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Scientific Reports May 2024Testicular adrenal rest tumor (TART) is a prevalent complication associated with congenital adrenal hyperplasia (CAH), culminating in gonadal dysfunction and...
Testicular adrenal rest tumor (TART) is a prevalent complication associated with congenital adrenal hyperplasia (CAH), culminating in gonadal dysfunction and infertility. Early hormonal intervention is preventive, but excessive glucocorticoid poses risks. Developing reliable methods for early TART diagnosis and monitoring is crucial. The present study aims to formulate a scoring system to identify high-risk infertility through analysis of TART ultrasound features. Grayscale and power Doppler ultrasound were employed in this retrospective study to evaluate testicular lesions in male CAH patients. Lesion assessment encompassed parameters such as range, echogenicity, and blood flow, and these were subsequently correlated with semen parameters. Results of 49 semen analyzes from 35 patients demonstrated a notable inverse correlation between lesion scores and both sperm concentration (r = - 0.83, P < 0.001) and progressive motility (r = - 0.56, P < 0.001). The ROC curve areas for evaluating oligospermia and asthenozoospermia were calculated as 0.94 and 0.72, respectively. Establishing a lesion score threshold of 6 revealed a sensitivity of 75.00% and specificity of 93.94% for oligospermia and a sensitivity of 53.85% and specificity of 100.00% for asthenozoospermia. These findings underscore the potential utility of incorporating ultrasound into routine CAH patient management, facilitating timely interventions to preserve male fertility.
Topics: Humans; Male; Adrenal Hyperplasia, Congenital; Adult; Retrospective Studies; Infertility, Male; Ultrasonography; Risk Assessment; Semen Analysis; Testis; Young Adult; Adrenal Rest Tumor
PubMed: 38802468
DOI: 10.1038/s41598-024-62954-8 -
Genes May 2024Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in... (Review)
Review
Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed.
Topics: Humans; Male; Spermatozoa; Sperm Motility; Asthenozoospermia; Infertility, Male; Teratozoospermia; DNA, Mitochondrial; Genetic Testing
PubMed: 38790229
DOI: 10.3390/genes15050600 -
Frontiers in Endocrinology 2024Multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by abnormal flagellar phenotypes, which is a particular kind of...
OBJECTIVE
Multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by abnormal flagellar phenotypes, which is a particular kind of asthenoteratozoospermia. Previous studies have reported a comparable intracytoplasmic sperm injection (ICSI) outcome in terms of fertilization rate and clinical pregnancy rate in patients with MMAF compared with those with no MMAF; however, others have conflicting opinions. Assisted reproductive technology (ART) outcomes in individuals with MMAF are still controversial and open to debate.
METHODS
A total of 38 patients with MMAF treated at an academic reproductive center between January 2014 and July 2022 were evaluated in the current retrospective cohort study and followed up until January 2023. Propensity score matching was used to adjust for the baseline clinical characteristics of the patients and to create a comparable control group. The genetic pathogenesis of MMAF was confirmed by whole exome sequencing. The main outcomes were the embryo developmental potential, the cumulative pregnancy rate (CLPR), and the cumulative live birth rate (CLBR).
RESULTS
Pathogenic variants in known genes of , , , , and were identified in patients with MMAF. Laboratory outcomes, including the fertilization rate, 2PN cleavage rate, blastocyst formation rate, and available blastocyst rate, followed a trend of decline in the MMAF group ( < 0.05). Moreover, according to the embryo transfer times and complete cycles, the CLPR in the cohort of MMAF was lower compared with the oligoasthenospermia pool ( = 0.033 and = 0.020, respectively), while no statistical differences were observed in the neonatal outcomes.
CONCLUSION
The current study presented decreased embryo developmental potential and compromised clinical outcomes in the MMAF cohort. These findings may provide clinicians with evidence to support genetic counseling and clinical guidance in specific patients with MMAF.
Topics: Humans; Male; Female; Pregnancy; Pregnancy Rate; Adult; Retrospective Studies; Sperm Injections, Intracytoplasmic; Sperm Tail; Embryonic Development; Asthenozoospermia; Infertility, Male; Spermatozoa
PubMed: 38745955
DOI: 10.3389/fendo.2024.1377780 -
Journal of Medical Case Reports May 2024Bacterial infection of embryo culture medium is rare but may be detrimental. The main source of embryo culture contamination is semen. Assisted reproduction centers...
BACKGROUND
Bacterial infection of embryo culture medium is rare but may be detrimental. The main source of embryo culture contamination is semen. Assisted reproduction centers currently lack consensus regarding the methods for preventing and managing embryo culture infection. In our recent case, a successful pregnancy was achieved with intracytoplasmic sperm injection after failed conventional in vitro fertilization owing to bacterial contamination.
CASE PRESENTATION
We present a case report of two consecutive in vitro fertilization-intracytoplasmic sperm injection cycles with photo and video documentation of the bacterial growth. A 36-year-old Hungarian woman and her 37-year-old Hungarian partner came to our department. They had two normal births followed by 2 years of infertility. The major causes of infertility were a closed fallopian tube and asthenozoospermia. Bacterial infection of the embryo culture medium was observed during in vitro fertilization and all oocytes degenerated. The source was found to be the semen. To prevent contamination, intracytoplasmic sperm injection was used for fertilization in the subsequent cycle. Intracytoplasmic bacterial proliferation was observed in one of the three fertilized eggs, but two good-quality embryos were successfully obtained. The transfer of one embryo resulted in a successful pregnancy and a healthy newborn was delivered.
CONCLUSION
Intracytoplasmic sperm injection may be offered to couples who fail conventional in vitro fertilization treatment owing to bacteriospermia, as it seems to prevent infection of the embryo culture. Even if bacterial contamination appears, our case encourages us to continue treatment. Nevertheless, the development of new management guidelines for the prevention and management of bacterial contamination is essential.
Topics: Humans; Sperm Injections, Intracytoplasmic; Female; Pregnancy; Adult; Fertilization in Vitro; Male; Embryo Culture Techniques; Pregnancy Outcome; Embryo Transfer; Semen
PubMed: 38745332
DOI: 10.1186/s13256-024-04521-3 -
Cureus Apr 2024This case report revolves around a 37-year-old woman and her 39-year-old husband, who have been married for seven years and were seeking treatment for infertility. The...
This case report revolves around a 37-year-old woman and her 39-year-old husband, who have been married for seven years and were seeking treatment for infertility. The husband has been diagnosed with asthenozoospermia for the past six years and has been on continued medication, and the woman has been diagnosed with polycystic ovarian syndrome (PCOS). To improve fertility outcomes, this case report enlightens the treatment and medical strategy for people with PCOS. Treatment included low-dose ovarian stimulation for the removal of immature eggs, and then in vitro maturation (IVM) of those oocytes was done. Later, intracytoplasmic sperm injection (ICSI) was performed to form the blast. The formed blasts were later cryopreserved till embryo transfer. This case report highlights the importance of preventing the risk of ovarian hyperstimulation syndrome (OHSS) in patients with PCOS.
PubMed: 38707084
DOI: 10.7759/cureus.57486 -
American Journal of Men's Health 2024
Topics: Humans; Male; Acetylcysteine; Asthenozoospermia; Carnitine; Meta-Analysis as Topic; Acetylcarnitine; Treatment Outcome
PubMed: 38686842
DOI: 10.1177/15579883241249109 -
Human Reproduction Open 2024Is the mutation causative for male infertility?
STUDY QUESTION
Is the mutation causative for male infertility?
SUMMARY ANSWER
Our collected data underline the complex and devastating effect of the single-gene mutation on the testicular molecular network, leading to male reproductive failure.
WHAT IS KNOWN ALREADY
Recent data have revealed mutations in genes related to axonemal dynein arms as causative for morphology and motility abnormalities in spermatozoa of infertile males, including dysplasia of fibrous sheath (DFS) and multiple morphological abnormalities in the sperm flagella (MMAF). The nexin-dynein regulatory complex (N-DRC) coordinates the dynein arm activity and is built from the DRC1-DRC7 proteins. DRC5 (TCTE1), one of the N-DRC elements, has already been reported as a candidate for abnormal sperm flagella beating; however, only in a restricted manner with no clear explanation of respective observations.
STUDY DESIGN SIZE DURATION
Using the CRISPR/Cas9 genome editing technique, a mouse gene knockout line was created on the basis of the C57Bl/6J strain. The mouse reproductive potential, semen characteristics, testicular gene expression levels, sperm ATP, and testis apoptosis level measurements were then assessed, followed by visualization of N-DRC proteins in sperm, and protein modeling . Also, a pilot genomic sequencing study of samples from human infertile males (n = 248) was applied for screening of variants.
PARTICIPANTS/MATERIALS SETTING METHODS
To check the reproductive potential of KO mice, adult animals were crossed for delivery of three litters per caged pair, but for no longer than for 6 months, in various combinations of zygosity. All experiments were performed for wild-type (WT, control group), heterozygous and homozygous male mice. Gross anatomy was performed on testis and epididymis samples, followed by semen analysis. Sequencing of RNA (RNAseq; Illumina) was done for mice testis tissues. STRING interactions were checked for protein-protein interactions, based on changed expression levels of corresponding genes identified in the mouse testis RNAseq experiments. Immunofluorescence staining was performed to detect the N-DRC complex proteins: Tcte1 (Drc5), Drc7, Fbxl13 (Drc6), and Eps8l1 (Drc3) in mouse spermatozoa. To determine the amount of ATP in spermatozoa, the luminescence level was measured. In addition, immunofluorescence staining was performed to check the level of apoptosis via caspase 3 visualization on mouse testis samples. DNA from whole blood samples of infertile males (n = 137 with non-obstructive azoospermia or cryptozoospermia, n = 111 samples with a spectrum of oligoasthenoteratozoospermia, including n = 47 with asthenozoospermia) was extracted to perform genomic sequencing (WGS, WES, or Sanger). Protein prediction modeling of human-identified variants and the exon 3 structure deleted in the mouse knockout was also performed.
MAIN RESULTS AND THE ROLE OF CHANCE
No progeny at all was found for the homozygous males which were revealed to have oligoasthenoteratozoospermia, while heterozygous animals were fertile but manifested oligozoospermia, suggesting haploinsufficiency. RNA-sequencing of the testicular tissue showed the influence of mutations on the expression pattern of 21 genes responsible for mitochondrial ATP processing or linked with apoptosis or spermatogenesis. In males, the protein was revealed in only residual amounts in the sperm head nucleus and was not transported to the sperm flagella, as were other N-DRC components. Decreased ATP levels (2.4-fold lower) were found in the spermatozoa of homozygous mice, together with disturbed tail:midpiece ratios, leading to abnormal sperm tail beating. Casp3-positive signals (indicating apoptosis) were observed in spermatogonia only, at a similar level in all three mouse genotypes. Mutation screening of human infertile males revealed one novel and five ultra-rare heterogeneous variants (predicted as disease-causing) in 6.05% of the patients studied. Protein prediction modeling of identified variants revealed changes in the protein surface charge potential, leading to disruption in helix flexibility or its dynamics, thus suggesting disrupted interactions of TCTE1 with its binding partners located within the axoneme.
LARGE SCALE DATA
All data generated or analyzed during this study are included in this published article and its supplementary information files. RNAseq data are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) under the accession number GSE207805. The results described in the publication are based on whole-genome or exome sequencing data which includes sensitive information in the form of patient-specific germline variants. Information regarding such variants must not be shared publicly following European Union legislation, therefore access to raw data that support the findings of this study are available from the corresponding author upon reasonable request.
LIMITATIONS REASONS FOR CAUTION
In the study, the fertilization performance of sperm from homozygous male mice was not checked.
WIDER IMPLICATIONS OF THE FINDINGS
This study contains novel and comprehensive data concerning the role of in male infertility. The gene is the next one that should be added to the 'male infertility list' because of its crucial role in spermatogenesis and proper sperm functioning.
STUDY FUNDING/COMPETING INTERESTS
This work was supported by National Science Centre in Poland, grants no.: 2015/17/B/NZ2/01157 and 2020/37/B/NZ5/00549 (to M.K.), 2017/26/D/NZ5/00789 (to A.M.), and HD096723, GM127569-03, NIH SAP #4100085736 PA DoH (to A.N.Y.). The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
PubMed: 38650655
DOI: 10.1093/hropen/hoae020 -
BMC Medical Genomics Apr 2024This report presents a clinical case of syndromic rod-cone dystrophy due to a splice site variant in the ARL2BP gene causing situs inversus, asthenozoospermia,...
A novel homozygous splice site variant in ARL2BP causes a syndromic autosomal recessive rod-cone dystrophy with situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts.
BACKGROUND
This report presents a clinical case of syndromic rod-cone dystrophy due to a splice site variant in the ARL2BP gene causing situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts. The presence of renal agenesis and cryptorchidism expands the clinical manifestations due to ARL2BP variants. The detailed, long-term follow-up contributes valuable insights into disease progression, aiding clinical diagnosis and patient management.
CASE PRESENTATION
The male patient complained of photophobia as the first symptom when he was 20 years old followed by nyctalopia, loss of central visual acuity and peripheral visual field ten years later. Genetic analysis identified a likely pathogenic homozygous variant (c.294-1G > C) involving the splicing acceptor site of intron 4. Reported symptoms together with full-field stimulus threshold testing, electroretinogram and advanced multimodal imaging allowed us to recognize the typical characteristics of a mixed retinal dystrophy. Despite the end-stage retinal disease, this patient still retained a useful residual vision at 63 years and had a slow disease progression during the last 5 years of evaluation.
DISCUSSION AND CONCLUSIONS
Our findings underscore the variable clinical presentation of ARL2BP variants, emphasizing the importance of a nuanced approach in diagnosing and managing patients. The presence of renal cysts warrants consideration of a differential diagnosis, particularly with Senior-Loken (SLS), Bardet-Biedl (BBS) and Joubert syndromes (JS) but also with Short Rib Thoracic Dysplasia 9, highlighting the need for careful phenotypic evaluation in these cases.
Topics: Humans; Male; Cone-Rod Dystrophies; Congenital Abnormalities; Homozygote; Kidney; Kidney Diseases; RNA Splice Sites; Situs Inversus; Syndrome; Middle Aged
PubMed: 38649918
DOI: 10.1186/s12920-024-01868-w -
International Journal of Molecular... Apr 2024Infertility is a global health challenge that affects an estimated 72.4 million people worldwide. Between 30 and 50% of these cases involve male factors, showcasing the...
Infertility is a global health challenge that affects an estimated 72.4 million people worldwide. Between 30 and 50% of these cases involve male factors, showcasing the complex nature of male infertility, which can be attributed to both environmental and genetic determinants. Asthenozoospermia, a condition characterized by reduced sperm motility, stands out as a significant contributor to male infertility. This study explores the involvement of the mitochondrial oxidative phosphorylation (OXPHOS) system, crucial for ATP production and sperm motility, in asthenozoospermia. Through whole-genome sequencing and in silico analysis, our aim was to identify and characterize OXPHOS gene variants specific to individuals with asthenozoospermia. Our analysis identified 680,099 unique variants, with 309 located within OXPHOS genes. Nine of these variants were prioritized due to their significant implications, such as potential associations with diseases, effects on gene expression, protein function, etc. Interestingly, none of these variants had been previously associated with male infertility, opening up new avenues for research. Thus, through our comprehensive approach, we provide valuable insights into the genetic factors that influence sperm motility, laying the foundation for future research in the field of male infertility.
Topics: Male; Humans; Asthenozoospermia; Oxidative Phosphorylation; Sperm Motility; Infertility, Male; Whole Genome Sequencing
PubMed: 38612930
DOI: 10.3390/ijms25074121 -
Diagnostics (Basel, Switzerland) Mar 2024(1) Background: Standard semen analysis methods may exhibit variability between observers and/or human error; therefore, additional methods are needed to overcome these...
Introducing a New Smartphone Applied Semen Analyzer, SpermCell™: A Cross-Sectional Validation Study with a Comparative Analysis and a Mini Patient Questionnaire on a Large Sample Cohort.
(1) Background: Standard semen analysis methods may exhibit variability between observers and/or human error; therefore, additional methods are needed to overcome these handicaps. We aimed to present a new smartphone-applied semen analyzer, Sperm Cell™, investigate its diagnostic efficacy by comparing it with the standard analysis method, and determine its user-friendly nature. (2) Methods: A cross-sectional study was conducted on a large sample cohort, including 102 men. Three semen analyses were performed for each semen sample. The first employed the standard manual method, whereas the others were smartphone-based analyses performed by technicians and patients. We compared major semen parameters between the three semen analyses. The user-friendly nature of the analyzer was also evaluated with a mini-questionnaire completed by the participants. (3) Results: The determined median sperm count, motile sperm count, and percentage of motile sperms, on standard manual semen analysis, were 50.00 × 10/mL (0-160 × 10/mL), 23.94 × 10/mL (0-108 × 10/mL) and 50.00% (0-73.00%), respectively. Median sperm count and motile sperm count were 50.52 × 10/mL (<1-150 × 10/mL) vs. 55.77 × 10/mL (<1-160 × 10/mL) and 23.34 × 10/mL (0-105 × 10/mL) vs. 23.53 × 10/mL (0-104 × 10/mL) for SpermCell™-based semen analysis performed by a technician and patients themselves, respectively. The percentages of motile sperms were 47.40% (0-67.00%) vs. 47.61% (0-80.20%), respectively. All the parameters were statistically similar between the three semen analysis methods ( > 0.05 for each). The SpermCell™ analysis results were correlated with the standard manual method with up to 0.85 correlation coefficients. Moreover, substantial diagnostic accuracy, sensitivity and specificity were obtained in determining the oligospermia and asthenozoospermia via the device-based analyses performed by technician and patients. The mini-questionnaire results revealed that the analyzer is useful. (4) Conclusions: The novel smartphone-applied semen analyzer is a helpful tool with acceptable diagnostic accuracy in determining the major semen parameters. It can be used as an efficient at-home point-of-care testing method in the initial assessment of couples with infertility concerns.
PubMed: 38611602
DOI: 10.3390/diagnostics14070689