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At least 19 recordsLinked to original sources
PubMed2026

Biallelic Variants in ATP1A4 Are Associated with Oligoasthenoteratozoospermia and Male Infertility.

Male infertility, often caused by structural and functional sperm defects, remains genetically unexplained in a substantial proportion of cases. ATP1A4 encodes a testis-specific isoform of the Na+, K+-ATPase, a membrane enzyme crucial for maintaining cellular ionic homeostasis. Previous studies on Atp1a4 knockout mice have demonstrated severe defects in sperm motility and flagellar architecture; however, the contribution of ATP1A4 variants to human male reproduction remains to be elucidated. In this study, we identified compound biallelic variants in ATP1A4, a missense variant (c.2578 T>A, p.Tyr860Asn) and a frameshift variant (c.2582del, p.Gly861Aspfs*5), in a patient presenting with severe oligoasthenoteratozoospermia. Both variants markedly affected ATP1A4 protein expression. Morphological analyses revealed coiled and folded flagella, disrupted mitochondrial sheaths, and irregular head morphology in the patient's spermatozoa. Expression profiling revealed that ATP1A4 was highly enriched in post-meiotic spermatids and localized along the entire flagellum of mature sperm in both humans and mice, indicating a critical role in flagellar assembly and structural integrity. Notably, intracytoplasmic sperm injection (ICSI) in this patient resulted in low fertilization efficiency and failed implantation, suggesting a potential adverse impact of ATP1A4 deficiency on sperm functional competence beyond motility. These findings broaden the genetic spectrum of oligoasthenoteratozoospermia and highlight ATP1A4 as a potential gene associated with human male infertility.

Male↗
PubMed1978

Vascular lesions in testes associated with male infertility in Cameroon. Possible relationship to parasitic disease.

Testicular biopsies in 40 of 41 infertile males with severe oligospermia in Cameroon presented massive subendothelial "fibrinoid" deposits in the small and medium sized vessels. Fibrinogen, complement and IgM were demonstrated in these deposits by immunofluorescence. Evidence strongly suggestive of parasitic testicular involvement was also observed in 2 cases. It is postulated that the "fibrinoid" deposits are the result of repeated formation and deposition of circulating immune complexes by reaction of antibodies with antigens. These antigens could be of various origins and in the cases described here they could be derived from living or dying parasites in the region. The accumulation and incorporation of the "fibrinoid" deposits may lead to vascular stenosis resulting in chronic ischaemia, tubular atrophy and fibrosis, and finally oligospermia.

Adult↗
PubMed1976

Elevated plasma testosterone and gonadotropin levels in infertile males with hyperthyroidism.

Little attention has been given the existence of male infertility in hyperthyroidism and the mechanisms adversely affecting spermatogenesis therein. The chance presentation of three young thyrotoxic men within a short period of time allowed us to document the common findings in all three of reversibly impaired semen quality. The unexpected finding of elevated testosterone and gonadotropin levels in each case, with return of these values to normal on attaining euthyroidism, and the finding of maturation arrest in one patient prior to treatment of his thyrotoxicosis, allow some considerations of the altered physiology and spermatogenic defect and suggest a need for further attention to this disorder.

Adult↗
PubMedDate not supplied

Treatment of male infertility with human gonadotrophins: selection of cases, management and results.

To obtain optimal results with gonadotrophic therapy (HMG/hCG) in infertile males, strict selection of patients is of paramount importance. The use of algorithmic schemes permits the exclusion of patients with primary testicular failure, genetic and non-endocrine causes of infertility. This paper describes a retrospective study on the results of gonadotrophic therapy in 25 severe oligozoospermic males, preselected according to the above scheme and in whom levels of FSH, LH and Testosterone before and during GnRH stimulation were assessed. This study indicates that low basal levels of FSH, concomitant with low or lack of FSH response to GnRH stimulation may be useful in selection of patients with a fair chance of success for gonadotrophic therapy.

Chorionic Gonadotropin↗
PubMed2026

A CCNA1 Missense Variant Associated With Chromatid Non-Disjunction in Abnormal-Headed Sperm and Male Infertility.

BACKGROUND: Macrozoospermia is a rare form of teratozoospermia characterized by tetraploids, large-headed spermatozoa with multiple flagella, usually caused by bi-allelic AURKC mutations. The etiology of atypical phenotypes with a lower proportion of large headed spermatozoa and single flagella however often remains unresolved. OBJECTIVE: To investigate the genetic cause of severe sperm-head abnormalities with moderate macrozoospermia without multiflagellated spermatozoa in a patient with repeated ICSI failure. An infertile male with three failed ICSI attempts underwent semen analysis, revealing complete teratozoospermia, including 25% macrocephalic spermatozoa. METHODS: Multi-probe FISH targeting chromosomes 13, 18, 21, X, Y assessed chromosomal segregation. Whole-exome sequencing (WES) was performed to identify a candidate variant associated with meiotic abnormalities. RESULTS: FISH analysis revealed a high proportion of spermatozoa with n (23) chromosomes and 2c DNA content, consistent with sister chromatid non-disjunction during meiosis II. WES identified a homozygous missense variation in CCNA1, coding for a protein described to be essential for meiotic progression and chromatin remodeling in male germ cells. DISCUSSION: The variant affects a highly conserved residue within a functional domain and is predicted to be deleterious. This study establishes the first clinical association between CCNA1 mutations and chromatid non-disjunction in human spermatogenesis. It highlights the limitations of current morphology-based diagnostic thresholds and supports cytogenetic and genomic assessment for severe teratozoospermia (especially head abnormalities) and ART failure. CONCLUSION: Expanding genetic screening panels to include CCNA1 may improve diagnostic precision and clinical management in atypical macrozoospermia cases.

ART failure↗
PubMed1979

Clomiphene test and clomiphene therapy in idiopathic male infertility.

Clomiphene citrate, 50 mg/day, was administered to 105 patients with idiopathic azoospermia or oligoasthenospermia. Plasma FSH, LH, testosterone, and in a few cases estradiol were evaluated on day 0 and day 15 of therapy. Twelve other patients with no treatment were assayed in the same way. Statistical analysis demonstrated that, as a group, the infertile male population responds normally to clomiphene administration. On the other hand, three types of individual responses were recorded: complete positive response, dissociated positive response, and negative response. Sixty-nine patients were randomly selected for clomiphene therapy, 50 mg/day for 100 days; however, of 54 who completed the treatment schedule, only 11 showed elevated sperm counts. A study of correlations between hormonal and semen responses to clomiphene indicates that a complete or dissociated endocrine response is not an accurate predictor of possible semen amelioration on long-term therapy; on the other hand, sperm characteristics did not improve in those patients who did not demonstrate a positive hormonal response, mainly testosterone, on the 15th day of therapy.

Adult↗
PubMedDate not supplied

Etiological factors of male infertility in Africa.

Of the 595 infertile African males studied, 192 (30.8%) were azoospermic and 413 (69.40%) had oligospermia. Azoospermia was caused by obstruction to the vas and/or epididymis in 44% of cases and testicular lesions in the remaining 56% of cases, whilst the oligospermia was probably caused by obstruction in 4.7% of cases and testicular lesions in 85.3%. Bilateral testicular biopsies were performed on 302 patients. A variety of pathological conditions were observed; the most prevalent was hypospermatogenesis, in 12% of cases. A significant portion (37.2%) of patients without testicular biopsies had clinically detectable testicular or epididymal abnormalities. There was a higher incidence (12%) of inflammatory testicular or prostatic conditions in this study as compared with those found in Europeans, suggesting that inflammatory conditions contribute more to male infertility in Africa. Only a single case of chromosomal abnormality was detected.

Adult↗
PubMed1992

[The present and the future of treatment of male infertility].

About 90% of male infertile patients are complaint of semen with poor quality, and of which majority are caused by idiopathic disturbance of spermatogenesis. To date, various trials have been made to stimulate spermatogenesis by means of pharmaceutical administrations, their efficacies were, however, poor as expected. The treatment of the patients with poor quality semen is, therefore, mainly focused on artificial insemination, such as intrauterine insemination (IUI) and in vitro fertilization-embryo transfer (IVF-ET), etc. (1) To inseminate the sperm artificially, it is necessary to separate progressively motile sperm with normal morphology from seminal plasma, immotile and abnormal sperm, leucocytes and bacteria. There are two methods for separating progressively motile sperm, one is the density gradient centrifugation and another is the diffusion by their own motility. We have developed various types of density gradients using Percoll, a modified silica gel; the mono-layer Percoll method and the cushion method are employed for sperm concentration, and the discontinuous Percoll density gradient with 4 steps and the continuous-step density gradient are capable of separating progressively motile sperm. The continuous-step density gradient have been employed for 271 cases of IUI, and successful 84 pregnancies were obtained with the pregnancy rate of 30.9%. (2) Cryopreservation of sperm produce various advantages in the treatment of male infertility. Cryoaccumulation of oligozoospermic semen is effective for obtaining a sufficient number of sperm, and frequent insemination with cryopreserved sperm increase the chance of fertilization. To improve the quality of cryopreserved sperm, ejaculated semen was concentrated prior freezing by means of the continuous-step density gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1979

Seminiferous tubule hypercurvature: A newly recognised common syndrome of human male infertility.

Testicular biopsy specimens from 42 of a series of 70 consecutive cases of primary male infertility and from 25 normal controls were morphometrically analysed. Although all the specimens from infertile males were normal by conventional histological standards, stereological measures of curvature in histological sections showed that cases of idiopathic male infertility had an abnormally increased curvature of seminiferous tubules.

Animals↗
PubMed2026

Plasmacytoid dendritic cell-mediated L-glutamate catabolism links gut microbiota to male infertility.

Emerging evidence suggests that gut microbiota composition influences male reproductive health; however, the immunometabolic mechanisms underlying this association remain insufficiently characterized. We investigated whether specific immune cell-mediated metabolic pathways, particularly plasmacytoid dendritic cell (pDC)-driven L-glutamate catabolism via the hydroxyglutarate pathway, contribute to the causal link between gut microbiota and male infertility. We conducted a 2-sample, 2-step Mendelian randomization (MR) analysis using inverse-variance weighting as the primary estimator and Bayesian weighted MR for robustness. Exposure data comprised 412 gut microbial taxa/metabolic pathways and 731 immune cell phenotypes from large European-ancestry genome-wide association studies. Male infertility genome-wide association studies data (1429 cases; 128,710 controls) were obtained from FinnGen R10. Only exposure-mediator-outcome pairs meeting stringent pleiotropy, heterogeneity, and reverse-causality criteria were retained for mediation analysis. Nine microbial taxa/metabolic pathways and 18 immune traits exhibited putative causal associations with male infertility. The L-glutamate degradation V pathway via hydroxyglutarate was linked to reduced infertility risk (inverse-variance weighting odds ratio [OR] = 0.68; 95% confidence interval, 0.52-0.89; P = .005). Two-step MR suggested that forward scatter area on pDCs may mediate this association, although the mediation effect was imprecise (effect = 0.0277; 95% confidence interval, -0.0348 to 0.0903). This study provides suggestive genetic evidence that pDC-mediated glutamate catabolism may connect gut microbial metabolic activity to male infertility. These findings highlight immunometabolic pathways as testable targets for mechanistic validation and microbiota-directed interventions.

Male↗
PubMed1975

Increased serum FSH levels correlated with low and high sperm counts in male infertile patients.

Serum FSH, LH and testosterone were measured in 57 (42) normal men and in 80 male infertile patients. In the former, mean (x) FSH was found to be 2.5 ng/ml with a range (x +/- 2 SD) from 0.25 ng/ml to 5.3 ng/ml, mean LH was 2.2 ng/ml with a range from 0.5 ng/ml to 5.6 ng/ml, and mean testosterone was 540 ng/100 ml with a range from 190 mg/ml to 890 ng/100 ml. Immunoassayable FSH was found to be elevated in 17 out of 42 presumably infertile males with sperm counts below 20 million/ml, and in 5 out of 12 men with sperm counts above 120 million/ml. There was no correlation between testosterone and sperm number, motility, and seminal fructose content. The concurrence of depressed spermatogenesis and elevated FSH levels seems to be a relatively good indicator for the presence of organic disorders of the testis.

Adolescent↗
PubMed1992

The relation of computer-based measures of sperm morphology and motility to male infertility.

We investigated the relation between various sperm characteristics, including morphometric parameters, and impaired fertility among 596 men who participated in a national study. Semen was collected and processed by using a standardized protocol, and sperm measurements were made using a computer-aided sperm analysis instrument. We defined infertility in two ways: (1) the inability to father a child after trying for a year or longer, and (2) the number of children fathered. We found that all measures of sperm motion were decreased among men with impaired fertility. After adjustment for the other motion parameters and various potential confounders, however, only the percentage of progressive cells was associated with infertility. One morphometric parameter, the mean length/width ratio, was consistently associated with both measures of infertility, even after adjustment for potential covariates. This measure was also strongly associated with infertility among various subgroups defined by poor sperm concentration, motility, and morphology. The sperm length/width ratio appears to be an important correlate of infertility in males.

Adult↗
PubMedDate not supplied

Assisted reproductive technologies in severe male infertility.

The increasing incidence of male subfertility as an indication for ART is first discussed. The tendency to use assisted reproduction techniques in such cases is attributed to the disappointing results of classical treatments. The Authors deal with two problems: the choice of the best treatment methods of the sperm and the choice of the best technique of ART for treating male infertility. The analysis of 138 couples treated for male subfertility showed that the centrifugation on discontinuous Percoll gradients (CDPG) and especially on the mini-Percoll (mini CDPG) offers the best results if compared with pellet swim up and other techniques. With reference to the technique of choice, an accurate analysis of tubal (TET and ZIFT) and uterine (IVF/ET) transfers shows that no advantage seems to be obtained with the more sophisticated and exacting tubal transfer. This final conclusion is presently evaluated on the basis of a retrospective study.

Embryo Transfer↗
PubMed2026

Association between seminal and serum iron parameters and male infertility: a systematic review and meta-analysis.

BACKGROUND: Iron is an essential trace element for normal spermatogenesis, yet excessive iron accumulation may impair male fertility. Preliminary studies imply a link between elevated iron levels and male infertility, but evidence remains limited without systematic quantitative synthesis. This metaanalysis assessed the association between iron concentrations and male infertility. METHODS: We systematically searched PubMed, CBM, CNKI and Cochrane Library. RevMan, Stata and R were used for data analysis. Randomeffects models pooled effect sizes, with forest and funnel plots generated to evaluate seminal and serum iron levels in male infertility. RESULTS: After screening studies published up to April 2025, a total of ten eligible articles involving 985 participants were finally included in this meta-analysis. Pooled results revealed that seminal and serum iron concentrations were notably higher in infertile males compared with fertile controls. Specifically, infertile men presented higher seminal iron levels (SMD&#x2009;=&#x2009;0.44, 95% CI: 0.12-0.76, P&#x2009;<&#x2009;0.05), as well as elevated serum iron levels (SMD&#x2009;=&#x2009;3.77, 95% CI: 1.68-5.87, P&#x2009;<&#x2009;0.05). The present results suggest that increased seminal and serum iron concentrations may be potentially correlated with male infertility risk.

Humans↗
PubMed1992

Treatment of male infertility by gamete micromanipulation.

Over the past decade, in vitro fertilization (IVF) has become a routine and acceptable tool in the treatment of infertility. However, major limitations in solving certain infertility problems still remain. Male infertility is one area in which only a small fraction of patients have benefited from IVF. Union of male and female gametes, either in vivo or in vitro, requires sperm penetration through the cumulus oophorus and the zona pellucida. Failure of fertilization despite the increased number of spermatozoa introduced into the oocyte's vicinity by IVF, has been shown to be directly related to abnormalities in sperm cell morphology and motility. The improved technology for micromanipulation of gametes has made it possible to circumvent the oocyte barriers to sperm penetration, thereby greatly reducing the number of normal sperm cells needed to achieve fertilization. This paper reviews the three major micromanipulative strategies which have been developed over the past five years, patient selection for the different procedures and the methods of sperm preparation to improve the yield of the applied technique.

Humans↗