Search

Background: Congenital unilateral absence of vas deferens has been diagnosed in fertile and normozoospermic males and is associated with the risk of unilateral renal absence or cystic fibrosis transmembrane conductance regulator mutations; but no prediction model currently exists to diagnose this condition., Objectives: The study aims to identify clinical and biological variables that may have a predictive value for the diagnosis of congenital unilateral absence of vas deferens in male partners of infertile couples MATERIALS AND METHODS: We designed a retrospective, cross-sectional, case-control study on electronic health records of a single tertiary-care andrological centre collected between 1998 and 2018. We included all subjects diagnosed with congenital unilateral absence of vas deferens using combined scrotal and transrectal ultrasounds. Controls were confirmed free of congenital unilateral absence of vas deferens by the same way. Both groups received standardised exploration procedures. Multivariable logistic regression model was built in a backward stepwise manner. Model performance and calibration were assessed. The study is reported according to TRIPOD statement., Results: We included 69 congenital unilateral absence of vas deferens cases and 78 controls. Cases had a lower semen volume than controls. The congenital unilateral absence of vas deferens risk was associated with history of cryptorchidism and both levels of semen fructose and α-glucosidase. These predictors were confirmed by a random forest algorithm. The area under the curve was 0.886 (95% interval: 0.81-0.92). Calibration was performed with the Hosmer-Lemeshow test (p = 0.88)., Discussion and Conclusion: History of cryptorchidism, semen fructose and α-glucosidase were identified as relevant and independent predictors for the diagnosis of congenital unilateral absence of vas deferens. The model enables to identify male patients with a high risk of congenital unilateral absence of vas deferens to whom a transrectal ultrasounds would be proposed to confirm the diagnosis, whatever their semen parameters. It will also help to address the risks of unilateral renal absence and of cystic fibrosis transmembrane conductance regulator mutations carrying during the management of infertile couples., (© 2021 American Society of Andrology and European Academy of Andrology.)

Background: The aim of these Association Française d'Urologie (AFU) and Société d'Andrologie de Langue Française (SALF) common recommendations are to provide practice guidelines for the French Urological and Andrological community regarding the evaluation of infertile men., Material and Methods: Literature search in PubMed using the keywords "male infertility", "diagnosis", "management" and "evaluation" limited to clinical articles in English and French prior to 1/01/2020. To inform the level of evidence, the HAS grading system (2013) was applied., Results: Concerning the evaluation of infertile men, the AFU and the SALF recommend : (1) a systematic interview exploring the family history, the fertility history of the man outside the couple, the patient's personal history that may have an impact on his fertility, lifestyle habits, treatments, symptoms and possible sexual difficulties of the couple; (2) a general physical examination to assess signs of hypogonadism and secondary sexual characters; (3) a scrotal physical examination performed by an urologist or andrologist to assess (i) the testes for volume and consistency, (ii) vas deferens and epididymes for total or partial absence or nodules, and (iii) presence of varicoceles; (4) Performing two semen analyses, according to World Health Organization guidelines, if the first one has at least one abnormaly; (5) a scrotal ultrasound as part of routine investigation, that can be completed with an endorectal pelvic ultrasound according to the clinic; (6) an endocrine evaluation with at least a Testosterone and FSH serum determination; (7) Karyotype analysis in infertile men with a sperm concentration ≤10 10 6 /mL; (8) assessment of Yq microdeletions in infertile men with a sperm concentration ≤1 10 6 /mL; (9) Cystic fibrosis transmembrane conductance regulator gene evaluation in case of suspicion for bilateral or unilateral congenital agenesis of vas deferens and seminal vesicles. The interest of tests analyzing DNA fragmentation (TUNEL, SCSA) is still under investigation., Conclusion: These guidelines can be applied in routine clinical practice in all infertile men., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Men with congenital unilateral absence of vas deferens were reported to be mainly azoospermic, with both unilateral renal absence and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) but some have neither., Objectives: To assess whether in infertile couples the male partners with congenital unilateral absence of vas deferens are mainly azoospermic men., Material and Methods: Retrospective study in a unique university hospital; reproductive, clinical, CFTR analysis and seminal data of male partners of infertile couples (from 1998 to 2018) were analysed. Diagnosis of congenital unilateral absence of vas deferens was based on transrectal ultrasounds (TRUS): complete or partial absence of one vas deferens with complete contralateral vas deferens confirmed in 63 men. Distribution of sperm count in three classes: azoospermia, oligozoospermia or normozoospermia. Ultrasound determination of renal status; seminal biomarkers assays; and search for CFTR mutations., Results: Among the 63 men, 39.7% displayed azoospermia, 27% oligozoospermia and 33.3% normozoospermia; 42% of the non-azoospermic men (16/38) had previously obtained a natural pregnancy. We found unilateral renal absence in 17/59 patients (29%). Among 50 men with CFTR testing, five carried an allele associated with cystic fibrosis belonging to the 29 men without renal anomalies, indicating a high allelic frequency (8.6%). The 63 patients displayed high rates of surgical histories for undescended testicles or inguinal hernia, low values of semen volume and of total seminal glycerophosphocholine., Conclusions: Our results indicate that men with congenital unilateral absence of vas deferens mainly display oligozoospermia or normozoospermia and that they were previously fertile. They clearly confirm, first, that CFTR testing is recommended in congenital unilateral absence of vas deferens men and it should be mandatory for those with normal kidneys; and, second, that TRUS is needed for the diagnosis of congenital unilateral absence of vas deferens. As congenital unilateral absence of vas deferens may be present whatever the sperm count, biological warnings are represented by semen volume and seminal epididymal markers and clinical warnings by surgical histories of undescended testes or inguinal hernia., (© 2019 American Society of Andrology and European Academy of Andrology.)

Background: While reproductive technologies are increasingly used worldwide, epidemiologic, clinical and genetic data regarding infertile men with combined genital tract and renal abnormalities remain scarce, preventing adequate genetic counseling., Methods: In a cohort-based study, we assessed the prevalence (1995-2014) and the clinical characteristics of renal disorders in infertile males with genital tract malformation. In a subset of 34 patients, we performed a detailed phenotype analysis of renal and genital tract disorders., Results: Among the 180 patients with congenital uni- or bilateral absence of vas deferens (CU/BAVD), 45 (25 %) had a renal malformation. We also identified 14 infertile men with combined seminal vesicle (SV) and renal malformation but no CU/BAVD. Among the 34 patients with detailed clinical description, renal disease was unknown before the assessment of the infertility in 27 (79.4 %), and 7 (20.6 %) had chronic renal failure. Four main renal phenotypes were observed: solitary kidney (47 %); autosomal-dominant polycystic kidney disease (ADPKD, 0.6 %); uni- or bilateral hypoplastic kidneys (20.6 %); and a complex renal phenotype associated with a mutation of the HNF1B gene (5.8 %). Absence of SV and azoospermia were significantly associated with the presence of a solitary kidney, while dilatation of SV and necroasthenozoospermia were suggestive of ADPKD., Conclusion: A dominantly inherited renal disease (ADPKD or HNF1B-related nephropathy) is frequent in males with infertility and combined renal and genital tract abnormalities (26 %). A systematic renal screening should be proposed in infertile males with CU/BAVD or SV disorders.

In non-azoospermic patients with low semen volume (LSV), looking for partial retrograde ejaculation (PRE) by searching sperm in the postejaculatory urine (PEU) is required. The use of a retro-ejaculatory index (R-ratio) was suggested to define PRE, but none of the studies indicated a specific threshold above which PRE must be considered. Our objective was to propose a threshold value for the R-ratio as indicative of PRE in patients with LSV selected to be devoid of any known causes or risk factors for retrograde ejaculation or LSV. Among our data base (2000-2009) including 632 patients with PEU, 245 male patients from infertile couples who had had a first semen analysis with LSV (< 2mL) and a second semen analysis associated with PEU, were selected on the previous criteria. A prospective control group was randomly constituted (2007-2008) of 162 first consulting male patients from infertile couples, with a normal semen volume (≥ 2mL) on a first semen analysis and who accepted to collect PEU with their usual second semen analysis, selected on the previous criteria. To define an R-ratio threshold indicative of PRE, we used a ROC curve analysis and a regression tree based on a classification and regression tree (CART) algorithm. Of the 245 LSV patients, 146 still presented low semen volume (< 2 mL) on the second semen analysis. From the use of the CART algorithm, two low (1.5% and 2.8%) and two high R-values (7.1% and 8.3%) were defined, according to the lower reference limit for semen volume of 2.0 mL (WHO 1999) or 1.5 mL (WHO 2010) respectively. As only one or no patient with normal semen volume was observed above the two high R-values, we suggest an R-value higher than the range of [7.1-8.3]% as indicative of PRE until confirmation by a prospective multicenter study., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate rates and reasons for treatment discontinuation in couples with male factor infertility and who failed to conceive., Design: Retrospective study., Setting: Male Sterility Center, University Hospital., Patient(s): A total of 407 couples consulting for male factor infertility and who discontinued treatment without conceiving., Intervention(s): None., Main Outcome Measure(s): Treatment, reasons for dropout, and reproductive outcomes after discontinuation., Result(s): Of the 407 patients, 218 (54%) had had fertility treatment (medical or surgical), and 189 (46%) underwent assisted reproductive techniques (ART) (intrauterine insemination [IUI], in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI]). The main reasons for dropout were painfulness of treatment (15% for patients with non-ART treatment vs. 32% for patients who had undergone ART), its ineffectiveness (12% vs. 26%), and separation of the couple (18% vs. 7%). Of the 407 patients, 27% consulted in another fertility center, 8% succeeded in having a child by ART with male partner sperm, 1% by ART with donor sperm, and 11% through adoption., Conclusion(s): About half of the couples consulting for male factor infertility discontinued fertility treatment, and of those who discontinued only a fifth finally succeeded in having a child. Although support is available to couples during fertility care, ART is a physical and psychological burden., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Most studies assessing the outcome of assisted reproductive technologies (ARTs) have reported live birth rates in couples by taking mainly the female factor into account. However, infertility is a couple's concern, and the majority of publications do not take into consideration the true impact of male infertility on having the desired number of children., Methods: We carried out a follow-up study to evaluate the probability of having a child during treatments at the Toulouse Male Sterility Centre and after discontinuation from 2000 through 2008. Couples were followed for at least 4 years until discontinuation of treatment or delivery of a live infant., Results: We were able to contact 65% of the 1735 male partners by telephone. Of the 1131 respondents, 56% had become parents (60% if adoption is included), 28% after ART, 16% by natural pregnancy, 8% after non-ART treatment and 4% after ART in another centre. The cumulative rates of success reached 64% [95% confidence interval (CI), 60-67] for men ≤35 years and women ≤35 years after 9 years, and 31% (95% CI, 24-39) in older patients. With optimistic analysis, which assumes that patients for whom no information was available have the same chance of success in having a child as those whose reproductive outcome was known, the cumulative rate of success was 48% (95% CI, 45-50) in the 1735 couples., Conclusions: More than half of couples consulting for male infertility succeeded in having a child. Male age over 35 years old appears as a key risk factor as well as the woman's age, and these findings should encourage couples to attempt parenthood earlier.

Objective: To determine, with the use of transmission electron microscopy (TEM), the proportion of patients with permanent unexplained asthenozoospermia (<30% motility) who have an abnormality of sperm axonemal and periaxonemal structures., Design: Retrospective study., Setting: A university-affiliated public hospital., Patient(s): Sixty-one infertile men whose semen was submitted to TEM analysis because of persistent unexplained asthenozoospermia., Main Outcome Measure(s): The results of quantitative TEM analysis of the tails of the spermatozoa., Intervention(s): None., Result(s): Based on a comparison with the axonemal anomalies observed in nine fertile control patients, the infertile population was divided into three groups: group I, with no detectable axonemal defects (26.2%); group II, with axonemal anomalies in either the midpiece or the principal piece (29.5%); and group III, with axonemal anomalies in both the midpiece and the principal piece (44.3%). However, defects in the mitochondrial sheath, fibrous sheath, and sperm head (acrosomic and postacrosomic cap) were observed in at least 50%, 30%, and 50%, respectively, of the patients in each group. The proportion of dense fiber anomalies of the midpiece increased significantly from group I to group III. No differences were observed between the three groups in sperm characteristics, anamnesis information, or clinical data., Conclusion(s): In patients with persistent unexplained asthenozoospermia, the frequent association of periaxonemal anomalies with axonemal deficiencies strongly suggests that axonemal deficiencies are not the unique cause of decreased motility.

In humans, as in most mammals, spermatogenesis is temperature dependent. This temperature dependence has been clearly demonstrated by several experimental studies showing that artificial increases in scrotum or testicle temperature in fertile men reduce both sperm output and quality. Our knowledge of the effects of occupational heat exposure on male fertility comes mostly from a small number of epidemiological studies. We conducted an extensive review of these published reports, focusing on methodology and design (retrospective or prospective; reference group; number of subjects) and principal results (using several indicators such as the time taken to obtain a pregnancy or sperm characteristics). We concluded that occupational heat exposure is a significant risk factor for male infertility, affecting sperm morphology and resulting in delayed conception. The limits and biases involved in this type of research are also discussed.

The usual testicular location, either low or high in the scrotum, as well as testis ascent into suprascrotal position at least once a week from a usually scrotal position reported by the patient to occur spontaneously and regularly, were recorded in 85 fertile and 1014 infertile men, including 95 with a history of cryptorchism. The frequency of at least one testis being in a high scrotal location was similar in fertile (16.5%) and non-cryptorchid infertile (17%) men but higher in previously cryptorchid infertile men (27.2%), a difference probably due to cryptorchism. Testicular ascent was more frequent when scrotal location was high rather than low. An ascending testis was encountered more frequently in previously cryptorchid (30.4%) than in non-cryptorchid infertile men without any history of cryptorchism (18.3%) or in fertile men (11.8%). Moreover, in infertile men, spermatogenesis was more depressed in cases of testicular ascent than when both testes were never ascending, independently of a varicocele. Testis ascent could be a risk factor for spermatogenesis in infertile men without any history of maldescended testicle.

Out of 85 fertile and 1014 infertile men, two (2.4%) and 95 (9.4%) respectively had a history of cryptorchidism. Thus cryptorchidism appears to be a risk factor for fertility since this difference was significant. Further comparisons showed that the volume of a former cryptorchid testis was smaller than the contralateral normally descended one and that sperm output/concentration was more impaired in bilateral than in unilateral cryptorchidism. A retractile testis, defined as a testis reported by the patient to be spontaneously and regularly, i.e. at least once a week, ascending up into a supra-scrotal position, was more frequent in infertile men with a history of cryptorchidism than in fertile men. Retractility was more frequent on the cryptorchid side, and was found more frequently after hormonal than after surgical treatment. Independently of all epidemiological and clinical parameters studied, retractility was associated with a lower sperm output. Among the infertile men with a history of cryptorchidism, 45% had an abnormally high scrotal temperature. This abnormal temperature represented a pejorative risk factor for fertility in this group, since it was associated with a more severely impaired spermatogenesis and a higher incidence of primary infertility than in infertile men with a history of cryptorchidism but normal scrotal temperatures.

Seminal hormonal patterns in fertile and infertile men were investigated. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone and oestradiol were assessed by radioimmunoassay, and dehydroepiandrosterone sulphate (DHAS) by bioluminescence assay, on blood and seminal plasma of 23 fertile men and 83 infertile men. For fertile men, mean FSH, LH, testosterone and DHAS concentrations were lower and mean oestradiol was higher in seminal than in blood plasma; prolactin did not differ. For infertile men, mean seminal FSH and LH showed a moderate but significant increase compared with fertile men; testosterone, DHAS and prolactin did not differ but mean seminal oestradiol was significantly increased. Of the infertile men, 53% had seminal oestradiol concentration above the 90th percentile value for fertile men. The meaning of this seminal oestradiol increase is unclear since it is not known whether it is the cause or the consequence of the alteration of spermatogenesis in infertile men. Further studies are required to explore the possible therapeutic implications.

Testicular volume was assessed in 1029 infertile men and found to be normal in 704; 71 patients had unilateral and 213 had bilateral testicular hypotrophy; 4 had unilateral and 37 had bilateral atrophy. Sperm count and motility decreased in accordance with testicular volume. The lowest mean sperm counts and lowest mean motility percentages were found in patients with bilateral testicular atrophy. An increase in mean FSH and LH was also significantly linked to decreasing testicular volume; the increase in the former was not related to a drop in sperm count. A significant correlation was found between testicular volume and spermatogenesis and testicular volume is considered to be a reliable indicator of testicular function.

A Negative correlation between spermatozoa output and serum gonadotropin levels, as well as between scrotal temperature and spermatozoa output, has been found in man. However, no studies have been done on the relationship between scrotal temperature and serum gonadotropin levels. This paper reports such data from 212 infertile men. The upper limit for normal scrotal temperature was defined as the 90th percentile value (35.3 C) of a control group of 64 fertile men whose mean serum FSH and LH levels were 6.0 +/- 0.8 (+/- SE) and 6.4 +/- 0.7 IU/L, respectively. This value for scrotal temperature (35.3 C) was used to classify infertile men into 3 groups: bilateral hyperthermia (n = 56), unilateral hyperthermia (n = 40), and bilateral normothermia (n = 116). In the unilateral and bilateral hyperthermic groups serum LH and FSH levels were significantly increased compared with those in the normothermic group. The mean serum testosterone values were similar in all groups. To study the relationships between serum gonadotropin levels or spermatozoa output and scrotal temperature, the infertile men also were divided into classes according to their spermatozoa output. These classes were subdivided into two groups, normothermic or hyperthermic, according to whether the left scrotal temperature was equal to or less than, or more than 35.3 C. For the infertile men whose spermatozoa output was more than 60 X 10(6) spermatozoa/ejaculate (normospermia), there was no significant difference between the serum gonadotropin levels of the normothermic (n = 42) and the hyperthermic (n = 20) groups. Among the oligospermic men (spermatozoa output, 0.1-60 X 10(6) spermatozoa/ejaculate), the hyperthermic group (n = 65) had significantly higher serum gonadotropin levels and significantly smaller testicular volumes than the normothermic group (n = 71). The two oligospermic groups also had significantly higher serum FSH values than the infertile normospermic groups. These results were not linked to the presence of a varicocele or a history of cryptorchidism, as the prevalence of varicocele and cryptorchidism was equally distributed within the groups studied. We conclude that the increase in serum gonadotropin levels in the case of a decrease in spermatozoa output is significantly greater in the presence of associated scrotal hyperthermia.

70 patients, out of a total of 664 infertile subjects with a varicocele, presenting a sperm count of less than 5 X 10(6)/ml, were operated and followed for a mean period of 8 months. 80% of the 70 varicoceles were voluminous, compared with 23% in the general population. There was a statistically significant difference between the presence of a large varicocele and the presence of testicular hypotrophy or a sperm count of less than 5 X 10(6)/ml. Histological examination of 80 testes revealed a defect of maturation in 36% of cases (T2), corresponding to reversible histological lesions. The histological lesions predominantly involved the tube (66%) followed by the basement membrane (52%) and the interstitium (42%). The difference between the pre- and post-operative sperm counts was statistically significant (p less than 0.001). We obtained a 36% paternity rate after a mean post-operative delay of 8 months. The authors consider that the larger the varicocele, the more severe the histological lesions (maturation defect = T2). These cases have a very good chance of post-operative improvement as a result of restoration of spermatogenesis. This improvement is more marked when the lesions of the basement membrane and interstitial lesions are less severe. This concept of a "large pathogenic varicocele" which responds well to surgical cure raises doubts about the concept of sub-clinical pathogenic reflux detected by Doppler examination or by phlebography resulting, far too often at the present time, in an embolisation procedure.

Scrotal temperatures, testicular volumes, and sperm characteristics were studied in 150 infertile, nonazoospermic men and in 37 fertile men, used as a control group. The mean scrotal temperature values of the infertile men were significantly greater than those observed in the fertile men (+0.4 degrees C for the right; +0.5 degrees C for the left). In the infertile men, it was found that the higher the scrotal temperature, the more alterated the sperm characteristics. The only clinical element that seemed to be linked to the existence of scrotal hyperthermia in the infertile men was testicular hypotrophy. Although the scrotal temperatures of the infertile men with varicocele were significantly higher than those of the fertile men, they did not significantly differ from those of the infertile men without varicocele. No other specific pathologic factor, infectious or surgical urogenital history was found to be responsible for the scrotal hyperthermia observed in the infertile men.

Glycerophosphocholine (GPC) was measured in seminal plasma from 65 fertile men, 276 infertile men and 10 men before and after vasectomy, using a new enzymatic method. Extra-epididymal excretion of GPC accounted for 30% of the total seminal levels of GPC. From a diagnostic point of view, GPC determination did not appear to be a specific tool which could discriminate between secretory and excretory azoospermia. Although the seminal content of GPC was related positively to the total sperm count in both fertile and infertile men, there was an inverse relationship between the level of GPC and sperm motility when considering classes displaying the same total sperm count. This was observed in all classes from infertile men as well as in fertile men with a total sperm count lower than 200 x 10(6) sperm/ejaculate. These results suggest a possible role of GPC in the regulation of human sperm motility, which warrants further investigation.