Examining the combined benefits of photobiomodulation and apigenin for the treatment of asthenozoospermia: An innovative therapeutic strategy.

Individuals suffering from asthenospermia, an infertility disorder, have reduced sperm motility. This study's goal was to identify the impacts of diverse photobiomodulation procedures on the motility of sperm in vitro in patients with asthenospermia, either in isolation or in combination with Apigenin. At 633 nm and 808 nm, the lasers are used with multiple dose values (0.6, 1.2, and 2.4) J/cm2 and altering Apigenin concentrations (5, 10, 25, and 50 µM). All of the photobiomodulation procedures were assessed. Assessing factors were the DNA fragmentation index, sperm viability, as well as progressive sperm motility. The progressive sperm motility results for 633 nm and 808 nm show a significant increase over 633 nm + 808 nm after 60 min after irradiation. Sperm motility increased more quickly under the 808 nm procedure than under the other procedures (p < 0.02). The observation of progressive sperm motility indicated that a 10 µM concentration of Apigenin created higher results than other concentrations (p < 0.01). Apigenin with 808 nm at 1.2 J/cm2 resulted in better sperm motility (p < 0.01) and decreased DNA fragmentation index. There was a notable increase (p < 0.05) in the DNA fragmentation index with the 633 nm + 808 nm procedure. At a 10 µM concentration of Apigenin, the DNA fragmentation index was lower than at a 50 µM concentration (p < 0.02). Neither Apigenin nor photobiomodulation significantly decreased sperm viability. The study suggests that asthenozoospermia patients may benefit from apigenin utilized alongside photobiomodulation, while further investigation is required.

Carnitine traffic and human fertility.

Carnitine is a vital molecule in human metabolism, prominently involved in fatty acid ß-oxidation within mitochondria. Predominantly sourced from dietary intake, carnitine also derives from endogenous synthesis. This review delves into the complex network of carnitine transport and distribution, emphasizing its pivotal role in human fertility. Together with its role in fatty acid oxidation, carnitine modulates the acety-CoA/CoA ratio, influencing carbohydrate metabolism, lipid biosynthesis, and gene expression. The intricate regulation of carnitine homeostasis involves a network of membrane transporters, notably OCTN2, which is central in its absorption, reabsorption, and distribution. OCTN2 dysfunction, results in Primary Carnitine Deficiency (PCD), characterized by systemic carnitine depletion and severe clinical manifestations, including fertility issues. In the male reproductive system, carnitine is crucial for sperm maturation and motility. In the female reproductive system, carnitine supports mitochondrial function necessary for oocyte quality, folliculogenesis, and embryonic development. Indeed, deficiencies in carnitine or its transporters have been linked to asthenozoospermia, reduced sperm quality, and suboptimal fertility outcomes in couples. Moreover, the antioxidant properties of carnitine protect spermatozoa from oxidative stress and help in managing conditions like polycystic ovary syndrome (PCOS) and endometriosis, enhancing sperm viability and fertilization potential of oocytes. This review summarizes the key role of membrane transporters in guaranteeing carnitine homeostasis with a special focus on the implications in fertility and possible treatments of infertility and other related disorders.

Case Report: The first case of successful pregnancy and live birth following laparoscopic resection of adenomyosis under real-time intraoperative ultrasound elastography guidance.

Objective: Adenomyosis-related infertility is increasingly being diagnosed, and surgical intervention has been suggested to improve fertility. Elastography, a noninvasive ultrasound technique, is promising for diagnosing and guiding the resection of adenomyosis. This report presents the first case of successful delivery after twin pregnancies achieved with IVF following intraoperative elastography-guided laparoscopic adenomyomectomy. Case report: A 35-year-old Japanese woman with uterine adenomyosis received a gonadotropin analog before surgery. Preoperative MRI revealed a 5.0 × 7.0 cm adenomyoma, leading to scheduled laparoscopic adenomyomectomy with intraoperative elastography. During surgery, elastography ensured the complete resection of the adenomyotic tissue while preserving the endometrium. Postoperative MRI confirmed the absence of residual adenomyosis. The patient underwent in vitro fertilization and embryo transfer, leading to a successful twin pregnancy after double blastocyst transfer. Despite a stable perinatal course, she required hospitalization to prevent preterm labor. At 32 weeks, an elective cesarean section delivered healthy twins. The intra- and post-operation was uncomplicated, and the patient and infants had an optimal health. Conclusion: This is the first reported case of a twin pregnancy resulting from vitrified-warmed embryo transfer after elastography-guided laparoscopic adenomyomectomy, culminating in a successful delivery via cesarean section. This technique allows precise resection and mitigates the risks of uterine rupture and placenta accreta spectrum disorders. Although promising, further studies are required to validate the safety and efficacy of this innovative surgical approach.

Mendelian randomization analysis and validation supports MEGF9 and MLLT11 as potential targets for the treatment of varicocele and male infertility.

Objective: A growing body of research suggests a link between varicocele and male infertility (MI). However, current evidence is mainly based on retrospective studies, which are prone to interference from confounding factors and cannot establish causal relationships. Mendelian randomization (MR) studies on the causal relationship between varicocele and MI are very limited. Therefore, this study conducted a two-sample MR study to elucidate the causal effect between the two. Methods: Download the data set GSE216907 from the GEO database, and use R software to screen differential genes in normal and varicocele tissue samples. The drug targets of Bu Shen Huo Xue Prescription (BSHXP) were derived from the Herb database. All genetic datasets were obtained using publicly available summary statistics based on individuals of European ancestry from the IEU GWAS database. MR analysis was performed using MR Egger, weighted median (WM) and inverse variance weighted (IVW) methods to assess the causal relationship between exposure and outcome and to validate the findings by comprehensively evaluating the effects of pleiotropic effects and outliers. The renal vein constriction method was used to establish a pathological model of varicocele infertility. The drug was administered continuously for 60 days and the relevant indicators of the rats were observed. Results: Obtain two therapeutic targets for varicocele through intersection analysis: MEGF9 and MLLT11, and were verified by molecular docking. MR analysis showed that MEGF9 was positively associated with MI (MR Egger, OR: 1.639, 95% CI: 1.124-2.391, P = 0.024; WM, OR: 1.235, 95% CI: 1.003-1.521, P = 0.047). MEGF9 is also positively associated with MI (IVW, OR: 1.35, 95% CI: 1.069-1.705, P = 0.012). Sensitivity analysis showed no heterogeneity and horizontal pleiotropy. The expression of MEGF9 and MLLT11 increased in the varicocele model group, while the expression decreased after treatment with low, medium, and high doses of BSHXP. In addition, the sperm number, motility, morphology, and fertility of rats in the model group were significantly lower than those in the control group (P<0.05). After BSHXP treatment, all indicators were significantly better than those of the model group (P<0.05). Conclusion: In conclusion, this study indirectly supports that varicocele causes MI. BSHXP inhibiting MEGF9 and MLLT11 may become a potential therapeutic target for alleviating varicocele and MI.

The gut microbiota: emerging biomarkers and potential treatments for infertility-related diseases.

Infertility is a disease of impaired fertility. With socioeconomic development, changes in human lifestyles, and increased environmental pollution, the problem of low human fertility has become increasingly prominent. The incidence of global infertility is increasing every year. Many factors lead to infertility, and common female factors include tubal factors, ovulation disorders, endometriosis, and immune factors. The gut microbiota is involved in many physiological processes, such as nutrient absorption, intestinal mucosal growth, glycolipid metabolism, and immune system regulation. An altered gut flora is associated with female infertility disorders such as polycystic ovary syndrome (PCOS), endometriosis (EMs), and premature ovarian failure (POF). Dysbiosis of the gut microbiota directly or indirectly contributes to the development of female infertility disorders, which also affect the homeostasis of the gut microbiota. Identifying the etiology and pathogenesis of infertility in patients is the focus of reproductive medicine physicians. We studied the developmental mechanism between the gut microbiota and PCOS, EMs, and POF from a new perspective, providing new ideas for diagnosing and treating female infertility diseases and specific reference values for eugenics.

Recent progress in metabolomics for analyzing common infertility conditions that affect ovarian function.

Background: Numerous efforts have been undertaken to identify biomarkers associated with embryo and oocyte quality to improve the success rate of in vitro fertilization. Metabolomics has gained traction for its ability to detect dynamic biological changes in real time and provide comprehensive metabolite profiles. This review synthesizes the most recent findings on metabolomic analysis of follicular fluid (FF) in clinical conditions leading to infertility, with a focus on the dynamics of energy metabolism and oocyte quality, and discusses future research directions. Methods: A literature search was conducted without time constraints. Main findings: The metabolites present in FF originate from five primary pathways: glycolysis, oxidative phosphorylation, lipid metabolism and ß-oxidation, nucleic acid synthesis, and ketogenesis. Metabolomic profiling can broadly categorize infertile women into two groups: those with infertility due to aging and endometriosis, and those with infertility associated with polycystic ovarian syndrome and obesity. In the former group, glycolysis and lipid metabolism are upregulated to compensate for mitochondrial dysfunction, whereas the latter group exhibits the opposite trend. Assessing the levels of glucose, pyruvate, lactate, and plasmalogens in FF may be valuable for evaluating oocyte quality. Conclusion: Metabolomic analysis, particularly focusing on energy metabolism in FF, holds promise for predicting female reproductive outcomes.

Pooled prevalence of hypothyroidism among Indian females with infertility: A systematic review & meta-analysis.

Background & objectives Studies suggest hypothyroidism is responsible for female infertility. This review aimed to determine the pooled prevalence of hypothyroidism in Indian infertile women so that hypothyroidism screening can be initiated, and policies are designed for prevalence reduction. Methods Electronic databases including PubMed, Google Scholar and Cochrane library were searched to obtain the relevant articles. Studies that reported the proportion of hypothyroidism in Indian infertile women were selected. Systematic procedures for study selection and data extraction were followed. Each study was evaluated for quality using the Joanna Briggs institute (JBI) critical appraisal checklist. To pool the effect sizes, a random effects model was utilized. Funnel plot and Egger's test were used to assess publication bias. To quantify heterogeneity among studies, I2 statistics were utilized. Subgroup and meta-regression analyses were used to further investigate the heterogeneity of pooled estimates. The sensitivity analysis done whereby each study was excluded in order to examine the influence of that study in the pooled estimate. A P-value of 0.05 or less was considered statistically significant. Results Out of 198 articles, a total of 20 studies involving 2396 cases met the inclusion criteria. The pooled prevalence of hypothyroidism in women with infertility was 28 per cent [95% confidence interval (CI): 20% to 36%] which was highest in Telangana at 62 per cent (n=1; 95% CI 48% to 74%) and lowest in Karnataka at 14 per cent (n=2; 95% CI: 10% to 18%). Interpretation & conclusions Infertile women have high proportion of hypothyroidism, suggesting that screening programmes during diagnostic workup for infertility may provide optimal care. The result of this meta-analysis will help design guidelines and earmark highest prevalence regions to initiate preventive and diagnostic measures for prevalence reduction in future.

Comparative effectiveness of sildenafil citrate and estradiol valerate as adjuvants during clomiphene citrate-assisted ovarian stimulation cycles in patients with unexplained infertility: a double-blind randomized controlled trial.

OBJECTIVE: This study aimed to assess the effect of sildenafil citrate and estradiol valerate as adjuvant therapy during ovarian stimulation cycles with clomiphene citrate in patients with unexplained infertility in Kisangani. METHOD: A double-blind, randomized controlled trial was conducted for two years at two specialized health facilities in Kisangani (University Clinics of Kisangani and "Clinique des Anges Kisangani"). The population included 148 patients, 74 of whom were on clomiphene citrate + sildenafil citrate (CCSC) regimens and 74 of whom were on clomiphene citrate + estradiol valerate (CCEV) regimens for three months. The primary indicator was the conception rate, with secondary outcomes encompassing endometrial thickness, appearance and vascularity, the number of mature follicles and ovulation rate. RESULTS: The two groups were comparable in terms of sociodemographic and clinical characteristics. The mean duration of attempting to conceive was 4.39 years versus 4.36 years (P = 0.839), while the mean AFC was 11.51 versus 11.46 (P = 0.831), in the CCSC group versus CCEV group respectively. Secondary infertility was the most frequent diagnosis in each of the two groups. The biochemical pregnancy rate was comparable between the two groups (P = 0.385), while the clinical pregnancy rate was significantly higher in the CCSC group versus CCEV group (P = 0.04). Both perifollicular flow and the ovulation rate were significantly higher in the CCSC group versus the CCEV group (P = 0.006 and P = 0.002 respectively). However, endometrial vascularity/thickness, and the number of Graafian follicles were not significantly different between the two groups. CONCLUSION: As an adjuvant, sildenafil increases the rate of clinical pregnancy more than does estradiol in patients with unexplained infertility undergoing ovarian stimulation with clomiphene citrate. STUDY REGISTRATION: PACTR 202,310,849,449,401 (Pan African Clinical Trials Registry).

Body Mass Index Combined With Inflammatory Factors Can Better Predict Varicocele.

Most patients with VC have no symptoms, so they are often discovered due to male infertility. Early identification of them is a matter of concern for clinicians. A retrospective analysis of clinical data from patients between January 1, 2021, and February 1, 2024, was conducted. Patients were divided into VC and non-VC groups. Propensity score matching (PSM) was performed at a ratio of 1:1, and two cohorts with homogeneous baseline status were selected. Multivariate binary logistic regression and receiver operating characteristic (ROC) curve were used to analyze independent risk factors and protective factors and to evaluate their diagnostic value individually and in combination. A p-value <0.05 was considered statistically significant. A total of 256 patients with similar clinical characteristics were further analyzed after PSM in a 1:1 ratio of the 423 patients included in the study. The two groups had statistically significant differences in systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and body mass index (BMI) (p<0.05). Multivariate binary logistic regression analysis showed that SII and NLR were independent risk factors for VC, while high BMI could reduce the prevalence of VC. The PLR differences were not significant. The ROC analysis showed that BMI, SII, and NLR could predict VC, with areas under the curve of 68.3% (cut-off value 22.32), 83.4% (cut-off value 357.57), and 83.2% (cut-off value 1.8), respectively. The combination of BMI and inflammatory factors was more accurate for predicting VC than BMI alone (87.5% vs. 68.3%, p=0.0001), SII (87.5% vs. 83.4%, p=0.0106), and NLR (87.5% vs 83.2%, p=0.0058). Both SII and NLR are independent risk factors for VC while BMI is an independent protective factor. The BMI, SII, and NLR values have the potential to predict VC. The BMI combined with these inflammatory factors can improve the accuracy of prediction.

"Protective effects of artichoke extract and Bifidobacterium longum on male infertility in diabetic rats".

Background: Diabetes is a major global health concern and plays a significant role in male infertility and hormonal abnormalities by altering the tissue structure of spermatogenic tubes and decreasing the number of spermatogonia. This study investigated the effect of artichoke (Cynara scolymus L) hydroalcoholic extract and Bifidobacterium longum probiotic on sexual hormones, oxidative stress, apoptosis pathway, and histopathological changes in testicular tissues of diabetic rats to find an adjuvant therapy to manage the infertility complications of diabetes. Methods: In this experiment, 96 male-rats were randomly selected from eight groups. Control, Sham (normal saline), DM group (IP injected with 60 mg/kg STZ), Cynara (400 mg/kg hydroalcoholic extract of Cynara scolymus L), BBL (received 1 × 109 CFU/ml/day Bifidobacterium longum), DM + Cynara, DM + BBL, and DM + Cynara + BBL groups. After 48 days of orally gavage, serum level of FBS (fasting blood sugar), Malondi-aldehyde (MDA), Total-Anti-Oxidant Capacity (TAC), FSH (Follicle-stimulating hormone), LH (Luteinizing hormone), Testosterone, Testis mRNA-expressions of Protamin (prm1), BCL2, and Caspase-9 genes, as well as stereological changes were measured. Results: In comparison to the diabetic group, the hydroalcoholic extract of Cynara scolymus L combined with the probiotic Bifidobacterium longum resulted in a substantial decrease in FBS (p < 0.001) and MDA(p < 0.05) concentrations, and the expression of the Caspase-9 gene (1.33-fold change). In addition, serum levels of TAC, LH, FSH, Testosterone were significantly increased (p < 0.05). mRNA expression of protamine (p = 0.016) and BCL2 (0.72-fold change) were detected. Furthermore, in comparison with diabetic rats, the Cynara scolymus L-and Bifidobacterium longum-treated groups showed a significant increase in the number of sexual lineage cells, total weight, sperm count, motility, normal morphology, volume of the testis, and volume and length of seminiferous tubules (p < 0.05). Conclusion: The findings demonstrated that Cynara scolymus L extract and Bifidobacterium longum supplement had great therapeutic potential, including antioxidant, anti-apoptotic, anti-diabetic, fertility index improvement, and sex hormone modulators.

The conserved genetic program of male germ cells uncovers ancient regulators of human spermatogenesis.

Male germ cells share a common origin across animal species, therefore they likely retain a conserved genetic program that defines their cellular identity. However, the unique evolutionary dynamics of male germ cells coupled with their widespread leaky transcription pose significant obstacles to the identification of the core spermatogenic program. Through network analysis of the spermatocyte transcriptome of vertebrate and invertebrate species, we describe the conserved evolutionary origin of metazoan male germ cells at the molecular level. We estimate the average functional requirement of a metazoan male germ cell to correspond to the expression of approximately 10,000 protein-coding genes, a third of which defines a genetic scaffold of deeply conserved genes that has been retained throughout evolution. Such scaffold contains a set of 79 functional associations between 104 gene expression regulators that represent a core component of the conserved genetic program of metazoan spermatogenesis. By genetically interfering with the acquisition and maintenance of male germ cell identity, we uncover 161 previously unknown spermatogenesis genes and three new potential genetic causes of human infertility. These findings emphasize the importance of evolutionary history on human reproductive disease and establish a cross-species analytical pipeline that can be repurposed to other cell types and pathologies.

Sperm are one of the most remarkable cells in nature, safely housing genetic information while also often moving through foreign environments in search of an egg to fertilize. Central for sexual reproduction, sperm cells of all shapes and sizes are found in animals, plants and even some species of fungi. You may be familiar with the streamlined structure of human sperm, for example, with its round head and flexible tail; but the sperm cells of fruit flies are about 300 times longer, and those found in mice have a hook-shaped head. Relatedly, the genes involved in the creation of reproductive cells often show rapid evolution, with their sequences quickly diverging between species. Due to the complexity of the network of genetic interactions taking place during sperm development, it has so far been difficult to fully isolate the 'core program' that governs sperm assembly and allows these cells to acquire their distinct identity. Whether this program could be conserved and shared across the tree of life, in particular, remains unclear. In response, Brattig-Correia, Almeida, Wyrwoll et al. first conducted analyses that allowed them to pinpoint the genes that were 'switched on' during the formation of human, mouse and fruit fly sperm. Assessing the 'age' of these genes showed that a large proportion had emerged early during evolution. Shared across the three species, these deeply conserved genes were shown to play a fundamental role in sperm cells acquiring and maintaining their identity. Further genetic experiments were conducted in fruit flies to refine these findings, highlighting a set of 161 previously unknown genes essential for sperm formation. By combining these results with genetic data from men unable to have children, Brattig-Correia, Almeida, Wyrwoll et al. were able to identify three new genes that could play a role in human infertility. This work emphasizes how our understanding of human reproductive development can benefit from examining this process in other species, and its evolutionary history. In particular, the knowledge gained from these comparative approaches could ultimately help develop better genetic tests and treatments for human infertility.

Association between female infertility and stroke mortality: evidence from the PLCO cancer screening trial.

Objective: While infertility affects about 15% of women during their reproductive years, its long-term impact on stroke mortality after this period remains unclear. This study aims to investigate the association between infertility and stroke mortality in women using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. Methods: We analyzed data from 75,778 female participants aged 55-74 years with a median follow-up of 16.84 years. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for stroke mortality, adjusting for potential confounders. Results: Among participants, 14.53% reported infertility. During follow-up, 1,159 women died from stroke. Compared to women without infertility, those with infertility had a higher risk of stroke mortality (HR 1.21, 95% CI 1.04-1.41, p = 0.016). This association remained statistically significant after adjusting for age, race, education level, marital status, smoking status, body mass index, history of hypertension, history of heart attack, history of diabetes mellitus, birth control pill use, hormone replacement therapy, endometriosis, first menstrual period and pregnancy history (HR 1.20, 95% CI 1.02-1.42, p = 0.029). Sensitivity and subgroup analyses yielded consistent results. Conclusion: The findings of this study indicate that infertility is associated with an increased risk of stroke mortality in women. Further research is needed to confirm these findings and elucidate the underlying mechanisms.

Intracytoplasmic sperm injection versus conventional in vitro fertilization in unexplained infertility.

Objective: To compare cumulative live birth rate (CLBR) and cost-effectiveness of intracytoplasmic sperm injection (ICSI) vs. conventional in vitro fertilization (cIVF). Design: Retrospective cohort study of cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Setting: Society for Assisted Reproductive Technology (SART) member IVF clinics in the United States. Patients: Patients with unexplained infertility who underwent first autologous retrieval cycles between January 2017 and December 2019 with linked fresh and frozen embryo transfers through December 2021. Interventions: ICSI vs. cIVF. Main Outcome Measures: The primary outcome was CLBR, defined as ≤1 live birth from a retrieval cycle and all linked embryo transfers. Secondary outcomes included two pronuclear (2PN) per oocyte retrieved, miscarriage rate, and total number of transferred or frozen embryos per 2PN. Subsamples with and without preimplantation genetic testing for aneuploidy (PGT-A) were analyzed. Outcomes were adjusted for age, body mass index, number of oocytes retrieved, length of follow-up, and clinic ICSI use rate. Results: A total of 18,805 patients with unexplained infertility were included. No difference in CLBR was found among cycles without genetic testing (54.4% ICSI vs. 57.5% cIVF) and with PGT-A (47.6% ICSI vs. 51.8% cIVF). Intracytoplasmic sperm injection cycles without genetic testing had a higher miscarriage rate (16.4% vs. 14.4%) but no difference was seen in cycles with PGT-A (13.9% ICSI vs. 13.2% cIVF). Intracytoplasmic sperm injection cycles had a significantly lower ratio of 2PN per oocyte retrieved without genetic testing (59.7% vs. 60.9%) and with PGT-A (63.3% vs. 65.8%). The ratio of embryos transferred or frozen per 2PN was not significantly different in cycles without genetic testing (49.4% vs. 49.6%) or with PGT-A (54.2% vs. 55.2%). Total fertilization failure occurred in 216 patients (4%) who underwent cIVF and in 153 patients (1.1%) who used ICSI.Compared with cIVF alone, an estimated additional $11,011,500 was charged to patients for ICSI without genetic testing and $9,010,500 was charged to patients for ICSI with PGT-A over 2 years by Society for Assisted Reproductive Technology clinics. On the basis of total fertilization failure rates, 35 patients would require treatment with routine ICSI to avoid a single cycle of total fertilization failure with cIVF. Conclusions: Routine use of ICSI in unexplained infertility is not warranted due to the additional cost and lack of CLBR benefit.

Which obstetrics-gynecology residency programs are training future reproductive endocrinology and infertility fellows? An observational study.

Objective: To identify where reproductive endocrinology and infertility (REI) fellows trained for residency. Design: Observational, cross-sectional study. Setting: Not applicable. Subjects: Reproductive endocrinology and infertility fellows. Interventions: Not applicable. Main Outcome Measures: Percentage of fellows who completed residency training at an institution with an REI fellowship program. Results: A total of 289 fellows were identified among the graduating fellowship classes from 2023-2027. Of those fellows, 69.9% completed residency at an institution that had an associated REI fellowship program, and 19.7% remained at the same institution for residency and fellowship. In the last 5 years, 34.4% of obstetrics and gynecology residency programs have had at least 1 resident enter REI fellowship. Conclusions: Most matriculated REI fellow physicians train at residency programs that have an associated REI fellowship program.

Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity.

Sperm production depends on proper Sertoli-germ cell interaction, and we hypothesized that receptor activator of nuclear factor κB ligand (RANKL) activity in Sertoli cells may influence spermatogenesis. Treatment with the RANKL inhibitor denosumab, normally used to treat osteoporosis, increased testicular weight, inhibin B, and germ cell proliferation in ex vivo testis cultures and in vivo in a humanized RANKL mouse. The effect on germ cell proliferation was positively associated with baseline serum concentrations of anti-müllerian hormone (AMH). In accordance, denosumab increased germ cell proliferation in ex vivo human testis cultures with low/moderate but not severe impairment of Sertoli cell function. In a placebo-controlled randomized clinical trial, denosumab had no effect on semen quality but increased sperm concentration in a subgroup of infertile men with serum AMH ≥38 pmol/L at baseline. In conclusion, high serum AMH may increase the probability of a beneficial response to denosumab treatment in infertile men, thus suggesting a possible venue for precision medicine in male infertility.

Fertility Preservation for Iatrogenic Infertility: Patient Barriers and Opportunities for the Reproductive Medicine Workforce.

Iatrogenic infertility can result from medically necessary treatments that reduce fertility potential such as gonadotoxic chemotherapy and radiation but also brain and pelvic surgery, biologics for autoimmune disease, and hormone therapy. Fertility preservation (FP) involves freezing embryos, oocytes, ovarian tissue, sperm, or testicular tissue for future procreation and may be the only option for some patients who hope to use their autologous gametes for future reproduction. Although there is a growing awareness to refer patients at risk for iatrogenic infertility to reproductive specialists, patients seeking FP continue to face a multitude of barriers. The most prohibitive factor is cost, but poor accessibility to specialty care, lack of education of providers and patients, and stigmatization around reproductive health may all lead to delayed referrals.We discuss several opportunities for the reproductive medicine workforce to help address barriers to FP. One method to make FP more accessible to patients in a shorter timeframe would be to make it more affordable through improved insurance coverage. Currently, there is no active federal legislation mandating that insurance plans cover FP; however, there have been several success stories at the state level. Additionally, education of providers and patients through multispecialty collaboration and targeted campaigns, can have a profound impact on expediting referral for fertility care. Promising new technologies and innovation in healthcare delivery are also on the horizon.Unaddressed fertility concerns are very distressing to patients and detrimental to their quality of life. Urologists can contribute significantly to improving the care for these patients clinically and through advocacy and education.

Does Sperm DNA Fragmentation Index Continuously Decrease Over Time After Varicocelectomy in Varicocele-Induced Infertility? A Systematic Review and Meta-Analysis.

Varicocele (VC) is the most frequent and reversible cause of male infertility. One of the preferred management strategies to alleviate this problem is varicocelectomy. However, there are no researchers who have explored the relationship between better timing and postoperative sperm DNA fragmentation index (DFI) improvement in patients. We conducted this meta-analysis by enrolling published studies to find out the best waiting time after varicocelectomy to wait for better improvement of sperm DFI. A literature search was conducted using PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases. The data from the pooled analysis were presented as mean difference (MD) along with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. Four studies were included after screening relevant literature. Statistical analysis revealed that after varicocelectomy, follow-up results within 3 months showed a significant improvement in sperm DFI compared with the preoperative period (MD: -3.66, 95% CI = [-5.17, -2.14], p < .00001), and follow-up results with 6 months showed a significant improvement in sperm DFI compared with the postoperative 3 months as well (MD: -1.51, 95% CI = [-2.73, -0.29], p = .02). Notably, no further improvement in sperm DFI was observed when the follow-up period reached 12 months (MD: -1.59, 95% CI = [-3.22, 0.05], p = .06). Six months after varicocelectomy may be the optimal time for sperm DFI compared with 12 months or even longer, which means it is also the preferable time for conception. However, more well-designed prospective studies are needed in the future to validate our conclusion.

Examining the Relationship Between Polystyrene Microplastics and Male Fertility: Insights From an In Vivo Study and In Vitro Sertoli Cell Culture.

BACKGROUND: While polystyrene microplastics (PS-MPs) are emerging as potentially significant health threats, linked to cancer and reproductive dysfunction, their precise effects on human health remain largely unknown. We aimed to investigate the underlying mechanisms promoting microplastic-induced damage in the reproductive system. METHODS: Thirty C57BL/6 male mice were randomly allocated into six equal-sized groups. Mice were exposed to fluorescent PS-MPs (5 µm, < 18%, green) at a dose of 1 and 3 mg/dL via oral gavage for 28 and 56 days, respectively (control, 0 mg/dL). The presence of antibodies and inflammatory and oxidative stress markers were evaluated using western blotting. Sperm analysis was also performed. Mouse testis Sertoli TM4 cells were divided into two groups: control (medium only) and PS-MPs (medium containing, 1,000 µg/mL) groups and cultured in vitro for 1, 24, 48, or 72 hours. The cells were cultured in a Ham's F12: Dulbecco's Modified Eagle Medium medium with 0.25% fetal bovine serum at 37°C with humidified atmosphere of 5% carbon dioxide in the air. Protein analyses for interleukin (IL)-6, IL-10, NADPH-oxidase (NOX)-2, NOX-4, hypoxia-inducible transcription factor (HIF)-2α, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß were performed using western blotting. RESULTS: The testes were evaluated after 28 and 56 days of exposure. Varying sizes of PS-MPs were detected in the testes (ranging from 5.870 to 7.768 µm). Significant differences in sperm concentration, motility, and the proportion of normal sperm were observed between the two groups. An increase in TGF-ß, HIF-2α, and NOX-4 levels was observed using western blot analysis. However, no dose-dependent correlations were observed between the two groups. In vitro evaluation of the PS-MPs group displayed PS-MP penetration of the lumen of Sertoli cells after 1 hour. Further PS-MP aggregation within Sertoli cells was observed at 24, 48, and 72 hours. A significant increase in inflammatory protein expressions (IL-10, TGF-ß, MCP-1, IL-6, TNF-α, and HIF-2α) was observed through western blotting, although oxidative agents did not show a significant increase. CONCLUSION: PS-MPs induced reproductive dysfunction in male mice provide new insights into PS-MPs-associated toxicity in mammals.

A Novel Homozygous Missense ZP1 Variant Result in Human Female Empty Follicle Syndrome.

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.