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Journal of General Internal Medicine Aug 2023Infertility care is provided to Veterans through the Veterans Health Administration (VHA) medical benefits package and includes infertility evaluation and many...
BACKGROUND
Infertility care is provided to Veterans through the Veterans Health Administration (VHA) medical benefits package and includes infertility evaluation and many infertility treatments.
OBJECTIVE
Our objective was to examine the incidence and prevalence of infertility diagnoses and the receipt of infertility healthcare among Veterans using Veterans Health Administration (VHA) healthcare from 2018 to 2020.
METHODS
Veterans using the VHA and diagnosed with infertility during October 2017-September 2020 (FY18-20) were identified in VHA administrative data and through VA-purchased care (i.e., community care) claims. Infertility was categorized among men as azoospermia, oligospermia, and other and unspecified male infertility, and among women as anovulation, infertility of tubal origin, infertility of uterine origin, and other and unspecified female infertility using diagnosis and procedure codes (ICD-10, CPT).
KEY RESULTS
A total of 17,216 Veterans had at least one VHA infertility diagnosis in FY18, FY19, or FY20, including 8766 male Veterans and 8450 female Veterans. Incident diagnoses of infertility were observed in 7192 male Veterans (10.8/10,000 person (p)-years) and 5563 female Veterans (93.6/10,000 p-years). A large proportion of Veterans who were diagnosed with infertility received an infertility-related procedure in the year of their incident diagnosis (males: 74.7, 75.3, 65.0%, FY18-20 respectively; females: 80.9, 80.8, 72.9%, FY18-20 respectively).
CONCLUSIONS
In comparison to a recent study of active duty servicemembers, we found a lower rate of infertility among Veteran men and a higher rate among Veteran women. Further work is needed to investigate military exposures and circumstances that may lead to infertility. Given the rates of infertility among Veterans and active duty servicemembers, enhancing communications between Department of Defense and VHA systems regarding sources of and treatment for infertility is essential to help more men and women benefit from infertility care during military service or as Veterans.
Topics: United States; Female; Humans; Male; Veterans; Veterans Health; United States Department of Veterans Affairs; Military Personnel; Infertility
PubMed: 36810630
DOI: 10.1007/s11606-023-08080-z -
Journal of Biomedical Science Feb 2023Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially impact male sterility, but the underlying mechanisms...
BACKGROUND
Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially impact male sterility, but the underlying mechanisms remain unclear. Previous reports suggested that C-type lectins play important roles in mediating virus-induced inflammatory reactions and pathogenesis. We thus investigated whether C-type lectins modulate ZIKV-induced testicular damage.
METHODS
C-type lectin domain family 5 member A (CLEC5A) knockout mice were generated in a STAT1-deficient immunocompromised background (denoted clec5astat1) to enable testing of the role played by CLEC5A after ZIKV infection in a mosquito-to-mouse disease model. Following ZIKV infection, mice were subjected to an array of analyses to evaluate testicular damage, including ZIKV infectivity and neutrophil infiltration estimation via quantitative RT-PCR or histology and immunohistochemistry, inflammatory cytokine and testosterone detection, and spermatozoon counting. Furthermore, DNAX-activating proteins for 12 kDa (DAP12) knockout mice (dap12stat1) were generated and used to evaluate ZIKV infectivity, inflammation, and spermatozoa function in order to investigate the potential mechanisms engaged by CLEC5A.
RESULTS
Compared to experiments conducted in ZIKV-infected stat1 mice, infected clec5astat1 mice showed reductions in testicular ZIKV titer, local inflammation and apoptosis in testis and epididymis, neutrophil invasion, and sperm count and motility. CLEC5A, a myeloid pattern recognition receptor, therefore appears involved in the pathogenesis of ZIKV-induced orchitis and oligospermia. Furthermore, DAP12 expression was found to be decreased in the testis and epididymis tissues of clec5astat1 mice. As for CLEC5A deficient mice, ZIKV-infected DAP12-deficient mice also showed reductions in testicular ZIKV titer and local inflammation, as well as improved spermatozoa function, as compared to controls. CLEC5A-associated DAP12 signaling appears to in part regulate ZIKV-induced testicular damage.
CONCLUSIONS
Our analyses reveal a critical role for CLEC5A in ZIKV-induced proinflammatory responses, as CLEC5A enables leukocytes to infiltrate past the blood-testis barrier and induce testicular and epididymal tissue damage. CLEC5A is thus a potential therapeutic target for the prevention of injuries to male reproductive organs in ZIKV patients.
Topics: Humans; Male; Mice; Animals; Zika Virus; Zika Virus Infection; Orchitis; Semen; Mice, Knockout; Inflammation; Lectins, C-Type; Receptors, Cell Surface
PubMed: 36803804
DOI: 10.1186/s12929-023-00906-6 -
ELife Feb 2023Centrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by Pericentriolar material 1 (PCM1). To study the requirement for centriolar...
Centrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by Pericentriolar material 1 (PCM1). To study the requirement for centriolar satellites, we generated mice lacking PCM1, a crucial component of satellites. mice display partially penetrant perinatal lethality with survivors exhibiting hydrocephalus, oligospermia, and cerebellar hypoplasia, and variably expressive phenotypes such as hydronephrosis. As many of these phenotypes have been observed in human ciliopathies and satellites are implicated in cilia biology, we investigated whether cilia were affected. PCM1 was dispensable for ciliogenesis in many cell types, whereas multiciliated ependymal cells and human retinal pigmented epithelial 1 (RPE1) cells showed reduced ciliogenesis. RPE1 cells displayed reduced docking of the mother centriole to the ciliary vesicle and removal of CP110 and CEP97 from the distal mother centriole, indicating compromised early ciliogenesis. Similarly, ependymal cells exhibited reduced removal of CP110 from basal bodies in vivo. We propose that PCM1 and centriolar satellites facilitate efficient trafficking of proteins to and from centrioles, including the departure of CP110 and CEP97 to initiate ciliogenesis, and that the threshold to trigger ciliogenesis differs between cell types.
Topics: Animals; Female; Humans; Mice; Cell Cycle Proteins; Centrioles; Centrosome; Cilia; Cytoskeletal Proteins
PubMed: 36790165
DOI: 10.7554/eLife.79299 -
Frontiers in Microbiology 2023Male infertility has always been one of the important factors affecting the infertility of couples of gestational age. The reasons that affect male infertility includes...
Male infertility has always been one of the important factors affecting the infertility of couples of gestational age. The reasons that affect male infertility includes living habits, hereditary factors, etc. Identifying the genetic causes of male infertility can help us understand the biology of male infertility, as well as the diagnosis of genetic testing and the determination of clinical treatment options. While current research has made significant progress in the genes that cause sperm defects in men, genetic studies of sperm content defects are still lacking. This article is based on a dataset of gene expression data on the X chromosome in patients with azoospermia, mild and severe oligospermia. Due to the difference in the degree of disease between patients and the possible difference in genetic causes, common classical clustering methods such as k-means, hierarchical clustering, etc. cannot effectively identify samples (realize simultaneous clustering of samples and features). In this paper, we use machine learning and various statistical methods such as hypergeometric distribution, Gibbs sampling, Fisher test, etc. and genes the interaction network for cluster analysis of gene expression data of male infertility patients has certain advantages compared with existing methods. The cluster results were identified by differential co-expression analysis of gene expression data in male infertility patients, and the model recognition clusters were analyzed by multiple gene enrichment methods, showing different degrees of enrichment in various enzyme activities, cancer, virus-related, ATP and ADP production, and other pathways. At the same time, as this paper is an unsupervised analysis of genetic factors of male infertility patients, we constructed a simulated data set, in which the clustering results have been determined, which can be used to measure the effect of discriminant model recognition. Through comparison, it finds that the proposed model has a better identification effect.
PubMed: 36778885
DOI: 10.3389/fmicb.2023.1092143 -
Medicine Feb 2023Intracytoplasmic sperm injection (ICSI) has become the most common method for couples with male factor infertility, and source of sperm for the procedure have evolved...
RATIONALE
Intracytoplasmic sperm injection (ICSI) has become the most common method for couples with male factor infertility, and source of sperm for the procedure have evolved over time. but few have examined testicular sperm extraction vs. ejaculated sperm use for severe oligozoospermia in the same assisted reproductive technology (ART) cycle.
PATIENT CONCERNS
Here, we evaluated the clinical outcomes after ICSI with testicular sperm or ejaculated in man with severe oligozoospermia in the same ART cycle. A couple who had failed the first ART cycle with ejaculated sperm, using the freshly ejaculated sperm and testicular sperm for ICSI during the second ART cycle by lack of enough sperm to fertilize in an ICSI attempt.
DIAGNOSES
The patient was diagnosed with severe oligozoospermia, and routine semen analysis revealed sperm concentration is less than 2 million/mL.
INTERVENTIONS
The patient using testicular sperm versus ejaculated sperm with ICSI assisted pregnancy in the same ART cycle.
OUTCOMES
We found that superior cleavage rate, number of embryos transferred and blastocyst rate with the use of testicular rather than ejaculated sperm-ICSI in the couple. The results described here suggest that use of testicular sperm may improve biologic outcomes, especially for couples with male-partner oligozoospermia who previous ICSI failures.
LESSONS
Our case report supported the efficacy of testicular sperm preference over ejaculated sperm for ICSI in men with severe male factor infertility. It is a paradigm shift concerning the use of ejaculated sperm as the preferable source of sperm for ICSI, add to the small amount of literature on testicular sperm extraction vs. ejaculated sperm use for severe oligozoospermia in the same ART cycle.
Topics: Pregnancy; Female; Male; Humans; Oligospermia; Sperm Injections, Intracytoplasmic; Semen; Sperm Retrieval; Spermatozoa; Infertility, Male; Pregnancy Rate
PubMed: 36749223
DOI: 10.1097/MD.0000000000032833 -
Open Life Sciences 2023Phytoestrogens and cold negatively influence male fertility. However, the combined effects of these two factors on male reproduction remain unknown. Herein, we studied...
Phytoestrogens and cold negatively influence male fertility. However, the combined effects of these two factors on male reproduction remain unknown. Herein, we studied the changes of sperm parameters and identify potential biomarkers involved in testis of rats, which were intervened by phytoestrogens combined with cold stress. Male Sprague-Dawley rats were randomly divided into control and model groups. The rats in the model group were fed an estrogen diet and placed in a climate chamber [10 ± 2°C; humidity of 75 ± 5%] for 12 h/daily. When compared with the control group after 24 weeks, the rats in the model group showed increased food intake, urine and stool outputs, and higher estradiol and follicle-stimulating hormone levels. However, lower sperm concentration, motility, and viability, and reduced testosterone levels were detected. The epithelial cells of the seminiferous tubules and epididymal ducts presented morphological abnormalities. Proteomic analysis showed that 24 testicular proteins were upregulated and 15 were downregulated. The identified proteins were involved in reticulophagy and stress response. Our findings suggest that the phytoestrogens combined with cold stress had negative effects on the reproductive function of male rats and provide the basis for the establishment of "course simulation" type of oligospermia animal model.
PubMed: 36742450
DOI: 10.1515/biol-2022-0531 -
Frontiers in Endocrinology 2022Oligoasthenoteratozoospermia (OAT) is a major cause of infertility in males. Only a few pathogenic genes of OAT have been clearly identified till now. A large number of...
INTRODUCTION
Oligoasthenoteratozoospermia (OAT) is a major cause of infertility in males. Only a few pathogenic genes of OAT have been clearly identified till now. A large number of OAT-affected cases remain largely unknown.
METHODS
Here, Whole-exome sequencing (WES) in 725 idiopathic OAT patients was performed. Ejaculated spermatozoa by OAT patients were microinjected into mouse oocytes to estimate fertilization potential. Diff-quick staining and transmission electron microscopy were performed to evaluate sperm morphology and ultrastructure. The protein expression level and localization In vitro were detected by Western Blotting and Immunocytochemistry.
RESULTS
We identified four X-linked hemizygous deleterious variants of TAF7L-namely, c.1301_1302del;(p.V434Afs*5), c.699G>T;(p.R233S), c.508delA; (p. T170fs), c.719dupA;(p.K240fs) -in five probands. Intracytoplasmic sperm injection (ICSI) were carried out in M1, M2-1and M3 patient's wife. However only M1 patient's wife became pregnant after embryo transfer. In vitro study demonstrated significantly reduced fertilization ability in patient with TAF7L mutation. The TAF7L mutation let to abnormal sperm head and impaired histone-to protamine exchange. Variant 719dupA (p. K240fs) resulted in producing a truncated TAF7L protein and localized massively within the nucleus. In addition, TAF7L expression were not able to be detected due to variants c.1301_1302del (p. V434Afs*5) and c.508delA (p. T170fs) In vitro.
CONCLUSION
Our findings support that TAF7L is one of pathogenic genes of OAT and deleterious mutations in TAF7L may cause impaired histone-to-protamine affected the chromatin compaction of sperm head.
Topics: Animals; Female; Humans; Male; Mice; Pregnancy; Asthenozoospermia; Fertilization in Vitro; Histones; Infertility, Male; Oligospermia; Protamines; Semen; TATA-Binding Protein Associated Factors; Transcription Factor TFIID
PubMed: 36714566
DOI: 10.3389/fendo.2022.1099270 -
European Review For Medical and... Jan 2023Recent studies have shown that there may be a deterioration in sperm parameters in patients who had recovered from COVID-19 disease. We aimed to investigate the...
OBJECTIVE
Recent studies have shown that there may be a deterioration in sperm parameters in patients who had recovered from COVID-19 disease. We aimed to investigate the relationship between COVID-19 disease and semen parameters in idiopathic male infertility patients.
PATIENTS AND METHODS
The study was conducted among male patients who applied with infertility between June 2021 and February 2022 following the approval of the Ethics Committee. Idiopathic infertility patients who could give semen analysis were included in the study. Detailed medical history of all patients was obtained. The presence of detectable causes of infertility was defined as exclusion criteria. The patients who had COVID-19 disease history (Reverse Transcriptase-PCR or Computed Tomography findings) in the last year were divided into two groups COVID-19 (+) and COVID-19 (-). The semen samples obtained from patients after a 3 day sexual abstinence in accordance with the WHO 2021 criteria were recorded.
RESULTS
A total of 42 male idiopathic infertility patients who met the criteria were included in the study. It was analyzed that both groups were similar in terms of sociodemographic characteristics, comorbidities, and habits (p>0.05). It was determined that 40.4% (n=17) had COVID-19 disease. The mean duration time after COVID-19 was 9.6 (4-17) months. Mean sperm concentration was found to be statistically significantly lower than the COVID-19 (-) group (41.59±17.4 vs. 58.8±21.9; p=0.021). Semen volume (3.05±0.7 vs. 3.32±0.6 mL; p>0.05), progressive sperm motility (34.05±20.96 vs. 43.00±16.94; p=0.12) and normal sperm morphology (3.47±1.42 vs. 3.08±1.41; p=0.41) were similar in both groups.The mean sperm concentration of the patients who recovered in the last 6 months (25.37±9.07 vs. 56.03±29.67 million/ml; p=0.013) compared to patients with >6 months after recovery (n=9) was found to be significantly lower.
CONCLUSIONS
The COVID-19 disease can cause a significant decrease in sperm concentration in idiopathic infertility patients, especially in the first 6 months, and the rates of oligospermia and asthenospermia are higher.
Topics: Humans; Male; Semen; Sperm Motility; COVID-19; Infertility, Male; Semen Analysis; Sperm Count; Spermatozoa
PubMed: 36647886
DOI: 10.26355/eurrev_202301_30891 -
Journal of Endocrinological... Jun 2023Infertility, which is defined as the inability to conceive after at least 12 months of regular unprotected sexual intercourses, affects about 15-20% of couples worldwide... (Review)
Review
BACKGROUND
Infertility, which is defined as the inability to conceive after at least 12 months of regular unprotected sexual intercourses, affects about 15-20% of couples worldwide and a male factor is involved in about half of the cases. The development of assisted reproductive technology (ART) made it possible to conceive also to individuals affected from severe oligospermia or azoospermia. However, the impact of the male factor on embryo development, implantation, prevalence of chromosomal abnormalities, genetic and epigenetic alterations, and clinical and obstetric outcomes is still controversial.
PURPOSE
This narrative review examines the indications, minimum access criteria, and outcomes by individual ART technique in relation to the male factor.
Topics: Pregnancy; Female; Humans; Male; Infertility, Male; Reproductive Techniques, Assisted; Azoospermia; Chromosome Aberrations; Infertility
PubMed: 36633791
DOI: 10.1007/s40618-022-02000-4 -
Scientific Reports Jan 2023Data on the clinical validity of DNA copy number variants (CNVs) in spermatogenic failure (SPGF) is limited. This study analyzed the genome-wide CNV profile in 215...
Data on the clinical validity of DNA copy number variants (CNVs) in spermatogenic failure (SPGF) is limited. This study analyzed the genome-wide CNV profile in 215 men with idiopathic SPGF and 62 normozoospermic fertile men, recruited at the Andrology Clinic, Tartu University Hospital, Estonia. A two-fold higher representation of > 1 Mb CNVs was observed in men with SPGF (13%, n = 28) compared to controls (6.5%, n = 4). Seven patients with SPGF were identified as carriers of microdeletions (1q21.1; 2.4 Mb) or microduplications (3p26.3, 1.1 Mb; 7p22.3-p22.2, 1.56 Mb; 10q11.22, 1.42 Mb, three cases; Xp22.33; 2.3 Mb) linked to severe congenital conditions. Large autosomal CNV carriers had oligozoospermia, reduced or low-normal bitesticular volume (22-28 ml). The 7p22.3-p22.2 microduplication carrier presented mild intellectual disability, neuropsychiatric problems, and short stature. The Xp22.33 duplication at the PAR1/non-PAR boundary, previously linked to uterine agenesis, was detected in a patient with non-obstructive azoospermia. A novel recurrent intragenic deletion in testis-specific LRRC69 was significantly overrepresented in patients with SPGF compared to the general population (3.3% vs. 0.85%; χ test, OR = 3.9 [95% CI 1.8-8.4], P = 0.0001). Assessment of clinically valid CNVs in patients with SPGF will improve their management and counselling for general and reproductive health, including risk of miscarriage and congenital disorders in future offspring.
Topics: Humans; Male; Azoospermia; DNA Copy Number Variations; Estonia; Oligospermia; Testis; Chromosome Deletion; Chromosome Duplication; Genetic Diseases, Inborn; Intellectual Disability; Mental Disorders
PubMed: 36631630
DOI: 10.1038/s41598-023-27750-w