and infertility. The data utilized in this study were obtained from publicly available genome‐wide association studies (GWAS) and validated IVs, which were employed to fulfil the essential assumptions of MR analysis. Results: The Mendelian randomisation analysis revealed a total of 27 statistically significant immune cell phenotypes out of 731. The risk factor with the largest odds ratio (OR) was CD28− CD25++ CD8+ %T cell [OR, 1.21; 95% confidence interval (CI), 1.04–1.42], while the protective factor with the largest OR was activated and resting Treg AC (OR, 0.89; 95% CI, 0.82–0.97). Conclusion: The present study has demonstrated a correlation between certain characteristics of immune cells and female infertility. These results provide clues for further research into the immune mechanisms of infertility and may inform the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose: Ovarian aging is closely related to a decrease in follicular reserve and oocyte quality. The precise molecular mechanisms underlying these reductions have yet to be fully elucidated. Herein, we examine spatiotemporal distribution of key proteins responsible for DNA double-strand break (DSB) repair in ovaries from early to older ages. Functional studies have shown that the γH2AX, RAD51, BRCA1, and RPA70 proteins play indispensable roles in HR-based repair pathway, while the KU80 and XRCC4 proteins are essential for successfully operating cNHEJ pathway. Methods: Female Balb/C mice were divided into five groups as follows: Prepuberty (3 weeks old; n = 6), puberty (7 weeks old; n = 7), postpuberty (18 weeks old; n = 7), early aged (52 weeks old; n = 7), and late aged (60 weeks old; n = 7). The expression of DSB repair proteins, cellular senescence (β-GAL) and apoptosis (cCASP3) markers was evaluated in the ovaries using immunohistochemistry. Result: β-GAL and cCASP3 levels progressively increased from prepuberty to aged groups (P < 0.05). Notably, γH2AX levels varied in preantral and antral follicles among the groups (P < 0.05). In aged groups, RAD51, BRCA1, KU80, and XRCC4 levels increased (P < 0.05), while RPA70 levels decreased (P < 0.05) compared to the other groups. Conclusions: The observed alterations were primarily attributed to altered expression in oocytes and granulosa cells of the follicles and other ovarian cells. As a result, the findings indicate that these DSB repair proteins may play a role in the repair processes and even other related cellular events in ovarian cells from early to older ages. [ABSTRACT FROM AUTHOR]

Female infertility affects a significant portion of the population, and recent studies suggest a potential link between glycemic control and reproductive health. This study investigates the association between serum glycated hemoglobin (HbA1c) levels and female infertility, utilizing data from the NHANES 2017–2020 and Mendelian randomization (MR) analysis. A cross-sectional study was conducted with 1578 women aged 20–45 who attempted pregnancy for at least one year. Serum HbA1c levels were analyzed in relation to infertility status, with multivariable logistic regression models adjusting for covariates such as age, body mass index, race/ethnicity, education, marital status, hypertension, and hyperlipidemia. Higher HbA1c levels were significantly associated with increased infertility risk. Each 1% increase in HbA1c was linked to higher odds of infertility (adjusted OR: 1.40, 95% CI: 1.15–1.69, p = 0.003). HbA1c levels ≥ 6.5% showed the strongest association. MR analysis employed single-nucleotide polymorphisms as instrumental variables to assess the causal relationship between HbA1c and infertility, confirming a causal relationship between higher genetically predicted HbA1c levels and infertility (OR: 1.82, 95% CI: 1.33–2.49, p = 0.00018). Sensitivity analyses supported the robustness of these findings. Elevated HbA1c levels are associated with an increased risk of female infertility, suggesting the importance of glycemic control in reproductive health management. [ABSTRACT FROM AUTHOR]

Infertility is defined as the inability to conceive within one year of unprotected intercourse, and the causes are equally distributed between both sexes. Genetics play a crucial role in couple infertility and respective diagnostic testing should follow available guidelines. Appropriate tiered genetic analyses require comprehensive physical examination of both partners in an infertile couple. A wide range of chromosomal and monogenic variants can be the underlying genetic cause of infertility in both women and men. Accurate clinical phenotyping, together with identification of the genetic origin, helps to recommend the proper treatment and to counsel couples on the success rates and potential risks for offspring. [ABSTRACT FROM AUTHOR]

Methodological limitations in studying the association between the use of fertility drugs and cancer include the inherent increased risk of cancer in women who never conceive, the increased risk of cancer because of factors (endometriosis and unopposed estrogen) associated with infertility, the low incidence of most of these cancers, and that the diagnosis of cancer is typically several years after fertility drug use. On the basis of available data, there does not appear to be an association between fertility drugs and breast, colon, or cervical cancer. There is no conclusive evidence that fertility drugs increase the risk of uterine cancer, although women with infertility are at higher risk of uterine cancer. There are insufficient data to comment on the risk of melanoma and non-Hodgkin lymphoma associated with fertility drug use. Women should be informed that there may be an increased risk of invasive and borderline ovarian cancers and thyroid cancer associated with fertility treatment. It is difficult to determine whether this risk is related to underlying endometriosis, female infertility, or nulliparity. [ABSTRACT FROM AUTHOR]

Female infertility is a major public health concern, and viral infections have been suggested as a potential cause. The recent emergence of coronaviruses, such as SARS-CoV-2, has raised concerns about their potential impact on female fertility. This systematic review aimed to evaluate the existing literature on the relationship between female infertility and viral diseases, with a particular focus on coronaviruses. A systematic review was conducted using relevant databases, including PubMed, Scopus, Web of Science, and Google Scholar. Studies published between 2009 and 2023 were included. The Critical Appraisal Skills Program (CASP) tool was used to assess the quality of the studies. Data extraction and synthesis was carried out to summarize the findings. 13 studies met the inclusion criteria and were included in the review. The review demonstrated that many type viruses including human papillomavirus (HPV), human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and coronaviruses van affect female reproductive system. Moreover, findings revealed that some viral infections such as HPV and HIV may be associated with female infertility. However, evidence on the effect of coronaviruses on female infertility was limited and inconclusive. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of painless transvaginal four-dimensional hysterosalpingo contrast sonography (TV 4-D HyCoSy) in reducing venous intravasation and its influencing factors through a retrospective comparative study on conventional TV 4-D HyCoSy. Materials and methods: A total of 451 patients were enrolled in this study from Jan. 2019 to Oct. 2021. There were 249 patients in the painless TV 4-D HyCoSy group and 202 patients in the conventional TV 4-D HyCoSy group. The incidence of venous intravasation and its related influencing factors were analyzed and compared between these two groups. The difficulty of image evaluation for the diagnosis was also compared. Results: There was no significant difference in the baseline characteristics between the painless group and the conventional group (p > 0.05). Compared with the conventional group, the painless group had a lower incidence of venous intravasation (16.9 vs. 24.8%; p = 0.039). Painless TV 4-D HyCoSy was more effective in reducing venous intravasation in patients with primary infertility (p = 0.032) without a history of pelvic surgery (p = 0.008) or ectopic pregnancy (p = 0.018). Logistic regression analysis demonstrated that painless TV 4-D HyCoSy and endometrial thickness > 5 mm were protective factors for venous intravasation. Moreover, the diagnostic procedure was easier in the painless group than in the conventional group (p = 0.002). Conclusions: Painless TV 4D-HyCoSy may be an effective mode in reducing the incidence of venous intravasation and improving the diagnosis of patency of fallopian tubes. [ABSTRACT FROM AUTHOR]

Background: Amenorrhea is defined as the cessation of menstruation; it is a significant clinical sign of reproductive dysfunction that affects 1.5-3% of women of childbearing age and is a leading cause of female infertility. The increasing incidence is attributed to better healthcare access and awareness. The Unani system of medicine offers a distinctive perspective on reproductive ailments, yet its terminology and concepts often diverge from modern medical understandings. Research Problem and Aim: This study aims to bridge the gap between classical Unani literature and contemporary medicine by exploring the etiopathogenesis (asbāb wa mahiyatul marazi) of Iβtibḥs al-Tamth (amenorrhea) and comparing it with conventional medical definition, types, causes and its pathogenesis, thereby enhancing understanding of it from both perspectives. Methodology: A systematic review was conducted in 2023, that includes: The primary and main sources of collection of material were from classical published books, manuscripts and their translations. The second type of sources of collection of material were from different types of available published and unpublished literature related to study topic i.e. journals, proceedings, thesis, reports, souvenir, dissertations etc. The third type of sources were from authentic digital material i.e. trusted online websites i.e. PubMed, internet archive etc. Results/Findings: The research revealed a structured understanding of Iḥtibās al-Tamth in Unani literature, highlighting its nuanced classification and etiological factors in comparison to conventional medicine. The findings underscore the potential for integrating Unani insights into contemporary gynaecological practices. Implications: This exploration contributes to a more comprehensive understanding of Iḥtibās al- Tamth (amenorrhea), suggesting that Unani medicine's holistic approach may offer alternative treatment avenues that could mitigate the side effects associated with conventional hormonal therapies. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is known as a chemical gas in nature with both enzymatic and non-enzymatic biosynthesis in different human organs. A couple of studies have demonstrated the function of H2S in regulating the homeostasis of the human body. Additionally, they have shown its synthesis, measurement, chemistry, protective effects, and interaction in various aspects of scientific evidence. Furthermore, many researches have demonstrated the beneficial impacts of H2S on genital organs and systems. According to various studies, it is recognized that H2S-producing enzymes and the endogenous production of H2S are expressed in male and female reproductive systems in different mammalian species. The main goal of this comprehensive review is to assess the potential therapeutic impacts of this gasotransmitter in the male and female urogenital system and find underlying mechanisms of this agent. This narrative review investigated the articles that were published from the 1970s to 2022. The review's primary focus is the impacts of H2S on the male and female urogenital system. Medline, CINAHL, PubMed, and Google scholar databases were searched. Keywords used in this review were "Hydrogen sulfide," "H2S," "urogenital system," and "urogenital tract". Numerous studies have demonstrated the therapeutic and protective effects of sodium hydrosulfide (Na-HS) as an H2S donor on male and female infertility disorders. Furthermore, it has been observed that H2S plays a significant role in improving different diseases such as ameliorating sperm parameters. The specific localization of H2S enzymes in the urogenital system provides an excellent opportunity to comprehend its function and role in various disorders related to this system. It is noteworthy that H2S has been demonstrated to be produced in endocrine organs and exhibit diverse activities. Moreover, it is important to recognize that alterations in H2S biosynthesis are closely linked to endocrine disorders. Therefore, hormones can be pivotal in regulating H2S production, and H2S synthesis pathways may aid in establishing novel therapeutic strategies. H2S possesses pharmacological effects on essential disorders, such as anti-inflammation, anti-apoptosis, and anti-oxidant activities, which render it a valuable therapeutic agent for human urogenital disease. Furthermore, this agent shows promise in ameliorating the detrimental effects of various male and female diseases. Despite the limited clinical research, studies have demonstrated that applying H2S as an anti-oxidant source could ameliorate adverse effects of different conditions in the urogenital system. More clinical studies are required to confirm the role of this component in clinical settings. [ABSTRACT FROM AUTHOR]

Background & Objective: Primary infertility affects a significant proportion of couples and is often attributed to female factors. Obesity, which is associated with increased levels of the hormone leptin, is a known risk factor for female infertility. The present study was conducted with aim to investigate the association between BMI and leptin levels in females with primary infertility. Materials & Methods: This cross-sectional study was performed on 100 women with primary infertility at Al-Nuaman Hospital and Al-Salama private hospital from September 2022 to March 2023. The participants were divided into four groups: Group 1 (normal weight, fertile), Group 2 (overweight infertile), Group 3 (obese infertile), and Group 4 (severely obese infertile) women, each consisting of 25 participants, categorized based on their BMI: normal BMI (18.5-24.9 kg/m²), overweight BMI (25-29.9 kg/m²), obesity BMI (=30 kg/m²), and severely obese BMI (35-40 kg/m²). The mean leptin levels were compared between the four groups using ANOVA, and the association between BMI and leptin levels was assessed using Pearson's correlation coefficient. Results: There was a highly significant correlation between primary infertility and the parameters (BMI and leptin) (P<0.001) and showed a positive correlation between leptin and BMI. Conclusion: It was shown that females with primary infertile and a high BMI have elevated serum leptin levels. This underscores the importance of weight management in addressing primary female infertility. [ABSTRACT FROM AUTHOR]

Cellular aging is considered as one of the main factors implicated in female infertility. We evaluated the expression of senescence-associated secretory phenotype (SASP) markers and additional molecular factors in an in vitro model of cellular aging. We induced genotoxic stress (UVB/UVA ray irradiation) in primary human endometrial cells obtained from female subjects of young reproductive age (<35 years of age). We assessed the expression levels of IL-6, IL-8, IL-1α, MMP3, SIRT-1, SIRT-6, TERF-1, and CALR at the mRNA level by RT-qPCR and at the protein level by immunofluorescence and confocal microscopy in primary human endometrial cells upon induction of genotoxic stress and compared them to untreated cells. Statistically significant differences were found for the expression of SIRT-1, SIRT-6, and TERF, which were found to be decreased upon induction of cell senescence through genotoxic stress, while IL-6, IL-8, IL-1α, MMP3, and p16 were found to be increased in senescent cells. We propose that these molecules, in addition to SAS-linked factors, could represent novel markers, and eventually potential therapeutic targets, for the aging-associated dysfunction of the female reproductive system. [ABSTRACT FROM AUTHOR]

Thyroid issues are common among women in their reproductive years, and women with thyroid dysfunction often encounter challenges with fertility. Arsenic is known for its toxic effects on the thyroid and ovaries, investigated independently. However, there is no known study directly or indirectly addressing the association between arsenic, thyroid function, and ovarian reserve. This study aims to investigate the effect of arsenic on thyroid function and its possible implications on ovarian follicular reserve. Female Balb/c mice were given sodium arsenite (0.2 ppm, 2 ppm, and 20 ppm) via drinking water for 30 days. Findings showed that arsenic decreased thyroid hormone levels (fT3 and fT4) while increasing TSH levels, which might have led to elevated levels of FSH and LH. Furthermore, arsenic treatment not only decreased thyroid follicle sizes but also altered the ovarian follicular count. The finding demonstrates that arsenic significantly reduced the expression of LAMP1, a lysosomal marker protein. This reduction leads to increased lysosomal permeability in the thyroid, resulting in a significant release of cathepsin B. These changes led to hypothyroidism, which might indirectly affect the ovaries. Also, the elevated levels of growth differentiation factor-8 in arsenic-treated ovaries indicate impaired folliculogenesis and ovulation. Furthermore, arsenic significantly increased the expressions of pAkt and pFoxo3a, implying that arsenic accelerated the activation of the primordial follicular pools. In conclusion, arsenic disrupts lysosomal stabilization, potentially leading to a decline in circulating fT3 and fT4 levels. This disturbance could, in turn, affect the estrous cycle and may alter the pattern of follicular development. [ABSTRACT FROM AUTHOR]

Abstract The composite dietary antioxidant index (CDAI) serves as a valuable instrument for evaluating the intake of dietary antioxidants. This research aims to clarify the connection between CDAI and the risk of female infertility by analyzing data from the National Health and Nutrition Examination Survey from 2013 to 2018. Participants underwent two 24-h dietary recall interviews to calculate CDAI. Female infertility was determined through two questionnaires. Logistic regression model, restricted cubic spline and subgroup analysis were employed to examine the association between CDAI and female infertility. The study encompassed 2162 participants. Participants with female infertility had lower CDAI levels compared to those without. Following adjustment for confounding variables, a negative association between CDAI levels and female infertility was observed (Q4 vs. Q1, OR [95% CI] 0.392 [0.193, 0.795], P = 0.016). RCS demonstrated a statistically significant linear negative relationship between CDAI and female infertility. Subgroup analysis showed no significant interaction. This study illustrates a negative link between the CDAI and female infertility, indicating that higher consumption of dietary antioxidants may be associated with a reduced risk of female infertility. Additional rigorously designed prospective studies are necessary to validate these results.

Abstract Background Obesity stands as an essential factor contributing to infertility in women. Early identification of obese individuals leads to favorable results for female infertility. The objective of this research is to assess the association between the age-adjusted visceral adiposity index (AVAI) and female infertility. Methods This study was conducted using NHANES data from 2013 to 2018, in which 1,231 women aged 20–45 were selected. Infertility was defined by survey questions. AVAI was calculated using anthropometric and serum data. Covariates included demographics and lifestyle factors. Statistical analysis with R, adjusting for covariates, and assessing nonlinearity and cutoff effects. Results The study of 1,231 women from the NHANES database revealed that 11.94% were diagnosed with infertility. Individuals with higher AVAI scores showed increased age, WC, BMI, and reduced HDL levels, with a positive correlation between AVAI and female infertility (OR = 1.42, 95%CI: 1.26–1.60). AVAI quartiles showed a pronounced relationship with female infertility risk, with the highest quartile showing the greatest risk(OR = 9.35,95% CI: 2.96–29.55). Nonlinear and threshold effects in the relationship between AVAI and female infertility were identified, with an inflection point at -9.70. Subgroup analyses indicated significant interactions between AVAI and educational status and BMI, particularly in women with a BMI below 25 kg/m2, where a high AVAI level was closely related to increased infertility risk(OR = 1.92, 95%CI: 1.44–2.58). Conclusion The study identifies a strong association between elevated AVAI scores and female infertility risk, especially in women with a BMI under 25 kg/m2. This suggests that AVAI could be a valuable predictor in female fertility assessments.

Abstract Ferroptosis is a novel type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides in cells and is closely related to various diseases. Female infertility is a global health concern, which is associated with a variety of factors. The etiology remains unknown in many women with infertility. With further investigation into the pathogenesis of infertility, a growing number of studies have demonstrated the close connections between infertility and ferroptosis. Through a literature review, it is found that ferroptosis is closely involved in endometriosis- and polycystic ovarian syndrome (PCOS)-associated infertility and tubal factor infertility. Iron overload increases the resistance to ferroptosis, and ferroptosis in some cells accelerates endometrial lesion growth. Moreover, iron overload may be hazardous to oocytes. This review may shed some light on the diagnosis and treatment of female infertility.

Abstract Pannexin1 (PANX1) is a highly glycosylated membrane channel-forming protein, which has been found to implicate in multiple physiological and pathophysiological functions. Variants in the PANX1 gene have been reported to be associated with oocyte death and recurrent in vitro fertilization failure. In this study, we identified a novel heterozygous PANX1 variant (NM_015368.4 c.410 C > T (p.Ser137Leu)) associated with the phenotype of oocyte death in a non-consanguineous family, followed by an autosomal dominant (AD) mode. We explored the molecular mechanism of the novel variant and the variant c.976_978del (p.Asn326del) that we reported previously. Both of the variants altered the PANX1 glycosylation pattern in cultured cells, led to aberrant PANX1 channel activation, affected ATP release and membrane electrophysiological properties, which resulted in mouse and human oocyte death in vitro. For the first time, we presented the direct evidence of the effect of the PANX1 variants on human oocyte development. Our findings expand the variant spectrum of PANX1 genes associated with oocyte death and provide new support for the genetic diagnosis of female infertility.

Abnormal interaction between granulosa cells and oocytes causes disordered development of ovarian follicles. However, the interactions between oocytes and cumulus granulosa cells (CGs), oocytes and mural granulosa cells (MGs), and CGs and MGs remain to be fully explored. Using single-cell RNA-sequencing (scRNA-seq), we determined the transcriptional profiles of oocytes, CGs and MGs in antral follicles. Analysis of scRNA-seq data revealed that CGs may regulate follicular development through the BMP15-KITL-KIT-PI3K-ARF6 pathway with elevated expression of luteinizing hormone receptor (LHR). Because internalization of the LHR is regulated by Arf6, we constructed LHRN316S mice by CRISPR/Cas9 to further explore mechanisms of follicular development and novel treatment strategies for female infertility. Ovaries of LHRN316S mice exhibited reduced numbers of corpora lutea and ovulation. The LHRN316S mice had a reduced rate of oocyte maturation in vitro and decreased serum progesterone levels. Mating LHRN316S female mice with ICR wild type male mice revealed that the infertility rate of LHRN316S mice was 21.4% (3/14). Litter sizes from LHRN316S mice were smaller than those from control wild type female mice. The oocytes from LHRN316S mice had an increased rate of maturation in vitro after progesterone administration in vitro. Furthermore, progesterone treated LHRN316S mice produced offspring numbers per litter equivalent to WT mice. These findings provide key insights into cellular interactions in ovarian follicles and provide important clues for infertility treatment. [ABSTRACT FROM AUTHOR]

INTRODUCTION. Polycystic ovary syndrome (PCOS) is the main cause of female infertility. Clinical practice guidelines on PCOS recommend combined oral contraceptives (COCs) as first-line therapy. Given the association of PCOS with a number of clinical conditions, including obesity, type 2 diabetes mellitus, metabolic syndrome, anxiety and depressive disorders, an increased risk of endometrial cancer, and cardiovascular diseases, it is important to describe and systematise data on the benefits and risks associated with COCs.AIM. This study aimed to review current data on the use of COCs in PCOS, focusing on the rationality of prescribing, the main risks of using COCs, and the measures to minimise these risks.DISCUSSION. Hirsutism is the most prominent clinical manifestation of hyperandrogenism; in PCOS, its prevalence is 65–75%. COCs containing progestins with anti-androgenic properties are effective in treating hirsutism and superior to anti-androgens alone. Women with PCOS are at increased risk of endometrial cancer due to prolongation of the oestrogen-dependent proliferative phase. This risk can be mitigated by the normalising effect of COCs on the menstrual cycle and the effect of the progestin component of COCs. This review highlights the controversial nature of data on the association of COCs with emerging or exacerbating mental disorders, impaired glucose tolerance, and arterial hypertension/other cardiovascular risks in PCOS. Since the main safety issue with COCs is their thrombogenicity, clinicians should take special care when prescribing medicinal products from this group to PCOS patients. Data on the effect of COCs on fertility in women with PCOS are limited, but there is published evidence of an adverse effect of long-term use of COCs on the results of assisted reproductive technologies.CONCLUSIONS. The key benefit of the non-contraceptive use of COCs in PCOS is in treating hyperandrogenism, mainly hirsutism. To achieve effect, the patient should take COCs containing progestins with anti-androgenic properties for at least 6 months. PCOS patients can also use COCs for contraception. Clinicians prescribing COCs to women with PCOS should consider the individual patient context, the aim of treatment, and any potential risks associated with COCs.

Leitong Wang, Baoshan Li, Dongkai Cheng Embryo Laboratory, Jinghua Hospital of Shenyang, Shenyang, Liaoning Province, 110000, People’s Republic of ChinaCorrespondence: Dongkai Cheng, Embryo Laboratory, Jinghua Hospital of Shenyang, No. 83, Zhongshan Road, Heping District, Shenyang, Liaoning Province, 110000, People’s Republic of China, Tel +86 17766533209, Email cheng_dongkai@126.comAbstract: Recent research findings have highlighted the pivotal roles played by lncRNAs in both normal human development and disease pathogenesis. LncRNAs are expressed in oocytes and early embryos, and their expression levels change dynamically once the embryonic genome is activated during early human embryonic development. Abnormal expression of lncRNAs was found in follicular fluid, granulosa cells and oocytes of patients, and these lncRNAs were related to cell proliferation and apoptosis, nuclear maturation and follicle development. The expression levels of some lncRNAs in cumulus cells demonstrate correlations with the quality of oocytes and early embryos. This paper aims to present a comprehensive overview of the influence of LncRNAs on the developmental process of human oocytes as well as their involvement in certain infertility-related diseases.Keywords: cumulus cells, female infertility, lncRNA, oocyte

Infertility is becoming more of a growing health problem every year. It affects women at a slightly higher rate than men of childbearing age. Shift work, including night work, is undertaken by a relatively large proportion of the population. Sleep is essential for the proper functioning of the human body. There is a growing body of scientific evidence supporting the fact that both partial sleep deficiency and total sleep deprivation are associated with reproductive dysfunction in women. This can cause difficulties in conceiving a child. It seems that an attempt to eliminate this problem could be made by hiring more workers, which would translate into less strain on individual workers. The purpose of this study was to present the current state of knowledge on the impact of shift work on women’s reproductive functions. To this end, internet databases were reviewed, using the words: female infertility, sex steroid hormones, circadian rhythm, night shift work.

Background. Pelvic inflammatory disease (PID) is a significant gynecological problem. The main treatment strategy involves antibacterial drugs to eliminate the infection in combination with anti-inflammatory, infusion, transfusion, anticoagulant, and desensitization therapy. Chronic inflammatory processes can induce changes in the immune system, thus reducing the effectiveness of treatment, causing adhesions, obstruction of the fallopian tubes, and infertility. It emphasizes the importance of developing new PID treatment methods, including using agents with immunomodulatory, antioxidant, and enzymatic activity that can increase the body's overall resistance to infections. Aim. To evaluate the effectiveness of Longidase® in treating pelvic adhesions to improve the outcomes in chronic PID. Materials and methods. The study included 50 women of reproductive age with established chronic PID and adhesions aged 18 to 42 years with a mean age of 29.4±5.8 years. The subjects were randomly assigned to two groups comparable in their main prognostic features. Patients of the main group (30 people) received treatment with Longidase® 3000 IU 1 suppository rectally once every 3 days, 10 doses, then 1 suppository once every 5 days, 5 doses (the total course is 15 doses of Longidase suppositories 3000 IU). Patients in the control group (20 people) received placebo. The treatment course was 55 days. The patients were followed up for up to 140 days from the start of therapy. Results. The results show no significant changes and the negative effect of the treatment on the blood chemistry parameters in both groups. In 35% of patients in the main group, the level of peptide-bound oxyproline did not change; 46% responded to therapy with its increase and 11% with a decrease, which indicates the activation of the decomposition of collagen proteins and a decrease in their synthesis. Analysis of individual levels of circulating immune complexes (CIC) before and after treatment showed a significant decrease in CIC in the main group (Longidase) vs. control group (36.1±1.4 and 30.8±0.8, respectively), which indicates a decrease in the severity of the inflammation. The pain relief, more pronounced during treatment in the main group than in the control group (30% vs. 15%), is probably due to the resolution of the chronic inflammation and correlates with changes in CIC. The onset of pregnancy in 10 (33.3%) patients in the main group indicates the effectiveness of bovhyaluronidase azoximer (Longidase®) as an anti-inflammatory and anti-fibrotic agent. Conclusion. The study showed the possibility of using Longidase 3000 IU suppositories in the complex therapy of patients with pelvic adhesions due to chronic PID

Abstract Fatigue, an increasingly acknowledged symptom in various chronic diseases, has garnered heightened attention, during the medical era of bio-psycho-social model. Its persistence not only significantly compromises an individual’s quality of life but also correlates with chronic organ damage. Surprisingly, the intricate relationship between fatigue and female reproductive health, specifically infertility, remains largely unexplored. Our exploration into the existing body of evidence establishes a compelling link between fatigue with uterine and ovarian diseases, as well as conditions associated with infertility, such as rheumatism. This observation suggests a potentially pivotal role of fatigue in influencing overall female fertility. Furthermore, we propose a hypothetical mechanism elucidating the impact of fatigue on infertility from multiple perspectives, postulating that neuroendocrine, neurotransmitter, inflammatory immune, and mitochondrial dysfunction resulting from fatigue and its co-factors may further contribute to endocrine disorders, menstrual irregularities, and sexual dysfunction, ultimately leading to infertility. In addition to providing this comprehensive theoretical framework, we summarize anti-fatigue strategies and accentuate current knowledge gaps. By doing so, our aim is to offer novel insights, stimulate further research, and advance our understanding of the crucial interplay between fatigue and female reproductive health.

Abstract Background Sleep health and obesity may affect the risk of female infertility. However, few studies focused on the interaction of obesity and sleep health on the female infertility risk. This study aimed to evaluate the combined impact of trouble sleeping / sleep duration and overweight/obesity/ abdominal obesity on the risk of female infertility. Methods The data for this cross-sectional study was obtained from National Health and Nutritional Examination Survey, which provided information on trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and confounding factors. Adopted weighted univariate and multivariate logistic regression models to explore the relationship between trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and the risk of infertility, respectively, and the combined effect of trouble sleeping and overweight/obesity, trouble sleeping and abdominal obesity, sleep duration and overweight/obesity, sleep duration and abdominal obesity, on the female infertility risk. Results This study included a total of 1,577 women, and 191 were diagnosed with infertility. Women with infertility had a higher proportion of people with overweight/obesity, abdominal obesity, sleep duration ≤ 7 h and trouble sleeping than those with non-infertility. The result indicated that trouble sleeping [odds ratio (OR) = 2.25, 95% confidence intervals (CI): 1.49–3.39], sleep duration ≤ 7 h (OR = 1.59, 95% CI: 1.03–2.48), and the combined impact of abdominal obesity and trouble sleeping (OR = 2.18, 95% CI: 1.28–3.72), abdominal obesity and sleep duration ≤ 7 h (OR = 2.00, 95% CI: 1.17–3.40), overweight/obesity and trouble sleeping (OR = 2.29, 95% CI: 1.24–4.26), and overweight/obesity and sleep duration ≤ 7 h (OR = 1.88, 95% CI: 1.01–3.49) were associated with increased odds of infertility, respectively. Conclusion There was combined effects of trouble sleeping/sleep duration ≤ 7 h and overweight/obesity/ abdominal obesity on increased odds of female infertility.