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Andrology Jul 2018Oligo-astheno-teratozoospermia is frequently reported in men from infertile couples. Its etiology remains, in the majority of cases, unknown with a variety of factors to... (Review)
Review
BACKGROUND
Oligo-astheno-teratozoospermia is frequently reported in men from infertile couples. Its etiology remains, in the majority of cases, unknown with a variety of factors to contribute to its pathogenesis. The aim of this European Academy of Andrology guideline was to provide an overview of these factors and to discuss available management options.
MATERIALS AND METHODS
PubMed was searched for papers in English for articles with search terms: male infertility and oligo-astheno-teratozoospermia. For evidence-based recommendations, the GRADE system was applied. Issues related to urogenital infections/inflammations have not been included in this document as they will be covered by separate guidelines.
RESULTS
For men with oligo-astheno-teratozoospermia, the European Academy of Andrology recommends: A general physical examination to assess signs of hypogonadism. A scrotal physical examination to assess (i) the testes and epididymes for volume and consistency, (ii) deferent ducts for total or partial absence, and (iii) occurrence of varicocoele. Performing two semen analyses, according to World Health Organization guidelines to define an oligo-astheno-teratozoospermia. An endocrine evaluation. A scrotal ultrasound as part of routine investigation. Karyotype analysis and assessment of Yq microdeletions in infertile men with a sperm concentration ≤5 × 10 /mL. Cystic fibrosis transmembrane conductance regulator gene evaluation in case of suspicion for incomplete congenital obstruction of the genital tract. Against quitting physical activity to improve the chance of achieving pregnancy. Against androgen replacement therapy to improve the chance of achieving pregnancy. Assisted reproduction techniques to improve the chance of achieving pregnancy, in case other treatment options are not available or not efficient. Androgen replacement therapy in patients with biochemical/clinical signs of hypogonadism, after completion of the fertility treatment.
CONCLUSION
These guidelines can be applied in clinical work and indicate future research needs.
Topics: Humans; Male; Oligospermia
PubMed: 30134082
DOI: 10.1111/andr.12502 -
Journal of Zhejiang University....With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including... (Review)
Review
With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS), become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of EA/TEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/TEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome (PCOS), pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligospermia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.
Topics: Acupuncture Points; Analgesia; Animals; Asthenozoospermia; Clinical Trials as Topic; Electroacupuncture; Embryo Transfer; Female; Genital Diseases, Female; Humans; Infertility, Female; Infertility, Male; Kidney; Male; Medicine, Chinese Traditional; Oligospermia; Oocyte Retrieval; Oocytes; Ovarian Reserve; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Reproductive Medicine; Transcutaneous Electric Nerve Stimulation; Uterus
PubMed: 28271655
DOI: 10.1631/jzus.B1600437 -
Deleterious variants in X-linked CFAP47 induce asthenoteratozoospermia and primary male infertility.American Journal of Human Genetics Feb 2021Asthenoteratozoospermia characterized by multiple morphological abnormalities of the flagella (MMAF) has been identified as a sub-type of male infertility. Recent...
Asthenoteratozoospermia characterized by multiple morphological abnormalities of the flagella (MMAF) has been identified as a sub-type of male infertility. Recent progress has identified several MMAF-associated genes with an autosomal recessive inheritance in human affected individuals, but the etiology in approximately 40% of affected individuals remains unknown. Here, we conducted whole-exome sequencing (WES) and identified hemizygous missense variants in the X-linked CFAP47 in three unrelated Chinese individuals with MMAF. These three CFAP47 variants were absent in human control population genome databases and were predicted to be deleterious by multiple bioinformatic tools. CFAP47 encodes a cilia- and flagella-associated protein that is highly expressed in testis. Immunoblotting and immunofluorescence assays revealed obviously reduced levels of CFAP47 in spermatozoa from all three men harboring deleterious missense variants of CFAP47. Furthermore, WES data from an additional cohort of severe asthenoteratozoospermic men originating from Australia permitted the identification of a hemizygous Xp21.1 deletion removing the entire CFAP47 gene. All men harboring hemizygous CFAP47 variants displayed typical MMAF phenotypes. We also generated a Cfap47-mutated mouse model, the adult males of which were sterile and presented with reduced sperm motility and abnormal flagellar morphology and movement. However, fertility could be rescued by the use of intra-cytoplasmic sperm injections (ICSIs). Altogether, our experimental observations in humans and mice demonstrate that hemizygous mutations in CFAP47 can induce X-linked MMAF and asthenoteratozoospermia, for which good ICSI prognosis is suggested. These findings will provide important guidance for genetic counseling and assisted reproduction treatments.
Topics: Animals; Asthenozoospermia; Cohort Studies; Female; Gene Deletion; Genes, X-Linked; Hemizygote; Humans; Infertility, Male; Male; Mice, Inbred C57BL; Mutation; Mutation, Missense; Pedigree; Phenotype; Sperm Injections, Intracytoplasmic; Sperm Motility; Sperm Tail; Spermatozoa; Exome Sequencing; Mice
PubMed: 33472045
DOI: 10.1016/j.ajhg.2021.01.002 -
Acta Bio-medica : Atenei Parmensis Sep 2019Infertility due to genetic mutations that cause other defects, besides infertility, is defined as syndromic. Here we describe three of these disorders for which we... (Review)
Review
Infertility due to genetic mutations that cause other defects, besides infertility, is defined as syndromic. Here we describe three of these disorders for which we perform genetic tests. 1) Hypopituitarism is an endocrine syndrome characterized by reduced or absent secretion of one or more anterior pituitary hormones with consequent dysfunction of the corresponding peripheral glands. Deficiencies in all the hormones is defined as pan-hypopituitarism, lack of two or more hormones is called partial hypopituitarism, whereas absence of a single hormone is defined as selective hypopituitarism. Pan-hypopituitarism is the rarest condition, whereas the other two are more frequent. Several forms exist: congenital, acquired, organic and functional. 2) The correct functioning of the hypothalamic-pituitary-gonadal axis is fundamental for sexual differentiation and development during fetal life and puberty and for normal gonad function. Alteration of the hypothalamic-pituitary system can determine a condition called hypogonadotropic hypogonadism, characterized by normal/low serum levels of the hormones FSH and LH. 3) Primary ciliary dyskinesia is frequently associated with infertility in males because it impairs sperm motility (asthenozoospermia). Primary ciliary dyskinesia is a group of genetically and phenotypically heterogeneous disorders that show morpho-structural alterations of the cilia. Adult women with primary ciliary dyskinesia can be subfertile and have an increased probability of extra-uterine pregnancies. This is due to delayed transport of the oocyte through the uterine tubes.
Topics: Ciliary Motility Disorders; Female; Genetic Predisposition to Disease; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Hypogonadism; Hypopituitarism; Infertility; Male
PubMed: 31577259
DOI: 10.23750/abm.v90i10-S.8764 -
American Journal of Human Genetics Jan 2022Asthenoteratozoospermia, defined as reduced sperm motility and abnormal sperm morphology, is a disorder with considerable genetic heterogeneity. Although previous...
Asthenoteratozoospermia, defined as reduced sperm motility and abnormal sperm morphology, is a disorder with considerable genetic heterogeneity. Although previous studies have identified several asthenoteratozoospermia-associated genes, the etiology remains unknown for the majority of affected men. Here, we performed whole-exome sequencing on 497 unrelated men with asthenoteratozoospermia and identified DNHD1 bi-allelic variants from eight families (1.6%). All detected variants were predicted to be deleterious via multiple bioinformatics tools. Hematoxylin and eosin (H&E) staining revealed that individuals with bi-allelic DNHD1 variants presented striking abnormalities of the flagella; transmission electron microscopy (TEM) further showed flagellar axoneme defects, including central pair microtubule (CP) deficiency and mitochondrial sheath (MS) malformations. In sperm from fertile men, DNHD1 was localized to the entire flagella of the normal sperm; however, it was nearly absent in the flagella of men with bi-allelic DNHD1 variants. Moreover, abundance of the CP markers SPAG6 and SPEF2 was significantly reduced in spermatozoa from men harboring bi-allelic DNHD1 variants. In addition, Dnhd1 knockout male mice (Dnhd1) exhibited asthenoteratozoospermia and infertility, a finding consistent with the sperm phenotypes present in human subjects with DNHD1 variants. The female partners of four out of seven men who underwent intracytoplasmic sperm injection therapy subsequently became pregnant. In conclusion, our study showed that bi-allelic DNHD1 variants cause asthenoteratozoospermia, a finding that provides crucial insights into the biological underpinnings of this disorder and should assist with counseling of affected individuals.
Topics: Alleles; Animals; Asthenozoospermia; Axoneme; Computational Biology; DNA Mutational Analysis; Disease Models, Animal; Dyneins; Flagella; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Infertility, Male; Male; Mice; Mice, Knockout; Mitochondria; Mutation; Pedigree; Phenotype; Semen Analysis; Sperm Tail; Exome Sequencing
PubMed: 34932939
DOI: 10.1016/j.ajhg.2021.11.022 -
Medicine Dec 2021Acupuncture is widely used for oligospermia and asthenozoospermia in China, but its effect is unclear. We aimed to determine the effectiveness and safety of acupuncture... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acupuncture is widely used for oligospermia and asthenozoospermia in China, but its effect is unclear. We aimed to determine the effectiveness and safety of acupuncture in treating oligospermia and asthenozoospermia.
METHODS
An electronic search for randomized controlled trials evaluating acupuncture treatment in patients with oligospermia and asthenozoospermia published from database inception to October 2018 was conducted in PubMed, EMBASE, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database (VIP Database), the Wan-Fang Database, the China National Knowledge Infrastructure and the Cochrane Library. We established search terms related to 3 areas (oligospermia, asthenozoospermia, and acupuncture). Two authors independently screened all identified citations and extracted the data. The methodological quality of the included trials was assessed using the Cochrane criteria.
RESULTS
Seven studies with a total of 527 subjects were screened according to inclusion and exclusion standards, and most of the studies had significant methodological weaknesses. Seven randomized controlled trials tested the effects of acupuncture compared with placebo acupuncture and conventional medications in patients with oligospermia and asthenozoospermia. The results of this study suggest that acupuncture alone has no clear superiority in improving sperm motility (standard mean difference [SMD] = 1.13, 95% confidence interval [CI]: -0.64 to 2.89), the sperm concentration (SMD = 0.32, 95% CI: 0.27-0.92) or semen volume compared with placebo acupuncture. No significant difference was found between acupuncture alone and conventional medications in improving sperm motility (SMD = -0.53, 95% CI: -2.54 to 1.48), the sperm concentration (SMD = -1.10, 95% CI: -1.48 to -0.72) or semen volume. However, adjuvant acupuncture may enhance the effect of medications on improving sperm motility (SMD = 4.10, 95% CI: 1.09-7.12) and the sperm concentration (SMD = 1.07, 95% CI: 0.739-1.40), but the study heterogeneity was too high to establish robust conclusions.
CONCLUSION
These results suggest that the current evidence does not support acupuncture as an effective treatment for oligospermia and asthenozoospermia; therefore, acupuncture is not currently recommended as a treatment for these conditions. However, owing to the high risk of bias among the included studies, the evidence is limited, and more large-scale, high-quality clinical trials are needed in the future.
TRIAL REGISTRATION NUMBER
PROSPERO CRD42018083885.
Topics: Acupuncture Therapy; Asthenozoospermia; Humans; Male; Oligospermia; Randomized Controlled Trials as Topic; Sperm Motility; Treatment Outcome
PubMed: 35049183
DOI: 10.1097/MD.0000000000027816 -
Asian Journal of Andrology 2022Idiopathic asthenozoospermia, a common factor in male infertility, is characterized by altered sperm motility function in fresh ejaculate. Although the β-defensin 126...
Idiopathic asthenozoospermia, a common factor in male infertility, is characterized by altered sperm motility function in fresh ejaculate. Although the β-defensin 126 (DEFB126) protein is associated with asthenozoospermia, DEFB126 gene polymorphisms have not been extensively studied. Therefore, the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation. Screening was performed by semen analysis, karyotype analysis, and Y microdeletion detection, and 102 fertile men and 106 men with asthenozoospermia in Chengdu, China, were selected for DEFB126 gene sequence analyses. Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected. rs11467417 (317-318 del/del), rs11467497 (163-166 wt/del), c.152T>C, and c.227A>G were significantly different between the control and asthenozoospermia groups, likely representing high-risk genetic factors for asthenozoospermia among males. DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion. The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus, and the rs11467417 binucleotide deletion produces a non-stop messenger RNA (mRNA). The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces. Based on in silico analysis, the amino acids 51M and 76K are located in the highly conserved domain; c.152T>C (M51T) and c.227A>G (K76R) are predicted to be damaging and capable of changing alternative splice, structural and posttranslational modification sites of the RNA, as well as the secondary structure, structural stability, and hydrophobicity of the protein, suggesting that these mutations are associated with asthenozoospermia.
Topics: Male; Humans; Asthenozoospermia; Sperm Motility; Homozygote; Polymorphism, Single Nucleotide; Semen; Sequence Deletion; Spermatozoa; Nucleotides; beta-Defensins
PubMed: 35381696
DOI: 10.4103/aja2021115 -
EBioMedicine Oct 2023Asthenozoospermia is the primary cause of male infertility; however, its genetic aetiology remains poorly understood. Adenylate kinase 9 (AK9) is highly expressed in the...
BACKGROUND
Asthenozoospermia is the primary cause of male infertility; however, its genetic aetiology remains poorly understood. Adenylate kinase 9 (AK9) is highly expressed in the testes of humans and mice and encodes a type of adenosine kinase that is functionally involved in cellular nucleotide homeostasis and energy metabolism. We aimed to assess whether AK9 is involved in asthenozoospermia.
METHODS
One-hundred-and-sixty-five Chinese men with idiopathic asthenozoospermia were recruited. Whole-exome sequencing (WES) and Sanger sequencing were performed for genetic analyses. Papanicolaou staining, Haematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were used to observe the sperm morphology and structure. Ak9-knockout mice were generated using CRISPR-Cas9. Sperm adenosine was detected by liquid chromatography-mass spectrometry. Targeted sperm metabolomics was performed. Intracytoplasmic sperm injection (ICSI) was used to treat patients.
FINDINGS
We identified five patients harbouring bi-allelic AK9 mutations. Spermatozoa from men harbouring bi-allelic AK9 mutations have a decreased ability to sustain nucleotide homeostasis. Moreover, bi-allelic AK9 mutations inhibit glycolysis in sperm. Ak9-knockout male mice also presented similar phenotypes of asthenozoospermia. Interestingly, ICSI was effective in bi-allelic AK9 mutant patients in achieving good pregnancy outcomes.
INTERPRETATION
Defects in AK9 induce asthenozoospermia with defects in nucleotide homeostasis and energy metabolism. This sterile phenotype could be rescued by ICSI.
FUNDING
The National Natural Science Foundation of China (82071697), Medical Innovation Project of Fujian Province (2020-CXB-051), open project of the NHC Key Laboratory of Male Reproduction and Genetics in Guangzhou (KF202004), Medical Research Foundation of Guangdong Province (A2021269), Guangdong Provincial Reproductive Science Institute Innovation Team grants (C-03), and Outstanding Young Talents Program of Capital Medical University (B2205).
Topics: Humans; Pregnancy; Female; Male; Animals; Mice; Asthenozoospermia; Nucleotides; Semen; Spermatozoa; Infertility, Male
PubMed: 37713809
DOI: 10.1016/j.ebiom.2023.104798 -
International Journal of Medical... 2021Asthenozoospermia, one of the most common causes of male infertility, is a complicate multifactorial pathological condition that genetic factors are involved in....
Asthenozoospermia, one of the most common causes of male infertility, is a complicate multifactorial pathological condition that genetic factors are involved in. However, the epigenetic signature and mechanism of asthenozoospermia still remain limited. Our study aimed to confirm the key microRNAs (miRNAs) and genes in asthenozoospermia and demonstrate the underlying epigenetic regulatory mechanisms. We screened out and pooled previous studies to extracted potential differentially expressed miRNAs (DEMs). GSE22331 and a published profile dataset were integrated to identify differentially expressed genes (DEGs). Pathway and gene ontology analysis were performed using DAVID. A protein-protein network (PPI) was constructed using STRING. The target genes of DEMs were predicted using TargetScan and the miRNA-mRNA network was built. We reported 3 DEMs and 423 DEGs by pooling included dataset and published studies. Pathway analysis showed that these DEGs might participate in signaling pathways regulating pluripotency of stem cells, Wnt signaling pathway and Notch signaling pathway. 25 hub genes were identified, and the most significant gene was BDNF. We screened out the overlapped DEGs between the predicted target genes of 3 DEMs and the 423 DEGs. Finally, a potential miRNA-mRNA regulatory network was constructed. This study firstly pooled several published studies and a GEO dataset to determine the significance of potential miRNAs and genes, such as miR-374b, miR-193a, miR-34b, BDNF, NTRK2, HNRNPD and EFTUD2 in regulating asthenozoospermia and underscore their interactions in the pathophysiological mechanism. Our results provided theoretical basis and new clues for potential therapeutic treatment in asthenozoospermia. Validations and are required in future studies.
Topics: Asthenozoospermia; Computational Biology; Databases, Genetic; Datasets as Topic; Gene Expression Profiling; Gene Regulatory Networks; Humans; Male; MicroRNAs; RNA, Messenger; Signal Transduction
PubMed: 33746583
DOI: 10.7150/ijms.54460 -
International Journal of Molecular... Mar 2021MicroRNAs applications were vastly studied throughout the years, spanning from potential cancer biomarkers to targeted therapies for various diseases. Out of these... (Review)
Review
MicroRNAs applications were vastly studied throughout the years, spanning from potential cancer biomarkers to targeted therapies for various diseases. Out of these utilizations, this paper focuses on their role in male infertility. Approximately 10-15% of worldwide couples are affected by infertility. Out of these, 50% are due to male determinants. The majority of cases still have an undetermined cause. Previous studies have found that the aberrant expression of microRNAs could be linked to certain reproductive dysfunctions in males. Further on, this study looked into the most recent literature published on this subject in order to assess the connection between the up-/down-regulation of various microRNAs and the roles they play in male infertility. MicroRNAs were found to be abundant and stable in the seminal liquid, which led to a facile identification using regular RNA detection methods. It was observed that the concentration of microRNAs in semen was modified in the case of patients suffering from asthenozoospermia and azoospermia. Moreover, idiopathic male infertility was associated with a single nucleotide polymorphism of the microRNA binding site. Future studies should focus their attention on discovering future treatments against male infertility targeting specific microRNAs and also on developing new and improved contraceptive methods.
Topics: Adult; Argonaute Proteins; Asthenozoospermia; Azoospermia; Binding Sites; Gene Expression Regulation; Humans; Infertility, Male; Male; MicroRNAs; Polymorphism, Single Nucleotide; RNA-Induced Silencing Complex; Semen; Spermatogenesis
PubMed: 33805594
DOI: 10.3390/ijms22062910