Identification and clinical implication of a novel variant of SPAG17 gene resulting in Familial severe asthenozoospermia

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To investigate the association between SPAG17 gene variant and Familial severe asthenozoospermia, and to assess its impact on the outcome of intracytoplasmic sperm injection (ICSI). Two siblings (Probands 1 and 2) with severe asthenozoospermia from a Chinese family who presented at the Reproductive Medicine Center II of Gansu Maternity and Child Health Care Hospital (Gansu Provincial Central Hospital) in May 2023 were selected as study subjects. Clinical data were collected, and sperm morphology and ultrastructure (assessed by transmission electron microscopy) were analyzed. Pathogenic variants were screened using whole exome sequencing (WES) and verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Gansu Maternity and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). Probands 1 and 2 had primary infertility for 10 and 3 years, respectively, and both exhibited normal semen concentration, but the percentage of progressive motile sperm (PR) was significantly lower than the normal reference value (> 32.00%), measuring 2.33% ± 0.58% and 0.80% ± 0.45%, respectively. Additionally, the percentage of sperms with normal morphology was slightly below the reference range (> 4.00%), with the values of 3.36% ± 0.35% and 2.93% ± 1.36%. Both probands were found to harbor homozygous c.2188C>T (p.Q730*) nonsense variant of the SPAG17 gene (NM_206996.4), for which their mother was a heterozygous carrier (their father had already deceased). Both sibs underwent ICSI treatment using a long gonadotropin-releasing hormone agonist protocol during the follicular phase combined with assisted oocyte activation (AOA). The wife of Proband 1 ultimately gave birth to a healthy girl, whilst the wife of Proband 2 delivered two healthy girls. The homozygous c.2188C>T (p.Q730*) nonsense variant of the SPAG17 gene is closely related with the severe asthenozoospermia phenotype. Live births can be achieved through ICSI combined with AOA technology, though the overall utilizable embryo rate may be relatively low.

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  • Cite Count Icon 11
  • 10.1186/s12610-022-00155-x
ICSI outcomes for infertile men with severe or complete asthenozoospermia
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  • Basic and Clinical Andrology
  • Tong Chen + 10 more

BackgroundSevere or complete asthenozoospermia is a rare entity that can lead to male infertility. In this study, we explored whether different extents of severe or complete asthenozoospermia could affect intracytoplasmic sperm injection (ICSI) outcomes and compared the ICSI outcomes using testicular spermatozoa with those using ejaculated spermatozoa in couples with complete asthenozoospermia.ResultsNinety-seven couples with severe or complete asthenozoospermia who underwent ICSI between January 2014 and December 2018 were included. According to the sperm category used in ICSI, patients were categorized into four groups: ejaculated progressive motile sperm group (Ep-group), ejaculated non-progressive motile sperm group (En-group), ejaculated immotile sperm group (Ei-group), and testicular sperm group (TESE-group). We compared the baseline characteristics, hormone profile, semen parameters, normal fertilization, good-quality embryos on day 3, transferred embryos, and ICSI outcomes in the four groups. The clinical pregnancy rate was significantly increased in the Ep-group (65.4%, P = 0.019) and TESE-group (63.6%, P = 0.035) compared with that in the Ei-group (23.1%). The ongoing pregnancy rate in the Ei-group was significantly lower than that in the Ep-group (23.1% vs. 61.5%, P = 0.041). Moreover, the biochemical pregnancy rate, ongoing pregnancy rate, and live birth rate were much lower in the Ei-group than in the TESE-group (30.8% vs. 63.6%, 23.1% vs. 40.4% and 23.1% vs. 40.4%, respectively).ConclusionsIn couples with complete asthenozoospermia, testicular spermatozoa should be preferred to ejaculated spermatozoa for obtaining a better ICSI outcome. With the appropriate selection of testicular spermatozoa, the extent of severe or complete asthenozoospermia may not affect the ICSI outcomes. Future studies with a larger sample size are warranted to validate these findings.

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  • 10.1016/s0015-0282(00)01520-x
Effect of injected spermatozoa morphology on the outcome of intracytoplasmic sperm injection in humans
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Novel mutations in DNAH17 cause sperm flagellum defects and their influence on ICSI outcome.
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To identify new mutations in DNAH17 that cause male infertility and analyze intracytoplasmic sperm injection (ICSI) outcomes in patients with DNAH17 mutations. A total of five cases of new DNAH17 mutations exhibiting the multiple morphological abnormalities of the sperm flagella (MMAF) phenotype were identified through semen analysis and genetic testing. They were recruited at our reproductive medicine center from September 2018 to July 2022. Information on DNAH17 genetic mutations and ICSI outcomes was systematically explored following a literature review. Three novel compound mutations in DNAH17 were identified in patients with male infertility caused by MMAF. This study and previous publications included 21 patients with DNAH17 mutations. DNAH17 has been associated with asthenozoospermia and male infertility, but different types of DNAH17 variants appear to be involved in different sperm phenotypes. In 11 couples of infertile patients with DNAH17 mutations, there were 17 ICSI cycles and 13 embryo transplantation cycles. Only three men with DNAH17 variants ultimately achieved clinical pregnancy with their partners through ICSI combined with assisted oocyte activation (AOA). Loss-of-function mutations in DNAH17 can lead to severe sperm flagellum defects and male infertility. Patients with MMAF-harboring DNAH17 mutations generally have worse pregnancy outcomes following ICSI. ICSI combined with AOA may improve the outcome of assisted reproductive techniques (ARTs) for men with DNAH17 variants.

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Influence of the cumulus cells exposed to exogenous luteinizing hormone (LH) activity during ovarian stimulation on human embryo development and intracytoplasmic sperm injection (ICSI) outcomes
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Phenotypic Correlations of Testes Size with Semen Traits and the Productive Traits of Young Boars.
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Quality of frozen semen of Brahman bulls used for routine artificial insemination in Bangladesh
  • Aug 20, 2019
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Background: Semen must be of good quality to achieve satisfactory conception rate in any artificial insemination (AI) programme. The objectives of the present study were to evaluate the quality of frozen semen of Brahman bulls and compare the same semen derived from different sources. Methods: Fifteen frozen semen straws of Brahman bulls derived from 3 different sources (5 straws from each source) were evaluated with respect to volume, motility, concentration of spermatozoa and morphology of spermatozoa. Volume of semen was determined by micropipette, concentration was evaluated by haemocytometer technique, motility and progressive motility were evaluated by computer assisted sperm analyser (CASA), spermatozoa with normal acrosome, midpiece and tail were evaluated in formol-saline fixed semen and spermatozoa with normal head morphology were evaluated by Farley staining technique. Moreover, presence or absence of bacteria in semen was evaluated by Gram’s staining technique. Results: The overall semen volume, concentration, motile percentage, progressive motile percentage, percentage of spermatozoa with normal acrosome, midpiece and tail, and percentage of normal head morphology were 0.19±0.01 ml, 30.87±3.4x106/ml, 56.47±24.2 (%), 16.23±9.8 (%), 88.23±2.1 (%) and 95.1±1.6 (%), respectively. When compared, similar volume of semen (0.19 ml) was found in all frozen semen derived from different sources. The difference in percentage of motile spermatozoa between source B and C was significant (P<0.05). The difference in spermatozoa with normal acrosome, midpiece and tail in semen between source A and B was significant (P<0.05). The difference in the percentage of progressive motile spermatozoa, the concentration of spermatozoa and normal head morphology in semen among different sources of semen was not significant (P>0.05). The difference in percentage of motile spermatozoa, the percentage of progressive motile spermatozoa, the concentration of spermatozoa, normal acrosome, midpiece and tail, normal head morphology in semen between locally produced and foreign semen was not significant (P>0.05). All examined 15 semen samples were negative for presence of bacteria. Conclusions: Although the quality of frozen semen derived from Brahman bulls seems to be within normal limit, the post-AI conception rate should be determined to evaluate the fertilizing capacity of the used semen.

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Etiology and clinical characteristics of neonatal sepsis in different medical setting models: A retrospective multi-center study.
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  • Frontiers in pediatrics
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ObjectiveGeneral hospitals admit lower gestational age neonates than maternal and child health care centers, therefore associated with a higher morbidity and mortality. This study aimed to assess the etiology and clinical characteristics of neonatal sepsis in different medical setting models.MethodsNeonates admitted to 5 tertiary medical centers, including one national general hospital, two maternal and child health care hospitals and two regional general hospitals, in central-south China with culture-proven sepsis between January 2010 and December 2019 were included in the study. We compared maternal and neonatal characteristics, pathogen distribution, treatment and neonatal outcomes among 3 different medical setting models in this retrospective cohort.ResultsWe identified 757 episodes of culture-proven sepsis in 757 neonates. The predominant pathogens were coagulase-negative staphylococci, Klebsiella pneumoniae, Escherichia coli and Group B streptococci. A total of 683 neonates with detailed information were involved in further comparison; 54.6% were from the national general hospital, 35.9% were from the maternal and child health care hospital, and 9.5% were from the regional general hospital. Neonates in national and regional general hospitals had significantly lower gestational age and birthweight (P < 0.001). Patterns of pathogen distribution were different among these medical setting models. Early-onset sepsis was more common in maternal and child health care hospitals (61.4% vs. 42.1% vs. 46.7%, P < 0.001), while hospital-acquired late-onset sepsis was more common in national and regional general hospitals (32.7% vs. 33.3% vs. 11.4%, P < 0.001). The proportion of complications or comorbidities of neonates in maternal and child health care hospitals were significantly lower than neonates in national and regional general hospitals (P < 0.001). The case fatality rate was significantly higher in regional general hospitals (10.8% vs. 3.2% vs. 0.8%, P = 0.001).ConclusionWe report distinct patterns of clinical characteristics, pathogens and outcomes in patient subgroups with neonatal sepsis from national general hospital, maternal and child health care hospital and regional general hospital. It might have some implications for improvement of prevention, management and empirical antibiotic use in neonatal sepsis in different setting models, especially in resource-limited settings from middle and low-income countries.

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The relationship between isolated teratozoospermia and clinical pregnancy after in vitro fertilization with or without intracytoplasmic sperm injection: a systematic review and meta-analysis
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The relationship between isolated teratozoospermia and clinical pregnancy after in vitro fertilization with or without intracytoplasmic sperm injection: a systematic review and meta-analysis

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