Search Results (49)

Background: Complete environmental adaptation requires both survival and reproductive success. The hypoxic Qinghai-Tibet Plateau (>3000 m) challenges reproduction in indigenous species. Tibetan sheep, a key plateau-adapted breed, possess remarkable hypoxic tolerance, yet the genetic basis of their reproductive success remains poorly understood. Methods: We integrated transcriptomic and genomic data from Tibetan sheep and two lowland breeds (Small-tailed Han sheep and Hu sheep) to identify Tibetan sheep reproduction-associated genes (TSRGs). Results: We identified 165 TSRGs: four genes were differentially expressed (DEGs) versus Small-tailed Han sheep, 77 DEGs versus Hu sheep were found, and 73 genes were annotated in reproductive pathways. Functional analyses revealed enrichment for spermatogenesis, embryonic development, and transcriptional regulation. Notably, three top-ranked selection signals (VEPH1, HBB, and MEIKIN) showed differential expression. Murine Gene Informatics (MGI) confirmed that knockout orthologs exhibit significant phenotypes including male infertility, abnormal meiosis (male/female), oligozoospermia, and reduced neonatal weight. Conclusions: Tibetan sheep utilize an evolved suite of genes underpinning gametogenesis and embryogenesis under chronic hypoxia, ensuring high reproductive fitness—a vital component of their adaptation to plateaus. These genes provide valuable genetic markers for the selection, breeding, and conservation of Tibetan sheep as a critical genetic resource. Full article

Background: Wolfram syndrome (WFS), also known as DIDMOAD, is a rare monogenic neurodegenerative disorder characterized by four key components: non-autoimmune insulin-dependent diabetes mellitus (DM), optic atrophy, sensorineural hearing loss, and diabetes insipidus. Although it significantly affects quality of life, gonadal dysfunction, particularly hypogonadism, remains underrecognized. Methods: In total, 45 patients (25 men, 20 women) with genetically confirmed WFS from a single tertiary-care center were prospectively followed to assess gonadal function. Men underwent hormonal evaluations, semen analysis, imaging tests, and testicular biopsies. In women, data on age at menarche, menstrual irregularities, and age at menopause were recorded. Hormonal analyses, including anti-Müllerian hormone (AMH) levels, and imaging tests were also conducted. Results: Hypogonadism was identified in 19 men (76.0%), of whom 17 (68.0%) had hypergonadotropic hypogonadism and 2 (8.0%) had hypogonadotropic hypogonadism. Testicular biopsies showed seminiferous tubule damage, Sertoli cell predominance, and reduced Leydig cells. Azoospermia was observed in 12 patients, whereas others presented with oligozoospermia, teratozoospermia, or asthenozoospermia. Most patients exhibited low testosterone levels along with elevated LH and FSH, suggesting primary testicular failure, except for two cases of hypogonadotropic hypogonadism. Correlations between biomarkers, onset age and severity have been analyzed and provide important insights regarding medical treatment. In women, menstrual irregularities were universal, with 20% experiencing premature menopause. Four patients had low AMH levels, with ovarian atrophy in three and a postmenopausal uterus in two, indicating early hypogonadism risk. Conclusions: Gonadal dysfunction is a significant yet overlooked feature of WFS, requiring systematic evaluation during puberty and beyond. Proper management is essential to mitigate metabolic disturbances and psychological impacts, including infertility distress, relationship challenges, and quality of life concerns. Addressing sexual health is crucial as WFS patients live longer and aspire to establish relationships or start families. Full article

Background/Objectives: Male infertility is becoming a serious problem affecting about 7% of all men worldwide and is a major or contributory factor in 50% of infertile couples overall. Men with abnormal semen parameters have a significantly increased risk of aneuploidy, presenting a serious concern in programmes of assisted reproductive technologies. Recently, the introduction of preimplantation genetic testing for aneuploidies (PGT-A) has increased the pregnancy rate and live births. We investigated the effect of PGT-A on the success of IVF treatment in couples with the male factor of infertility. Methods: Two experimental groups and one control group were studied: Group A (110 couples)—male partners with abnormal semen parameters, with PGT-A; Group B (110 couples)—male partners with abnormal semen parameters, without PGT-A; and Group C (105 couples)—control, male partners with normal spermograms, with PGT-A. A Day 3 blastomere biopsy was followed by FISH-based PGT-A. A total of 880 embryos from Group A and 890 embryos from Group C was analysed. Results: In patients with abnormal semen parameters, embryonic aneuploidy was twice as common compared to the control (13.6% vs. 5.8%, p < 0.001). Group B had the lowest clinical pregnancy rate (28.2%), with two out of three pregnancies ending in a miscarriage. Only 10% of IVF cycles in this group resulted in live birth compared with 35.5% for Group A and 49.5% for Group C. Conclusions: Our data demonstrate that PGT-A screening as part of IVF treatment drastically increases the clinical pregnancy rate and chances of live birth in couples where male partners have semen abnormality. Full article

Background: Tribulus terrestris L. Zygophyllaceae (TT) is a plant that has been claimed to increase testosterone levels and improve sexual function, particularly erectile dysfunction, with potential benefits for male sexual health. Purpose: This systematic review aimed to evaluate the effectiveness of TT supplementation in improving sexual function and serum testosterone levels in men. Methods: We conducted a systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After searching the literature (n = 162), 52 studies were selected for full-text reading, and 10 studies were eligible for this review, comprising 9 clinical trials and 1 quasi-experimental study (a study without a control). The Jadad score revealed low methodological quality for 50% of the studies. Results: The studies involved 15 to 172 participants (total = 483) aged between 16 and 70 years with different health conditions: healthy men (n = 5), oligozoospermia (n = 1), erectile dysfunction (n = 1), erectile dysfunction associated with hypogonadism (n = 2), and unexplained infertility (n = 1). TT supplementation at doses of 400 to 750 mg/d for 1 to 3 months improved erectile dysfunction in 3 of the 5 studies that assessed this parameter. Eight out of ten studies did not report significant changes in androgen profile following TT supplementation, but the subjects in the neutral studies did not have low androgen levels at baseline. Therefore, only 2 studies showed significant intra-group increase in total testosterone levels, which had low clinical magnitude (60–70 ng/dL) and involved subjects with hypogonadism. Conclusions: TT supplementation has a low level of evidence regarding its effectiveness in improving erectile function in men with erectile dysfunction, and no robust evidence was found for increasing testosterone levels. Full article

This study aimed to compare sperm DNA fragmentation (SDF) levels between ejaculate and testicular sperm and evaluate clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles using testicular sperm (T-ICSI) versus ejaculate sperm (E-ICSI) in males with high ejaculate SDF, prior ICSI failures, or severe male infertility. A systematic review of major databases and a subsequent meta-analysis were performed to compare clinical outcomes in men with high SDF, oligozoospermia, or prior ICSI failures undergoing T-ICSI or E-ICSI. Thirteen studies met the inclusion criteria. Outcomes analyzed included SDF levels, fertilization rate (FR), clinical pregnancy rate (CPR), live birth rate (LBR) per embryo transfer (ET), and miscarriage rate (MR) per pregnancy. The mean difference (MD) and odds ratio (OR) were calculated for each outcome. Paired assessments of SDF showed significantly lower levels in testicular sperm compared to ejaculated sperm (MD = −25.42 [−31.47, −17.30], p < 0.00001). While no significant difference in FR was observed in T-ICSI cycles overall (OR = 0.94 [0.74, 1.20]), a subgroup analysis revealed significantly higher FR with E-ICSI in men with oligozoospermia and no prior ICSI failures (OR = 0.61 [0.52, 0.71], p < 0.00001). CPR was significantly higher in T-ICSI cycles (OR = 2.13 [1.35, 3.36], p < 0.001; n = 540 ET), along with a significantly lower MR (OR = 0.31 [0.14, 0.70], p = 0.004; n = 35) and increased LBR (OR = 2.40 [1.32, 4.36], p = 0.004; n = 446 ET). In conclusion, using testicular sperm in cases of elevated ejaculate SDF, oligozoospermia, or prior failed ICSI cycles enhances the selection of sperm with lower DNA damage, leading to improved pregnancy rates, reduced miscarriage rates, and higher live birth rates. However, the studies included were rated as having a moderate to serious risk of bias. Further well-designed randomized controlled trials are necessary to confirm these findings with stronger evidence. Full article

Background: The incidence of colorectal cancer (CRC) is increasing in the population under 50 years of age, with more than 10% of cases occurring in young adults. Fertility preservation counseling has therefore received increased attention in this younger patient population. The treatment of CRC is often based on multimodal therapies, including surgery, radiotherapy, chemotherapy, and, more recently, immunotherapy, which makes it difficult to estimate the expected effect of treatment on fertility. We, therefore, systematically analyzed the published literature on the gonadotoxic effects of CRC treatments to better advise patients on the risk of infertility and the need for fertility preservation measures. This systematic review and meta-analysis are part of the FertiTOX project, which aims to reduce the data gap regarding the gonadotoxicity of oncological therapies. Objectives: The aim of this review and meta-analysis is to evaluate the potential impact of CRC therapies on gonadal function to allow more accurate counseling regarding the risk of clinically relevant gonadotoxicity and the need for fertility preservation measures before oncological treatment. Materials and Methods: A systematic literature search was conducted in Medline, Embase, the Cochrane database of systematic reviews, and CENTRAL in March 2024. A total of 22 out of 4420 studies were included in the review. Outcomes were defined as clinically relevant gonadotoxicity, indicated by elevated follicle-stimulating hormone (FSH) and/or undetectable anti-Müllerian hormone (AMH) levels and/or the need for hormone replacement therapy in women and azoo-/oligozoospermia and/or low inhibin B levels in men. Studies with fewer than nine patients were excluded from the meta-analysis. Results: The qualitative analysis included 22 studies with 1634 subjects (775 women, 859 men). Treatment consisted of active surveillance after surgery (37.7%), chemotherapy (12.7%), radiation (0.2%), or radiochemotherapy (53.9%). In 0.5%, the therapy was not clearly described. The meta-analysis included ten studies and showed an overall prevalence of clinically relevant gonadotoxicity of 23% (95% CI: 13–37%). In women, the prevalence was 27% (95% CI: 11–54%), and in men, 18% (95% CI: 13–26%). A subanalysis by type of CRC was only possible for rectal cancer, with a prevalence of relevant gonadotoxicity of 39% (95% CI: 20–64%). In patients undergoing chemotherapy exclusively, the prevalence was 4% (95% CI: 2–10%). In those receiving only radiotherapy, the prevalence was 23% (95% CI: 10–44%); in contrast, it reached 68% (95% CI: 40–87%) in patients who received radiochemotherapy. Conclusions: This first meta-analysis of the clinically relevant gonadotoxicity of CRC therapies provides a basis for counseling on the risk of infertility and the need for fertility preservation measures. Despite the low prevalence of gonadotoxicity in cases receiving chemotherapy alone, fertility preservation is still recommended due to the uncertainty of subsequent therapy and the lack of large longitudinal data on individual treatment effects. Further prospective studies are needed to investigate the impact of CRC treatment on gonadal function and estimate the effect of new treatment modalities, such as immunotherapies. Full article

Background: Male factors contribute to approximately 50% of infertile couples. However, obvious causes remain unknown in many cases. This observational study aimed to investigate the associations of clinical and lifestyle parameters with sperm parameters. Methods: This study enrolled 41 men in infertile couples without obvious causes for male infertility from July 2023 to April 2024. Semen samples were evaluated for sperm number, motility, DNA fragmentation, and oxidative stress (OS) marker oxidation–reduction potential (ORP). Blood samples were analyzed for biochemical parameters, including advanced glycation end products (AGEs), and systemic OS marker diacron-reactive oxygen metabolites (d-ROMs). Skin-accumulated AGE levels were identified with an autofluorescence method. Lifestyle factors were assessed with a lifestyle questionnaire. Results: Most of the participants were under 40 years old and non-obese with normal clinical parameters. Multiple regression analyses revealed that body mass index, serum d-ROMs, and semen ORP levels were independently associated with decreased sperm number. Additionally, serum zinc and semen ORP levels were associated with sperm motility. Furthermore, serum zinc and high-density lipoprotein cholesterol levels were associated with sperm progressive motility and DNA fragmentation, respectively. The rest of the clinical and lifestyle factors, including skin-accumulated and serum AGE levels, were not correlated with any sperm parameters. Furthermore, serum d-ROM and semen ORP levels were not correlated with each other or any of the clinical and lifestyle factors. Conclusions: Our present study indicates that both systemic and local OS may be independently involved in sperm abnormality in healthy men without obvious causes for male infertility. Full article

Background/Objectives: Male infertility is a complex condition with various underlying genetic factors. microRNAs (miRNAs) play a crucial role in gene regulation, and their disruption can significantly impact fertility. This study aimed to identify variants within miRNA genes and elucidate their impact on male infertility. Methods: Whole genome sequencing was performed on blood samples from men with asthenozoospermia, oligozoospermia, and teratozoospermia, compared to normozoospermic controls. The analysis revealed a significant number of unique variants in each infertile group. We subsequently focused on variants in miRNA regions, followed by an in silico analysis to investigate the role of the identified variants and miRNAs in male infertility. Results: Focused analysis on miRNA genes identified 19 exclusive variants in teratozoospermic men, 24 in asthenozoospermic, and 27 in oligozoospermic, all mapping to pre-miRNAs or mature miRNAs. Functional analyses using Gene Ontology (GO) and KEGG pathways highlighted key biological processes and pathways disrupted by these variants and miRNA–mRNA interactions, including transcription regulation, signaling, and cancer-related pathways. Furthermore, six variants (rs17797090, rs1844035, rs7210937, rs451887, rs12233076, and rs6787734) were common across the infertile groups, suggesting their importance in male infertility or their potential as biomarkers. Common variants were also validated in another clinically relevant group of men. Some miRNAs with identified variants, such as hsa-miR-449b and hsa-miR-296, have been previously implicated in male infertility and exhibit differential expression between fertile and infertile men, according to the literature, too. Conclusion: These results provide new insights into the genetic basis of male infertility and open avenues for future research and therapeutic interventions. Full article

Affecting up to 15% of men worldwide, varicocele has been recognized as a cause of infertility, and its repair is associated with an improvement in conventional and bio-functional sperm parameters. Various surgical and radiological techniques exist for varicocele repair. However, it is unclear which technique is associated with greater clinical efficacy. This retrospective, single-center study aimed to compare the effectiveness of surgical treatment (Ivanissevich technique) versus radiological treatment (sclerotherapy) in a cohort of 94 patients with varicocele. After varicocele repair, a significant increase in sperm concentration was observed only in the group of patients treated with sclerotherapy. A significant reduction in the percentage of patients with oligozoospermia was found in the group of patients treated surgically. Patients undergoing surgical varicocelectomy had increased serum luteinizing hormone (LH) levels, decreased spermatid concentration, and increased percentage of spermatozoa in late apoptosis, probably as a result of surgical traumatism. In conclusion, the results of this study did not show a clear benefit of one technique over the other and confirm the findings of the current literature. However, it remains one of the few on the topic that also considers sperm bio-functional parameters among its outcomes and opens the research up to new considerations on the bio-functional sperm parameters. Full article

Objective: To study the effect of switching to a follicle-stimulating hormone (FSH) preparation other than that to which infertile male patients have not had an effective response. Patients and methods: Seventy-four normogonadotropinemic, non-obstructive, oligozoospermic patients who were poor responders to the administration of highly purified FSH (hpFSH) (Group 1 (n = 22) and Group 3 (n = 15)) or to recombinant human FSH (rhFSH) (Group 2 (n = 22) and Group 4 (n = 15)) were selected for this prospective study. After 3 months of washout from treatment with the first FSH preparation of choice, rhFSH was administered to patients in Groups 1 and 4 and hpFSH to those in Groups 2 and 3. Serum luteinizing hormone, FSH, total testosterone levels, conventional sperm parameters, testicular volume, and the number of pregnancies were evaluated at study entry and after the first and second treatment cycles. Results: Comparing treatment groups, the greatest improvement in sperm parameters was recorded in the groups of patients prescribed the switch in FSH preparation. Group 1 had the greatest benefit from therapy, with the highest pregnancy rate after the second treatment cycle. Indeed, eight couples achieved pregnancy (36.4%), compared to Groups 2 (n = 4; 18.2%), 3 (n = 1; 6.7%), and 4 (n = 2; 13.3%) (p = 0.04). Conclusions: The results of this study suggest that a therapeutic scheme involving the “switching” of the FSH preparation yields better results than a protocol using the same FSH preparation for six months. These findings, if confirmed by further studies, will help us better design a treatment strategy with FSH for infertile patients with oligozoospermia. Full article

Research across various species has demonstrated that the doublesex and mab-3-related transcription factor 3 (dmrt3) plays pivotal roles in testis development. However, the precise molecular mechanisms of dmrt3 remain unclear. In this study, we investigated the role of dmrt3 (dmrt3a) in testis development using the model organism medaka (Oryzias latipes). SqRT-PCR and ISH analyses revealed that dmrt3a is predominantly expressed in the testis, especially in the spermatid and spermatozoon. Using CRISPR/Cas9, we generated two dmrt3a homozygous mutants (-8 bp and -11 bp), which exhibited significantly reduced fertilization rates and embryo production. Additionally, the number of germ cells and sperm motility were markedly decreased in the dmrt3a mutants, manifesting as the symptoms of asthenozoospermia and oligozoospermia. Interestingly, RNA-Seq analysis showed that the deficiency of dmrt3a could lead to a significant downregulation of numerous genes related to gonadal development and severe disruptions in mitochondrial function. These results suggested that dmrt3a is essential for spermatogenesis and spermatozoa energy production. This paper provides new insights and perspectives for further exploring the molecular mechanisms underlying spermatogenesis and addressing male reproductive issues. Full article

In recent years, several studies have analyzed the composition of the male genital tract microbiota and its changes in infertility or in different situations associated with infertility. The aim of this narrative review is to obtain more insight on this topic; in particular, to describe actual evidence about changes in the semen microbiota in patients with infertility, male tract infections, or HPV infections. In semen, an increase in semen Prevotella spp. is associated with oligozoospermia and with obesity-associated asthenozoospermia; an increase in Pseudomonas is more frequently associated with asthenozoospermia and oligozoospermia; a reduction in Lactobacilli spp. (namely in Lactobacillus crispatus) may represent a marker of low semen quality. However, an increase in Lactobacillus iners is considered a risk factor for a reduced sperm concentration. In patients with prostatitis, there is a reduction in Lactobacillus spp. and an increase in Streptococcus spp., opening important perspectives about the role of probiotic treatments in these patients. Finally, an increase in Fusobacteria spp. was observed in patients with an HPV infection. In the conclusion, we underline the interactions between the seminal and vaginal microbiota, so that further studies should focus on the “couple genital microbiota”. Full article

Objectives: Evaluate the prevalence of genetic factors in a large population of infertile subjects and define the seminological, hormonal, and ultrasonographic features for each alteration. Methods: This single-center retrospective study included male partners of infertile couples undergoing genetic investigations due to oligozoospermia or azoospermia evaluated from January 2012 to January 2022. The genetic investigations consist of karyotype, CFTR gene mutations plus variant of the IVS8-5T polymorphic trait, Y chromosome microdeletion, and Next Generation Sequencing panel to analyze genes implicated in congenital hypogonadotropic hypogonadism (CHH). Results: Overall, 15.4% (72/466) of patients received a diagnosis of genetic cause of infertility. Specifically, 23 patients (31.9%) harbor mutations in the CFTR gene, 22 (30.6%) have a 47, XXY karyotype, 14 (19.4%) patients show a Y chromosome microdeletion, 7 (9.7%) have structural chromosomal anomalies, and 6 (8.3%) have CHH. Overall, 80.6% of patients were azoospermic and 19.4% oligozoospermic (sperm concentration 3.5 ± 3.8 million/mL). Almost all patients presented hormonal alterations related to the specific genotype, while the main ultrasound alterations were testicular hypoplasia, calcifications/microcalcifications, and enlarged/hyperechoic epididymis. Conclusions: The prevalence of genetic abnormalities in males of infertile couples was 15.4% in our Center. CFTR gene disease-causing variants resulted in more frequent, with various clinical features, highlighting the complexity and heterogeneity of the presentation. Other investigations are needed to understand if conditions like ring chromosomes and other translocations are related to infertility or are incidental factors. Full article

Male infertility accounts for approximately 40% of infertility cases. There are many causes of male infertility, including environmental factors, age, lifestyle, infections, varicocele, and cancerous pathologies. Severe oligozoospermia, cryptozoospermia, and azoospermia (obstructive and non-obstructive) are identified as severe male factor infertility, once considered conditions of sterility. Today, in vitro fertilization (IVF) techniques are the only treatment strategy in cases of male factor infertility for which new methodologies have been developed in the manipulation of spermatozoa to achieve fertilization and increase success rates. This review is an update of in vitro manipulation techniques, in particular sperm selection, emphasizing clinical case-specific methodology. The success of an IVF process is related to infertility diagnosis, appropriate choice of treatment, and effective sperm preparation and selection. In fact, selecting the best spermatozoa to guarantee an optimal paternal heritage means increasing the blastulation, implantation, ongoing pregnancy and live birth rates, resulting in the greater success of IVF techniques. Full article

Azoospermia and severe oligozoospermia represent the most extreme forms of male infertility. Despite their prevalence, the genetic foundations of these conditions are not well understood, with only a limited number of genetic factors identified so far. This study aimed to identify single-nucleotide polymorphisms (SNPs) linked to both azoospermia and severe oligozoospermia. We conducted a genome-wide association study (GWAS) involving 280 Greek males with normal semen parameters and 85 Greek males diagnosed with either azoospermia or severe oligozoospermia. Following rigorous quality control measures, our analysis identified seven SNPs associated with azoospermia/severe oligozoospermia. An in silico functional annotation was subsequently used to further investigate their role. These SNPs, found in regions not previously associated with male reproductive disorders, suggest novel genetic pathways that may contribute to these forms of infertility and pave the way for future studies. Additionally, this study sheds light on the significant role of noncoding RNAs in the pathogenesis of male infertility, with three of the identified SNPs situated in long intergenic non-coding RNAs (lincRNAs). Our findings highlight the intricate genetic landscape of azoospermia and severe oligozoospermia, underlining the necessity for more detailed studies to fully grasp the underlying mechanisms and their potential for informing diagnostic and therapeutic strategies. Full article