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Predictors of microsurgical varicocelectomy efficacy in male infertility treatment:critical assessment and systematization

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Asian Journal of Andrology 2023年第1期25卷 21-28页

作者： Azizbek B Shomarufov Vladimir A Bozhedomov Nikolay I Sorokin Igor P Matyukhov Abdukodir A Fozilov Shukhrat A Abbosov Armais A Kamalov Department of Urology and Andrology Faculty of Fundamental MedicineLomonosov Moscow State UniversityMoscow 119991Russia Department of Urology Tashkent Medical AcademyTashkent 100109Uzbekistan Republican Specialized Scientific-Practical Medical Center of Urology Tashkent 100109Uzbekistan

In this review,we tried to systematize all the evidence(from PubMed[MEDLINE],Scopus,Cochrane Library,EBSCO,Embase,and Google Scholar)from 1993 to 2021 on the predictors of microsurgical varicocelectomy efficacy in male infertility treatment.Regarding the outcomes of varicocele repair,we considered semen improvement and pregnancy and analyzed them separately.Based on the 2011 Oxford CEBM Levels of Evidence,we assigned a score to each trial that studied the role of the predictor.We systematized the studied predictors based on the total points,which were,in turn,calculated based on the number and quality of studies that confirmed or rejected the studied predictor as significant,into three levels of significance:predictors of high,moderate,and low clinical significance.Preoperative total motile sperm count(TMSC)coupled with sperm concentration can be a significant predictor of semen improvement and pregnancy after varicocelectomy.In addition,for semen improvement alone,scrotal Doppler ultrasound(DUS)parameters,sperm DNA fragmentation index(DFI),and bilateral varicocelectomy are reliable predictors of microsurgical varicocelectomy efficacy.

关键词： male infertility microsurgical varicocelectomy predictor pregnancy semen varicocele

Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm

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Asian Journal of Andrology 2023年第3期25卷 398-403页

作者： Juan Hua Lan Guo Yao Yao Wen Hu Yang-Yang Wan Bo Xu Department of Biochemistry and Molecular Biology School of Basic Medical SciencesAnhui Medical UniversityHefei 230032China Metabolic Disease Research Center School of Basic MedicineAnhui Medical UniversityHefei 230032China Hefei Xingzhike Biotechnology Co. Ltd.Hefei 230000China Reproductive and Genetic Hospital The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China

Teratozoospermia is a rare disease associated with male infertility.Several recurrent genetic mutations have been reported to be associated with abnormal sperm morphology,but the genetic basis of tapered-head sperm is not well understood.In this study,whole-exome sequencing(WES)identified a homozygous WD repeat domain 12(WDR12;p.Ser162Ala/c.484T>G)variant in an infertile patient with tapered-head spermatozoa from a consanguineous Chinese family.Bioinformatic analysis predicted this mutation to be a pathogenic variant.To verify the effect of this variant,we analyzed WDR12 protein expression in spermatozoa of the patient and a control individual,as well as in the 293T cell line,by Western blot analysis,and found that WDR12 expression was significantly downregulated.To understand the role of normal WDR12,we evaluated its mRNA and protein expression in mice at different ages.We observed that WDR12 expression was increased in pachytene spermatocytes,with intense staining visible in round spermatid nuclei.Based on these results,the data suggest that the rare biallelic pathogenic missense variant(p.Ser162Ala/c.484T>G)in the WDR12 gene is associated with tapered-head spermatozoa.In addition,after intracytoplasmic sperm injection(ICSI),a successful pregnancy was achieved.This finding indicates that infertility associated with this WDR12 homozygous mutation can be overcome by ICSI.The present results may provide novel insights into understanding the molecular mechanisms of male infertility.

关键词： male infertility tapered-head sperm teratozoospermia WD repeat domain 12(WDR12)

male infertility:A scoping review of prevalence,causes and treatments

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Asian pacific Journal of Reproduction 2021年第5期10卷 195-202页

作者： Kirati M.Shah Kanan G.Gamit Manan A.Raval Niraj Y.Vyas Ramanbhai Patel College of Pharmacy Charotar University of Science and Technology(CHARUSAT)CHARUSAT CampusOff.Nadiad-Petlad HighwayPIN 388421Dist.AnandGujaratIndia

male factor infertility has now become a major health disorder,affecting human reproduction and developing worldwide as a serious medical and social issue.It causes trauma,emotional instability,and mental stress in the affected couples.In nearly half of the analyzed cases,male-associated factors are the major contributors.The present review outlines a wide range of factors responsible for male infertility.We performed an in-depth literature review of the global index of infertility by using data from World Health Organization’s website,Elsevier’s,PubMed and Scopus databases as well as journals.The quality and quantity of semen,male hormonal imbalance,genetic deterioration,and reactive oxygen species are the fundamental causes of male factor infertility.In addition,air quality,water quality,noise pollution,lifestyle changes,improper diet consumption,malnutrition,exposure to chemicals and toxins,smoking habits,drug abuses,major diseases,and medications are also contributors to infertility issues that can temporarily or permanently influence male reproductive system.We also reviewed the prevalence of male infertility in different countries.

关键词： male infertility Aphrodisiac Spermatogenesis male sexual disorder Erectile dysfunction Libido Sexual desire Prevalence

Psychological, social, and sexual challenges affecting men receiving male infertility treatment: a systematic review and implications for clinical care

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Asian Journal of Andrology 2023年第4期25卷 448-453页

作者： Winston Wu Justin La Kathryn M Schubach Daniel Lantsberg Darren J Katz Department of Urology Western HealthSt AlbansVIC 3021Australia Department of Urology Kaiser Permanente San Rafael Medical CenterSan RafaelCA 94903USA Men’s Health Melbourne MelbourneVIC 3000Australia Reproductive Services Unit The Royal Women’s HospitalParkvilleVIC 3052Australia Melbourne IVF East MelbourneVIC 3002Australia Department of Surgery Western PrecinctUniversity of MelbourneParkvilleVIC 3010Australia

In recent years, social research surrounding the consequences of infertility has increasingly focused on the male perspective;however, a gap exists in the understanding of men’s experiences of male infertility treatment. This review aims to synthesize theexisting evidence concerning the psychological, social, and sexual burden of male infertility treatment on men, as well as patientneeds during clinical care. A systematic search identified 12 studies that are diverse in design, setting, and methods. Psychologicalevaluations have found that urological surgery may have a lasting impact on infertility-specific stress, and treatment failure canlead to feelings of depression, grief, and inadequacy. Men tended to have an avoidant coping mechanism throughout fertilitytreatment, and their self-esteem, relationship quality, and sexual functions can be tied to outcomes of treatment. Partner bonds canbe strengthened by mutual support and enhanced communication;couple separation, however, has been noted as a predominantreason for discontinuing male infertility treatment and may be associated with difficult circumstances surrounding severe maleinfertility. Surgical treatments can affect the sexual functioning of infertile men;however, the impact of testicular sperm extractionoutcomes appears to be psychologically driven whereas the improvements after microsurgical varicocelectomy are only evident inhypogonadal men. Clinically, there is a need for better inclusion, communication, education, and resource provision, to addressreported issues of marginalization and uncertainty in men. Routine psychosocial screening in cases of severe male infertility andfollow-up in cases of surgical treatment failure are likely beneficial.

关键词： male infertility male infertility treatment patient experience patient-centered care psychosocial sexual

Guijiajiao(Colla Carapacis et Plastri,CCP)prevents male infertility via gut microbiota modulation

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Chinese Journal of Natural Medicines 2023年第6期21卷 403-410页

作者： SHENG Wen XU Wenjing DING Jin LU Baowei LIU Lumei HE Qinghu ZHOU Qing College of Traditional Chinese Medicine Hunan University of Chinese MedicineChangsha 410000China Andrology Laboratory Hunan University of Chinese MedicineChangsha 410000China Department of Dermatology The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410000China Department of Andrology Affiliated Bao'an Hospital of Traditional Chinese MedicineThe Seventh Clinical Medical CollegeGuangzhou University of Traditional Chinese MedicineShenzhen 518000 College of Integrated Traditional Chinese and Western Medicine Hunan University of Chinese MedicineChangsha 410000 College of Traditional Chinese Medicine Hunan University of MedicineChangsha 410000 Department of Andrology The First Hospital of Hunan University of Chinese MedicineChangsha 410000

male infertility is a significant cause of psychosocial and marital distress in approximately 50% of couples who are unable to conceive,with male factors being the underlying cause.Guijiajiao(Colla Carapacis et Plastri,CCP)is a Traditional Chinese Medicine commonly used to treat male infertility.The present study aimed to investigate the potential mechanisms underlying the preventive effects of CCP on male infertility.An infertile male rat model was established using cyclophosphamide(CTX),and CCP was administered for both treatment and prevention.Fecal microbiota transplantation(FMT)was also performed to explore the role of gut microbiota in the CCP-mediated prevention of male infertility in rats.Sperm motility and concentration were determined using a semiautomatic sperm classification analyzer.Subsequently,histopathological analysis using HE staining was performed to examine the changes in the small intestine and testis.Moreover,the serum levels of lipopolysaccharide(LPS)and testosterone were measured by ELISA.In addition,immunohistochemistry was conducted to detect CD3 expression in the small intestine,while RT-qPCR was employed to assess the expressions of interleukin-1 beta(IL-1β),cluster of differentiation 3(CD3),Monocyte chemoattractant protein-1(MCP-1),and C-X-C motif chemokine ligand 10(CXCL-10)in the small intestine and epididymis.Finally,gut microbiota was analyzed by 16S rRNA sequencing.CCP improved sperm motility,number,and concentration in CTX-induced infertile male rats.CCP increased the serum testosterone level,inhibited the immune cell infiltration of the intestinal lamina propria,and promoted the aggregation of CD3+T cells in CTX-induced male infertility rats.CCP also inhibited the expressions of MCP-1,CXCL-10,and IL-1βin the epididymis of male infertility rats.At the genus level,CTX led to a reduction in the abundance of Lactobacillus,Clostridia_UCG.014,and Romboutsia in the intestinal tract of rats.In contrast,CCP decreased the abundance of Ruminococcus and increased the abundance of Romboutsi

关键词： Colla Carapacis et Plastri Fecal microbiota transplantation male infertility Gut microbiota Spermatogenesis ability

male infertility microsurgical training

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Asian Journal of Andrology 2013年第1期15卷 61-66页

作者： Akanksha Mehta Philip S Li Center for male Reproductive Medicine and Microsurgery Cornell Institute for Reproductive Medicine Department of Urology Weill Cornell Medical College New York NY10065 USA

Microsurgical training is imperative for urologists and clinical andrologists specializing in male infertility. Success in male infertility microsurgery is heavily dependent on the surgeon＇s microsurgical skills. Laboratory-based practice to enhance microsurgical skills improves the surgeon＇s confidence, and reduces stress and operating time, benefiting both the patient and the surgeon. This review provides guidelines for setting up a microsurgical laboratory to develop and enhance microsurgical skills using synthetic and animal models. The role of emerginE techniaues, such as robotic-assisted microsureerv, is also discussed.

关键词： laboratory male infertility microsurgery training vasoepididymostomy vasovasostomy

Investigation of the genetic etiology in male infertility with apparently balanced chromosomal structural rearrangements by genome sequencing

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Asian Journal of Andrology 2022年第3期24卷 248-254页

作者： Matthew Hoi Kin Chau Ying Li Peng Dai Mengmeng Shi Xiaofan Zhu Jacqueline Pui Wah Chung Yvonne K Kwok Kwong Wai Choy Xiangdong Kong Zirui Dong Department of Obstetrics and Gynaecology The Chinese University of Hong KongHong KongChina Shenzhen Research Institute The Chinese University of Hong KongShenzhen 518057China Hong Kong Hub of Paediatric Excellence The Chinese University of Hong KongHong KongChina Genetics and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China The Chinese University of Hong Kong-Baylor College of Medicine Joint Center for Medical Genetics Hong KongChina

Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1%of azoospermia or severe oligospermia.However,the underlying mechanisms of pathogenesis and etiologies are still largely unknown.Herein,we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number variants.In addition,high read-depth genome sequencing(GS)(30-fold)was performed to investigate point mutations causative of male infertility.Mate-pair GS(4-fold)revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 rearrangements.Overall,the breakpoints caused truncations of 30 RefSeq genes,five of which were associated with spermatogenesis.Furthermore,the breakpoints disrupted 43 topological-associated domains.Direct disruptions or potential dysregulations of genes,which play potential roles in male germ cell development,apoptosis,and spermatogenesis,were found in all cases(n=6).In addition,high read-depth GS detected dual molecular findings in case MI6,involving a complex rearrangement and two point mutations in the gene DNAH1.Overall,our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male infertility.We demonstrated the complexity of chromosomal structural rearrangements,potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.

关键词： azoospermia balanced structural rearrangements genome sequencing male infertility severe oligospermia

A novel loss-of-function variant in PNLDC1 inducing oligo-astheno-teratozoospermia and male infertility

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Asian Journal of Andrology 2023年第5期25卷 643-645页

作者： Si-Yi Zhao Lan-Lan Meng Zhao-Li Du Yue-Qiu Tan Wen-Bin He Xiong Wang The First Clinical College of Guangzhou Medical University Guangzhou 511436China National Engineering and Research Center of Human Stem Cells and Institute of Reproductive and Stem Cell Engineering School of Basic Medical ScienceCentral South UniversityChangsha 410008China Reproductive and Genetic Hospital of CITIC-Xiangya and Clinical Research Center For Reproduction and Genetics in Hunan Province Changsha 410008China Yinfeng Gene Technology Co. Ltd.Jinan 250000China Reproductive Medicine Center Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityYantai 264000China

male infertility is a major reproductive disorder,which is clinically characterized by highly heterogeneous phenotypes of abnormal sperm count or quality.To date,five male patients with biallelic loss-of-function(LOF)variants of PARN-like ribonuclease domain-containing exonuclease 1(PNLDC1)have been reported to experience infertility with nonobstructive azoospermia.The aim of this study was to identify the genetic cause of male infertility with oligo-astheno-teratozoospermia(OAT)in a patient from a Chinese Han family.Whole-exome and Sanger sequencing analyses identified a homozygous LOF variant(NM_173516.2,c.l42C>T,p.Gln48Ter)in PNLDC1.Hematoxylin and eosin staining revealed that the spermatozoa of the patient with OAT had an irregular head phenotype,including microcephaly,head tapering,and globozoospermia.Consistently,peanut agglutinin staining of the spermatozoa revealed a complete or partial loss of the acrosome.Furthermore,the disomy rate of chromosomes in the patient’s spermatozoa was significantly increased compared with that of a fertile control sample.We reported an LOF variant of the PNLDC1 gene responsible for OAT.

关键词： loss-of-function variant male infertility oligo-astheno-teratozoospermia PARN-like ribonuclease domain-containing exonuclease 1

The association between mutations in ubiquitin-specific protease 26(USP26)and male infertility:a systematic review and meta-analysis

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Asian Journal of Andrology 2022年第4期24卷 422-429页

作者： Qin-Yu Li Yu-Cong Zhang Chao Wei Zhuo Liu Guo-Da Song Bing-Liang Chen Man Liu Ji-Hong Liu Li-Cheng Wu Xia-Ming Liu Department of Urology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Geriatric Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

During recent decades,the association between mutations in ubiquitin-specific protease 26(USP26)and male infertility remains doubtful.We conducted this meta-analysis to evaluate the association between mutations in USP26 and male infertility according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)2020 guidelines.It was registered in the International Prospective Register of Systematic Reviews(PROSPERO;CRD42021225251).PubMed,Web of Science,and Scopus were systematically searched for comparative clinical studies,which were written in English and provided eligible data.Studies were included when they compared USP26 mutations in azoospermic,oligozoospermic,and asthenozoospermic patients with controls with normal sperm parameter values or whose partners had experienced spontaneous pregnancy.Pooled odds ratio(OR)with 95%confidence interval(CI)was calculated with random effect models.Overall,twelve studies with 3927 infertility patients and 4648 healthy controls were included.The association between overall USP26 mutations and infertility was not significant(OR=1.60,95%CI:0.51-5.01).For specific mutations,the pooled ORs were 1.65(95%CI:1.02-2.69)for cluster mutation(including 370-371insACA,494T>C,and 1423C>T),1.80(95%CI:0.35-9.15)for c.576G>A,1.43(95%CI:0.79-2.56)for c.1090C>T,and 3.59(95%CI:2.30-5.59)for c.1737G>A.Our results suggest that several mutations(cluster mutation,c.1737G>A)may play roles in male infertility,while others(c.576G>A and c.1090C>T)do not show notable associations with male infertility.More high-quality clinical researches are needed for validation.

关键词： azoospermia haplotype male infertility mutation ubiquitin-specific protease 26