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• 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]

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]

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]

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]

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]

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.

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.

Background: Thin endometrium (TE) is a common cause of female infertility in clinical practice. Platelet-rich Plasma (PRP) therapy becomes a novel treatment for thin endometrium; however, its clinical application remains controversial. This meta-analysis aims to evaluate the therapeutic effects of intrauterine autologous PRP infusion in women with thin endometrium through relevant randomized controlled trials (RCTs). Methods: We systematically searched studies published in English from inception until June 2024 in databases such as PubMed, The Cochrane Library, Embase, Web of Science, and MEDLINE. Search terms included "Platelet-Rich Plasma," "thin endometrium," "endometrial thickness," "infertility," "pregnancy," "reproduction," and "adverse reactions". RCTs identified through the search were subjected to systematic review and meta-analysis, and data were analyzed using fixed-effects or random-effects models based on heterogeneity. Results: Eight RCTs involving 678 patients with thin endometrium were included. Patients receiving PRP infusion demonstrated significantly superior outcomes compared to the control group in endometrial thickness (MD: 1.23, 95%CI: 0.87 to 1.59, P = 0.000), clinical pregnancy rate (RR: 2.04, 95%CI: 1.52 to 2.76, P = 0.000), live birth rate (RR: 2.46; 95%CI: 1.57 to 3.85, P = 0.000), cycle cancellation rate (RR: 0.46, 95%CI: 0.23 to 0.93, P = 0.000), and embryo implantation rate (RR: 2.71; 95%CI: 1.91 to 3.84, P = 0.000). There were no statistically significance in spontaneous abortion rate (RR: 0.85, 95%CI: 0.40 to 1.78, P = 0.659), chemical pregnancy rate (RR: 1.84, 95%CI: 0.72 to 4.72, P = 0.204) and endometrial vascular improvement rate (RR: 1.10; 95%CI: 0.89 to 1.38, P = 0.367) between the two groups. The limitations of this study includes that, we only included single lauguage for literature research, the sample size and heterogeneity which could cause criteria bias. Conclusion: Intrauterine PRP infusion may be an effective and safe treatment for women with thin endometrium. Further high-quality, large-sample, randomized controlled trials are needed to validate the reliability of our results. Trial registration: The review protocol is registered on PROSPERO with registration number CRD42023490421, and no modifications were made to the information provided at registration. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) is a second messenger for many signal pathways, and changes in intracellular Ca2+ concentration ([Ca2+]i) are an important signaling mechanism in the oocyte maturation, activation, fertilization, function regulation of granulosa and cumulus cells and offspring development. Ca2+ oscillations occur during oocyte maturation and fertilization, which are maintained by Ca2+ stores and extracellular Ca2+ ([Ca2+]e). Abnormalities in Ca2+ signaling can affect the release of the first polar body, the first meiotic division, and chromosome and spindle morphology. Well-studied aspects of Ca2+ signaling in the oocyte are oocyte activation and fertilization. Oocyte activation, driven by sperm-specific phospholipase PLCz, is initiated by concerted intracellular patterns of Ca2+ release, termed Ca2+ oscillations. Ca2+ oscillations persist for a long time during fertilization and are coordinately engaged by a variety of Ca2+ channels, pumps, regulatory proteins and their partners. Calcium signaling also regulates granulosa and cumulus cells’ function, which further affects oocyte maturation and fertilization outcome. Clinically, there are several physical and chemical options for treating fertilization failure through oocyte activation. Additionally, various exogenous compounds or drugs can cause ovarian dysfunction and female infertility by inducing abnormal Ca2+ signaling or Ca2+ dyshomeostasis in oocytes and granulosa cells. Therefore, the reproductive health risks caused by adverse stresses should arouse our attention. This review will systematically summarize the latest research progress on the aforementioned aspects and propose further research directions on calcium signaling in female reproduction. [ABSTRACT FROM AUTHOR]

DNA damage is a key factor affecting gametogenesis and embryo development. The integrity and stability of DNA are fundamental to a woman's successful conception, embryonic development, pregnancy and the production of healthy offspring. Aging, reactive oxygen species, radiation therapy, and chemotherapy often induce oocyte DNA damage, diminished ovarian reserve, and infertility in women. With the increase of infertility population, there is an increasing need to study the relationship between infertility related diseases and DNA damage and repair. Researchers have tried various methods to reduce DNA damage in oocytes and enhance their DNA repair capabilities in an attempt to protect oocytes. In this review, we summarize recent advances in the DNA damage response mechanisms in infertility diseases such as PCOS, endometriosis, diminished ovarian reserve and hydrosalpinx, which has important implications for fertility preservation. [ABSTRACT FROM AUTHOR]

Periwinkle (Catharanthus roseus (L.) G. Don) is renowned for its diverse colors and resilience to harsh climates. Still, most commercial cultivars predominantly display flat petals. Using cultivars representing non-wavy, medium-wavy, and extreme-wavy flower forms, we examined morphological differences in both their mature leaves and floral organs. Phenotypes of self-pollinated (S1) and cross-pollinated (F1, F2) populations further underscored their morphological distinctions. Specifically, the extreme-wavy type displayed elliptical leaves, broader than the non-wavy type, with a pronounced acute apex and a notably wrinkled blade surface. The non-wavy type also bore intensely wavy petal margins and exhibited a smaller flower diameter, with a notable absence of a functional pistil, indicating female sterility. The insights gained allowed for early differentiation during the seedling period. This study suggests that the inheritance of these flower forms is regulated by an allele WAVY (Wv), which exhibits incomplete dominance. Concretely, the non-wavy form arises from a recessive homozygous expression (wvwv), the extreme-wavy from a dominant homozygous expression (WvWv), and the medium-wavy from a heterozygous expression (Wvwv). This study provides clarity on morphological descriptions and inheritance patterns of wavy flower forms, facilitating strategic breeding of diverse flower forms in periwinkle. [ABSTRACT FROM AUTHOR]

Background: The correlation between oxidative stress and female infertility pathogenesis was established, and the oxidative balance score (OBS) can serve as a measure of overall oxidative stress burden within an individual. Prior reports have not addressed the relationship between OBS and female infertility. This study endeavors to investigate the association between infertility risk in female and OBS. Methods: The analysis focused on data from the National Health and Nutrition Examination Survey 2013-2018. OBS was determined from 16 dietary components and 4 lifestyle components. Multivariate logistic regression was employed to investigate the relationship between OBS and female infertility. Further stratified analysis was conducted to examine the associations across various subgroups. To elucidate the dose-response relationship between infertility risk in female and OBS, a restricted cubic spline function was employed. Results: The study included a total of 1410 participants. Through weighted multivariable logistic regression analysis, we observed a consistent inverse correlation between OBS and the risk of female infertility [OR (95% CI) = 0.97 (0.95, 0.99), p = 0.047]. When participants were segregated into quartiles based on OBS, those in the highest quartile had a 61% [OR (95% CI) = 0.39 (0.2, 0.79), p = 0.01] reduced risk of infertility compared to those in the lowest quartile of OBS. A trend test assessing OBS by quartile also revealed the relationship between OBS and female infertility. This correlation remained constant across both dietary and lifestyle OBS. Additionally, lifestyle OBS and female infertility exhibited a nonlinear association. A sensitivity analysis verified the consistency of our findings. Conclusion: The study found that a higher OBS is associated with a lower prevalence of female infertility. These results emphasized the potential role of oxidative homeostasis in the pathogenesis of infertility and highlighted the importance of follow-up studies and prevention strategies. [ABSTRACT FROM AUTHOR]

Endometriosis (EM), characterized by the presence of endometrial-like tissue outside the uterus, is the leading cause of chronic pelvic pain and infertility in females of reproductive age. Despite its high prevalence, the molecular mechanisms underlying EM pathogenesis remain poorly understood. The endocannabinoid system (ECS) is known to influence several cardinal features of this complex disease including pain, vascularization, and overall lesion survival, but the exact mechanisms are not known. Utilizing CNR1 knockout (k/o), CNR2 k/o, and wild-type (WT) mouse models of EM, we reveal contributions of ECS and these receptors in disease initiation, progression, and immune modulation. Particularly, we identified EM-specific T cell dysfunction in the CNR2 k/o mouse model of EM. We also demonstrate the impact of decidualization-induced changes on ECS components, and the unique disease-associated transcriptional landscape of ECS components in EM. Imaging mass cytometry (IMC) analysis revealed distinct features of the microenvironment between CNR1, CNR2, and WT genotypes in the presence or absence of decidualization. This study, for the first time, provides an in-depth analysis of the involvement of the ECS in EM pathogenesis and lays the foundation for the development of novel therapeutic interventions to alleviate the burden of this debilitating condition. [ABSTRACT FROM AUTHOR]

This research has suggested a link between major depressive disorder (MDD) and infertility, with interleukin‐18 (IL‐18) being proposed as a potential mediator due to its connections to both conditions. A Mendelian randomization (MR) approach was utilized in this study, which drew on genetic data from 500,199 European participants studied for MDD, along with additional IL‐18 and reproductive health data from the FinnGen consortium and GWAS datasets. Single nucleotide polymorphisms were employed as instrumental variables to examine the causal relationships between MDD, genetically predicted IL‐18 levels, and infertility. In our study, bidirectional MR analysis revealed a significant inverse causal relationship between MDD and genetically predicted IL‐18 levels, with a higher genetic predisposition to MDD, correlating with reduced IL‐18 levels (β: −0.40; 95% confidence interval (CI): −0.69 to −0.11; P = 7.09 × 10−3). Additionally, MDD is found to significantly increase the risk of female infertility. Notably, genetically predicted IL‐18 levels demonstrated a protective effect against female infertility (odds ratio (OR): 0.92; 95% CI: 0.86–0.98; P = 1.17 × 10−2). Mediation analysis indicated that genetically predicted IL‐18 levels partially mediated the impact of MDD on female infertility associated with cervical, vaginal, other or unspecified origin, accounting for up to 14.61% of this effect. No evidence of pleiotropy or heterogeneity was detected. The role of genetic predispositions to MDD in influencing genetically predicted IL‐18 levels, and subsequently, female infertility, was highlighted by our study, offering insights into the complex interplay between mental health and reproductive biology. These findings contribute to a deeper understanding of the genetic and molecular pathways influencing these conditions, suggesting new directions for research and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]