AZF microdeletion screening is routinely performed in the diagnostic work-up for male infertility; however, some issues remain debated. In this study, we provide insights into the sperm concentration cutoff value for routine testing, the predictive value of AZFc deletion for testicular sperm retrieval and the Y-background contribution to the interpopulation variability of deletion frequencies. In the Spanish population, partial AZFc rearrangements have been poorly explored and no data exist on partial duplications. In our study, 27/806 (3.3%) patients carried complete AZF deletions. All were azoo/cryptozoospermic, except for one whose sperm concentration was 2 Â 10 6 /ml. In AZFc-deleted men, we observed a lower sperm recovery rate upon conventional TESE (9.1%) compared with the literature (60-80% with microTESE). Haplogroup E was the most represented among non-Spanish and hgr P among Spanish AZF deletion carriers. The analysis of AZFc partial rearrangements included 330 idiopathic infertile patients and 385 controls of Spanish origin. Gr/gr deletion, but not AZFc partial duplications, was significantly associated with spermatogenic impairment. Our data integrated with the literature suggest that: (1) routine AZF microdeletion testing could eventually include only men with r2 Â 10 6 /ml; (2) classical TESE is associated with low sperm recovery rate in azoospermic AZFc-deleted men, and therefore microTESE should be preferred; (3) Y background could partially explain the differences in deletion frequencies among populations. Finally, our data on gr/gr deletion further support the inclusion of this genetic test in the work-up of infertile men, whereas partial AZFc duplications do not represent a risk for spermatogenic failure in the Spanish population.

Background: A recent meta-analysis (Human Reproduction Update 23, 2017 and 265) reported positive sperm retrieval rates (SRR) in 50% of patients with Klinefelter syndrome (KS) undergoing testicular sperm extraction (TESE). However, these results do not reflect the rates of SR that we observe in clinical practice. We assessed the rate and potential predictors of SR in Klinefelter patients in the real-life setting. Materials and Methods:We reviewed clinical data of 103 KS men who underwent TESE between 08/2008 and 03/2019 at five tertiary referral Andrology centers. Patients underwent testis ultrasound, hormonal evaluation, and genetic testing. All patients were azoospermic based on the 2010 WHO reference criteria. Conventional TESE (cTESE) or microsurgical TESE (mTESE) was performed based on the surgeon's preference. We used descriptive statistics and logistic regression models to describe the whole cohort.Results: Median (IQR) patient's age was 32 (24-37) years. Baseline serum FSH and total testosterone levels were 29.5 (19.9-40.9) mUI/mL and 3.8 (2.5-11.0) ng/mL, respectively. Conventional TESE and mTESE were performed in 38 (36.5%) and 65 (63.5%) men, respectively. The sperm retrieval rate was 21.4% (22/103 men). Fifteen patients used spermatozoa for ICSI and five ended in live birth children. Patients with positive SR were similar to those with a negative TESE in terms of clinical, hormonal, and procedural parameters (all P > .05). Logistic regression analyses confirmed the lack of association between clinical, hormonal, and procedural parameters with SR outcome. Discussion: Given the conflicting results in the literature regarding SRR in KS, patients should be carefully counseled regarding TESE outcomes based on data from published literature and local results.

A retrospective observational study was undertaken to gain new insight into the relationship between total testicular volume and levels of serum testosterone, luteinising hormone, follicle-stimulating hormone, prolactin and clinical variables. A total of 312 men with sexual dysfunction or infertility were divided into groups A and B (156 each) on the basis of basal plasma testosterone ≤5 nmol/L of ≥12 nmol/L respectively. Group A was subclassified in A (primary hypogonadism) and A (secondary hypogonadism). There were significant differences in total testicular volume between group A (15.33 ± 11.94 ml) and group B (36.74 ± 6.9; p < .001) and also between subgroup A (11.07 ± 8.49 ml) and subgroup A (23.62 ± 13.04 ml; p < .001). Only 13.5% of patients in group B had a total testicular volume <30 ml. Differences in all studied parameters were found between group A and group B. There were no variations when comparing age, body mass index and testosterone in groups A and A . The use of total testicular volume and body mass index together for predicting testosterone levels yields a sensitivity and specificity of 85.3% and 86.5% respectively. Logistic regression analysis, univariate and multivariate models, using the measurement of total testicular volume resulted in a high capacity to predict testosterone levels.

Objective: To evaluate whether SOHLH2 intronic variation contributes to the genetic predisposition to male infertility traits, including severe oligospermia (SO) and different nonobstructive azoospermia (NOA) clinical phenotypes. Design: Genetic association study.

Background:The exact mechanism of varicocele-related infertility is still elusive, therefore, the current challenges for its management lie in determining which patients stand to benefit most from surgical correction. The authors aimed to assess the clinical factors affecting semen improvement after left microsurgical subinguinal varicocelectomy (MSV) in relation to patient age, ultrasound varicocele grading (USVG), and presence of a right subclinical varicocele (RSV).Methods:From 2010 to 2017 a total of 228 infertile patients underwent left MSV for clinical varicocele. Descriptive statistics were used to describe the cohort and verify the surgical benefit in terms of semen improvement, in addition, subsets of patients were selected according to clinical covariates. Logistic regression modeling was applied to evaluate the presence of RSV, operative time, age, and USVG as explanatory variables.Results:Sperm concentration (SC), progressive sperm motility (PSM), and normal sperm morphology (NSM) increased significantly after surgery (p = 0.002; p = 0.011; p = 0.024; respectively). Mean SC improved after MSV in ⩾35 year-old patients and the grade 3 USVG group (p = 0.01; p = 0.02; respectively). Logistic regression modeling showed a that the probability of SC improvement was 76% lower in subjects presenting RSV (p = 0.011). In addition, patients with a grade 3 USVG presented a three-times greater probability of SC improvement compared with patients with a lower USVG (p = 0.035). In addition, older patients showed a greater probability of SC improvement after MSV (p = 0.041).Conclusions:MSV is an effective varicocele-related infertility treatment that should also be offered to older patients. In addition, patients with a higher USVG benefit from surgery. In infertile men with an RSV in association with a left clinical disease, a bilateral varicocele repair should be considered.

No abstract

The association between impaired spermatogenesis and TGCT has stimulated research on shared genetic factors. Y chromosome-linked partial AZFc deletions predispose to oligozoospermia and were also studied in TGCT patients with controversial results. In the largest study reporting the association between gr/gr deletion and TGCT, sperm parameters were unknown. Hence, it remains to be established whether this genetic defect truly represents a common genetic link between TGCT and impaired sperm production. Our aim was to explore the role of the following Y chromosome-linked factors in the predisposition to TGCT: (i) gr/gr deletion in subjects with known sperm parameters; (ii) other partial AZFc deletions and, for the first time, the role of partial AZFc duplications; (iii) DAZ gene dosage variation. 497 TGCT patients and 2030 controls from two Mediterranean populations with full semen/andrological characterization were analyzed through a series of molecular genetic techniques. Our most interesting finding concerns the gr/gr deletion and DAZ gene dosage variation (i.e., DAZ copy number is different from the reference sequence), both conferring TGCT susceptibility. In particular, the highest risk was observed when normozoospermic TGCT and normozoospermic controls were compared (OR = 3.7; 95% CI = 1.5-9.1; p = 0.006 for gr/gr deletion and OR = 1.8; 95% CI = 1.1-3.0; p = 0.013 for DAZ gene dosage alteration). We report in the largest European study population the predisposing effect of gr/gr deletion to TGCT as an independent risk factor from impaired spermatogenesis. Our finding implies regular tumour screening/follow-up in male family members of TGCT patients with gr/gr deletion and in infertile gr/gr deletion carriers.

YAO et Al. | INTRODUC TI ONSince the first case of coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported in Wuhan, China, it has rapidly spread and affected more than 21 million people worldwide as of 17 August 2020. 1 SARS-CoV-2 uses angiotensin-converting enzyme II (ACE2) to enter host cells, similar to SARS-CoV, which emerged 18 years ago. 2 COVID-19 induces respiratory-predominant multiorgan dysfunction, including myocardial, renal, enteric and hepatic dysfunction, which coincides with the tissue expression of ACE2. 3 Meanwhile, several studies have shown that ACE2 is expressed in human testes (eg spermatogonia, Leydig cells and Sertoli cells), 4,5 suggesting that the testes may be another organ affected by COVID-19.Numerous viruses have been detected in human semen. 6 Viruses may persist in semen and last longer in seminal fluid than in other body fluids due to the immune privilege of the testes and the contribution of the blood-testes barrier to resistance to therapeutic agents. 7,8 Semen may also have higher loads of viruses, such as Zika virus, than blood. 9,10 Therefore, the testes may act as a reservoir of virus, which may cause imprecise evaluation of viral clearance in patients. Viruses, including Zika virus, Ebola virus, cytomegalovirus and human immunodeficiency virus (HIV), have been isolated from semen and can be sexually transmitted. 6,11,12 Furthermore, some viruses (eg HIV, Zika virus, herpes simplex virus (HSV) and human papillomavirus) can adhere to or be internalized by spermatozoa, 7,13 which may pose a risk for embryonic infection and cause adverse reproductive outcomes.On the other hand, many viruses, such as mumps virus, HIV and HSV, 7,14 have been found to impair semen quality, and they may directly interact with spermatozoa or affect spermatogenesis by inducing local inflammation. [15][16][17] Previous studies found that SARS, 1 of the 3 epidemic coronaviruses to emerge in the past 20 years and that shows similar clinical presentations to COVID-19, 18 could cause orchitis 19 and focal testicular atrophy. 20 Considering the tens of millions of COVID-19 cases and that men are more vulnerable to COVID-19 than women, [21][22][23] it is imperative to determine the effect of COVID-19 on male reproduction. 24 Several studies have been performed on this topic. However, the results are controversial. For example, some researchers have reported that SARS-CoV-2 was not detected in the male reproductive tract, [25][26][27][28][29][30][31][32][33][34] while others reported that SARS-CoV-2 RNA was found in the semen or testes of COVID-19 patients. 35,36 There are also unknown factors regarding COVID-19 and male reproduction.Orchitis and broad destruction of the testes were found in deceased COVID-19 patients, 35,37 while the pathological characteristics in survivors remain unknown. In this review, we summarize the current research focusing on the effects of COVID-19 on male reproduction from the following 3 aspects: detection of SARS-CoV-2 in...