Azoospermia: Is it worth waiting for the confirmation of the semen abnormality to start an infertility assessment?

Azoospermia is found in about 1% of men in the general population and in about 10%-15% of infertile men. Upon discovery of semen analysis abnormality, another test must be performed after an interval of 3 months before any other infertility work-up. This research aimed at evaluating the benefit of waiting for the control test. This retrospective monocentric descriptive study was carried out in the fertility center of the University Hospital of Saint Etienne. All consecutive azoospermic patients diagnosed between January, 2012 and December, 2019 were included. For each patient, two consecutive semen analyses performed 3 months apart were studied. The main focas was on patients whose second semen analysis would have modified the infertility work-up. Amongst the 172 cases under study, the second semen analysis revealed the presence of sperm for three men. Only one of these 3 modified semen analyses was normal. In the observed azoospermic population, sperm was found on the second test in 1.7%. An infertility assessment is necessary after the discovery of azoospermia in the first semen analysis in 99.5%. These results suggest that it is useless to wait three stressful months before starting an infertility assessment for azoospermic population.

Assessment of Blood Plasma Free-amino Acid Levels in Infertile Men.

BACKGROUND/AIM: The objective of this study was to investigate the significance of the blood levels of free amino acids (AAs) in infertile men. PATIENTS AND METHODS: Ninety-three men who underwent examinations for infertility were included. The concentrations of 20 AAs were measured and compared in four groups (normospermia, obstructive azoospermia, oligozoospermia, non-obstructive azoospermia) based on semen analysis and clinical parameters. RESULTS: When the 93 men were divided into normospermia, obstructive azoospermia, oligozoospermia, and non-obstructive azoospermia groups, no significant differences were found in the concentrations of the 20 AAs between them. We then compared 49 men diagnosed with normozoospermia or oligozoospermia according to the median sperm motility and morphology abnormalities rates (30% and 20%, respectively). Men with low motility rates had significantly lower levels of tryptophan and alanine, and men with high abnormal morphology rates had significantly lower levels of aspartate and glutamate. CONCLUSION: AAs are probably involved in the pathogenesis of male infertility, particularly oligozoospermia.

Increased Mortality Among Men Diagnosed With Impaired Fertility: Analysis of US Claims Data.

OBJECTIVE: To determine whether male infertility or impaired spermatogenesis is associated with mortality. METHODS: The Optum de-identified Clinformatics Data Mart database was queried from 2003 to 2017. Infertile men were compared to subjects undergoing semen analysis (ie, infertility testing). Infertile men with oligozoospermia or azoospermia were included. Mortality was determined by data linkage to the Social Security Administration Death Master File. Results were adjusted for age, smoking, obesity, year of evaluation, and health care visits as well as for most prevalent comorbidities. We separately examined men with prevalent or incident cardiovascular disease and cancer diagnoses to determine associations with mortality. RESULTS: A total of 134,796 infertile men and 242,282 controls were followed for a mean of 3.6 and 3.1 years respectively. Overall, infertile men had a higher risk of death (Hazard Ratio [HR]= 1.42, 95% CI: 1.27-1.60) The diagnosis of azoospermia was associated with a significantly increased risk of death (HR= 2.01, 95% CI: 1.60-2.53) with a higher trend among men with oligospermia (HR: 1.17, 95% CI: 0.92-1.49) compared to controls. Subanalysis was done excluding prevalent cardiovascular and malignant disease (alone and combined) showing similar hazard ratios. CONCLUSION: Male infertility is associated with a higher risk of mortality especially among azoospermic men. Prevalent disease (which is known to be higher among infertile men) did not explain the higher risk of death among infertile men. The implications for treatment and surveillance of infertile men require further study.

A comprehensive assessment of predictors of fertility outcomes in men with non-obstructive azoospermia undergoing microdissection testicular sperm extraction.

BACKGROUND: Microdissection testicular sperm extraction (microTESE) in men with non-obstructive azoospermia (NOA) is the procedure that results in the highest number of sperm cells retrieved for in vitro fertilization (IVF). This study presents a novel assessment of predictors of sperm retrieval as well as downstream embryology and pregnancy outcomes in cases of men with NOA undergoing microTESE. METHODS: A retrospective chart review of 72 men who underwent microTESE for predictors of fertility outcomes including sperm retrieved at microTESE, embryology progression to embryo transfer (ET), clinical pregnancy, live birth, and surplus sperm retrieved for additional IVF/intracytoplasmic injection cycles beyond one initial cycle. Statistical models for each of these outcomes were fitted, with a p-value of < 0.05 considered significant for the parameters estimated in each model. RESULTS: Seventy-two men underwent microTESE, and 51/72 (70.8%) had sperm retrieved. Of those, 29/43 (67.4%) reached ET. Of the couples who underwent ET, 21/29 (72.4%) achieved pregnancy and 18/29 (62.1%) resulted in live birth. Of the men with sperm retrieved, 38/51 (74.5%) had surplus sperm cryopreserved beyond the initial IVF cycle. Age, testicular volume, FSH, and testicular histopathology were assessed as predictors for sperm retrieved at microTESE, progression to ET, pregnancy, live birth, and surplus sperm. There were no preoperative predictors of sperm retrieval, clinical pregnancy, or live birth. Age predicted reaching ET, with older men having increased odds. FSH level had a negative relationship with surplus sperm retrieved. Men with hypospermatogenesis histology had higher rates of sperm retrieval, clinical pregnancy, live birth, and having surplus sperm. CONCLUSIONS: Men who underwent microTESE with a hypospermatogenesis histopathology had better outcomes, including higher rates of sperm retrieval, clinical pregnancy, live birth, and having surplus sperm retrieved. Increasing male partner age increased the odds of reaching ET. No other clinical factors were predictive for the outcomes considered.

Evaluation, Treatment, and Insurance Coverage for Couples With Male Factor Infertility in the US: A Cross-Sectional Analysis of Survey Data.

OBJECTIVE: To characterize the evaluation, treatment, and insurance coverage among couples with male factor infertility in the United States. MATERIALS AND METHODS: A cohort of 969 couples undergoing fertility treatment with a diagnosis of male factor infertility were identified from an online survey. The proportion of men that were seen/not seen by a male were compared. Insurance coverage related to male factor was also assessed. RESULTS: Overall, 98.0% of the men reported at least one abnormal semen parameter. Of these, 72.0% were referred to a male fertility specialist with the majority being referred by the gynecologist of their female partner. As part of the male evaluation, 72.2% had blood hormone testing. Of the 248 men who were not recommended to see a male fertility specialist, 96.0% had an abnormal semen analysis including 7.6% who had azoospermia. Referral to a male fertility specialist was largely driven by severity of male factor infertility rather than socioeconomic status. Insurance coverage related to male factor infertility was poor with low coverage for sperm extractions (72.9% reported 0-25% coverage) and sperm freezing (83.7% reported 0-25% coverage). CONCLUSION: Although this cohort includes couples with abnormal semen parameters, 28% of the men were not evaluated by a male fertility specialist. In addition, insurance coverage for services related to male factor was low. These findings may be of concern as insufficient evaluation and coverage of the infertile man could lead to missed opportunities for identifying reversible causes of infertility/medical comorbidities and places an unfair burden on the female partner.

Fine-Needle Aspiration Cytology of the Testes for the Classification of Azoospermia and Its Value in the Assessment of Male Infertility.

BACKGROUND: Infertility is an ever-increasing problem in today's world. It can be due to male or female causes. Azoospermia seen in 5-10% of infertile men is due to obstructive or non-obstructive causes. Traditionally, testicular biopsy is the gold standard for evaluation. Fine-needle aspiration (FNA), however, is minimally invasive, provides qualitative and quantitative information about spermatogenesis, and can aid in assisted reproductive techniques making it a novel technique for the evaluation of male infertility. OBJECTIVE: We aimed to classify different causes of azoospermia into different patterns based upon FNA, and assess the utility of cell indices in classifying cases into different patterns. METHOD: We conducted a prospective and a retrospective study of 42 azoospermic males, confirmed on semen analysis, over a period of 5 years. Patients were subjected to FNA of the testes. Smears were prepared, air-dried, wet-fixed, and then stained with May-Grünwald Giemsa and Papanicolaou stains, respectively. Cells were identified using predetermined morphologic criteria, and various indices were calculated followed by statistical analysis of the observations. RESULTS: The mean age of 40 patients who satisfied the adequacy criteria was 32.75 years (range 22-48 years). Thirty-four patients had primary infertility and 6 had secondary infertility. Of these, 12 had normal spermatogenesis, 8 had hypo-spermatogenesis, 3 had early and 7 had late maturation arrest, 6 had Sertoli cell-only syndrome (SCOS), and there were different results in each testicle in 4 cases. The Sperm Index (SI) was significantly higher in all cases of normal spermatogenesis than in any of the hypo-spermatogenesis cases (p = 0.009). The Sertoli Index (SEI) in cases of hypo-spermatogenesis and maturation arrest was significantly higher than in cases of normal spermatogenesis (p < 0.001). The Sperm-Sertoli Index (SSI) also showed significant differences between cases of hypo-spermatogenesis and normal spermatogenesis (p < 0.001). These indices were useful in categorising patients with azoospermia. CONCLUSION: FNA helps to easily and accurately identify all types of testicular cells without biopsy. SI, SEI, and SSI are powerful cell indices for assessing the extent of spermatogenesis and classifying various causes of azoospermia. Bilateral sampling and multiple aspirations give a better mapping of spermatogenesis within the testes. Testicular FNA can thus play a very important role in the evaluation of male infertility.

An easy, reproducible and cost-effective method for andrologists to improve the laboratory diagnosis of nonobstructive azoospermia: a novel microcentrifugation technique.

This study describes a new method of microcentrifugation as an improved, viable, cost-effective option to the classical Cytospin apparatus to confirm azoospermia. Azoospermic semen samples were evaluated for cryptozoospermia by a centrifugation method similar to that of World Health Organization guidelines (2010; entire specimen centrifuged at 3000g for 15 min, and aliquots of the pellet examined). Then, if no sperm were detected, the pellet from that procedure was resuspended in culture medium, centrifuged (2000g for 15 min), and the entire pellet spread on a 4 X 6mm area of a slide and stained using the Christmas tree method (Nuclear-Fast solution and picric acid). The entire stained area was examined for the presence or absence of sperm. A total of 148 azoospermic samples (after standard WHO diagnosis) were included in the study and 21 samples (14.2%) were identified as sperm-positive. In all microcentrifugation slides, intact spermatozoa could be easily visualized against a clear background, with no cellular debris. This novel microcentrifugation technique is clearly a simple and effective method, with lower cost, increasing both sensitivity and specificity in confirming the absence or presence of spermatozoa in the ejaculate. It may represent a step forward of prognostic value to be introduced by andrology laboratories in the routine evaluation of patients with azoospermia in the initial semen analysis.

An easy, reproducible and cost-effective method for andrologists to improve the laboratory diagnosis of non-obstructive azoospermia: a novel microcentrifugation technique

ABSTRACT This study describes a new method of microcentrifugation as an improved, viable, cost-effective option to the classical Cytospin apparatus to confirm azoospermia. Azoospermic semen samples were evaluated for cryptozoospermia by a centrifugation method similar to that of World Health Organization guidelines (2010; entire specimen centrifuged at 3000g for 15 min, and aliquots of the pellet examined). Then, if no sperm were detected, the pellet from that procedure was resuspended in culture medium, centrifuged (2000g for 15 min), and the entire pellet spread on a 4 X 6mm area of a slide and stained using the Christmas tree method (Nuclear-Fast solution and picric acid). The entire stained area was examined for the presence or absence of sperm. A total of 148 azoospermic samples (after standard WHO diagnosis) were included in the study and 21 samples (14.2%) were identified as sperm-positive. In all microcentrifugation slides, intact spermatozoa could be easily visualized against a clear background, with no cellular debris. This novel microcentrifugation technique is clearly a simple and effective method, with lower cost, increasing both sensitivity and specificity in confirming the absence or presence of spermatozoa in the ejaculate. It may represent a step forward of prognostic value to be introduced by andrology laboratories in the routine evaluation of patients with azoospermia in the initial semen analysis.

Reduced Postvasectomy Semen Analysis Testing With the Implementation of Special Clearance Parameters.

OBJECTIVE: To determine the applicability of postvasectomy special clearance parameters (<100,000 nonmotile sperm/mL on semen analysis) suggested by the American Urological Association and to define the associated cost savings with avoidance of further testing. MATERIALS AND METHODS: We retrospectively reviewed the cohort of men undergoing vasectomy from December 2009 to August 2012 at a single institution. Patient demographics and postvasectomy semen analysis (PVSA) results were collected for clearance parameter comparisons. RESULTS: During the study period, 230 patients underwent vasectomy with a mean ± SD age of 36.4 ± 6.5 years. Among the cohort, 83.5% were married and 95.2% had one or more children. The initial PVSA was completed by 111 (48.3%) patients at a mean of 17.8 weeks (range 4-45) following vasectomy. Sperm was identified on initial PVSA in 40 patients (36.0%); 1 patient was found to have motile sperm. Of 39 patients, 38 (97.4%) with nonmotile sperm on PVSA could be cleared to cease other contraceptives based on the most recent clearance guidelines. For those completing an initial PVSA, postvasectomy clearance increased from 64.0% to 98.2% representing a potential cost savings of $2356 in repeat semen testing. CONCLUSION: Postvasectomy contraceptive clearance can be greatly increased when rare nonmotile sperm parameters are included although postvasectomy semen testing compliance remains poor.

Hormonal imbalances and psychological scars left behind in infertile men.

The effect of infertility on the psychological well-being of couples has been the subject of increasing attention in recent years. The frustration of couples of a relatively young age (ie, in their fourth decades) provokes not only anxiety and depression but also negative effects on the relationships. The objective of this study was to evaluate the effect of a diagnosis of male infertility on anxiety and depression in the men themselves and in fertile female spouses. The prospective cross-sectional study consisted of 264 participants, 72 males diagnosed with nonobstructive azoospermia (NOA) and their fertile spouses and 60 fertile couples attending our university between January 1, 2009, and April 30, 2010. The Beck Anxiety Inventory, Beck Depression Inventory (BDI), and hormone levels were measured during initial and follow-up visits. In NOA men, follicle-stimulating hormone and luteinizing hormone were positively associated with anxiety, in contrast to testosterone, which was inversely associated with anxiety. After the diagnosis of NOA, producing no testicular sperm, the panic intensity among men increased significantly, whereas their spouses exhibited less panic. By contrast, fertile female partners of NOA men reported higher BDI scores after the initial diagnosis of azoospermia, whereas their partners recorded higher levels of depression after the absence of testicular sperm was discovered. Insomnia was the most common complaint for both sexes after the diagnosis of azoospermia. Hormonal abnormalities had a negative effect on the quality of life. Physicians and clinicians should acknowledge the immense psychosocial effect of the diagnosis of male infertility on both males and their fertile female partners.

An update on the clinical assessment of the infertile male. [corrected].

Male infertility is directly or indirectly responsible for 60% of cases involving reproductive-age couples with fertility-related issues. Nevertheless, the evaluation of male infertility is often underestimated or postponed. A coordinated evaluation of the infertile male using standardized procedures improves both diagnostic precision and the results of subsequent management in terms of effectiveness, risk and costs. Recent advances in assisted reproductive techniques (ART) have made it possible to identify and overcome previously untreatable causes of male infertility. To properly utilize the available techniques and improve clinical results, it is of the utmost importance that patients are adequately diagnosed and evaluated. Ideally, this initial assessment should also be affordable and accessible. We describe the main aspects of male infertility evaluation in a practical manner to provide information on the judicious use of available diagnostic tools and to better determine the etiology of the most adequate treatment for the existing condition.

An update on the clinical assessment of the infertile male

Male infertility is directly or indirectly responsible for 60 percent of cases involving reproductive-age couples with fertility-related issues. Nevertheless, the evaluation of male infertility is often underestimated or postponed. A coordinated evaluation of the infertile male using standardized procedures improves both diagnostic precision and the results of subsequent management in terms of effectiveness, risk and costs. Recent advances in assisted reproductive techniques (ART) have made it possible to identify and overcome previously untreatable causes of male infertility. To properly utilize the available techniques and improve clinical results, it is of the utmost importance that patients are adequately diagnosed and evaluated. Ideally, this initial assessment should also be affordable and accessible. We describe the main aspects of male infertility evaluation in a practical manner to provide information on the judicious use of available diagnostic tools and to better determine the etiology of the most adequate treatment for the existing condition.

[Assessment of azoospermia and histological evaluation of spermatogenesis]. / Bilan d'une azoospermie et évaluation histologique de la spermatogenèse.

Azoospermia may be obstructive (blockage of the genital ducts) or non-obstructive (a lack of testicular production). The distinction is based on an ensemble of clinical, spermiological, hormonal, ultrasound, genetic and histological data. Azoospermia is the main indication for testicular biopsy for therapeutic and diagnostic purposes. Testicular spermatozoids are processed in the reproductive biology laboratory (simultaneously with oocyte retrieval or not) for in vitro fertilization with intra-cytoplasmic sperm injection. The histological study of spermatogenesis is usually performed on a testicular biopsy sample taken at the same time and provides additional diagnostic information on infertility. Histological alterations in the testicular tissues are frequently observed in azoospermic men. In non-obstructive azoospermia, three histological situations prevail: hypospermatogenesis, Sertoli-cell-only syndrome and germ cell arrest. One can distinguish between pure forms (in which all the seminiferous tubules have the same appearance) and mixed forms (in which the tubules' aspects are heterogeneous). Hypospermatogenesis is highly prevalent in azoospermia and is characterized by a low, basal level of spermatozoid production. The prevalence of Sertoli-cell-only syndrome varies from 27 to 68% and the mean spermatozoid recovery rate is between 16 and 33%. Germ cell arrests are rare phenotypes and have a poor prognosis for spermatozoid recovery. Overall, histological examination (still the only way to fully describe spermatogenesis) must be qualitative and quantitative, with the adoption of a standardized, universally understood terminology. It is essential to compare the histological data with (i) recovery of testicular spermatozoids, (ii) clinical, ultrasound, hormonal and genetic data and (iii) the outcome of IVF/ICSI procedures.