Epidemiological and Clinical Aspects of Male Infertility in Patients Consulting at the Urology Department of the Yaounde Central Hospital

Introduction: About 10 to 15% of couples in the world and 20 to 30% in Cameroon consult for infertility problems. Infertility is of male origin in 40% of cases. Our objective was to evaluate the epidemiological and clinical aspects of male infertility in our setting. Methods: This was a cross-sectional and descriptive study, with retrospective data collection from the files of patients received for male infertility, over 5 years and 6 months (from January 1st, 2016 to April 30th, 2021) at the Urology Department of the Yaounde Central Hospital. Phone calls were made to patients with incomplete records for completion following a verbal consent. Data reported on data collection forms were entered into a data entry form designed on CSPro software version 7.2. The database was later exported for descriptive statistics using the IBM SPSS software version 23. Qualitative variables were summarized in frequencies and percentages while quantitative variables were summarized in means with their standard deviations for normally distributed data, or medians and interquartile ranges otherwise. Results: Out of 110 patients whose records were analyzed, the median age was 37.0 years, with an interquartile range of 8.3, with 55.5% in the age group 30 to 39 years. Of these 95 (86.4%) were married, 58 (52.7%) were from the West region, 76 (69.1%) were employed. Past history was dominated by mumps 40 (36.4%), varicocele surgery 25 (22.7%), alcoholism 87 (79.1%) and smoking 15 (13.6%). A disorder of spermatogenesis was found in all our patients: 37 (33.6%) azoospermia, 27 (24.6%) asthenospermia and 26 (23.7%) oligospermia patients. Paraclinical evidence of chlamydia and gonococcal infections were found respectively in 38 (34.5%) and 14 (12.7%) patients, varicocele and testicular dystrophy respectively in 95 (86.4%) and 38 (34.5%) patients. Infertility was primary in 67 (60.9%) patients. Conclusion: Most patients with infertility were in their thirties, had risky social habits and comorbidities. An early start of health promotion activities, comorbidities prevention and early detection of spermogram abnormalities would make it possible to reduce the frequency of male infertility.

The role of small non-coding RNAs(sncRNAs)in male infertility:A scoping review

Objective:To give a brief overview of the field of epigenetics and the potential predictive power that small non-coding RNA(sncRNA)may hold in relation to improving the treatment and diagnosis of male infertility.Methods:PRISMA-ScR was used as the scoping review guideline for this investigation.All article data here have been accessed from MEDLINE–PubMed,Science Direct,EBSCO,Scopus,Sage Journals,and Google Scholar.The terms"small non coding RNA,male,infertility,miRNA,sperm"were used in the search between 2015 and 2023.Results:The study comprised 35 publications in total.Several sncRNAs,miR-155,miR-16,miR-196,miR-525-3p,miR-891 were found to be effective in regulating the mechanism of spermatozoa processing in the infertility of men.sncRNA can be used as a biomarker of male infertility.Conclusions:sncRNAs can act as biomarkers for the diagnosis of reproductive diseases.Actually,by recognizing sncRNAs and their mechanisms,a new way to treat infertile men would be paved.The functional annotation of sncRNAs in spermatogenesis is still in its infancy but has enormous potential.This is despite the fact that many potential sncRNAs have been found to date with the use of cutting-edge technology and publicly accessible sncRNA annotation tools.

Effects of Medicines and Supplements on Spontaneous Pregnancy and Semen Parameters in Male Infertility:A Systematic Review Update and Network Meta-Analysis

In this study,we used a network meta-analysis(NMA)to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best treatment.Medline,Excerpta Medica Database(EMBASE),Ovid,and China National Knowledge Infrastructure(CNKI),were searched for the period from January 1990 to June 2021 using the keywords"male infertility,""medical therapy,""supplement/nutrient therapy,"and related terms.Randomized controlled trials(RCTs)investigating medicines(mainly follicle-stimulating hormone(FSH),androgen,and clomiphene/tamoxifen)or supplements(mainly zinc,selenium,vitamin C or E,carnitine,coenzyme Q10(CoQ10),or combined treatment)for idiopathic infertile men were selected for meta-analysis.Preferred reporting items for systematic reviews and meta-analysis(PRISMA)was used for data extraction,and a risk-of-bias tool and grades of recommendation,assessment,development,and evaluation(GRADE)system adapted to the NMA were employed to assess the quality of the evidence.The primary outcomes were live birth and spontaneous pregnancy rate(SPR).The secondary outcomes were sperm parameters(including concentration,progressive motility,and morphology)and side effects.In total,65 RCTs involving 7541 men with sperm abnormalities but normal hormone levels were included.A total of 36 studies reported SPR but only three reported live birth rates.The quality of the included studies was found to be moderate to high.Compared with a placebo or being untreated,carnitine plus vitamins significantly improved SPR(relative risk(RR)=3.7,95%confidence interval(95%CI),1.6-8.5);fatty acids significantly increased sperm concentrations(mean difference(MD)=12.5×10^(6)mL-1,95%CI,3.1×10^(6)-22.0×10^(6));and selective estrogen receptor modulator(SERM)plus CoQ10 significantly improved sperm progressive motility(MD=11.0%,95%CI,0.1%-21.9%)and normal sperm morphology(MD=11.0%,95%CI,4.6%-17.4%).The most optimal intervention was carnitine plus vitamins and fatty acids for SPR and sperm concentrations,respectively,even after excluding trials at a high risk of bias.Compared with a placebo or being untreated,FSH(RR=4.9,95%CI,1.1-21.3)significantly increased SPR,whereas SERM plus kallikrein increased sperm concentration(MD=16.5×10^(6)mL^(-1),95%CI,1.6×10^(6)-31.4×10^(6)),and SERM plus CoQ10 significantly improved sperm progressive motility(MD=11.3%,95%CI,7.3%-15.4%)and normal morphology(MD=11.2%,95%CI,5.4%-16.9%)in men with oligoasthenozoospermia(OA).In terms of side effects,fatty acids and pentoxifylline were associated with foul breath and/or a bad taste(RR=8.1,95%CI,1.0-63.5)and vomiting(RR=8.0,95%CI,1.0-63.0),respectively.In conclusion,the optimal treatment for male infertility for live birth is still unknown.Carnitine plus vitamins and FSH are likely to be better than other therapies in achieving successful spontaneous pregnancy in couples overall and in cou ples with men with OA,respectively.The efficacy of other treatments on pregnancy outcomes warrants further verification.

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

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.

Conventional treatment options and herbal remedies for male infertility:An overview

Male infertility is responsible for an estimated 50%of all cases of infertility.Treatments for male infertility include surgery,in-vitro fertilization,hormone therapy,and herbal remedies.Assisted reproductive technologies and methods have made it possible to identify and treat previously untreatable causes of male infertility.Currently available treatments for male infertility are prohibitively expensive,difficult to obtain,necessitate a lengthy course of treatment,and have a host of side effects.Herbal therapy offers male infertility treatment that is less expensive and has fewer side effects than other treatments.The current review focuses on the various treatment options for male infertility.

Yq AZF microdeletions in male infertility:An update on the phenotypic spectrum,epidemiology and diagnostics

According to the latest data,globally 15%of couples have infertility and male infertility contributes to 10%of all cases.Infertility can be caused by certain biological changes in the gonads and the reproductive system like azoospermia,oligospermia,asthenospermia,teratozoospermia and hypospermatogenesis.Genetic causes of azoospermia include chromosomal abnormalities,Y chromosome microdeletions and deletion or other mutations of Y-linked genes.The maximum number of the genes are located in the azoospermia factor region of the long arm(Yq)of the Y chromosome.Y chromosome microdeletion is known as the second major genetic cause of spermatogenetic failure.This article aims to review the latest updates on the involvement of Yq microdeletions in male infertility.The diagnostics,prevalence and phenotypic spectrum related to Yq gene microdeletions are discussed.

Mechanism of cuscuta-medlar treating male infertility based on network pharmacological method

Objective:To predict couplet medicinals Cuscuta-Medlar(CM)in treat male infertility and analyze their potential mechanisms by the network pharmacology method.Method:TCMSP,BATMAN and literature were used to obtain components of CM,and male infertility targets were predicted by OMIM and GeneCards databases.Cytoscape software was used to construct the"component-target-disease"network.The STRING web site was used for the analysis of Protein-to-protein interaction(PPI)data between compounds and disease.DAVID 6.8 was carried on GO analysis and KEGG pathway analysis.Result:A total of 52 active ingredients and 242 potential targets of CM were obtained,with 7661 male infertility related genes retrieved from disease database.Then 113 common targets were obtained.Biological processes were related to enzyme binding,signaling receptor binding and molecular function regulator.The biological pathways mainly included TNF signaling pathway,apoptosis-related signaling pathway,PI3K/AKT signaling pathway,FoxO signaling pathway,Thyroid hormone signaling pathway and toll-like receptor signaling pathway.Conclusion:CM may treat male infertility by inhibiting inflammation,inhibiting apoptosis and promoting spermatogenesis.

Bilateral Retractile Testis: A Possible Risk Factor for Male Infertility

Healthy youth is an asset and strength for economic and social growth of any society. Developmental changes during puberty of youngsters need proper guidance to avoid future physical, physiological and psychological ailments. Bilateral Retractile Testis (BRT) is a health problem if remains unnoticed till adolescence can lead to tribulations. BRT may affect testicular parenchyma and spermatogenesis. Cremasteric muscles (muscles attached with testes) pull the testes up into groin so it randomly moves up and down and do not reside in its natural pouch always. It has been a controversial issue in male infertility as retraction may affect infertility. Objective: To estimate the prevalence of male infertility among patients with Bilateral Retractile Testis. Methodology: A total of 200 male patients were enrolled after the power calculation, with different reproductive health problems between the age of 18 - 40 years during the year 2016 at Reproductive health clinic Jinnah Post Graduate Medical Center (JPMC), Karachi. 25 male patients were reported with infertility and BRT. The data was collected using self-developed questionnaire including outdoor patients’ physical check-up, manual testicular examination as size and shape were done. Patient height, weight, blood pressure, their lifestyle, and dressing regarding wearing tight jeans habits were asked. Semen analysis was carried out showing abnormality in sperm count, motility or morphology and entered and analysed in the SPSS version 10. Means and percentages were calculated. Result: Out of 200 male infertile patients, a total of 25 (12.5%) patients with a diagnosis of BRT were found in the sample with the mean age of 29 years. Moreover, it was identified that those having BRT also have low motility of the sperms. Based on the results it was concluded that BRT is a possible cause of male infertility in Pakistani population. Conclusion: BRT is a possible risk factor to affect sperm motility and low sperm motility can lead to male infertility. The study estimates the prevalence of 12.5% among our sampled men.

Assess of the Value of Semen Examination Items in the Diagnosis of Male Infertility

Background: Although semen analysis is a basic method to evaluate male fertility, there was a certain deviation between the semen examination and the actual situation in clinical application. Objective: To evaluate the application value of semen examination items in the diagnosis of male infertility. Method: Males recruited from the Third Affiliated Hospital of Sun Yat-sen University from June 2017 to December 2018 were divided into three groups: normal fertility group, physical examination group (premarital physical examination), and male infertility group. Each group received the following examination such as semen analysis (including semen volume, sperm concentration, progressive motility, total motility, round cell concentration), acrosin activity, and sperm morphology. All the semen analysis items mentioned above were operated according to the WHO laboratory manual for the examination and procession of human semen (Fifth edition) and related documents. Results: The normal fertility group and physical examination group showed significantly higher levels in sperm concentration, progressive motility, total motility, and sperm morphology than those in the male infertility group (P < 0.05);both the normal fertility group and the physical examination group have a higher qualified rate in sperm concentration, progressive motility, total motility and sperm morphology than the male infertility group, all P < 0.001. The percentage of patients having all qualified items in each group was 28.13%, 6.67%, and 6.51% separately. Conclusion: The diagnosis efficiency was higher in sperm concentration, progressive motility, total motility, and sperm morphology than in other semen examination items. A more objective and efficient method of semen examination should be explored to facilitate the diagnoses of male infertility in the future.

Treatment of male infertility from damp heat physique

Male infertility is a common and frequently-occurring disease in andrology clinics.Its pathogenesis and clinical symptoms are complex and changeable.The treatment of traditional Chinese medicine is mostly based on dialectical treatment.Modern physicians headed by Professor Wang Qi respected the theory of physique,combined body differentiation,disease differentiation and syndrome differentiation,and put forward a new diagnosis and treatment concept of"quality differentiation and treatment".Big clinical data has confirmed that there is a correlation between Damp-Heat(Etiological terms.It refers to a disease.The combination of heat and dampness.)physique and male infertility.In order to improve the therapeutic effect of male infertility due to Damp-Heat,through the differentiation and treatment of male infertility and the analysis of the theory of Damp-Heat physique,combined with the investigation and research results of Damp-Heat physique and modern doctors’experience in the treatment of male infertility from the perspective of Damp-Heat In summary,it is concluded that correcting the formation and development of Damp-Heat physique clinically has important clinical basis and therapeutic advantages for the prevention and treatment of male infertility.

Reviving Fertility:Phytochemicals as Natural Allies in the Fight against Non-genetic Male Infertility

Background:Male infertility poses a growing challenge to the healthcare system,with its prevalence on the rise.Unhealthy lifestyle,food,and addictions such as smoking,alcoholism,etc.accelerate the occurrence.While several approaches are being investigated to prevent and treat this condition,each therapeutic approach has its drawbacks.Traditional medications continue to play a crucial role in the healthcare system.In recent years,there has been a shift towards determining the efficacy of phytochemicals(or,herbal drugs)as remedies.Objective:To evaluate the effect of various herbs,plant,metabolites,or a part of plant in management of non-genetic male infertility.Methods:The male infertility-associated keywords were searched in PubMed,excluding those non-English writen papers.A total of 146 pertinent and closely connected records were included for full reading and inclusion in the systemic evaluation.Results:The manuscript focuses on individual herbal drug components,their active ingredients,their role in improving the condition and quality of life,and decreasing the prevalence of male infertility.Conclusion:Herbal medicinal plants show promising outcomes to treat male infertility.Herbal alternatives are appealing and have regained popularity.The future holds promise for some of these herbal treatments to advance with many showing improved outcomes in males with infertility issues.

Spermotrend Improves Semen Quality and Infertility in Men with Varicocele —Spermotrend and Male Infertility

Background: Infertility affects 8% - 12% of couples globally, with approximately half of the cases reported in males. Oxidative stress is a common factor increased in the varicocele condition and particularly affects spermatozoa, due to their sensitivity to oxidative signals and testicular hypotrophy. The objective of this clinical trial is to study the effectiveness of Spermotrend in the improvement of sperm parameters in male infertility. Methods: A total of 170 males aged > 18 years with a diagnosis of infertility and varicocele were consecutively enrolled in a Phase II, open-label clinical trial. Spermotrend was administered 1 capsule (450 mg) orally every 8 hours for 6 months and was evaluated through semen analysis at 4 and 6 months of follow-up. Results: The trial results show a significant improvement following the administration of Spermotrend over 6 months in sperm concentration (44.1% at baseline vs. 64.1% at 6 months), sperm survival (28.2% with sperm survival ≥ 2 hours vs.56.5%), normalization of sperm morphology (31.2% vs. 72.9%). Varicocele condition decreased in all patients and, by the end of the study, 55.3% of patients had normal venous flow and dilation. Only 5.9% of the patients showed grade 2 varicocele at the end of the study, while 38.8% showed grade 1 varicocele, with no patients showing grade 3 varicocele. Regarding testicular hypotrophy, 90.6% of the patients completed the study with normalized testicular volume by recovering normal venous flow. Conclusion: A short-term course of Spermotrend may significantly improve sperm parameters associated with male infertility. Clinical Trial Registration: The clinical trial protocol was registered in the international clinical trial registry, ClinicalTrials.gov, with the code: NCT05222841 on 15/06/2021.

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

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.

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

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.

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

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.

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

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 Romboutsia in infertile male rats.Additionally,FMT experiments proved that the gut microbiota of CCP-treated rats facilitated testicular tissue recovery and spermatogenesis while also reducing the serum LPS level in infertile male rats.CCP improves the spermatogenic ability of infertile male rats by restoring gut microbiota diversity and inhibiting epididymal inflammation.

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

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.

A systematic review and meta-analysis of clinical trials implementing aromatase inhibitors to treat male infertility

Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio.In this subset of patients,and particularly in those with hypogonadism,elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic–pituitary–testicular axis by suppressing follicle-stimulating hormone(FSH)and luteinizing hormone(LH)production and impaired spermatogenesis.Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment.We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males.Overall,eight original articles were included and critically evaluated.Either steroidal(Testolactone)or nonsteroidal(Anastrozole and Letrozole)aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile.While the evidence is promising,future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.

Rescue of male infertility through correcting a genetic mutation causing meiotic arrest in spermatogonial stem cells

Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells(SSCs).However,such therapy for infertility has not been experimentally investigated yet.In this study,a mouse model with an X-linked testis-expressed 11(TEX11)mutation(Tex11PM/Y)identified in azoospermia patients exhibited meiotic arrest due to aberrant chromosome segregation.Tex11PM/Y SSCs could be isolated and expanded in vitro normally,and the mutation was corrected by clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated endonuclease 9(Cas9),leading to the generation of repaired SSC lines.Whole-genome sequencing demonstrated that the mutation rate in repaired SSCs is comparable with that of autonomous mutation in untreated Tex11PM/Y SSCs,and no predicted off-target sites are modified.Repaired SSCs could restore spermatogenesis in infertile males and give rise to fertile offspring at a high efficiency.In summary,our study establishes a paradigm for the treatment of male azoospermia by combining in vitro expansion of SSCs and gene therapy.

Exploring the potential impact of nutritionally actionable genetic polymorphisms on idiopathic male infertility:a review of current evidence

Infertility affects about 15%of the world's population.In 40%-50%of infertile couples,a male factor underlies the problem,but in about 50%of these cases,the etiology of male infertility remains unexplained.Some clinical data show that lifestyle interventions may contribute to male reproductive health.Cessation of unhealthy habits is suggested for preserving male fertility;there is growing evidence that most preexisting comorbidities,such as obesity and metabolic syndrome,are highly likely to have an impact on male fertility.The analysis of genetic polymorphisms implicated in metabolic activity represents one of the most exciting areas in the study of genetic causes of male infertility.Although these polymorphisms are not directly connected with male infertility,they may have a role in specific conditions associated with it,that is,metabolic disorders and oxidative stress pathway genes that are potentially associated with an increased risk of male infertility due to DNA and cell membrane damage.Some studies have examined the impact of individual genetic differences and gene-diet interactions on male infertility,but their results have not been synthesized.We review the current research to identify genetic variants that could be tested to improve the chances of conceiving spontaneously through personalized diet and/or oral vitamin and mineral supplementation,by examining the science of genetic modifiers of dietary factors that affect nutritional status and male fertility.