Male Factor Infertility Research Articles

The power of 810nm near-infrared photobiomodulation therapy for human asthenozoospermia.

Sperm motility is a crucial factor in male fertility. Photobiomodulation (PBM) has been reported to increase sperm motility, but a consistent approach suitable for identifying standardizable protocols is lacking. We collected asthenozoospermic (n = 70) and normozoospermic (n = 20) semen. The asthenozoospermic samples were irradiated with an 810nm diode laser, in continuous wave mode, at 0.25W, 0.5W, 1W and 2W for 60s on a circular area of 1cm2through a novel handpiece with an innovative flat-top profile. Sperm motility was assessed immediately, after 30 and 60min. A sample size calculator, unpaired t-test and one-way ANOVA with post-hoc Tukey HSD tests were used for statistics. One and 2W were the most effective outputs in increasing progressive motility compared to control (p < 0.001). The maximum effect was immediately after 1W-PBM (p < 0.001) and decreased after 60min (p < 0.001). Time physiologically decreased vitality (p < 0.001), but less in the 1W-PBM samples (p < 0.05). 1W-PBM did not affect chromatin condensation. Asthenozoospermic samples displayed an impairment of 80% in oxygen consumption and ATP production and a slight inefficiency of oxidative phosphorylation compared to normozoospermic samples (p < 0.001). 1W-PBM partially restored the functionality of aerobic metabolism (p < 0.001) by recovery of oxidative phosphorylation efficiency. PBM did not affect lactate dehydrogenase (glycolysis pathway). No irradiated samples increased accumulated malondialdehyde, a marker of lipidic peroxidation. In conclusion, PBM improves progressive motility in asthenozoospermia through increased mitochondrial energetic metabolism without harmful oxidative stress.

Transplantation of human umbilical cord-derived mesenchymal stem cells improves age-related ovarian functional decline via regulating the local renin–angiotensin system on inflammation and oxidative stress

BackgroundAge-related reproductive aging is a natural and irreversible physiological process, and delaying childbearing is increasingly common all over the world. Transplantation of mesenchymal stem cells (MSCs) is considered a new and effective therapy to restore ovarian function, but the relevant mechanisms remain unclear. Recently, it has been found that there is a local Renin–angiotensin system (RAS) in human ovary and it plays a key role.MethodsAfter collecting follicular fluid from women who received oocyte retrieval for pure male factor infertility, the level of RAS components in it were detected, and the correlation analysis by linear regression. Then, the in vivo experiments on female C57BL/6 mice were designed to measure ovarian function, and the transcription and translation levels of RAS pathway were detected by molecular biology methods. Moreover, the role of RAS in regulating inflammation and oxidative stress in the co-culture system were explored in in vitro experiments on KGN cells.ResultsFirst, a total of 139 samples of analyzable follicular fluid were obtained. The local RAS of ovary, which is independent of systemic RAS (P > 0.05), is affected by age (Pearson r < 0, P < 0.05) and related to ovarian function, inflammation, oxidative stress indexes and assisted reproduction laboratory outcomes (P < 0.05). Next, the ovary/body weight of aging mice decreased significantly and serum sex hormones levels changed significantly (P < 0.01). The number of functional follicles decreased, while the atresia follicles increased (P < 0.05). After MSCs transplantation, all the above measures have been partially recovered (P < 0.05). Although several RAS components in aging ovary changed, MSCs only improved the expression level of AT1R (P < 0.05). Furthermore, the secretion ability and mitochondrial membrane potential of aging KGN cells decreased, while the intracellular ROS level and the aging cells ratio increased (P < 0.01). All the above measures have been partially recovered when co-cultured with MSCs (P < 0.05). After Ang(1–7) were added into the co-culture system, the above have been more significantly restored compared with Ang II (P < 0.05). Nevertheless, there was no statistical difference in estradiol level no matter which one was added (P > 0.05).ConclusionsTogether, our findings indicate that a novel possible mechanism to explain how stem cells restore age-related ovarian functional decline.

Pharmacological therapies for male infertility.

Male factor infertility is a multifaceted problem that affects approximately 50% of couples suffering from infertility. Causes of male infertility include endocrine disturbances, gonadotoxins, genetic abnormalities, varicocele, malignancies, infections, congenital or acquired urogenital abnormalities, iatrogenic factors, immunological factors, and idiopathic reasons. There are a variety of treatment options for male infertility, depending on the underlying cause(s). These can include surgical treatments, medical/hormonal therapies, and assisted reproductive techniques (ART), which can be combined with surgical sperm retrieval (SSR) if necessary. In this review article, the pharmacological therapies for male infertility are grouped by their underlying causes. Some of these therapies are targeted and specific, while others are used empirically to treat idiopathic male infertility. This will include treatments to optimize infertility in patients who have hypogonadism, ejaculatory dysfunction, infections, or idiopathic male infertility. Finally, we will provide an overview of the future directions of pharmacological therapies for male infertility. Significance Statement Male infertility is a significant worldwide problem. Detailed knowledge of the pharmacological therapies available will ensure the prescription of appropriate therapy and avoid the use of unnecessary or harmful treatments.

Evaluation of serum inhibin B and inhibin B/FSH ratio in the diagnosis of non-obstructive azoospermia and oligozoospermia.

Infertility affects approximately 15 % of couples globally, with 50 % cases of male factor infertility. Precise assessment of spermatogenesis is essential for evaluating male infertility. Recent studies suggest serum inhibin B as a promising biomarker for testicular function. This study aims to evaluate the diagnostic utility of serum inhibin B in predicting male infertility, particularly focusing on its relationship with sperm count. A cross-sectional study was conducted on 80 adult men (mean age 31.4±6.89 years) presenting with infertility at gynecology and urology outpatient departments. Semen analysis was performed following WHO (2010) guidelines, and serum inhibin B levels were quantified. The correlation between serum inhibin B levels and sperm parameters was assessed using Pearson's correlation test. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic accuracy of serum inhibin B and the inhibin B/FSH ratio for non-obstructive azoospermia (NOA) and oligozoospermia. A significant positive correlation was observed between serum inhibin B and sperm count (r=0.94, p<0.001). ROC analysis demonstrated that the inhibin B/FSH ratio had the highest diagnostic accuracy for NOA and oligozoospermia (AUC=0.986), with sensitivity of 100 % and specificity of 91.67 %. Serum inhibin B alone also showed high diagnostic value (AUC=0.965 for NOA and 0.969 for oligozoospermia). Serum inhibin B is a reliable biomarker for assessing male infertility, particularly in evaluating spermatogenic function. The inhibin B/FSH ratio provides superior diagnostic accuracy for NOA and oligozoospermia, offering valuable clinical utility in male infertility diagnosis.

Identification and Manipulation of Spermatogonial Stem Cells with the Aim of Inducing Spermatogenesis in Vitro.

Assisted reproduction techniques for infertile men with non-obstructive azoospermia require a sufficient number of functional germ cells produced in vitro. Understanding the mechanisms that allow the resumption of spermatogenesis outside the testicular environment is crucial for fertility preservation in these patients. A review of the literature was conducted using databases such as PubMed, Scopus and Web of Science, with keywords including "spermatogonial stem cell," "germ cells," "male factor infertility," and "enrichment and propagation of SSCs in vitro." Currently, two models-"in vivo" and "in vitro"-have been developed for producing haploid germ cells. The "in vivo" models include spermatogonial stem cell transplantation and testicular xenograft techniques. In contrast, the "in vitro" models consist of conventional culture systems, organ culture, and three-dimensional culture systems, all designed to induce spermatogenesis in vitro. These culture systems enable the simulation of the seminiferous epithelium in vitro, which facilitates better regulation of cell-signaling pathways that control the self-renewal and differentiation of SSCs. This review provides up-to-date information on the organization of SSCs, focusing on the identification, proliferation, and differentiation of spermatogonia in vitro.

Semen static oxidation-reduction potential is not helpful in evaluating male fertility.

Infertility affects a significant percentage of couples worldwide, with male infertility contributing substantially in a considerable number of cases. Research indicates that oxidative stress is a critical factor impacting male fertility. To explore the relationship between semen static oxidation-reduction potential (sORP), sperm parameters, and validated biomarkers of oxidative stress in infertile men. This cross-sectional study involved 202 men diagnosed with idiopathic male factor infertility and male partners from couples with unexplained infertility. Multivariable linear regression to query the associations between sORP, sperm parameters, and oxidative aggression biomarkers (lipid peroxidation, mitochondrial membrane potential, annexin V, and sperm DNA fragmentation). SORP has no linear association with any semen analysis parameter. Furthermore, its relationship with validated biomarkers of oxidative stress was inconsistent. sORP was inversely related to lipid peroxidation (multivariable linear regression coefficient: -0.64), positively associated with sperm DNA fragmentation (multivariable linear regression coefficient: 3.20), and unrelated to mitochondrial membrane potential or annexin V. There is no clear or consistent relationship between sORP and validated oxidative aggression biomarkers or sperm parameters. Our findings suggest that sORP is unlikely to be helpful in the evaluation of a male with idiopathic infertility.

The Human 8-oxoG DNA Glycosylase 1 (OGG1) Ser326Cys Polymorphism in Infertile Men.

8-hydroxy-2'-deoxyguanosine (8-OHdG) is a form of oxidative DNA damage caused by oxidative stress (OS), which is considered a major factor in male infertility. The cellular defense system against 8-OHdG involves base excision repair (BER) with the enzyme 8-Oxoguanine DNA glycosylase 1 (OGG1). However, studies on the single-nucleotide polymorphism (SNP) OGG1 Ser326Cys have demonstrated that the Cys326Cys genotype could be the cause of an increment in oxidative DNA damage. In this study, the OGG1 Ser326Cys polymorphism and its effect on DNA oxidation were evaluated in 118 infertile men. Polymorphic screening was performed using TaqMan allelic discrimination assays, and oxidative DNA damage was evaluated through the quantification of 8-OHdG and total antioxidant capacity (TAC); in addition, electrical bioimpedance spectroscopy (EBiS) measurements were used as a reference for different electrical properties associated with 8-OHdG concentrations. The detected Cys (G) allele frequency (0.4) was higher compared to the allele frequency reported in the "Allele Frequency Aggregator" (ALFA) and "Haplotype Map" (HapMap) projects for American populations (0.21-0.29), suggesting that the Cys (G) allele carrier could be a factor associated with American infertile populations. The values of 8-OHdG were twofold higher in carriers of the Cys326Cys (GG) genotype than the other genotypes and, in concordance, the TAC levels were threefold lower in Cys326Cys (GG) genotype carriers compared to the other genotypes. Moreover, the EBiS magnitude exhibited potential for the detection of different oxidative damage in DNA samples between genotypes. The Cys326Cys (GG) genotype is associated with oxidative DNA damage that could contribute to male infertility.

Medical therapy for male infertility.

To provide up-to-date evidence and clinical guidance on the role of medical therapy in the context of hormonal imbalances affecting human spermatogenesis. Compelling evidence has accumulated over the years regarding the role of gonadotropins, selective estrogen modulators, and aromatase inhibitors to either improve or restore spermatogenesis in men with hormonal abnormalities (e.g. hypogonadotropic/hypergonadotropic hypogonadism, hyperprolactinemia) or supraphysiologic levels (e.g. exogenous testosterone/anabolic steroid use). Despite the increasing number of studies being performed, most of the available evidence relies on small nonrandomized studies, mainly in men with hypergonadotropic hypogonadism or with history of exogenous testosterone/anabolic steroid use. As such, the efficacy of medical therapy is highly variable emphasizing the necessity of randomized clinical trials and individualized approaches. This narrative review provides clinical guidance on medical therapies for male factor infertility based on the most up-to-date evidence, focusing on treatments for hormonal abnormalities (either hypogonadotropic or hypergonadotropic hypogonadism and hyperprolactinemia) and supraphysiologic levels (and exogenous testosterone/anabolic steroid use) to improve spermatogenesis.

Impact of GnRH antagonist pretreatment on oocyte yield after ovarian stimulation: A retrospective analysis.

The study investigates whether a 3-day pretreatment course with a GnRH antagonist in the early follicular phase has an impact on the number of retrieved COCs in a GnRH antagonist stimulation protocol. This is a retrospective single center crossover study involving women who did not conceive after one GnRH antagonist stimulation cycle ("standard cycle") and proceeded with another GnRH antagonist stimulation cycle preceded by early administration of GnRH antagonist for 3 days ("pretreatment cycle") with fresh embryo transfer or frozen embryo transfer. 430 patients undergoing 860 cycles were included. The mean female age was 34.4 ± 4.8 years. Indications for fertility treatment included unexplained infertility (34.3%), male-factor infertility (33.3%), age (16.9%), PCOS (8.2%), tubal (4.7) and endometriosis (2.6%). All cycles were divided into two groups: group 1 (standard, 430 cycles) and group 2 (pretreatment, 430 cycles). The mean duration of stimulation was similar in both groups (10.3 vs 10.3 days, p = 0.28). The starting dose of gonadotropin (234.9 vs 196.8 IU, p<0.001), total amount of gonadotropin used (2419 vs 2020 IU, p<0.001), the total number of retrieved COCs (10 vs 7.8 p<0.001) and the number of mature oocytes (8 vs 5.8 p<0.001) were significantly higher in group 2 than in group 1. The Generalized estimating equation (GEE) regression analysis showed that the pretreatment strategy had a significant positive effect on the number of COCs (coefficient 2.4, p <0.001 after adjusting for known confounders (age, indication, stimulation dose, type, and duration of stimulation). In conclusion, A 3-day course of GnRH antagonist pretreatment increases the number of COCs obtained after ovarian stimulation.

The role of S-palmitoylation of C4BPA in regulating murine sperm motility and complement resistance

The epididymis and epididymosomes are crucial for regulating sperm motility, a key factor in male fertility. Palmitoylation, a lipid modification involving the attachment of palmitic acid to cysteine residues, is essential for protein function and localization. Additionally, this modification plays a vital role in the sorting of proteins into exosomes. This study investigates the role of S-palmitoylation at the Cys15 residue of the C4b binding protein alpha chain (C4BPA) in murine sperm motility. Our findings revealed high expression of C4BPA mRNA in the caput epididymis, with the protein present across all regions of the epididymis. Palmitoylation of C4BPA in epididymal epithelial cells was essential for its enrichment in epididymosomes and on sperm, thereby maintaining sperm motility. Inhibition of palmitoylation significantly reduced sperm motility and the localization of C4BPA on sperm. Additionally, palmitoylated C4BPA in exosomes resisted complement C4 attacks, preserving motility, unlike mutated C4BPA (C15S). These results highlight the critical role of palmitoylated C4BPA in protecting sperm from complement attacks and maintaining motility, suggesting that reversible palmitoylation of epididymal proteins could be explored as a therapeutic strategy for male contraception. Our study underscores the importance of post-translational modifications in sperm function and presents new insights into potential male contraceptive methods.

9233 Sperm-carried IGF2: a Spark Contributing To Embryo Growth And Development

Abstract Disclosure: R. Cannarella: None. O.J. Rando: None. R.A. Condorelli: None. C. Sandrine: None. S. Romano: None. A. Guglielmino: None. Q. Yin: None. H. Gustafsson: None. F. Mancuso: None. C. Bellucci: None. G. Luca: None. S. La Vignera: None. A.E. Calogero: None. Background: Sperm RNAs can regulate early embryo development. A potential key regulator of growth is insulin-like growth factor 2 (IGF2), a highly conserved paternally-imprinted gene involved in cell growth and proliferation that is expressed in human spermatozoa. Animal research supports the positive impact of IGF2-supplemented cultures on embryo quality. However, the role of sperm-carried IGF2 in the early development of the human embryo is unknown. Objective: To study whether sperm-carried IGF2 mRNA influences the morphokinetics of the human embryo. Design: Prospective, uncontrolled, observational pilot study. Setting: University-affiliated fertility center. Subjects: We enrolled 16 patients undergoing assisted reproductive techniques (ART) for idiopathic or male factor infertility and 10 healthy fertile controls with proven paternity. Couples with female factor infertility due to reduced oocyte reserve were excluded, while those with tubal factor or anovulation were included. Main Outcome Measure(s): After clinical use, an aliquot of the sperm samples employed for ART was used to evaluate IGF2 mRNA levels. Embryo kinetics were recorded and correlated with the amount of IGF2 mRNA, correcting for female age, body mass index (BMI), anti-Müllerian hormone (AMH) levels, and oocyte quality. To provide mechanistic insights into the human data, a transcriptome analysis was performed of parthenotes obtained from twelve-week-old superovulated mice injected with Igf2 mRNA plus Gfp mRNA (experimental group, n=20) or Gfp mRNAs (control group, n=20). Pathway enrichment analysis was then performed using g:Profiler g:GOSt and EnrichR. Results: Sperm IGF2 mRNA negatively correlated with time to 2-cell stage (t2), t3, t4, t5, and time to expanded blastocyst (tEB), independently of maternal age, BMI, AMH, and oocyte quality. IGF2 mRNA index &amp;gt;4.9 predicted the ability of the embryo to reach the blastocyst stage at day 5, with a sensitivity of 100% and specificity of 71.6% (AUC 0.845; p&amp;lt;0.001). The distribution of sperm IGF2 levels differs significantly between morphologically good or poor embryos, with the lowest levels more frequently associated with morphologically poor embryos (61.9%) than with good ones (38.1%) (p=0.0091). Furthermore, sperm-derived IGF2 levels were significantly lower in subfertile men compared to fertile controls with proven paternity. Transcriptome analysis of Igf2-injected embryos demonstrated differential expression of 101 genes activating pathways regulating early embryo development. Conclusion: Sperm-carried IGF2 mRNA can support early embryo development, independently of female factors. Larger studies are needed to confirm this finding and to investigate its role as a clinical marker to predict the chances of obtaining blastocysts that can be implanted in infertile couples undergoing ART. Presentation: 6/1/2024

7110 Sperm-carried IGF2: a Spark Contributing To Embryo Growth And Development

Abstract Disclosure: R. Cannarella: None. O.J. Rando: None. R.A. Condorelli: None. C. Sandrine: None. S. Romano: None. A. Guglielmino: None. Q. Yin: None. H. Gustafsson: None. F. Mancuso: None. C. Bellucci: None. G. Luca: None. S. La Vignera: None. A.E. Calogero: None. Background: Sperm RNAs can regulate early embryo development. A potential key regulator of growth is insulin-like growth factor 2 (IGF2), a highly conserved paternally-imprinted gene involved in cell growth and proliferation that is expressed in human spermatozoa. Animal research supports the positive impact of IGF2-supplemented cultures on embryo quality. However, the role of sperm-carried IGF2 in the early development of the human embryo is unknown. Objective: To study whether sperm-carried IGF2 mRNA influences the morphokinetics of the human embryo. Design: Prospective, uncontrolled, observational pilot study. Setting: University-affiliated fertility center. Subjects: We enrolled 16 patients undergoing assisted reproductive techniques (ART) for idiopathic or male factor infertility and 10 healthy fertile controls with proven paternity. Couples with female factor infertility due to reduced oocyte reserve were excluded, while those with tubal factor or anovulation were included. Main Outcome Measure(s): After clinical use, an aliquot of the sperm samples employed for ART was used to evaluate IGF2 mRNA levels. Embryo kinetics were recorded and correlated with the amount of IGF2 mRNA, correcting for female age, body mass index (BMI), anti-Müllerian hormone (AMH) levels, and oocyte quality. To provide mechanistic insights into the human data, a transcriptome analysis was performed of parthenotes obtained from twelve-week-old superovulated mice injected with Igf2 mRNA plus Gfp mRNA (experimental group, n=20) or Gfp mRNAs (control group, n=20). Pathway enrichment analysis was then performed using g:Profiler g:GOSt and EnrichR. Results: Sperm IGF2 mRNA negatively correlated with time to 2-cell stage (t2), t3, t4, t5, and time to expanded blastocyst (tEB), independently of maternal age, BMI, AMH, and oocyte quality. IGF2 mRNA index &amp;gt;4.9 predicted the ability of the embryo to reach the blastocyst stage at day 5, with a sensitivity of 100% and specificity of 71.6% (AUC 0.845; p&amp;lt;0.001). The distribution of sperm IGF2 levels differs significantly between morphologically good or poor embryos, with the lowest levels more frequently associated with morphologically poor embryos (61.9%) than with good ones (38.1%) (p=0.0091). Furthermore, sperm-derived IGF2 levels were significantly lower in subfertile men compared to fertile controls with proven paternity. Transcriptome analysis of Igf2-injected embryos demonstrated differential expression of 101 genes activating pathways regulating early embryo development. Conclusion: Sperm-carried IGF2 mRNA can support early embryo development, independently of female factors. Larger studies are needed to confirm this finding and to investigate its role as a clinical marker to predict the chances of obtaining blastocysts that can be implanted in infertile couples undergoing ART. Presentation: 6/1/2024

7110 Sperm-carried IGF2: a Spark Contributing To Embryo Growth And Development

Abstract Disclosure: R. Cannarella: None. O.J. Rando: None. R.A. Condorelli: None. C. Sandrine: None. S. Romano: None. A. Guglielmino: None. Q. Yin: None. H. Gustafsson: None. F. Mancuso: None. C. Bellucci: None. G. Luca: None. S. La Vignera: None. A.E. Calogero: None. Background: Sperm RNAs can regulate early embryo development. A potential key regulator of growth is insulin-like growth factor 2 (IGF2), a highly conserved paternally-imprinted gene involved in cell growth and proliferation that is expressed in human spermatozoa. Animal research supports the positive impact of IGF2-supplemented cultures on embryo quality. However, the role of sperm-carried IGF2 in the early development of the human embryo is unknown. Objective: To study whether sperm-carried IGF2 mRNA influences the morphokinetics of the human embryo. Design: Prospective, uncontrolled, observational pilot study. Setting: University-affiliated fertility center. Subjects: We enrolled 16 patients undergoing assisted reproductive techniques (ART) for idiopathic or male factor infertility and 10 healthy fertile controls with proven paternity. Couples with female factor infertility due to reduced oocyte reserve were excluded, while those with tubal factor or anovulation were included. Main Outcome Measure(s): After clinical use, an aliquot of the sperm samples employed for ART was used to evaluate IGF2 mRNA levels. Embryo kinetics were recorded and correlated with the amount of IGF2 mRNA, correcting for female age, body mass index (BMI), anti-Müllerian hormone (AMH) levels, and oocyte quality. To provide mechanistic insights into the human data, a transcriptome analysis was performed of parthenotes obtained from twelve-week-old superovulated mice injected with Igf2 mRNA plus Gfp mRNA (experimental group, n=20) or Gfp mRNAs (control group, n=20). Pathway enrichment analysis was then performed using g:Profiler g:GOSt and EnrichR. Results: Sperm IGF2 mRNA negatively correlated with time to 2-cell stage (t2), t3, t4, t5, and time to expanded blastocyst (tEB), independently of maternal age, BMI, AMH, and oocyte quality. IGF2 mRNA index &amp;gt;4.9 predicted the ability of the embryo to reach the blastocyst stage at day 5, with a sensitivity of 100% and specificity of 71.6% (AUC 0.845; p&amp;lt;0.001). The distribution of sperm IGF2 levels differs significantly between morphologically good or poor embryos, with the lowest levels more frequently associated with morphologically poor embryos (61.9%) than with good ones (38.1%) (p=0.0091). Furthermore, sperm-derived IGF2 levels were significantly lower in subfertile men compared to fertile controls with proven paternity. Transcriptome analysis of Igf2-injected embryos demonstrated differential expression of 101 genes activating pathways regulating early embryo development. Conclusion: Sperm-carried IGF2 mRNA can support early embryo development, independently of female factors. Larger studies are needed to confirm this finding and to investigate its role as a clinical marker to predict the chances of obtaining blastocysts that can be implanted in infertile couples undergoing ART. Presentation: 6/1/2024

GnRH antagonist protocol with hCG triggering ameliorates fertilization defect caused by failure of cumulus cell pentraxin-3 expression in unilateral endometriomas.

The aim of the study was to determine the expression pattern of long pentraxin 3 (PTX3) mRNA in cumulus cells (CCs) isolated from metaphase II oocytes of women with unilateral endometrioma undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist (GnRHa) protocol. A total of 60 CC samples, 30 from the affected ovary and 30 from the contralateral ovary, were collected from 12 patients with unilateral endometrioma who underwent flexible GnRHa protocol with recombinant human chorionic gonadotropin (rhCG) trigger. Thirty CC samples collected from the left ovary of 12 women with male factor infertility were used as external controls. Long PTX3 mRNA expression in each group was analyzed by real-time polymerase chain reaction (RT-PCR). Relative gene expression (fold-change) was calculated according to the 2-ΔΔCt equation. Fertilization rates after intracytoplasmic sperm injection (ICSI) were recorded for each group. CC-PTX3 mRNA expression in the unilateral endometrioma group was significantly lower than the mRNA expression of the disease-free ovary (0.90±0.01 vs. 0.25±0.02, p<0.01). CC-PTX3 mRNA expression of MII oocytes of the disease-free ovary was found to be similar to the control group (1.02±0.03 vs. 0.90±0.01, p=0.107). A significant 3.6-fold downregulation was observed in the CC-PTX3 mRNA expression of the endometrioma group compared to the CC-PTX3 mRNA expression in the contralateral ovary. CC-PTX3 mRNA expression in the endometrioma group was downregulated 4.08-fold compared to the CC-PTX3 mRNA expression of the control group (1.02±0.03 vs. 0.25±0.02, p<0.001). The cumulus morphologies of the endometrioma group with low CC-PTX3 expression and the groups with normal CC-PTX3 levels were similar. Fertilization rates of the endometrioma group were similar to the contralateral ovary and control groups. Unilateral endometrioma reduces CC-PTX3 expression but does not affect disease-free ovaries. The GnRHa protocol improved the fertilization rates, suggesting that failed CC-PTX3 expression is an in vivo pathology.

Male factor infertility and implication of fertility treatment in low resource settings

Introduction: The prevalence of infertility has increased worldwide. The etiological factors are also changing in trend and prominence. Male infertility is driving the epidemic in many regions of the world. Therefore, the aim of this study was to explore male factor infertility in the Gambia. Methodology: The design was a longitudinal descriptive study of subfertile couples at a specialist tertiary hospital in Banjul, the Gambia, from August 2022 to May 2023. Data were extracted from patients folders and entered into a computer database. Descriptive statistics were used to analyze the data and results expressed in tables, graphs, and percentages. Results: Total number of subfertile couples analyzed was 152: male factor 69 (45.4%), ovulation disorder 34 (22.4%), tubal factor 20 (13.2%), uterine factor 8 (5.3%), and unexplained 21 (13.8%). The median age of male folk was 50 years, with an age range of 31 to 64 years. The rates of asthenoteratozospermia, oligospermia, and azospermia were 37.8%, 36.2%, and 26%, respectively. In azoospermic males, over 75% had elevated FSH (12–44 miu/mL). Conclusions: The prevalence of male infertility is at 45.4%, which is 3-fold and 2-fold higher than tubal and ovarian factors, respectively. Male infertility is a problem with obvious implications. The predominant types of male infertility we observed in this study will almost always require multidisciplinary care and ICSI.

The prevalence and etiology of infertility in a tertiary specialist hospital in the Gambia

Background: Infertility is a public health problem that has received little or no attention in most sub-Saharan Africa, especially in the Gambia. The prevalence of infertility in the Gambia is increasing from 9.0% in 1998 to 14.3% in 2017. Tubal factor was the predominant leading cause for decades, but recent reviews suggest that male factor is driving the epidermic of infertility worldwide. Therefore, the aim of this study was to determine the prevalence and etiological factors of infertility in our practice. Methodology: The design was a retrospective quantitative study. Data collection tool was developed and variables were retrieved from case notes between August 2022 to March 2023 at a specialist hospital in the Gambia. The data were entered into a computer database and analyzed using descriptive statistics. Results: Total number of women in the reproductive age of 15–49 years that attended gynecology clinic was 1475. Two hundred eighty-five couples (285) had infertility. The prevalence of infertility is 19.3% ~1:5 couples. The causes showed male factor 69 (45.4%), ovulation disorder 34 (22.4%), tubal factor 20 (13.2%), uterine factor 8 (5.3%), and unexplained 21(13.8%). Ovarian factors showed age-related poor ovarian reserve. Overall, male factor infertility was 53%, and female factor infertility was 47%. Conclusions: The prevalence of infertility is increasing and male factor is 3-folds and 2-folds higher than tubal and ovarian factors, respectively. The study observed increasing desire of fertility among female in advanced age. Universal access to assisted reproductive technology is essential.

Azoospermia factor gene microdeletions in infertile men with non-obstructive azoospermia and normal karyotype: First case-control study from Kashmir

BackgroundMicro-deletions in the Y chromosome are recognized as the causative factor for male infertility. The prevalence of Y chromosome micro-deletions exhibits variation among infertile males across different areas and races globally. The study of Y chromosome micro- deletions is crucial among genetic variables owing to their ability to transmit genetic defects to the progeny. Microdeletion of the azoospermia factor (AZF) region associated with the long arm of the Y chromosome (Yq) has three sub-regions (AZFa, AZFb, and AZFc) that play an important role in spermatogenesis. The genes associated with the AZF region of the Y chromosome are believed to play a crucial role in the process of spermatogenesis by performing several activities such as gene silencing, transcription, ubiquitination, and maintenance of microtubule networks. Due to the absence of epidemiological research on Y chromosome micro-deletions in ethnic infertile male population of Kashmir, our study sought to examine the Y chromosome micro-deletions among non-obstructive azospermic infertile men in Kashmir. ObjectiveThe research was aimed to establish the frequency and characteristics of micro-deletions in the AZF region of Y chromosome in infertile males of our population with non-obstructive Azoospermia and normal Karyotype. MethodsA total of 120 subjects were included in the study. Samples from 60 male patients with fertility issues (non-obstructive azoospermia) and an equal number of samples from normal men having established fatherhood (biological fathers) were taken for the study. The average age in years of cases and controls were 32.80 and 34.88 respectively. A total of 26.66 % of cases and 13.33 % of controls were found to be consanguineous, 36.66 % of cases and 40 % of controls were urban while 63.33 % of cases and 60 % of controls were from rural population. Molecular analysis was performed by multiplex polymerase chain reactions (PCR) using sequence tagged sites (STS) from 3 different regions of AZF of Y chromosome. To assess the frequency of AZF micro-deletions, molecular analysis was performed by multiplex polymerase chain reactions (PCR) using sequence tagged sites (STS) from 3 different regions of the Y chromosome (sY84 and sY86 for AZFa region; sY127 and sY134 for AZFb; sY254 and sY255 for AZFc region). ResultsIn the present study a total of 9 out of 60 cases (15 %) were found to have Y chromosome micro- deletions in AZF region of Yq arm. The most frequent micro deletions were observed in AZFb region, 8 out of 60 cases (13.33 %) from AZFb region were found to have deletions.5 out of 60 cases (8.33 %) were reported with deletions associated to AZFc region region and 6.66 % of cases were found to harbor deletions in both AZFb and AZFc region. However no deletion was reported in the AZFa region in all the studied cases. No micro-deletions were reported in the controls during the study. ConclusionThe study represents the first report on the incidence of Y chromosome microdeletions in infertile men from our population. The findings from the present study indicate the prevalence of these gene microdeletions as a major contributing factor to the etiology of infertility in males. This study emphasizes that the multiplex PCR based screening is a reliable method in ruling Y chromosome micro deletions as a factor in the pathogenicity of male infertility and recommends genetic testing prior to planning of any reproductive assistance.

Single nucleotide polymorphisms of CFAP43 and TEX14 associated with idiopathic male infertility in a Vietnamese population.

Male infertility is a multifactorial disease due to spermatogenesis impairment, with etiology remaining unknown for roughly one-third of infertile cases. Several studies have demonstrated that genetic variants are male infertility risk factors. CFAP43 and TEX14 are involved in the spermatogenesis process. The present study aimed to assess the association between single-nucleotide polymorphisms (SNPs) in CFAP43 (rs17116635 and rs10883979) and TEX14 (rs79813370 and rs34818467) and idiopathic male infertility in a Vietnamese population. A cohort of 206 infertile men and 195 controls were recruited for the study. CFAP43 and TEX14 SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes of randomly selected samples, accounting for 10% of the total, were confirmed using Sanger sequencing. The obtained data were analyzed using statistical methods. The results showed that 4 SNPs (rs17116635, rs10883979, rs79813370, and rs34818467) were in accordance with Hardy-Weinberg Equilibrium (HWE; P > .05). CFAP43 rs10883979 and TEX14 rs79813370 were associated with male infertility. For CFAP43 rs10883979, in the recessive model, the combination AA + AG was associated with male infertility when compared to the GG genotype (OR = 0.26; 95% CI: 0.06-0.85; P = .02). For TEX14 rs79813370, a protective effect against infertility risk was identified in the presence of the T allele of rs79813370 when compared to the G allele (OR = 0.48; 95% CI: 0.32-0.72; P < .001). Our results suggest that CFAP43 rs10883979 and TEX14 rs79813370 are likely associated with male infertility in the Vietnamese population, in which the G allele of rs79813370 may be a risk factor for male infertility.

A germline PAF1 paralog complex ensures cell type-specific gene expression.

Animal germline development and fertility rely on paralogs of general transcription factors that recruit RNA polymerase II to ensure cell type-specific gene expression. It remains unclear whether gene expression processes downstream from such paralog-based transcription is distinct from that of canonical RNA polymerase II genes. In Drosophila, the testis-specific TBP-associated factors (tTAFs) activate over a thousand spermatocyte-specific gene promoters to enable meiosis and germ cell differentiation. Here, we show that efficient termination of tTAF-activated transcription relies on testis-specific paralogs of canonical polymerase-associated factor 1 complex (PAF1C) proteins, which form a testis-specific PAF1C (tPAF). Consequently, tPAF mutants show aberrant expression of hundreds of downstream genes due to read-in transcription. Furthermore, tPAF facilitates expression of Y-linked male fertility factor genes and thus serves to maintain spermatocyte-specific gene expression. Consistently, tPAF is required for the segregation of meiotic chromosomes and male fertility. Supported by comparative in vivo protein interaction assays, we provide a mechanistic model for the functional divergence of tPAF and the PAF1C and identify transcription termination as a developmentally regulated process required for germline-specific gene expression.

Влияние распространенных бактериальных инфекций на индекс фрагментации ДНК сперматозоидов. Обзор литературы

Sperm DNA fragmentation is an important factor in male infertility, miscarriage and unsuccessful ART cycles. The purpose of thisreview wasto summarize and briefly analyze the available data on the effect of common infections of the male genitourinary tract on sperm DNA fragmentation (SDF), the mechanisms of their influence, efficacy and outcomes of treatment. Based on the results of these studies, it can be said that Chlamydia trachomatis, Ureaplasma spp. and Mycoplasma genitalium have a significant effect and lead to a pronounced increase in SDF. The effect of opportunistic bacteria on SDF depends on the type of microorganisms, their diversity and quantity. The presence of certain bacteria is associated with higher levels of ,some are presumably associated with beneficial effects and lower levels of SDF. Candidiasis can presumably affect SDF, but the available data are insufficient for an accurate answer. Treatment ofsuch infectionsleads to a decrease in sperm DNA fragmentation index, an increase in the effectiveness of ART and spontaneous pregnancy rates. Keywords: sperm DNA fragmentation, infection, male infertility, oxidative stress, fertility, semen analysis, sperm, sperm chromatin.