Identification of novel homozygous missense and deletion mutations manifesting oligospermia infertility in Kashmiri population.

BACKGROUND: Human male infertility has a lot of known molecular components that have an accurate diagnosis, such as Y chromosome deletion and monogenic causes. Only 4% of all infertile males are diagnosed with genetic causes, while 60-70% of infertile men remain without an accurate diagnosis and are classified as unexplained. Oligospermia is a major cause of human male infertility. Its etiology and pathogenesis are linked to genetic abnormalities. The majority of genetic causes related to human male infertility remain unclear. RESULTS: Generally, we found a significant association between the specific type of disease and gender (p = 0.003), and the regression value (R2 ) for this association was 0.75. Association of the type of disease with body mass index was not significant (p = 0.34). There was no statistically significant difference (p = 0.40) among disease types with patients occupations. All explored mutations are listed for primary and secondary infertility in relation to the oligospermia condition. p.Arg286X is the outcome of a mismatch mutation in which the nucleotide change resulted in the substitution of Arg (arginine) amino acid with X (any amino acid) at position 286 in the Hyal3 gene of primary infertile patients having oligospermia. In primary infertile patients with the p.Arg286X mutation, a frameshift deletion mutation was also found just after the 25 nucleotide sequences of the Hyal3 genes of the second mutated exon. This deletion mutation was only detected in patients with primary infertility and was not found in people with secondary infertility or healthy controls. The other mutations in secondary infertile patients with oligospermia were: p.Lys168Ser, replacement of lysine (Lys) with serine (Ser) at position 168; p.Lys168The, replacement of lysine (Lys) with threonine (The) at position 168; p.His113X, substitution of histidine (His) with an unknown amino acid (X) at position 113; p.Pro162X, substitution of proline (Pro) with an unknown amino acid (X) at position 162; and p.Phe157X, phenylalanine (Phe) substitution with an unknown amino acid (X) at position 157. CONCLUSION: This study clarifies the site of novel mismatch and frameshift deletion mutations in the Hyal3 gene in primary infertile oligospermia patients.

[Epidemio-clinical and seminal profile of the man consulting for the desire to procreate: current situation in Lubumbashi, in the Democratic Republic of Congo]. / Profil épidémio-clinique et séminal de l'homme consultant pour désir de procréation: état des lieux à Lubumbashi, en République Démocratique du Congo.

Introduction: in Lubumbashi, as in upscale areas where explorations of fertility are very clever, the spermogram remains the essential analysis in the diagnosis of male infertility. This is the cause of 40% of couple infertility. The spermogram is the first step in identifying seminal abnormalities. The objective of this study was to determine the epidemiological-clinical and seminal profile of the man consulting for the desire to procreate in Lubumbashi. Methods: this was a cross-sectional study. We received 202 subjects in Lubumbashi, whose spermogram was performed from August 1st, 2020 to July 31st, 2021. The semen parameters were studied and interpreted according to WHO standards (2010) with studies of factors associated with their disturbance. Bivariate and multivariate analyzes had been carried out. The statistical significance threshold was set at p < 0.05. Results: the epidemiological-clinical profile of the respondents was as follows: the most represented age group was 30 to 39 years; infertility was primary in 80.69% of cases; the duration of the desire for paternity was 2 years at most in 44.55% of cases. The sperm abnormalities found were: oligozoospermia (40.09%), azoospermia (11.38%), asthenozoospermia (18.31%) and teratozoospermia (10.39%). Oligozoospermia was significantly associated with varicocele (ORa = 10.9 [3.0-39.5]; p < 0.0001), genital infection (ORa =2.7 [1.0-7, 2]; p = 0.041) and obesity (ORa = 2.6 [1.0-7.9]; p = 0.020) while azoospermia was the cure for inguinal hernia (ORa = 4.2 [1.0-17.2]; p = 0.049) and malnutrition (ORa =6.0 [1.2-29.7]; p = 0.027). Asthenozoospermia was significantly associated with the age group of 40 to 49 years (ORa = 6.6 [1.2-37.4]; p = 0.034), tobacco (ORa =7.5 [2.7 -21.0]; p = 0.000), undernutrition (ORa = 7.7 [1.0-61.9]; p = 0.045) and overweight (ORa =3.8 [1.3-11, 5]; p=0.019). Teratozoospermia was significantly associated with smoking (ORa = 5.6 [1.8-17.7]; p = 0.003) and overweight (ORa =5.3 [1.2-23.3]; p = 0.027). Conclusion: more than half of the respondents had, of the three main fertility parameters, at least one that was disturbed. Sperm count was the most affected parameter. Alcohol, tobacco, genital infection and malnutrition were the most common risk factors for the abnormalities observed.

Acute orchitis deciphered: Coxsackievirus B strains are the main etiology and their presence in semen is associated with acute inflammation and risk of persistent oligozoospermia.

Although various viruses are considered to be the clinical cause for acute orchitis, it is completely unclear to what extent and which viruses are etiologically involved in acute orchitis and what the clinic and course of these patients are like. Therefore, a prospective study was set up to decipher acute isolated orchitis. Between July 2007 and February 2023, a total of 26 patients with isolated orchitis were recruited and compared with 530 patients with acute epididymitis. We were able to show for isolated orchitis, that (1) orchitis is usually of viral origin (20/26, 77%) and enteroviruses with coxsackievirus B strains (16/26, 62%) are predominant, (2) virus isolates could be received from semen indicating the presence of replication-competent virus particles, (3) a polymerase chain reaction (PCR) for enteroviruses should be conducted using semen provided at the onset of disease, because the virus is not detectable in serum/urine, (4) there is a circannual occurrence with the maximum in summer, (5) orchitis is associated with a characteristic inflammatory cytokine panel in the semen and systemic inflammation, (6) orchitis is usually rapidly self-limiting, and (7) about 30% of patients (6/20) suffer ongoing oligozoospermia. These seven emerging aspects are likely to fundamentally change thinking and clinical practice regarding acute isolated orchitis.

Spontaneous pregnancies post-microsurgical varicocelectomy in infertile men with severe oligozoospermia: a preliminary vietnamese report.

Background: This study evaluated whether microsurgical varico-celectomy performed in infertile men with severe oligozoospermia (SO) resulted in improved semen parameters or increased rates of spontaneous pregnancy (SP) and performed a cost-effectiveness analysis comparing intrauterine insemination (IUI), in vitro fertilization (IVF), and varicocelectomy. Methods: This study included 25 patients with SO who underwent microsurgical varicocelectomy between September 2019 and May 2022, which resulted in post-surgical SP in all cases. Men with azoospermia, abnormal karyotype, or Y-chromosome microdeletion were excluded from the study. Serum luteinizing, follicle-stimulating, and testosterone hormones were measured preoperatively. Semen was analyzed every 3 months postoperation. The incidence of SP was recorded at each visit. Cost-effectiveness for assisted reproductive technologies was calculated based on reported costs. Several parameters were evaluated as potential predictors of the response to microsurgical varicocelectomy using univariate and multivariate analyses. Results: After a mean postoperative observation period of 7 months, 25 couples with SP after microsurgical varicocelectomy were recruited. The mean sperm concentration increased from 3 million/mL (interquartile range [IQR]: 2-5 million/mL) to 12 million/mL (IQR: 5-17 million/mL; p<0.05), and mean sperm motility improved from 4% (IQR: 3%-6%) to 7.6% (p<0.05). Total motile sperm count (TMSC) increased to 3.08 million (IQR: 1.02-5.83 million) from a preoperative value of 0.34 million (IQR: 0.16-0.83 million). A cost-effectiveness analysis comparing IVF with varicocelectomy indicates that varicocelectomy may represent a better first-line option for infertile men with very low preoperative TMSC. However, further research remains necessary to confirm this result. Conclusion: Varicocelectomy should be discussed as a treatment option for men with SO and may improve sperm quality and fertility potential, resulting in SP.

Contribution to a better analysis of spermatic and ultrasound testicular parameters in the follow-up of male infertility at the Histology Embryology Cytogenetic Laboratory of Cheikh Anta Diop University (UCAD).

INTRODUCTION: In Senegal, marital infertility is a real problem for society. We undertook the study of this subject to make an analysis of the spermatic parameters of the infertile Senegalese man and to better understand the impact of testicular morphological anomalies on male fertility. PATIENTS AND METHODS: We conducted a cross-sectional, descriptive, retrospective study of 100 infertile patients followed at the Histology-Embryology-Cytogenetics laboratory of UCAD in Dakar, during the year 2020. Sperm parameters, presence of varicocele, and testicular volume were evaluated in our patients. RESULTS/DISCUSSION: The mean age of the patients was 35.17±8.7 years. A history of sexually transmitted infections was found in 57% of patients. The mean duration of infertility was 5.67±3.2 years. The mean sperm count was 14,871,230/ml±4,950,000. Necrospermia was the most frequent abnormality found (60%), followed by asthenospermia (51%). The high rate of necrospermia could be explained by the high frequency of sexually transmitted infections. Other abnormalities were oligospermia (48%, including 09% cryptospermia), azoospermia (19%), teratospermia (19%), and hypospermia (13%). The predominance of azoospermia and oligospermia should prompt a search for a genetic predisposition in these subjects. The mean testicular volume was 10.3±4.9 cc on the right and 9.5±4.8 cc on the left. A single or bilateral varicocele was found in 43% of subjects. Patients with azoospermia and teratospermia were associated with testicular hypotrophy with a significant value (p=0.04). CONCLUSION: Overall, the senegalese man consulting for infertility is a young adult, married for an average of 5 years. Necrospermia is the most frequently found anomaly. The severity of both qualitative and quantitative abnormalities should lead to a systematic search for a genetic origin. The etiological research of infertile patients must be done within a multidisciplinary framework to propose better management of these patients.

Initial Andrological Evaluation of the Infertile Male.

Evaluation of a man presenting for couple infertility starts with obtaining a thorough medical history, and the couple's reproductive and sexual history. Semen analysis, according to World Health Organization recommendations, is the cornerstone of male partner evaluation. A comprehensive physical examination is essential for every male partner, with adequate assessment of the development of secondary sexual characteristics. However, more complex testing than semen analysis (eg, sperm DNA fragmentation index) may be required in selected cases. For men with oligozoospermia or azoospermia, a hormonal evaluation should be performed, including at least total testosterone, follicle stimulating hormone, and luteinising hormone. Genetic testing should be offered to azoospermic men and those with severe oligozoospermia. Ultrasound of the genitourinary tract can provide additional information in select cases. PATIENT SUMMARY: A complete medical history, physical examination, and semen analysis are essential components of the initial evaluation of men being assessed for infertility. The evaluation must proceed in parallel for male and female partners to optimise management for infertile couples.

Onco-Testicular Sperm Extraction (oncoTESE): A Contemporary Concept Review and Report of Australian Sperm Retrieval Rates and Fertility Outcomes.

OBJECTIVE: To assess sperm retrieval rates of Onco-Testicular Sperm Extraction (oncoTESE) in men with testicular tumors and coexisting severe spermatogenic impairment. METHODS: Multi-centre Australian wide retrospective review of oncoTESE procedures performed within the last 10 years. Patients were postpubertal adults having a testicular tumor requiring orchidectomy, with severe oligozoospermia or nonobstructive azoospermia. Ipsilateral testicular sperm extraction was performed following radical inguinal orchidectomy. A contralateral micro-testicular sperm extraction was performed if no sperm or insufficient amounts were initially achieved. Surgical sperm retrieval rates, live birth rates and post operative serum testosterone were recorded. RESULTS: Four surgeons compiled a total 13 patients. The mean age was 34.9 years. Seven of 13 were germ cell tumor (GCT), 4 of 13 had non-GCT and 2 of 13 contained benign lesions. Twelve of 13 patients were azoospermic and 1 was severely oligozoospermic. Sperm was found in 6 of 7 GCT patients; 3 of 7 were found in the ipsilateral testis whilst the remaining 4 underwent contralateral micro-testicular sperm extraction; sperm was retrieved in 3 of 4. The respective mean pre and post orchidectomy testosterone was 12.0 vs 14.1nmol/L (GCT cohort). Cryopreserved sperm has been used in assisted reproduction in 2 of 13 patients, with median follow up of 38.7 months. Including use of both cryopreserved and fresh sperm, 6 pregnancies were achieved, including 5 healthy live births and 1 miscarriage. CONCLUSION: OncoTESE appears feasible, with acceptable sperm retrieval and subsequent live birth rates, following assisted reproduction. Despite significant underutilisation in the Australian population, oncoTESE should be considered in the management for TC patients with severe oligozoospermia, or nonobstructive azoospermia.

Central role of ultrasound in the evaluation of testicular function and genital tract obstruction in infertile males.

BACKGROUND: Scrotal color Doppler ultrasonography and transrectal ultrasonography provide crucial information about the clinical status of testes and male accessory glands. OBJECTIVE: To analyze the impact of ultrasound in the evaluation of infertile males. MATERIALS AND METHODS: A total of 1120 records from infertile men were retrospectively evaluated (from January 2016 up to June 2020). Data on physical examination, semen analysis, sperm culture, scrotal color Doppler ultrasonography and transrectal ultrasonography, as well as sex hormones were analyzed. Among them, 238 reports from oligozoospermic/azoospermic infertile patients (P) fulfilling the inclusion criteria were considered for data analysis. Patients were subdivided into two groups according to follicle-stimulating hormone (FSH) values (Pa with FSH < 8 U/L and Pb with FSH ≥ 8 U/L). Sixty-three fertile volunteers (mean ± SD years) were enrolled as controls (C). RESULTS: A higher prevalence of ultrasound abnormalities was recorded in P compared to C. Pb group had significantly lower bitesticular volume compared to Pa and C. Pa had a higher prevalence of transrectal ultrasonography abnormalities than Pb (69.9% vs. 38.4%), whereas Pb had a higher prevalence of abnormalities at scrotal color Doppler ultrasonography (60.0% vs. 28.3%, both p < 0.01). Bitesticular volume was inversely proportional to the number of altered seminal parameters and able to predict gonadotropin levels. A bitesticular volume <17 cc was associated with a higher risk of azoospermia (odds ratio = 1.799). Intratesticular vascularization was inversely correlated with gonadotropin levels and directly correlated with sperm count. A higher prevalence of prostate and seminal vesicle alterations was detected in patients and in Pa group, when compared with Pb group. DISCUSSION AND CONCLUSION: Ultrasound abnormalities are correlated with seminal parameters and may guide the clinician in the diagnostic workflow of male infertility, suggesting spermatogenesis impairment or genital tract obstructions.

Pregnancy results after intracytoplasmic sperm injection-embryo transfer in patients with infertility due to non-obstructive azoospermia and oligoasthenoteratozoospermia.

This study evaluated pregnancy results after fresh and frozen embryo transfer in males with infertility due to non-obstructive azoospermia and oligoasthenoteratozoospermia. In this retrospective study, a total of 801 embryo transfer cycles were followed up, including 423 fresh embryo transfers and 378 frozen embryo transfers in which intracytoplasmic sperm injection (ICSI) was performed because of male infertility. This study included females aged 28-38 years without uterine, endometrial, ovarian and tubal abnormalities and with regular menstrual cycles (n=801), and males aged 28-38 years with non-obstructive azoospermia and oligoasthenoteratozoospermia. Descriptive statistical methods and the independent t-test were used in the comparison of two groups with normal distribution, the Mann-Whitney U test was used in the comparison of two groups without normal distribution, and the Chi-square test was used to compare categorical variables. There were no statistically significant differences between the fresh embryo transfer group and frozen embryo transfer group in terms of rates of pregnancy, biochemical pregnancy, clinical pregnancy, live birth rate, and abortion rate. There was no difference between fresh embryo transfer and frozen embryo transfer in terms of pregnancy results in couples with non-obstructive azoospermia and oligoasthenoteratozoospermia as male infertility factor.

Tratamiento empírico de la oligoastenoteratozoospermia idiopática / Empiric therapy for idiopathic oligoasthenoteratozoospermia

El factor masculino supone el 50% de las causas de infertilidad en parejas infértiles, siendo en más del 30% de origen desconocido. En estos casos, el tratamiento médico empírico puede plantearse como una opción previa a la aplicación de una técnica de reproducción asistida. El tratamiento empírico puede dividirse en 2 categorías: hormonal, tales como gonadotropinas, antiestrógenos e inhibidores de la aromatasa, y antioxidante, tales como vitaminas, oligoelementos y carnitinas, entre otros. Aunque la evidencia científicamente aceptable es limitada debido a la ausencia de grandes ensayos clínicos aleatorizados y controlados, revisiones sistemáticas y metaanálisis recientemente publicados muestran que el tratamiento con gonadotropinas, antiestrógenos y antioxidantes resulta en un aumento de la tasa de embarazos y nacidos vivos y en una mejora en los parámetros seminales. Es por ello que, en determinadas situaciones, el tratamiento médico empírico para la infertilidad idiopática puede considerarse con el objetivo de mejorar la calidad seminal y consecuentemente el potencial fértil espontáneo

Male infertility accounts for 50% of the causes of infertile couples, being more than 30% of unknown etiology. In these cases, empiric treatment can be an option prior to the application of assisted reproduction techniques. Empiric treatment can be categorized as hormonal, such as gonadotropins, antiestrogens and aromatase inhibitors, and antioxidant, with vitamins, trace elements and carnitine, among others. Although scientifically acceptable evidence is limited due to the absence of large randomized and controlled clinical trials, recent systematic reviews and meta-analyses show that treatment with gonadotropins, antiestrogens and antioxidants increases pregnancy and live birth rates and improves seminal parameters. Empiric medical treatment for idiopathic infertility can be considered in specific cases in order to improve semen quality and spontaneous fertility

Empiric therapy for idiopathic oligoasthenoteratozoospermia. / Tratamiento empírico de la oligoastenoteratozoospermia idiopática.

Male infertility accounts for 50% of the causes of infertile couples, being more than 30% of unknown etiology. In these cases, empiric treatment can be an option prior to the application of assisted reproduction techniques. Empiric treatment can be categorized as hormonal, such as gonadotropins, antiestrogens and aromatase inhibitors, and antioxidant, with vitamins, trace elements and carnitine, among others. Although scientifically acceptable evidence is limited due to the absence of large randomized and controlled clinical trials, recent systematic reviews and meta-analyses show that treatment with gonadotropins, antiestrogens and antioxidants increases pregnancy and live birth rates and improves seminal parameters. Empiric medical treatment for idiopathic infertility can be considered in specific cases in order to improve semen quality and spontaneous fertility.

A homozygous RPL10L missense mutation associated with male factor infertility and severe oligozoospermia.

OBJECTIVE: To identify the genetic cause of male factor infertility characterized by severe oligozoospermia. DESIGN: Genetic studies. SETTING: Medical university. PATIENT(S): Two infertile brothers with severe oligozoospermia in a consanguineous Han Chinese family, 414 additional patients with oligo-/azoospermia, and 223 fertile (control) subjects. INVENTION(S): None. MAIN OUTCOME MEASURE(S): Genetic analyses using whole-exome and Sanger sequencing were performed for two brothers with severe oligozoospermia. The effects of an identified candidate causative mutation were investigated in silico and in vitro. Whole-exome sequencing screening for the candidate mutation was conducted in 414 patients with oligo-/azoospermia and 223 fertile subjects. RESULT(S): A homozygous missense variant (NM_080746:c.A257C: p.H86P) in RPL10L was identified in the two affected brothers and shown to cosegregate with the severe oligozoospermia phenotype. The mutation was absent in public databases, including the 1000 Genomes Project and the Exome Aggregation Consortium. All queried databases predicted the mutation to be damaging, consistent with the fact that it decreased protein levels in vitro. Subsequent mutation screening identified three additional heterozygous RPL10L mutations in three of 414 subjects with oligo-/azoospermia, but no RPL10L mutations among 223 fertile subjects. CONCLUSION(S): Our findings implicate RPL10L as a novel candidate gene in the pathogenesis of human male factor infertility and severe oligozoospermia.

Whole Exome Sequencing Identifies a Rare Nonsense Mutation in FAM47C as a Possible Cause of Severe Oligospermia in Brothers With Varicocele.

Varicocele is a common cause of impaired semen parameters in men with infertility. Here, we investigated genetic variants as possible causes of varicocele with impaired semen parameters using whole exome sequencing in a family with 2 brothers with severe oligospermia, 1 unaffected brother, father, and the mother. Results showed a premature stop codon alteration on Chromosome X (37028866 CT) in the gene FAM47C. The affected brothers were found to be hemizygous for the variant, while the mother was a heterozygous carrier. In conclusion, identifying men with varicocele that would have impaired spermatogenesis, using approaches like whole-exome sequencing, can be paradigm shifting.

Experimental Study of the Effectiveness of Phenolic Antioxidants in Male Infertility Caused by Pathospermia.

The effect of phenolic antioxidants (dihydroquercetin, p-tyrosol, dibornol) on the morphology, functions, and redox processes in the reproductive cells of male rats was studied on the model of experimental pathospermia. All antioxidants reduced the percentage of degenerative forms of spermatozoa. Dibornol was most effective. Dihydroquercetin and p-tyrosol did not increase the total number of spermatozoa and the percentage of their mobile forms. These indicators were improved only by dibornol. After administration of all test drugs, the antioxidant potential of spermatozoa increased and did not significantly differ from the baseline values.

Impact of overactive bladder on retrograde ejaculation

ABSTRACT Purpose: To evaluate the impact of overactive bladder disorder on patients diagnosed with retrograde ejaculation. Materials and Methods: Retrospective analysis of prospective collected database made. Questionnaires conducted in urology polyclinics in five different centers. Main Outcome Measure(s): International Index of Erectile Function - 5 (IIEF - 5), Overactive Bladder 8 - Question Awareness Tool (OAB - V8), urodynamics, semen analysis. The participants of the study were n = 120 patients. There was retrograde ejaculation (RE) in only n = 47 patients (non / minimal symptomatic patients), n = 73 patients had RE and overactive (OAB) complaints (symptomatic patients) and received anticholinergic treatment (trospium), n = 37 control group patients who only had OAB and received an anticholinergic. Results: While no difference was observed in overactive bladder examination and urodynamic values between the non / minimal symptomatic group and the symptomatic group (p > 0.05), sperm was detected and identified as fructose positive in post - ejaculation urine in the symptomatic group. Thus, it was possible to demonstrate the differences between symptomatic patients and non - symptomatic patients. Consequently, following three - month daily treatment with trospium 30 mg 2 x 1 in the control group and the symptomatic group, it was observed that an evident increase was observed in the sperm count and ejaculate volume in the symptomatic group and that no change was observed in the control group (p < 0.05). Conclusion: This clinical study is the first of its kind in terms of revealing the coexistence of RE with OAB upon performing urodynamics and showing that treatment is possible in selected patients.

Impact of overactive bladder on retrograde ejaculation.

PURPOSE: To evaluate the impact of overactive bladder disorder on patients diagnosed with retrograde ejaculation. MATERIALS AND METHODS: Retrospective analysis of prospective collected database made. Questionnaires conducted in urology polyclinics in five different centers. MAIN OUTCOME MEASURE(S): International Index of Erectile Function - 5 (IIEF - 5), Overactive Bladder 8 - Question Awareness Tool (OAB - V8), urodynamics, semen analysis. The participants of the study were n = 120 patients. There was retrograde ejaculation (RE) in only n = 47 patients (non / minimal symptomatic patients), n = 73 patients had RE and overactive (OAB) complaints (symptomatic patients) and received anticholinergic treatment (trospium), n = 37 control group patients who only had OAB and received an anticholinergic. RESULTS: While no difference was observed in overactive bladder examination and urodynamic values between the non / minimal symptomatic group and the symptomatic group (p > 0.05), sperm was detected and identified as fructose positive in post - ejaculation urine in the symptomatic group. Thus, it was possible to demonstrate the differences between symptomatic patients and non - symptomatic patients. Consequently, following three - month daily treatment with trospium 30 mg 2 x 1 in the control group and the symptomatic group, it was observed that an evident increase was observed in the sperm count and ejaculate volume in the symptomatic group and that no change was observed in the control group (p < 0.05). CONCLUSION: This clinical study is the first of its kind in terms of revealing the coexistence of RE with OAB upon performing urodynamics and showing that treatment is possible in selected patients.

Two cases of complex balanced autosomal translocations associated with severe oligozoospermia.

Complex balanced autosomal translocation is rare and can lead to impaired spermatogenesis in males; however, its effects on oligozoospermia have rarely been reported. We report here two cases of rare complex balanced translocation in men with infertility. The karyotype of the first case was 46,XY,der(1)t(1;12)(p22;p11.2)ins(9;1)(p24;q25q23),der(9)ins(9;1),der(12)t(1;12)·ish der(1)t(1;12)(RP11-636B1+;RP11-659D23+)ins(9;1)(RP11-118P13+),der(9)ins(9;1),der(12)t(1;12). And the patient showed severe oligozoospermia with adult schizophrenia without other abnormalities. The karyotype of the second patient was 46,XY,der(5)t(5;11)(q14;p11.2),der(11)t(11;18)(p11.2;q11.2),der(18)t(5,18)(q14;p11.3)add(18)(q11.2?)·ish der(5)t(5;11)(RP11-846K3+,RP11-89B9+),der(11)t(11;18)(RP11-89B9-,RP11-170L12+,RP11-469N6+),der(18)t(5;18)(RP11-125L2+,RP11-29M13+)add(18)(q11.2?), and the patient displayed severe oligozoospermia without other abnormalities. The two cases were verified by fluorescent in situ hybridization, and no abnormalities were found by genome-wide copy number variation analysis. To our knowledge, these two cases of complex autosomal karyotypes have not been reported previously. Although rare, these cases suggest that complex balanced translocations may be important causes of oligozoospermia. We speculate that the balanced translocation hinders germ cell meiosis and causes impaired spermatogenesis. Accordingly, the two reported patients have very low probabilities of giving birth to a normal child; therefore, we suggest choosing donor semen or adopting a child.

Characterization of microbiota in male infertility cases uncovers differences in seminal hyperviscosity and oligoasthenoteratozoospermia possibly correlated with increased prevalence of infectious bacteria.

PROBLEM: Sexually transmitted diseases and other infections of male genitourinary tract are thought to negatively impact reproductive health, affecting semen quality. Despite a possible link between bacteria and infertility, few studies attempted to characterize seminal microbiota in healthy and diseased subjects. METHODS OF THE STUDY: A high-throughput sequencing of 16S ribosomal RNA gene was performed in a cohort of infertility-related cases (N = 89) and controls (N = 29) using a pooled sample approach. RESULTS: A global characterization of microbiota was obtained at low cost, without compromising the identification of bacterial taxa. This strategy allowed us to detect changes in the microbiota of infertility-related phenotypes, such as an increment of Proteobacteria in seminal hyperviscosity, and to separate this later group from oligoasthenoteratozoospermia based in bacterial (family/genus) abundances. CONCLUSION: We provide data for a likely contribution of bacteria into seminal hyperviscosity and oligoasthenoteratozoospermia, partially correlated with an increment of Neisseria, Klebsiella, and Pseudomonas pathogens and a reduction in Lactobacillus probiotic agent.

Gonadal function in adult male patients with congenital adrenal hyperplasia.

CONTEXT: Current knowledge on gonadal function in congenital adrenal hyperplasia (CAH) is mostly limited to single-center/country studies enrolling small patient numbers. Overall data indicate that gonadal function can be compromised in men with CAH. OBJECTIVE: To determine gonadal function in men with CAH within the European 'dsd-LIFE' cohort. DESIGN: Cross-sectional clinical outcome study, including retrospective data from medical records. METHODS: Fourteen academic hospitals included 121 men with CAH aged 16-68 years. Main outcome measures were serum hormone concentrations, semen parameters and imaging data of the testes. RESULTS: At the time of assessment, 14/69 patients had a serum testosterone concentration below the reference range; 7 of those were hypogonadotropic, 6 normogonadotropic and 1 hypergonadotropic. In contrast, among the patients with normal serum testosterone (55/69), 4 were hypogonadotropic, 44 normogonadotropic and 7 hypergonadotropic. The association of decreased testosterone with reduced gonadotropin concentrations (odds ratio (OR) = 12.8 (2.9-57.3)) was weaker than the association between serum androstenedione/testosterone ratio ≥1 and reduced gonadotropin concentrations (OR = 39.3 (2.1-732.4)). Evaluation of sperm quality revealed decreased sperm concentrations (15/39), motility (13/37) and abnormal morphology (4/28). Testicular adrenal rest tumor (TART)s were present in 39/80 patients, with a higher prevalence in patients with the most severe genotype (14/18) and in patients with increased current 17-hydroxyprogesterone 20/35) or androstenedione (12/18) serum concentrations. Forty-three children were fathered by 26/113 patients. CONCLUSIONS: Men with CAH have a high risk of developing hypothalamic-pituitary-gonadal disturbances and spermatogenic abnormalities. Regular assessment of endocrine gonadal function and imaging for TART development are recommended, in addition to measures for fertility protection.