Nonazoospermic Men Research Articles

Distribution and Positive Predictive Value of Follicle Stimulating Hormone Among Nonazoospermic Men.

Our goal was to characterize the distribution of follicle stimulating hormone (FSH) in fertile and subfertile nonazoospermic men, and to determine the ability of various FSH thresholds to predict fertility status. We performed a retrospective cohort study of 1389 nonazoospermic men who presented for fertility evaluation. Men with at least 2 semen analyses and 1 FSH level were included. Men were dichotomized into fertile and subfertile groups based on total motile sperm count. FSH was evaluated within a multivariable model, and positive predictive values (PPVs) for subfertility were used to assess the clinical utility of various FSH thresholds. One thousand fifteen (80%) men were classified as fertile and 274 (20%) as subfertile. Age, presence of varicocele, and testosterone levels were not statistically different between the groups. Median FSH was 4.0 vs 6.0 (P < .001) among fertile vs subfertile men. Multiple FSH thresholds ranging from 2.9 to 9.3 performed similarly in predicting fertility status (PPV 0.49-0.59). Only FSH thresholds above the 95th percentile (12.1) had PPVs greater than 0.7. The highest PPV (0.84) was seen at an FSH of 20.8 (99th percentile). While there were significant differences in FSH levels among fertile and subfertile nonazoospermic men, multiple FSH cutoffs between 2.2 and 9.3 performed poorly for prediction of fertility status as determined by total motile sperm count. It was not until the 95th percentile FSH value that a clinically useful level of predictability for subfertility was reached, indicating that FSH should not be used as a standalone test of fertility status. Nonetheless, FSH testing remains clinically useful and may be most informative in the setting of extreme values or discordant FSH and semen analysis results.

ICSI using testicular spermatozoa after failure of ICSI with ejaculated spermatozoa could be a good choice: A propensity score-matched cohort study.

Ejaculated spermatozoa are considered to possess a higher fertilisation potential than testicular spermatozoa. In selected cases, the use of testicular spermatozoa from non-azoospermic infertile men resulted in a higher implantation and pregnancy rate than the use of ejaculated spermatozoa. The primary objective was to compare the live birth rate and cumulative live birth rate between couples with failed intracytoplasmic sperm injection procedure using ejaculated spermatozoa who subsequently had an intracytoplasmic sperm injection cycle with testicular spermatozoa and those who subsequently had an intracytoplasmic sperm injection cycle with ejaculated spermatozoa. The secondary objective was to determine the indications for the use of testicular spermatozoa after intracytoplasmic sperm injection failure with ejaculated spermatozoa. A retrospective study of matched couples using propensity score matching analysis was performed. After an intracytoplasmic sperm injection failure (cycle_1), intracytoplasmic sperm injection with either ejaculated spermatozoa (ejaculated sperm group), or testicular spermatozoa (testicular sperm group), was performed (cycle_2). The matching was on intracytoplasmic sperm injection performed in cycle_1 according to spermatozoa used (testicular or ejaculated) in cycle_2. Logistic regression was used to evaluate the influence of sperm origin on cumulative live birth rate. Univariate analysis on parameters of cycle_1 was used to identify the prognostic factors to propose an intracytoplasmic sperm injection with testicular spermatozoa in case of cycle_1 failure. The study outcomes were live birth rate and cumulative live birth rate. Among the 6034 couples available, 63 were selected to constitute the testicular sperm group and 63 were selected by propensity score matching to constitute the ejaculated sperm group. After matching, the DNA fragmentation index was higher in the testicular sperm group (13.43%±9.65% vs. 8.93%±4.47%, p=0.013); no significant difference was observed for the fertilisation rate, the number of obtained embryos, blastulation rate and frozen embryo rate. In cycle_2, the live birth rate was higher in the testicular group (22.2% vs. 0.0%, p<0.001), as was the cumulative live birth rate (25.4% vs. 6.3%, p=0.065). The prognostic factors identified for the proposal of intracytoplasmic sperm injection procedure with testicular spermatozoa after intracytoplasmic sperm injection failure with ejaculated spermatozoa were: teratozoospermia, cryptozoospermia and high DNA fragmentation index. According to the present study and current knowledge, the use of testicular spermatozoa after failed intracytoplasmic sperm injection procedure in non-azoospermic men could be proposed instead of sperm donation in case of high sperm DNA fragmentation index, cryptozoospermia and teratozoospermia. A good oocyte response to ovarian stimulation during the previous assisted reproductive technology attempt will increase the chance of success. Although the main limitation of the current study is its retrospective nature, the use of the propensity score matching to perform causal inference study increases its reliability. The present study supports that the use of testicular spermatozoa outside the classical indication of azoospermia is a good option when the indication is well established. However, before proposing a testicular biopsy, an improvement in sperm characteristics should be considered by treating the causes of sperm alteration.

MP30-08 EVALUATING THE CHANGES IN SEMEN PARAMETERS OVER TIME FOR MEN WITH AZOOSPERMIA FACTOR C (AZFc) MICRODELETIONS

You have accessJournal of UrologyCME1 Apr 2023MP30-08 EVALUATING THE CHANGES IN SEMEN PARAMETERS OVER TIME FOR MEN WITH AZOOSPERMIA FACTOR C (AZFc) MICRODELETIONS Jessica Marinaro, Jonathan Gal, Anna Mielnik, and Peter Schlegel Jessica MarinaroJessica Marinaro More articles by this author , Jonathan GalJonathan Gal More articles by this author , Anna MielnikAnna Mielnik More articles by this author , and Peter SchlegelPeter Schlegel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003258.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Men with complete azoospermia factor C (AZFc) microdeletions may have variable degrees of spermatogenic failure. While some are persistently azoospermic, most intermittently or consistently have sperm in the ejaculate. It has been proposed that these men may experience a temporal decline in semen quality with age. The objective of this study was to assess changes in semen parameters over time among men with complete AZFc deletions. METHODS: We retrospectively reviewed 163 men with complete AZFc deletions who were tested at our center from 4/1996 to 7/2022. Of these, 41 had ≥2 semen analyses performed (SA). ANOVA tests were used to compare mean demographic values between azoospermic, intermittently azoospermic, and non-azoospermic men. Wilcoxon matched-pairs signed rank tests were used to compare initial and final semen analyses. RESULTS: In total, 179 SAs were reviewed. The mean number of SAs per patient was 4.4 ± 2.2. The mean time between each SA was 189.6 ± 420.0 days, and the mean time between the first and last SA was 638.9 ± 850.9 days. Of 41 men, 13 (32%) were azoospermic, 9 (22%) intermittently azoospermic, and 19 (46%) were non-azoospermic. Of the non-azoospermic men, most (n=14, 73.7%) had severe oligospermia (<1 million/mL).Of 9 men with intermittent azoospermia, most had an increase in sperm concentration (n=8, 89%), total sperm count (TSC) (n=8, 89%), and total motile sperm count (TMSC) (n=6, 67%) between the first and last SA. Similarly, most non-azoospermic men also had an increase in sperm concentration (n=12, 63%), TSC (n=11, 58%), and TMSC (n=11, 58%). In comparing semen parameters, men with intermittent azoospermia had an increase in sperm concentration (p=0.0078) and TSC (p=0.0078) between the first and last SA, but no change in TMSC. There was no difference in concentration, TSC, or TMSC over time for non-azoospermic men.While non-azoospermic men were older (mean: 37.0 +/- 5.6 years; p=0.004) versus intermittently azoospermic (mean: 33.4 +/- 3.3 years) or azoospermic men (mean: 30.3 +/- 5.6 years), there were no differences in baseline testosterone (p=0.24), baseline FSH (p=0.31), or testis size (p=0.17 right, p=0.50 left). CONCLUSIONS: In this study, there was no significant decline in sperm concentration, TSC, or TMSC over time for men with complete AZFc deletions; rather, sperm number tended to increase over time. These data suggest that men with AZFc deletions are not at substantive risk of decline in sperm production and do not need to take aggressive early measures for fertility preservation. Source of Funding: Authors JM and JG are supported in part by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e393 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jessica Marinaro More articles by this author Jonathan Gal More articles by this author Anna Mielnik More articles by this author Peter Schlegel More articles by this author Expand All Advertisement PDF downloadLoading ...

MP30-11 DISTRIBUTION OF FOLLICLE STIMULATING HORMONE (FSH) LEVELS AMONG FERTILE AND SUBFERTILE NON-AZOOSPERMIC MEN

You have accessJournal of UrologyCME1 Apr 2023MP30-11 DISTRIBUTION OF FOLLICLE STIMULATING HORMONE (FSH) LEVELS AMONG FERTILE AND SUBFERTILE NON-AZOOSPERMIC MEN Solomon Hayon, Sai Kaushik S.R. Kumar, Xinlei Mi, Anthony Kang, Jasmine Lin, Daniel Greenberg, Robert Brannigan, and Joshua Halpern Solomon HayonSolomon Hayon More articles by this author , Sai Kaushik S.R. KumarSai Kaushik S.R. Kumar More articles by this author , Xinlei MiXinlei Mi More articles by this author , Anthony KangAnthony Kang More articles by this author , Jasmine LinJasmine Lin More articles by this author , Daniel GreenbergDaniel Greenberg More articles by this author , Robert BranniganRobert Brannigan More articles by this author , and Joshua HalpernJoshua Halpern More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003258.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While the clinical utility of FSH is well-established in the diagnosis and management of azoospermic men, the utility of FSH in non-azoospermic men is unclear. First, we characterized the distribution of FSH in fertile and subfertile non-azoospermic men. Second, we sought to determine an optimal FSH threshold that would distinguish between these groups. METHODS: We performed a retrospective analysis of men presenting for fertility evaluation between 2002 and 2020. Men with at least two semen analyses (SA) over a one-month period and one FSH level within 6 months of their index SA were included. Men with semen volume < 1.0cc, azoospermia, or men on hormonal medications were excluded. Men with at least one SA with total motile sperm count (TMSC) ≥ 20 million were classified as fertile, while men who had <20 million TMSC on both SAs were classified as subfertile. FSH was evaluated as an independent variable to determine a threshold that would predict fertility status. A multivariable logistic regression using dichotomized FSH with a broad range of FSH thresholds and other clinical variables was used to predict fertility status. We determined the area under the curve (AUC) for each FSH threshold via 5-fold cross-validation, repeated 1000 times. The optimal FSH threshold was selected according to the mean AUC. RESULTS: Among 1876 men, 1115 (59.4%) were fertile and 275 (14.7%) were subfertile. Age, varicocele, and testosterone were similar between groups. Median FSH was 4.00 vs 5.96 (p<0.001) among fertile vs subfertile men. AUC analysis was performed for FSH thresholds corresponding to the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentile FSH level for each cohort. While the FSH threshold of 5.6 had the highest AUC for prediction of fertility status (0.663), multiple additional thresholds ranging from 4.0 to 9.4 had very similar AUCs. Positive predictive value of FSH increased with higher FSH thresholds. CONCLUSIONS: This is the first large-scale study to characterize FSH values in non-azoospermic men. While there are significant differences in FSH among fertile and subfertile non-azoospermic men, no single FSH cutoff had high accuracy for prediction of fertility status. These findings suggest that the utility of FSH in non-azoospermic men may be greatest in identifying men with extreme FSH values, which may guide further clinical management. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e394 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Solomon Hayon More articles by this author Sai Kaushik S.R. Kumar More articles by this author Xinlei Mi More articles by this author Anthony Kang More articles by this author Jasmine Lin More articles by this author Daniel Greenberg More articles by this author Robert Brannigan More articles by this author Joshua Halpern More articles by this author Expand All Advertisement PDF downloadLoading ...

Sperm Retrieval in Non-azoospermic Patients with Persistent Ejaculation Dysfunction.

Infertility is a common disease that affects 15 to 20% of couples at some point in their lives. Among infertile couples, male factor accounts for 50% of infertile cases. Assisted reproductive techniques are the gold standard approach in case of failure in medical or surgical treatments. Moreover, the role of the urologist in these approaches is to provide appropriate sperm on the day of oocyte pick-up. However, sperm retrieval procedure is quite different in azoospermic and non-azoospermic men. Although most cases of infertile patients are not azoospermic, their ejaculation disorder prevents obtaining sperm for assisted reproductive techniques. This review article explains common problems of sperm retrieval in non-azoospermic patients with persistent ejaculatory dysfunction and introduces some management strategies. In fact, it is possible to design a classic approach for managing such patients, which definitely reduces the problems faced by clinicians as well.

PD36-02 HISTOLOGICAL EVIDENCE OF SPERMATOGENIC FAILURE IN MEN WITH HIGH SPERM DNA FRAGMENTATION INDEX

You have accessJournal of UrologyCME1 May 2022PD36-02 HISTOLOGICAL EVIDENCE OF SPERMATOGENIC FAILURE IN MEN WITH HIGH SPERM DNA FRAGMENTATION INDEX Taras Shatylko, Inessa Telezhnikova, Safar Gamidov, Alikhan Tambiev, Alina Popova, and Vlada Kometova Taras ShatylkoTaras Shatylko More articles by this author , Inessa TelezhnikovaInessa Telezhnikova More articles by this author , Safar GamidovSafar Gamidov More articles by this author , Alikhan TambievAlikhan Tambiev More articles by this author , Alina PopovaAlina Popova More articles by this author , and Vlada KometovaVlada Kometova More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002594.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recurrent pregnancy loss and IVF failures may be attributed, among other factors, to sperm DNA fragmentation (SDF). Many conditions and lifestyle factors potentially cause sperm DNA damage, but it is currently unknown where exactly this damage occurs – in testis, epididymis or other portion of seminal tract. Various studies have demonstrated lower SDF index in testicular sperm when compared to ejaculated sperm. Intracytoplasmic testicular sperm injection (Testi-ICSI) is a controversial technique using surgically retrieved sperm from non-azoospermic men to improve IVF outcomes. We sought to evaluate histopathology of seminiferous tubules obtained during sperm retrieval for Testi-ICSI. METHODS: This is an ongoing prospective study. The inclusion criteria are: recurrent pregnancy loss or at least 2 IVF failures, elevated DNA fragmentation index (TUNEL >15%). The exclusion criteria are: known female factor causing pregnancy loss or IVF failures, abnormal karyotype, oligozoospermia (concentration <15 × 106; total sperm count <39 × 106), treatable causes of increased SDF index, history of hormone therapy. Eighteen patients underwent testicular sperm extraction (TESE) for Testi-ICSI. A portion of extracted tissue was sent to pathology. Specimens taken from 5 patients undergoing TESE for obstructive azoospermia (duration of obstruction less than 5 years) were used as controls. Bergmann-Kliesch score (BKS) was used to assess seminiferous tubules histology. Fisher’s exact test and Mann-Whitney test were used as a part of statistical analysis. RESULTS: Median DNA fragmentation index for ejaculated sperm was 26% (interquartile range [IQR]: 23-30). Median percentage of seminiferous tubules containing elongated spermatids was 74% (IQR: 61-89), while in control specimens it was 92% (IQR: 90-95), which was a statistically significant difference (p=0.0251). Median BKS in Testi-ICSI specimens was 7 (IQR: 6-9), which was significantly lower than in control specimens (median: 9; IQR: 9-10; p=0.0271). Hypospermatogenesis was a dominant histological pattern in 10 of 18 Testi-ICSI specimens (55.5%), while all control specimens had features of normal spermatogenesis (p=0.0457). CONCLUSIONS: High prevalence of hypospermatogenesis in non-oligozoospermic patients was an unexpected finding. In theory, Testi-ICSI should work better in cases of post-testicular sperm DNA damage. However, we have found histological evidence of spermatogenic failure in some patients, which hints at probable testicular origin of SDF, which is yet to be correlated with Testi-ICSI outcomes. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e633 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taras Shatylko More articles by this author Inessa Telezhnikova More articles by this author Safar Gamidov More articles by this author Alikhan Tambiev More articles by this author Alina Popova More articles by this author Vlada Kometova More articles by this author Expand All Advertisement PDF DownloadLoading ...

Changes in Semen Analysis over Time: A Temporal Trend Analysis of 20 Years of Subfertile Non-Azoospermic Men.

To examine trends of population-level semen quality over a 20-year period. We performed a retrospective review of data from the andrology lab of a high volume tertiary hospital. All men with semen samples between 2000 and 2019 were included and men with azoospermia were excluded. Semen parameters were reported using the World Health Organization (WHO) 4th edition. The primary outcome of interest was changes in semen parameters over time. Generalized least squares (GLS) with restricted cubic splines were used to estimate average-monthly measurements, adjusting for age and abstinence period. Contrasts of the estimated averages based on GLS between the first and last months of collection were calculated. A total of 8,990 semen samples from subfertile non-azoospermic men were included in our study. Semen volume decreased over time and estimate average at the beginning and end were statistically different (p<0.001). Similarly sperm morphology decreased over time, with a statistically significant difference between estimated averages from start to finish (p<0.001). Semen pH appeared to be increasing over time, but this difference was not significant over time (p=0.060). Sperm concentration and count displayed an increase around 2003 to 2005, but otherwise remained fairly constant over time (p=0.100 and p=0.054, respectively). Sperm motility appeared to decrease over time (p<0.001). In a large sample of patients presenting to a single institution for fertility assessment, some aspects of semen quality declined across more than two decades. An understanding of the etiologies and driving forces of changing semen parameters over time is warranted.

Testicular Sperm Aspiration (TESA) or Microdissection Testicular Sperm Extraction (Micro–tese): Which Approach is better in Men with Cryptozoospermia and Severe Oligozoospermia?

ObjectivesTo evaluate and compare sperm retrieval outcomes by testicular sperm aspiration (TESA) and micro–dissection testicular sperm extraction (micro-TESE) in non-azoospermic men. MethodsWe conducted a retrospective study of 145 consecutive testicular sperm retrievals in men with cryptozoospermia (n = 56) or severe oligozoospermia (n = 84). The decision to perform a TESA or a micro-TESE was made after thorough discussion of the pros and cons of these procedures with the couple. Final assessment of sperm recovery, on the day of ICSI, was reported either as successful (available sperm for ICSI) or unsuccessful (no sperm for ICSI). ResultsMean sperm concentration, sperm motility, testicular volume and serum FSH level of men undergoing TESA were not significantly different from those of men undergoing micro-TESE. In men with severe oligozoospermia (<5 million/ml), sperm recovery was successful in 95% (18/19) of those who underwent micro-TESE and in 92% (60/65) of those who underwent TESA (P > 0.05). In men with cryptozoospermia, sperm recovery was successful in 88% (42/48) of men who underwent micro-TESE and 25% (2/8) of men who underwent TESA (P < .001). ConclusionsThese data indicate that in men with severe oligozoospermia, TESA and micro-TESE are equally successful sperm retrieval techniques. However, in men with cryptozoospermia, sperm retrieval rates are significantly higher with micro-TESE than TESA.

European Association of Urology Guidelines Panel on Male Sexual and Reproductive Health: A Clinical Consultation Guide on the Indications for Performing Sperm DNA Fragmentation Testing in Men with Infertility and Testicular Sperm Extraction in Nonazoospermic Men

Accumulating evidence has highlighted the contribution of oxidative stress and sperm DNA fragmentation (SDF) in the pathophysiology of male infertility. SDF has emerged as a novel biomarker of risk stratification for patients undergoing assisted reproductive technologies. Studies have also supported the use of testicular over ejaculated sperm at the time of intracytoplasmic sperm injection, as testicular sperm may have lower SDF than ejaculated samples. The European Association of Urology Working Panel on Male Sexual and Reproductive Health provides an evidence-based consultation guide on the indications for SDF testing in male infertility and also for testicular sperm extraction (TESE) in nonazoospermic men. We present the limitations and advantages of SDF testing and a framework to ensure that it is appropriately utilised in clinical practice. Furthermore, we critically appraise the current literature advocating the use of TESE in nonazoospermic men. Patient summaryThis article reviews the evidence supporting the use of sperm DNA fragmentation testing in the assessment of male infertility and testicular sperm extraction in nonazoospermic men.

Should Scrotal Color Doppler Ultrasound Be Routinely Indicated in Fertility Evaluation of Non-Azoospermic Men?

Objective: Scrotal ultrasound is not a routine investigation in the clinical approach to male infertility analysis. This study aims to identify the role of testicular Doppler ultrasound in male infertility assessment and its relation to semen parameters in non-azoospermic men. Methods: Cross-sectional descriptive analysis of 558 men from infertile couples were examined at the Hue Center for Reproductive Endocrinology and Infertility, Hue University Hospital from June 2016 to May 2018. Some cohort characteristics, semen analysis and testicular Doppler ultrasound were analyzed. Men with acute systemic diseases, acute urinary tract infection, hepatic dysfunction, malignant diseases, retrograde ejaculation, cryptorchidism or azoospermia were excluded. Results: The mean volumes of the right and left testicles were 8.87 and 8.77 ml, respectively. The total volume of the 2 sides was 17.63 ± 4.34 ml (95% confidence interval 17.27-18.00 ml). The mean right resistive index (RI) was 0.61 ± 0.23, and the mean left RI was 0.59 ± 0.01. The rate of normal semen quality was 23.2% in group with varicocele and 30.6% in group with non-varicocele. The ultrasound results from the normal semen group were much different from those of the abnormal semen group regarding testicular volume: mean right testis volume: 9.67 ± 1.88 vs. 8.75 ± 2.34 ml, p = 0.0096; mean left testis volume: 9.54 ± 1.78 vs. 8.51 ± 2.44 ml, p = 0.0047; mean total volume of 2 sides: 19.21 ± 3.60 vs. 17.26 ± 4.59 ml, p = 0.005 (varicocele group); mean right testis volume: 9.21 ± 2.21 vs. 8.63 ± 2.21 ml, p = 0.029 (non-varicocele group). The other indexes of color Doppler ultrasound (peak systolic velocity, end diastolic velocity, RI) were not found to correlate with semen quality. Conclusions: Testicular volume which has a close relation to the semen parameters could be used as a clinical prediction factor for the quality of semen.

Sperm retrieval and intracytoplasmic sperm injection outcomes with testicular sperm aspiration in men with severe oligozoospermia and cryptozoospermia.

Several studies addressed the role of testicular sperm aspiration with intracytoplasmic sperm injection (ICSI) in azoospermic men, but few have included non-azoospermic men. The aim of this study was to evaluate testicular sperm aspiration (TESA) sperm retrieval rates and ICSI outcomes in men with severe oligozoospermia. Data were collected retrospectively from 88 consecutive, non-azoospermic, infertile men with idiopathic severe oligozoospermia who underwent TESA between January 2011 and January 2018. Patients were categorized into four groups according to sperm concentration: <5 and >1 million/ml (group 1), <1 and > 0.1 million/ml (group 2), <0.1 million/ml (group 3), and cryptozoospermia (group 4). Mean male age was 37±7 years and the mean female age was 33±4 years. Sperm was recovered successfully in 90% (79/88) of the men overall and in 100% (30/30) of the men in group 1, 97% (29/30) of the men in group 2, 88% (15/17) of the men in group 3, and 45% (5/11) of the men in group 4. Most (65%, 57/88) of the couples had an embryo transfer (ET). The overall clinical pregnancy rate per ET was 46% (26/57). The clinical pregnancy rates (per ET) were 43% (9/21) in group 1, 65% (13/20) in group 2, 36% (4/11) in group 3, and 0% (0/5) in group 4. Our data indicate TESA allows for high sperm retrieval rates and acceptable ICSI pregnancy rates in men with severe oligozoospermia. However, in our experience, TESA sperm retrieval rates and ICSI outcomes are poor in cryptozoospermic men.

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

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. To assess whether in infertile couples the male partners with congenital unilateral absence of vas deferens are mainly azoospermic men. 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. 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. 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.

Extended indications for sperm retrieval: summary of current literature.

Sperm retrieval combined with intracytoplasmic sperm injection (ICSI) is the treatment of choice for couples with untreatable azoospermia-related infertility. However, an increasing body of evidence has been mounting, suggesting that ICSI with testicular sperm instead of ejaculated sperm (when both are available) increases pregnancy outcomes in some specific scenarios. This has led to the exploration of extended indications for sperm retrieval. This review summarizes the current literature concerning sperm retrieval and ICSI for non-azoospermic men with elevated sperm DNA fragmentation, oligozoospermia, and cryptozoospermia.

Testicular sperm for intracytoplasmic sperm injection in non-azoospermic men: a paradigm shift.

In recent years, growing evidence has challenged the notion that sperm quantity and quality are not essential for the success of assisted reproductive technology. DNA fragmentation assessments on ejaculated and testicular sperm harvested from non-azoospermic infertile men have reported a remarkable decrease in DNA damage in spermatozoa directly retrieved from the seminiferous tubules. Moreover, emerging evidence using molecular genetic techniques indicates that aneuploidy rates are lower in testicular sperm than in ejaculated counterparts. The use of testicular sperm from non-azoospermic men with high sperm DNA fragmentation in semen has translated into a higher pregnancy rate and reduced risk of miscarriage. In light of these observations, the time have come for a paradigm shift concerning the use of ejaculated sperm as the preferable source of sperm for intracytoplasmic sperm injection (ICSI). Despite the need for further confirmatory research, the current evidence corroborates the safe utilization of testicular spermatozoa for ICSI in non-azoospermic men with high sperm DNA fragmentation in semen with a positive impact on chances of pregnancy.

Revisiting aneuploidy profile of surgically retrieved spermatozoa by whole exome sequencing molecular karyotype.

Previous studies, including our own, have reported that spermatozoa isolated from the testis have remarkably higher occurrence of aneuploidy once isolated from azoospermic men. This notion, however, did not translate into a lower pregnancy rate nor a greater proportion of miscarriages. Indeed, ICSI offspring generated from surgically retrieved gametes did not suffer from increased karyotypic aneuploidy than children generated from ejaculated specimens. In recent years, aneuploidy assessments on a larger number of cells and utilizing more chromosome probes have reported a progressive decrease in chromosomal aberrations in spermatozoa directly retrieved from the seminiferous tubules. In light of the availability of more accurate molecular genetic techniques, we have decided to challenge the notion that sampling epididymal and testicular tissues yields spermatozoa with higher incidence of aneuploidy than those retrieved in the ejaculate. In a retrospective manner, we have carried out an analysis by FISH with 9 chromosome probes on at least 1000 cells from the ejaculates of 87 consenting men and the specimens of 6 azoospermic men, while spermatozoa of fertile donors were used as control. Aneuploidy by FISH yielded 0.9% for the donor control but rose in the study group to 3.6% in the ejaculated, 1.2% for the epididymal, and 1.1% for testicular spermatozoa. There were no differences in autosomal or gonosomal disomies, nor nullisomies. In this group, once the specimens of these men were used for ICSI, ejaculated spermatozoa yielded a 22% clinical pregnancy rate that resulted in 62.5% pregnancy loss. The surgically retrieved specimens yielded a 50% clinical pregnancy rate that progressed to term. To confirm our findings, in a prospective analysis, DNA sequencing was carried out on the ejaculates and surgical samples of 22 men with various spermatogenic characteristics. In this comparison, the findings were similar with actually a higher incidence of aneuploidy in the ejaculated spermatozoa (n = 16) compared to those surgically retrieved (n = 6) (P<0.0001). For this group, the clinical pregnancy rate for the ejaculated specimens was 47.2% with 29.4% pregnancy loss, while the surgically retrieved yielded a 50% clinical pregnancy rate, all progressing to term. A subsequent prospective combined assessment on ejaculated and surgically retrieved spermatozoa by FISH and NGS was performed on non-azoospermic men with high DNA fragmentation in their ejaculate. The assessment by FISH evidenced 2.8% chromosomal defects in the ejaculated and 1.2% in testicular biopsies while by NGS became 8.4% and 1.3% (P = 0.02), respectively. Interestingly, we evidenced a pregnancy rate of 0% with ejaculated while 100% with the testicular spermatozoa in this latter group. This indicates that improved techniques for assessing sperm aneuploidy on a wider number of cells disproves earlier reports and corroborates the safe utilization of testicular spermatozoa with a positive impact on chances of pregnancy.

Unmet needs in male reproductive health care.

Women came first when medicine turned its head towards fertility. Perhaps this was simply because babies appeared from women, and so it was sensible to assume that the woman was at fault if a couple could not conceive. Perhaps it was that in the male-dominated doctoring days at the genesis of reproductive health care, men found it difficult to imagine that they themselves could be the problem in making babies. But whatever the reason, in the current era while epidemiology and physiology point to a very credible ‘about half male and about half female’ approach when assigning reasons for inability to conceive, care for the man lags far behind in the number of practitioners available, the understanding of the science involved and the therapeutic instruments available. So what can move the field of male reproductive medicine forward? The first is in the diagnosis. Historically, sperm in the ejaculate was an obvious place to start when discerning problems with male fertility. Azoospermia, the lack of sperm in the ejaculate, is plainly a reason for male infertility. Sadly, it's also the only pattern of information derived from microscopic observation of the male gamete that clearly prognosticates male reproductive potential. From the beginnings of analysing semen, the substantial overlap between bulk seminal parameters in fertile and infertile populations has been recognised (MacLeod. Fertil Steril 1950;1(4):347–61). We need better ways to prognosticate, which likely includes genomics, epigenetics, proteomics and metabolomics of both the man and his sperm. Likewise, as reproduction is less concerned with the average sperm and more about the exceptional one, we require better ways of characterising the ultimately successful swimmer, and as assisted reproductive technology seeks the best sperm, we need non-destructive means of identifying the single best sperm to choose for in vitro fertilisation. But the diagnosis is always a prequel to treatment. One of the clearest advances in male reproductive medicine in the past half-century was the development of a surgical technique of testicular sperm extraction to identify sperm in men with azoospermia due to spermatogenic dysfunction, thus allowing biological fatherhood in the most severely afflicted infertile men (Schlegel. Hum Reprod 1999;14(1):131–5.) But this technique had an extraordinary consequence, which was to provide a binary outcome – sperm retrieved or not. And this binary outcome could be tested against therapeutic endocrine protocols, which previously had only the terribly inaccurate and variable semen analysis as a possible endpoint. Suddenly, endocrine stimulation protocols for the man could be studied and demonstrated effective (Hussein et al. BJU Int 2013;111:E110–4). And these medical interventions may also be effective in non-azoospermic men, especially when diagnoses are improved and more directed at the individual infertile man. Of course, all of these opportunities are only realised if the studies demonstrating their utility and efficacy are rigorously performed and as incontrovertible as possible. We must insist on clear outcomes for the male gamete, especially in the context of how it functions in embryogenesis and the later stages of development. But the opportunities are nonetheless promising and alluring. CN reports personal fees from Ferring Investigator, Educator Scientific Study, CME Activity Support, personal fees from Merck Educator CME Activity Support, personal fees from NexHand Co-Founder Medical Device Company, during the conduct of the study; and ASRM Journal Editor Medical Communications AUA Journal Section Editor Medical Communications Co-Editor in Chief, Fertility and Sterility. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Methods of surgical sperm extraction and implications for assisted reproductive technology success.

Intracytoplasmic sperm injection offers a chance to surpass severe forms of male factor infertility, including azoospermia. Retrieval of the male gamete from the epididymis or testis provides the chance for biological parenthood for the affected men. In this review, we scrutinize the recent evidence about the surgical sperm retrieval methods for use in association with ICSI. We provide a historical overview of the surgical sperm retrieval methods development, its indication in both azoospermic and non-azoospermic men, and the technical aspects of each method. We also present and critically discuss the evidence concerning the success of ICSI using non-ejaculated sperm and the consequences of this approach to the health of resulting offspring.

Frequency of Chromosomal Abnormalities in Subpopulations of Infertile Males among Chinese Hakka Population

The frequency of chromosomal abnormalities is supposed to be elevated in infertile males as well as shown negative correlation of sperm concentration. Cytogenetic analysis, recommended by guidelines in infertile men, is expensive. Hence, it may be good for recognize riskiest men with chromosomal abnormalities, potentially by analyzing sperm concentration outside of the parameters. Aim to evaluate the frequency of chromosomal abnormalities in different subpopulations among Hakka population, we assessed several clinical parameters in infertile men. A total of 1291 azoospermic men and men apply for in-vitro fertilization (IVF) treatment, were analyzed for semen parameters, hormone levels, Y chromosome microdeletions and medical history, related to chromosomal abnormalities. Chromosomal abnormalities were detected 46 of 1291 men (3.6%) in our study. Correlation was no shown between chromosomal abnormalities and sperm parameters except for sperm volume (OR 0.76, P=0.029). Significantly, azoospermia was related to an increased frequency of chromosomal abnormalities (OR 32.24, P<0.001). Elevated gonadotropic hormone levels, meaningfully, was related to the risk of carrying a chromosome abnormality (OR 4.38, P<0.001). Lower rate of chromosomal abnormalities was observed in infertile males with positive andrologic history (OR 0.21, P=0.003). Previous miscarriages, related to an increased frequency of chromosomal abnormalities, were discovered in non-azoospermic men (OR 4.78, P=0.003). The results indicated that azoospermic men with hypergonadotrophic as well as an eventless andrologic history have frequently risk of chromosomal abnormalities.

Altered PIWI-LIKE 1 and PIWI-LIKE 2 mRNA expression in ejaculated spermatozoa of men with impaired sperm characteristics.

In about half the cases of involuntary childlessness, a male infertility factor is involved. The PIWI-LIKE genes, a subclade of the Argonaute protein family, are involved in RNA silencing and transposon control in the germline. Knockout of murine Piwi-like 1 and 2 homologs results in complete infertility in males. The aim of this study was to analyze whether the mRNA expression of human PIWI-LIKE 1–4 genes is altered in ejaculated spermatozoa of men with impaired sperm characteristics. Ninety male participants were included in the study, among which 47 were with normozoospermia, 36 with impaired semen characteristics according to the World Health Organization (WHO) manual, 5th edition, and 7 with azoospermia serving as negative control for the PIWI-LIKE 1–4 mRNA expression in somatic cells in the ejaculate. PIWI-LIKE 1–4 mRNA expression in the ejaculated spermatozoa of the participants was measured by quantitative real-time PCR. In nonazoospermic men, PIWI-LIKE 1–4 mRNA was measurable in ejaculated spermatozoa in different proportions. PIWI-LIKE 1 (100.0%) and PIWI-LIKE 2 (49.4%) were more frequently expressed than PIWI-LIKE 3 (9.6%) and PIWI-LIKE 4 (15.7%). Furthermore, a decreased PIWI-LIKE 2 mRNA expression showed a significant correlation with a decreased sperm count (P = 0.022) and an increased PIWI-LIKE 1 mRNA expression with a decreased progressive motility (P = 0.048). PIWI-LIKE 1 and PIWI-LIKE 2 mRNA expression exhibited a significant association with impaired sperm characteristics and may be a useful candidate for the evaluation of the impact of PIWI-LIKE 1–4 mRNA expression on male infertility.

Revisiting aneuploidy characteristics of surgically retrieved spermatozoa by dna sequencing (NGS)

To challenge the notion that sampling epididymal and testicular tissues yields spermatozoa with higher incidence of aneuploidy than those retrieved in the ejaculate. Nine chromosome FISH was carried out on 2 donor controls, the ejaculates of 67 men, and surgical specimens of 6 azoospermic men. DNA sequencing technology was carried out on the ejaculates and surgical samples of 20 men. A combined assessment was performed on non-azoospermic men with high DNA fragmentation in their ejaculate. ICSI pregnancy outcome was also analyzed and compared. Consenting men treated for infertility provided their specimens. FISH was performed on at least 1000 spermatozoa with a threshold of >1.6% with 2-3% FISH error. DNA was extracted and amplified from a comparable number of spermatozoa by PCR-based random hexamer amplification (average DNA concentration 610±102ng/ul and quality of 1.7±0.1nm). By NGS, duplications and deletions by Copy Number Variants (CNVs) were then calculated for all chromosomes by CASAVA and VarScan2 software programs. A total of 67 couples were included in our study (maternal age 35.8±4yrs and paternal age 39.4±8yrs). Aneuploidy by FISH yielded 0.9% for the donor control but rose in the study group to 3.6% in the ejaculated, 1.2% for the epididymal, and 1.1% for testicular spermatozoa. There were no differences in autosomal or gonosomal disomies, nor nullisomies. In this group, the ejaculated spermatozoa yielded 22% clinical pregnancy rate and 50% with the surgically retrieved specimens. NGS yielded 1.2% for the control while in the study was 11.1% for the ejaculated specimen and decreased to 1.8% in the epididymal and 1.5% for the testicular (P<0.0001). The pregnancy rate for the ejaculated specimen was 47.2% and 50% for the surgically retrieved. Simultaneous aneuploidy assessment on the ejaculated and testicular samples in the same individual evidenced a sperm chromatin fragmentation (SCF) of 20% in the ejaculate while on the testicular spermatozoa was only 8%. The pregnancy rate was 0% with ejaculated while 100% with the testicular spermatozoa. Aneuploidy assessment by FISH evidenced 2.8% in the ejaculated and 1.2% in testicular biopsy while with NGS became 8.4% and 1.3% in testicular biopsy (P=0.02), respectively. This study challenges the dogma that testicular spermatozoa conceal a higher proportion of aneuploidy. This implies that testicular gametes do not contribute to chromosomally related pregnancy losses. Moreover, this may explain why offspring from testicular biopsy do not evidence higher autosomal or gonosomal aneuploidy than those resulting from ejaculated spermatozoa.