Female Infertility Research Articles

Efficacy and Safety of Human Umbilical Cord Mesenchymal Stem Cells in Improving Fertility in Polycystic Ovary Syndrome Mice

Background: Polycystic ovary syndrome (PCOS) is the most prevalent reproductive endocrine illness in women of reproductive age and is one of the most important causes of female infertility. The pathogenesis of PCOS is complex. Although mesenchymal stem cell therapy is anticipated to be a successful treatment for PCOS, its long-term safety, including tumorigenesis in patients, remains unknown. Objective: This study aimed to confirm the efficacy and safety of human umbilical cord mesenchymal stem cells in improving fertility in PCOS mice. Methods: In this study, dehydroepiandrosterone (DHEA) was used to construct a C56BL/6 mouse PCOS model, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used as a treatment, and the reproductive phenotype was observed in parallel breeding experiments to confirm the efficacy of the treatment. A 4-month follow-up period, final blood tests, and organ histology were carried out to confirm the long-term safety of the treatment. Results: After hUC-MSCs treatment, the sex hormone disorder of mice was corrected, the morphology and function of the ovary were improved, the number of offspring was significantly increased compared to the control group, and no adverse reactions related to stem cell transplantation such as tumor formation were found within 4 months. Conclusion: The treatment of hUC-MSCs is safe and effective in treating PCOS over the long term.

Trends in acupuncture for infertility: a scoping review with bibliometric and visual analysis.

Unexplained recurrent implantation failure and the high cost of assisted reproductive techniques for those experiencing infertility have increasingly resulted in the use of acupuncture. However, the trends and research status of acupuncture on infertility resulting in natural conception have not been systematically summarized. This scoping review and knowledge graph analysis aimed to summarize existing clinical studies on acupuncture for infertility that resulted in natural conception. Seven databases, namely, PubMed, Embase, the Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, were searched up to August 2023 (updated on 1 April). Two authors independently identified related clinical studies and systematic reviews, and extracted data from included studies on acupuncture for infertility; any discrepancies were resolved by discussion or judged by a third author. A meta-analysis was conducted based on randomized controlled trials (RCTs), and data were synthesized using risk ratios with 95% confidence intervals. Of the 310 articles meeting the inclusion criteria, 274 were primary studies, 7 were systematic reviews, and 29 were case reports. Reported adverse events included mild ovarian irritation and early signs of miscarriage. Out of the 274 primary studies, there were 40 (14.60%) cases of male infertility and 234 (85.40%) cases of female infertility. Current research highlights on acupuncture for infertility focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and luteinized unruptured follicle syndrome (LUFS), while acupuncture for male infertility was a hotspot in the early research stage. The meta-analysis also suggested that acupuncture was more effective than human chorionic gonadotropin (HCG) [RR = 1.89, 95% CI (1.47, 2.42), 11 RCTs, 662 participants]. Acupuncture combined with HCG was comparable to HCG [RR = 2.33, 95% CI (1.53, 3.55), four RCTs, 259 participants]. Compared with no treatment, acupuncture resulted in a higher pregnancy rate [RR = 22.12, 95% CI (1.39, 353.09), one RCT, 47 participants]. There was no statistical difference between acupuncture combined with HCG plus letrozole and HCG plus letrozole [RR = 1.56, 95% CI (0.84, 2.89), one RCT, 84 participants]. Current research highlights on acupuncture for infertility resulting in natural conception focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and LUFS, while studies on male infertility and female infertility caused by blockage in the fallopian tube, thin endometrium, and other factors were insufficient. Well-designed confirmatory clinical studies are still needed as the research hypotheses of most studies were unclear.

Pattern of hysterosalpingographic findings among women with infertility in Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Hysterosalpingography (HSG) is a radiological procedure that is routinely done for female fertility workup in most clinical settings. Hysterosalpingography (HSG) is primarily done to assess tubal patency, but it can detect cervical, uterine, and peritoneal diseases. As such, it remains a valuable tool in the evaluation of female infertility in our environment, where the high prevalence of infertility has been largely attributed to tubo-peritoneal factors. It was a retrospective cross-sectional descriptive study. A total of 215 HSG reports of women with infertility at the Department of Radiology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria, were reviewed retrospectively. Data on sociodemographic profile, reproductive profile, infertility profile, and HSG reports were obtained from the case records and archives of the Department of Radiology on a proforma. The obtained data was analyzed using SPSS version 20. Most of the clients were within the age range of 35 to 44 years. Secondary infertility accounted for 58.6% of cases of infertility. Abnormal HSG was reported in 70.2% of cases. Tuboperitoneal pathology was the most common abnormality, detected in 46% of cases. Uterine and cervical pathologies were seen in 38.1 and 15.3% of cases, respectively. A total of 116 (53.9%) of the cases had a combination of abnormalities. Abnormal HSG was significantly associated with secondary infertility and a history of induced abortion (p=0.006 and ˂0.001, respectively). Tuboperitoneal pathologies are still a common cause of infertility in our environment. HSG remains a valid tool for female infertility workup.

Oocyte Maturation and miRNAs: Studying a Complicate Interaction to Reveal Possible Biomarkers for Female Infertility.

Cellular metabolism, apoptosis, fertilization, and proliferation of granulosa cells belong to a battery of processes where microRNAs can be detected and associated with infertility. The aim of the present review is to focus on mammalian oocyte maturation events and the association between oocyte growth and miRNA expression. PubMed/Medline, Google Scholar and Scopus databases were searched, and 33 studies were included. Regarding the correlation among miRNA expression and the regulation of granulosa cells and cumulus cells, the most important miRNAs were let-7b, let-7c and miR-21. Additionally, the loss of Dicer, an enzyme involved in miRNA biogenesis, is probably a crucial factor in oogenesis, oocyte maturation and embryogenesis. Furthermore, miRNAs interfere with different cellular mechanisms like apoptosis, steroidogenesis, genome integrity, angiogenesis, antioxidative response and, consequently, oocyte maturation. Hence, it is of major importance to clarify the role and mechanism of each miRNA as understanding its action may develop new tools and establish new diagnostic and treatment approaches for infertility and ovarian disorders.

Reproductive toxicology of environmental endocrine-disrupting chemicals in women: a cohort study protocol.

Introduction: Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive health outcomes, including male and female infertility, poor-pregnancy outcomes, and increased risk of diseases in childhood and beyond. To investigate the effects of EDCs and lifestyle on all aspects of reproduction (including early oocyte development, fertilization, embryo development, embryo implantation, abortion, and preterm birth). Methods: We performed this cohort study on patients receiving in vitro fertilization (IVF) treatment. Biological samples including urine, serum, follicular fluid, semen, fetal tissue, decidua, and placenta, were obtained. Results: By studying the correlations between reproductive outcomes and environmental pollutant exposure and lifestyle, we determined the toxicological mechanisms and health effects of EDCs on female reproductive health. We found that higher concentrations of per- and polyfluoroalkyl substances were correlated with polycystic ovary syndrome (PCOS). Using specific biomarkers, we also detected the concentrations of organophosphorus flame retardants (OPFRs) in urine and found that OPFRs may disrupt hormone homeostasis. Discussion: All of these results reveal EDCs may disrupt female reproduction.

Identification of novel compound heterozygous ZFP36L2 variants implicated in oocyte maturation defects and female infertility.

To explore the pathogenesis of oocyte maturation defects. Whole exome sequencing was conducted to identify potential variants, which were then confirmed within the pedigree through Sanger sequencing. The functional characterization of the identified variants responsible for the disease, including their subcellular localization, protein levels, and interactions with other proteins, was verified through transient transfection in HeLa cells in vitro. Additionally, we employed real-time RT-PCR and single-cell RNA sequencing to examine the impact of ZFP36L2 pathogenic variants on mRNA metabolism in both HeLa cells and mouse or human oocytes. A novel compound heterozygous variant in ZFP36L2 (c.186T > G, p.His62Gln and c.869C > T, p.Pro290Leu) was discovered in a patient with oocyte maturation defects. Our findings indicate that these variants lead to compromised binding capacity of the ZFP36L2-CONT6L complex and impaired mRNA degradation in HeLa cells and mouse oocytes. Furthermore, we characterized the changes in the human oocyte transcriptome associated with ZFP36L2 variants, with a particular emphasis on cell division, mitochondrial function, and ribosome metabolism. This study broadens the mutation spectrum of ZFP36L2 and constitutes the first report of human oocyte transcriptome alterations linked to ZFP36L2 variants. In conjunction with existing knowledge of ZFP36L2, our research lays the groundwork for genetic counseling aimed at addressing female infertility.

Combined impact of sleep and obesity on female infertility in the NHANES 2017–2020

BackgroundSleep 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.MethodsThe 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.ResultsThis 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.ConclusionThere was combined effects of trouble sleeping/sleep duration ≤ 7 h and overweight/obesity/ abdominal obesity on increased odds of female infertility.

Deletion of Fbxw7 in oocytes causes follicle loss and premature ovarian insufficiency in mice.

Premature ovarian insufficiency (POI) is one of the important causes of female infertility. Yet the aetiology for POI is still elusive. FBXW7 (F-box with 7 tandem WD) is one of the important components of the Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligase. FBXW7 can regulate cell growth, survival and pluripotency through mediating ubiquitylation and degradation of target proteins via triggering the ubiquitin-proteasome system, and is associated with tumorigenesis, haematopoiesis and testis development. However, evidence establishing the function of FBXW7 in ovary is still lacking. Here, we showed that FBXW7 protein level was significantly decreased in the ovaries of the cisplatin-induced POI mouse model. We further showed that mice with oocyte-specific deletion of Fbxw7 demonstrated POI, characterized with folliculogenic defects, early depletion of follicle reserve, disordered hormonal secretion, ovarian dysfunction and female infertility. Impaired oocyte-GCs communication, manifested as down-regulation of connexin 37, may contribute to follicular development failure in the Fbxw7-mutant mice. Furthermore, single-cell RNA sequencing and insitu hybridization results indicated an accumulation of Clu and Ccl2 transcripts, which may alter follicle microenvironment deleterious to oocyte development and accelerate POI. Our results establish the important role of Fbxw7 in folliculogenesis and ovarian function, and might provide valuable information for understanding POI and female infertility.

EE24 Analysis of out-of Pocket Payment Associated to Female Infertility in Hungary between 2015-2022

EE24 Analysis of out-of Pocket Payment Associated to Female Infertility in Hungary between 2015-2022

EE232 Annual Health Insurance Treatment Cost of Female Infertility Associated with Male Factors Based on Routinely Collected Financing Data between 2010-2019

EE232 Annual Health Insurance Treatment Cost of Female Infertility Associated with Male Factors Based on Routinely Collected Financing Data between 2010-2019

CLINICAL PRESENTATIONS AND SURGICAL MANAGEMENT OF UTERINE SEPTUM-ASSOCIATED INFERTILITY: A CASE SERIES STUDY

Uterine septum, a congenital uterine anomaly, is implicated in female infertility and adverse reproductive outcomes. This retrospective descriptive case series examines eight patients treated for primary or secondary infertility associated with uterine septum. Diagnostic evaluations, surgical interventions, and postoperative outcomes are presented. Hysteroscopic septum resection emerged as the primary surgical intervention, with varying success rates in achieving pregnancy postoperatively. Factors influencing outcomes include patient age, septum morphology, and associated comorbidities. Individualized treatment strategies and adjunctive therapies such as hormonal manipulation and assisted reproductive techniques are crucial for optimizing fertility outcomes. While promising, long-term reproductive prognosis post-surgery remains uncertain, warranting further research and prospective studies. This study underscores the complexity of uterine septum-associated infertility and emphasizes the need for a multidisciplinary approach to management, aiming to enhance reproductive outcomes and fulfill the reproductive aspirations of affected individuals.

Female Infertility

Female Infertility

Side effects of Sexually Transmitted Infections (STIs) on female fertility: diagnostic and treatment strategies – a literature review

Sexually transmitted infections (STIs) have detrimental effects on overall health and can cause infertility in males and females. Untreated infections like gonorrhea or chlamydia may lead to pelvic inflammatory disease (PID), causing damage and obstruction of the fallopian tubes. Human papillomavirus (HPV) infections, particularly high-risk strains, may progress to cervical cancer, requiring invasive treatments and may cause fertility loss. Herpes simplex virus (HSV) outbreaks can disrupt sexual contact, affecting conception attempts. Syphilis, is another sexually transmitted disease, if left untreated, can lead to epididymitis and erectile dysfunction in males, indirectly influencing fertility. Early detection and treatment of these STIs are crucial to protect infertility in males and females.

Effects of physical activity on infertility in reproductive females

ObjectivesTo explore the relationship between different types of physical activity and female infertility.MethodsThis study analyzed data from 2,796 female participants aged 18–44 years in the United States, obtained from the National Health and Nutrition Examination Survey (NHANES) database spanning the years 2013 to 2020. Multiple logistic regression analyses and generalized linear models were used to explore the relationship between different types of physical activity and infertility after adjusting for potential confounding factors.ResultsWe found a non-linear relationship between recreational activities and infertility with an inflection point of 5.83 h/week (moderate intensity), while work activities and traffic-related activities did not. On the left side of the inflection point, there was no significant association between recreational activity time and infertility (OR = 0.93, 95% CI: 0.86 to 1.02, P = 0.1146), but on the right side of the inflection point, there was a positive association between recreational activity time and the risk of infertility (OR = 1.04, 95% CI: 1.02 to 1.06, P = 0.0008).ConclusionsThe relationship between different types of physical activity and female infertility varies. We acknowledge the potential influence of confounding variables on this relationship. However, we have already adjusted for these potential variables in our analysis. Therefore, our findings suggest that appropriate recreational activity programs are essential for promoting reproductive health in women of reproductive age. Nevertheless, it is important to note that the observed association does not imply causality. Given the limitations of cross-sectional studies, further prospective cohort studies are needed to explore the causal relationship while accounting for additional confounding factors.

Etiology and Treatment of Infertility in Tertiary Care Center of Anand, Gujarat, India

This study sought to investigate the etiology and risk factors contributing to infertility, assess the efficacy of fertility-inducing drugs, and analyze the treatment modalities' impact on the quality of life for infertile patients. Spanning a 6-month duration, the research incorporated 50 patients, and risk factors were discerned through a tailored case report form reflecting daily routines and habits. A comparative analysis of Letrozole, Clomiphene citrate, and Metformin was conducted based on existing literature. Predominant causes of female infertility encompassed tubal factors, ovulatory disorders, endometriosis, and unexplained factors. Common risk factors included advanced age, smoking, alcohol consumption, abnormal body weight, and excessive caffeine intake. The study highlighted that while no single risk factor exclusively caused infertility, the presence of multiple factors heightened the likelihood of its development. Clomiphene emerged as the most effective fertility-inducing medication among the three drugs examined. Categories: Obstetrics/Gynecology

Serum Adiponectin Marker in Women with Polycystic Ovary Syndrome

Background: One of the leading causes of female infertility is polycystic ovarian syndrome (PCOS). Adiponectin is one of many adipokines adipose tissue releases that affect insulin resistance (IR). Objective: To measure PCOS participants' IR, adiponectin, and serum insulin levels. Materials and Procedures: a case-control study involving 80 patients with PCOS (40 obese and 40 nonobese) and 80 controls (40 obesity and 40 nonobese). Adiponectin was measured using an enzyme-linked immunosorbent assay, while serum levels of insulin and FBS were measured using a chemiluminescent automated immunoassay system (ECL). Results: Regardless of body mass index and PCOS, women had lower levels of adiponectin and higher levels of blood fasting glucose, insulin, and IR compared to the relevant with a p-value of ≤0.001 for controls. Conclusion: According to weight, blood adiponectin levels inversely correspond to IR. It can, therefore, act as an indicator in PCOS-affected women.

Role of Uttarbasti in Both Male and Female Infertility

Role of Uttarbasti in Both Male and Female Infertility

Role of Uttarbasti in Both Male and Female Infertility Phosphodiesterase Inhibitors: A Review

Role of Uttarbasti in Both Male and Female Infertility Phosphodiesterase Inhibitors: A Review

Biallelic FANCA variants detected in sisters with isolated premature ovarian insufficiency.

Premature ovarian insufficiency is a common form of female infertility affecting up to 4% of women and characterised by amenorrhea with elevated gonadotropin before the age of 40. Oocytes require controlled DNA breakage and repair for homologous recombination and the maintenance of oocyte integrity. Biallelic disruption of the DNA damage repair gene, Fanconi anemia complementation group A (FANCA), is a common cause of Fanconi anaemia, a syndrome characterised by bone marrow failure, cancer predisposition, physical anomalies and POI. There is ongoing dispute about the role of heterozygous FANCA variants in POI pathogenesis, with insufficient evidence supporting causation. Here, we have identified biallelic FANCA variants in French sisters presenting with POI, including a novel missense variant of uncertain significance and a likely pathogenic deletion that initially evaded detection. Functional studies indicated no discernible effect on DNA damage sensitivity in patient lymphoblasts. These novel FANCA variants add evidence that heterozygous loss of one allele is insufficient to cause DNA damage sensitivity and POI. We propose that intragenic deletions, that are relatively common in FANCA, may be missed without careful analysis, and could explain the presumed causation of heterozygous variants. Accurate variant curation is critical to optimise patient care and outcomes.

Advancements in the detection and implications of sperm-immobilizing antibodies in female infertility

This review highlights over five decades of research on sperm-immobilizing antibodies (SI-Abs), which are crucial for understanding female infertility due to their effects on sperm motility and fertilization. Since the 1960s, Isojima et al. have made significant strides, notably with the Sperm Immobilization Test (SIT), which revolutionized the quantification of SI-Abs and their roles in infertility. Drawing from a comprehensive PubMed search on "the sperm immobilization test" and "sperm immobilizing antibody," our review underscores the critical insights gained into SI-Abs' impact on reproductive functions. SI-Abs result from the body's response to sperm antigens, potentially leading to infertility by affecting post-intercourse sperm function. However, the presence of anti-sperm antibodies does not guarantee infertility, indicating a complex relationship between these antibodies and reproductive outcomes. Isojima et al.'s pioneering studies paved the way for SIT and sperm immobilization titer (SI50), tools that have clarified the link between SI-Abs and infertility, focusing on disrupted sperm mobility and fertilization as key infertility mechanisms. Clinically, interventions such as in-vitro fertilization (IVF), which bypasses or eliminates SI-Abs, have improved pregnancy rates, whereas Freund's complete adjuvant therapy has deepened our understanding of infertility mechanisms. The SI50 value is crucial for predicting fertility treatment success and guiding therapeutic decisions based on antibody levels. In summary, the evolution of SI-Abs research has provided new hope for addressing infertility, significantly enriching the field of reproductive immunology, and highlighting the need for ongoing investigation.