Knowledge, professional attitudes, and training among health professionals regarding male contraceptive methods.

OBJECTIVES: Health professionals are at the forefront of information and acceptability regarding contraceptive methods, however only one study evaluated their knowledge of male contraception (MC) including hormonal MC (HMC) and thermal MC (TMC). Our objective was to evaluate the knowledge, professional attitudes, and training of French practitioners regarding the management of couple contraception by male contraception (MC). STUDY DESIGN: We designed a descriptive, cross-sectional, multicentre study in 2,396 French practitioners belonging to national or regional institutions involved in contraception. We solicited practitioners by e-mail to complete an anonymous questionnaire; we analysed their knowledge, professional attitudes, and training regarding the management of couple contraception by MC. RESULTS: The overall participation rate was 18% (427/2,396). Condoms, withdrawal, and vasectomy were known by 98%, 89%, and 76% of the population, respectively. Hormonal MC and Thermal (TMC) were known by 10% and 24% of the population, respectively. Fifty-five percent of the population never or infrequently offered MC during a couple's contraceptive request consultation. Only 14% of the population had ever participated in training on MC; 96% wanted to be better trained on MC, and 87% expressed a willingness to participate in training on the subject. CONCLUSIONS: Health professionals involved in contraception have unsatisfactory knowledge about MC methods based on spermatogenesis inhibition and are eager to have more information about them. To advance the acceptability and dissemination of MC methods, it seems imperative to enhance research in the field and to provide health professionals with an adapted training programme.

Genetics of the congenital absence of the vas deferens.

Congenital absence of the vas deferens (CAVD) may have various clinical presentations depending on whether it is bilateral (CBAVD) or unilateral (CUAVD), complete or partial, and associated or not with other abnormalities of the male urogenital tract. CBAVD is usually discovered in adult men either during the systematic assessment of cystic fibrosis or other CFTR-related conditions, or during the exploration of isolated infertility with obstructive azoospermia. The prevalence of CAVDs in men is reported to be approximately 0.1%. However, this figure is probably underestimated, because unilateral forms of CAVD in asymptomatic fertile men are not usually diagnosed. The diagnosis of CAVDs is based on clinical, ultrasound, and sperm examinations. The majority of subjects with CAVD carry at least one cystic fibrosis-causing mutation that warrants CFTR testing and in case of a positive result, genetic counseling prior to conception. Approximately 2% of the cases of CAVD are hemizygous for a loss-of-function mutation in the ADGRG2 gene that may cause a familial form of X-linked infertility. However, despite this recent finding, 10-20% of CBAVDs and 60-70% of CUAVDs remain without a genetic diagnosis. An important proportion of these unexplained CAVDs coexist with a solitary kidney suggesting an early organogenesis disorder (Wolffian duct), unlike CAVDs related to CFTR or ADGRG2 mutations, which might be the result of progressive degeneration that begins later in fetal life and probably continues after birth. How the dysfunction of CFTR, ADGRG2, or other genes such as SLC29A3 leads to this involution is the subject of various pathophysiological hypotheses that are discussed in this review.

[AFU and SALF recommendations for the evaluation of male infertility]. / Recommandations de l'AFU et de la SALF concernant l'évaluation de l'homme infertile.

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 ≤10 106/mL; (8) assessment of Yq microdeletions in infertile men with a sperm concentration ≤1 106/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.

Truncating Mutations in the Adhesion G Protein-Coupled Receptor G2 Gene ADGRG2 Cause an X-Linked Congenital Bilateral Absence of Vas Deferens.

In 80% of infertile men with obstructive azoospermia caused by a congenital bilateral absence of the vas deferens (CBAVD), mutations are identified in the cystic fibrosis transmembrane conductance regulator gene (CFTR). For the remaining 20%, the origin of the CBAVD is unknown. A large cohort of azoospermic men with CBAVD was retrospectively reassessed with more stringent selection criteria based on consistent clinical data, complete description of semen and reproductive excurrent ducts, extensive CFTR testing, and kidney ultrasound examination. To maximize the phenotypic prioritization, men with CBAVD and with unilateral renal agenesis were considered ineligible for the present study. We performed whole-exome sequencing on 12 CFTR-negative men with CBAVD and targeted sequencing on 14 additional individuals. We identified three protein-truncating hemizygous mutations, c.1545dupT (p.Glu516Ter), c.2845delT (p.Cys949AlafsTer81), and c.2002_2006delinsAGA (p.Leu668ArgfsTer21), in ADGRG2, encoding the epididymal- and efferent-ducts-specific adhesion G protein-coupled receptor G2, in four subjects, including two related individuals with X-linked transmission of their infertility. Previous studies have demonstrated that Adgrg2-knockout male mice develop obstructive infertility. Our study confirms the crucial role of ADGRG2 in human male fertility and brings new insight into congenital obstructive azoospermia pathogenesis. In men with CBAVD who are CFTR-negative, ADGRG2 testing could allow for appropriate genetic counseling with regard to the X-linked transmission of the molecular defect.

Real-life users of hormonal or thermal male contraception: An analysis of female partners' motivation, experience, and satisfaction.

BACKGROUND: Two male contraceptive methods that inhibit spermatogenesis currently exist: thermal male contraception and hormonal male contraception. Only five studies have been conducted on the acceptability of these methods among men; among women, only the hypothetical acceptability of such a male contraceptive approach as the sole contraception method used by a couple has been evaluated. OBJECTIVES: To evaluate the motivation, experience, and satisfaction of female partners in couples using hormonal male contraception or thermal male contraception as the sole contraception. MATERIALS AND METHODS: In this cross-sectional study, 123 male users of hormonal male contraception or thermal male contraception as the couple's sole contraception method were asked to invite their female partner to participate in an anonymous online survey. The questionnaire included 95 questions exploring population characteristics, contraceptive and pregnancy history, motivations for choosing hormonal male contraception or thermal male contraception, the experience of the women in the successive phase of use, relationships with their partner, and satisfaction with the contraception method. RESULTS: The response rate among participating women was 69% (59/86). The two main reasons for choosing male contraceptive were the desire to share the contraception role in the couple (65%) and the desire of the man to take charge of the contraception (61%). The sexual satisfaction score increased significantly between the contraceptive methods used before hormonal male contraception or thermal male contraception and the phase of contraceptive use (p < 0.01). The overall satisfaction level with thermal male contraception or hormonal male contraception was rated at 3.7 ± 0.6 out of 4. Women mostly recommended hormonal male contraception or thermal male contraception because of the share of contraceptive responsibility and mental load (n = 23/54, 43%). DISCUSSION: This population of women seemed to have struggled to find a contraceptive method that suited them, but most took advantage of thermal male contraception or hormonal male contraception and trusted their male partner to take charge of contraception use. CONCLUSION: The positive evaluation from women in partnerships using thermal male contraception and hormonal male contraception should encourage the development of these methods.

Cumulative parenthood rates in 1735 couples: impact of male factor infertility.

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.

Development of a multivariable prediction model for congenital unilateral absence of the vas deferens in male partners of infertile couples.

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.

Thermal male contraception: A study of users' motivation, experience, and satisfaction.

PURPOSE: The aim of this study is to evaluate the motivations, experience, and acceptability of thermal male contraception (TMC) in male partners of couples requesting the use of TMC as the only couple contraceptive. MATERIALS AND METHODS: To the 72 men of couples seeking male contraception and using TMC between 2011 and 2019, we suggested an anonymous online survey (93 questions) exploring population characteristics, contraceptive histories, motivations for choosing TMC, patient experience at the successive phases of use, relations with partner and environment, and satisfaction with this method. RESULTS: Sixty-seven men agreed to participate (93% response rate); 63 responses were complete and were analyzed (94% participation rate). The main motivations for choosing TMC were "not using hormones" (n = 59/63, 94%) and using a method regarded as "natural" (n = 49/63, 78%). Most of the men surveyed (68%) adopted the method in less than 2 weeks. During the contraception use phase (n = 59 men), they described significantly improved sexual satisfaction, compared to that experienced with their previous contraceptive methods, and they reported high confidence (100% rather/totally confident partner) and support (88% rather/totally supporting partner) from their partner. Most men (n = 35/59, 59%) also reported improved self-esteem. The main negative point was discomfort, reported by 24% of the men. The overall satisfaction score of using this method was 3.78 ± 0.46/4, and 100% of the men reported that they would recommend the method to other men. DISCUSSION AND CONCLUSION: Men using TMC successfully assumed the responsibility for and performed a daily task to provide couple contraception. This positive evaluation, together with the already published contraceptive efficacy and reversibility of TMC, should encourage the development of this method.

Male partners of infertile couples with congenital unilateral absence of the vas deferens are mainly non-azoospermic.

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.

Oral midodrine for prostaglandin e1 induced priapism in spinal cord injured patients.

PURPOSE: We evaluated midodrine as oral treatment for pharmacologically induced priapism in spinal cord injured patients. MATERIALS AND METHODS: From 2004 to 2007 we treated 354 spinal cord injured patients with intracavernous injection of prostaglandin E1 to induce erection. Prolonged erection or priapism occurred in 14 cases (1.3% of intracavernous injections). High blood pressure and bradycardia (autonomic dysreflexia) were noted in 2 tetraplegic cases. Except in 2 patients oral midodrine was used as the only therapeutic approach to this event because of its alpha stimulant properties. RESULTS: All patients returned to the flaccid penile state within 30 to 45 minutes after midodrine administration. Oral midodrine was well tolerated with few side effects and without increasing the incidence of autonomic dysreflexia. At 6 months complete erection could be again induced by intracavernous injection in all treated patients. CONCLUSIONS: Midodrine administered orally is a simple and efficient treatment for the priapism induced by intracavernous injection of prostaglandin E1. It could be the first line therapeutic approach before more aggressive procedures.

Mild experimental increase in testis and epididymis temperature in men: effects on sperm morphology according to spermatogenesis stages.

BACKGROUND: A mild increase in testicular and epididymal temperatures in men, bulls and rams (pendulous scrotum) inhibits spermatogenesis and increases the percentage of sperm with an abnormal morphology. However, the stages of spermatogenesis that are most sensitive to a mild increase in testicular temperature in men are unknown. The aim of the present study was to explore the effects of a mild induced increase in testicular and epididymal temperature (i.e., testicular temperature maintained below the core body temperature) on sperm morphology in humans depending on the physiological time of spermatogenesis and epididymal transit. METHODS: Five healthy volunteers were enrolled in an experimental study in which testicular and epididymal temperatures were increased by maintaining the testes in a supra-scrotal position with a specially designed underwear worn 15±1 h a day for 120 consecutive days. Semen collection was scheduled on specific days depending on spermatogenic stages and epididymal transit. RESULTS: Sperm morphology and the multiple anomalies index (MAI) were analysed before, during and after heating. This mild induced increase in testicular and epididymal temperatures resulted in a significant rise in the percentage of morphologically abnormal spermatozoa on day 34 of heating, which remained elevated throughout the heating period and persisted until 45 days after cessation of heating. The MAI was significantly increased on day 20 throughout the heating period and persisted 45 days after cessation of heating. An increase in the percentage of anomalies in the sperm head, acrosome or tail occurred on days 34 and/or 45 of heating. Abnormal sperm morphology and MAI reverted to control values 73 days after cessation of heating. CONCLUSIONS: A mild sustained increase in testicular and epididymal temperature in man leads morphological abnormalities in spermatozoa mainly due to an impairment of spermiogenesis and meiosis.

Experimental mild increase in testicular temperature has drastic, but reversible, effect on sperm aneuploidy in men: A pilot study.

In mammals testicular and epididymal temperature increase impairs spermatogenesis. This experimental study investigates the effects of a mild testis temperature increase (i.e. testis temperature remains below core body temperature) on sperm aneuploidy in men. In 5 fertile volunteers a testicular temperature increase was induced by maintaining the testes at suprascrotal position using specially designed underwear for 15 ±â€¯1 h daily for 120 consecutive days. After heating men were followed for next 180 days. A control group (27 men) was recruited. Semen samples were collected before, during and after heating period and analyzed for chromosomes X, Y and 18 for aneuploidy using FISH. A total of 234,038 spermatozoa were studied by FISH. At day 34 of heating, mean sperm aneuploidy values were not modified. From day 34 of heating until day 45 post heating, FISH evaluation was not possible due to the drastic fall of sperm count. At day 45 post-heating total sperm aneuploidy percentage was twice higher than before heating whereas. Sex disomy (sperm XY18), sex chromosome nullisomy (sperm 18) were significantly higher than controls. These effects were completely reversed at 180 days post heat exposure. Conclusion: A mild rise in testicular temperature significantly increases sperm aneuploidies, reflecting an effect on the meiosis stage of spermatogenesis. The effect of heating was reversible and suggests that recovery of aneuploidy to normal values requires at least two cycles of spermatogenesis. Nonetheless, the low number of volunteers was a limitation of this pilot study and warrants further research on larger population.

Meeting report: measuring endocrine-sensitive endpoints within the first years of life.

An international workshop titled "Assessing Endocrine-Related Endpoints within the First Years of Life" was held 30 April-1 May 2007, in Ottawa, Ontario, Canada. Representatives from a number of pregnancy cohort studies in North America and Europe presented options for measuring various endocrine-sensitive endpoints in early life and discussed issues related to performing and using those measures. The workshop focused on measuring reproductive tract developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and infant anthropometry. To the extent possible, workshop participants strove to develop or recommend standardized measurements that would allow comparisons and pooling of data across studies. The recommended outcomes include thigh fat fold, breast size, vaginal cytology, AGD, location of the testis, testicular size, and growth of the penis, with most of the discussion focusing on the genital exam. Although a number of outcome measures recommended during the genital exam have been associated with exposure to endocrine-disrupting chemicals, little is known about how predictive these effects are of later reproductive health or other chronic health conditions.

Are men ready to use thermal male contraception? Acceptability in two French populations: New fathers and new providers.

BACKGROUND: Since the 1970s, international research has actively pursued hormonal male contraception (HMC) and, to a lesser extent, thermal male contraception (TMC). Although the efficacy of TMC has been confirmed in limited populations, its acceptability has not been studied in either potential users or potential prescribers. METHODS: A cross-sectional descriptive multicentre study of potential male users of TMC (new fathers) and potential prescribers of TMC (new providers) was conducted between November 2016 and February 2017.The participants completed a 3-part survey, and their responses were evaluated to i) determine their socio-demographic profiles; ii) identify personal experiences with contraception; and iii) gauge the participants' knowledge, interest and preference for male contraception, particularly TMC. For new providers only, the survey included a fourth part to evaluate professional experience with male contraception. RESULTS: The participation rate was 51% for new fathers (305 NFs) and 34% for new providers (300 NPs, including 97 men (male new providers, MNPs) and 203 women (female new providers, FNPs)). Only 3% of NFs and 15% of NPs knew about TMC (including 26% of the MNPs and 10% of the FNPs, p<0.01). After reading information on TMC, new fathers were significantly less willing to try TMC (29%) than were new providers (40%) (p<0.01). The 3 main advantages of TMC for the new fathers included the following factors: "natural" (52%), "without side effects" (38%) and "non-hormonal" (36%). The main disadvantages were "lengthy wear time" (56%), "daily undergarment wear" (43%) and "concern about possible discomfort" (39%). CONCLUSIONS: Young male and female providers have limited knowledge of male contraception, are interested in further information and would generally prescribe TMC to their patients. Successful expansion of the use of male contraception, including TMC, would require distribution of better information to potential users and providers.

Effect of posture and clothing on scrotal temperature in fertile men.

Investigation of the effects of body position and clothing on the temperature of the scrotum has given discordant results. The aim of the present study was to evaluate these effects in 13 fertile male volunteers in successive positions each held for 15 minutes, either Supine, Standing, Seated with legs apart, and Seated with legs crossed (n = 8) or Standing, Seated with legs crossed, and Standing (n = 5), at first naked and then clothed. The Standing naked position was that in which scrotal temperature reached the lowest point. Clothing increased the scrotal temperature compared with the naked state, whatever the position. The Seated with legs crossed position had specific characteristics: in the naked state, it was thermogenic and increased scrotal temperature as much as clothing in the Supine or Standing positions; in the clothed state, the increase in temperature was less than expected, which could indicate that local mechanisms are involved. Moreover, the Seated with legs crossed position had a persisting effect on scrotal temperature in the next position. These results have both pathophysiological and epidemiological implications.

[Non-deferential male contraception: review of the literature]. / Contraceptions masculines non déférentielles: revue de la littérature.

OBJECTIVES: To review the state of progress of the various male contraceptive methods (with the exception of deferential methods). MATERIAL AND METHODS: A review of the literature was performed by using the key words: male/contraception, limiting the search to original articles in English and French. Articles on vasectomy and the other deferential methods of contraception are not considered in the present review. RESULTS: Three methods of male contraception are widely used at the present time: withdrawal, male condom and vasectomy, although other types of male contraception have been shown to be effective, including hormonal contraception, which appears to be the most promising technique and the subject of the majority of research. Other contraceptive methods (immunological, thermal...) could constitute possible alternatives. CONCLUSION: Male contraception remains under-used, as only male condoms are commonly used (apart from withdrawal and vasectomy). Consequently, new research protocols in the field of male contraception must be strongly encouraged.

Diagnosis of Partial Retrograde Ejaculation in Non-Azoospermic Infertile Men with Low Semen Volume.

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.

The spectrum of renal involvement in male patients with infertility related to excretory-system abnormalities: phenotypes, genotypes, and genetic counseling.

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.

The human epididymis: its function in sperm maturation.

BACKGROUND: Spermatozoa acquire their fertilizing ability and forward motility properties during epididymal transit. Our knowledge of gamete physiology is based on studies conducted in laboratory and domestic species; our knowledge of these processes in humans is limited. Medical indications for assisted reproductive technologies (ART) have progressed to include male infertility. Surgical procedures allow collection of spermatozoa from all along the human excurrent ducts, and the former have been used with some success in reproductive medicine. This has raised questions over the role of the epididymis in human sperm physiology. OBJECTIVE AND RATIONALE: To reanalyze what we now know about epididymal physiology in humans and to assess the relevance of laboratory animal models for understanding human physiology and the pathophysiology of the epididymis. SEARCH METHODS: A systematic bibliographic search of PubMed for articles published in English before May 2015 was carried out using the search terms 'epididymis' and 'sperm maturation'. Literature on the consequences of vasectomy on the epididymis was also searched. OUTCOMES: Whereas the proximal epididymis is almost exclusively occupied by efferent ducts, the sperm reservoir capacity is poorly developed in humans. At the molecular level, the human transcriptome and proteome show some segment specificity; conflicting results persist with regard to secretome variation along the tubule. The number of genes regulated along the excurrent ducts in men is lower when compared to rodent species, but remains significant. It is challenging to reconcile biochemical and physiological studies with clinical data obtained from men undergoing reanastomosis of the vas deferens at different points along the excurrent duct. We propose that vasectomy/vasovasostomy is a model to understand the consequences of obstruction on epididymis function in humans. WIDER IMPLICATIONS: Despite the scarcity of biological material available, the interspecies variability of the male reproductive tract urges us to use modern molecular and cellular biology tools to better understand human epididymis physiology in order to apply ART in a more responsible manner.