Role of Genetic Testing in Male Infertility

Male-factor infertility is responsible for 30-55% of all infertility cases. The causes of male infertility include varicocele, endocrine disorders, genital tract infections, genetic disorders and idiopathic. It is estimated that genetic abnormalities contribute to 50% of male infertility. In daily practice, the diagnosis of male infertility has been based on history taking, relevant physical examination, hormone tests and basic semen analysis with a strong emphasis on the assessment of sperm concentration, motility, and morphology. Although recent development in assisted-reproductive technologies such as in vitro fertilization and intrauterine insemination increases the chance of clinical pregnancy and live birth, genetic counseling and testing should always beperformed whenever genetic risks are related to the cause of infertility for the identification of possible genetic abnormalities and to assess the risk of transmitting the genetic defects to future generations. Genetic defects affect male infertility by disrupting hormonal homeostasis, spermatogenesis, and sperm quality. These genetic defects include chromosomal abnormalities (e.g. Klinefelter Syndrome), Y chromosome deletions, and cystic fibrosis transmembrane conductance regulator gene mutations. The utilization of genetic counseling and testing is also important to predict the success of sperm retrieval in men with certain genetic abnormalities. Toname a few, genetic analysis at the chromosomal level (karyotyping), androgen receptor gene mutations test, cystic fibrosis test, and Y chromosome microdeletions analysis should be considered in the diagnosis of male factor infertility where genetic risks are present

Efficacy Quotient of ESWL Piezolith Richard Wolf 3000 Machine in Patientswith Ureteral Stones in Dr. Cipto MangunkusumoNational Hospital 2008 - 2011

Extracorporeal shockwave lithotripsy (ESWL) is the most common method of ureteral stone management. Since 2008, RSCM has ben using ESWL piezolith 3000 richard wolf and efficacy quotient (EQ) value have not yet studied. The study aims was to determine the efficacy quotient (EQ) of ESWL using piezolith richard wolf 3000 machine for ureteral stone by analyzing free-stone rate with location of stones, number of stones, stone burden, stone opacity, obstruction and kidney function. This cross sectional study was carried out in January 2008-December 2011, with multivariate analytical study. Ninety five percent (n=113) of 119 patients were declared stone free after the first ESWL. EQ value was 0.89. Stone size was the correlated with stone free rate (p<0.05). It is concluded that ESWL procedure using richard wolf piezolith 3000 machine patients had better EQ and better stone-free rate than previous reports using similar machines

Association Between Sertoli Cell-Only Syndrome, Varicocele and FSH Level in Azoospermic Patients

A varicocele is the most frequent causes of infertility because it causes damage to the testes that could increase the levels of FSH. The objectives of this study were to determine the relationship of varicocele history and the condition of Sertoli cell-only syndrome (SCOS) based on Johnson criteria from testicular biopsy and the relationship of SCOS with FSH levels or testicular volume in azoospermic patients. This cross-sectional study (110 samples) used data from testicular biopsy of azoospermic patients at the Biology Department FKUI and the medical records of Urology Department FKUI-RSCM in 2011-2015. Johnson’s criteria for most patients were 5 with a mean criteria of 4.42 (±1.997). The Johnson criteria of 2 in the biopsy results or SCOS is 21 (19.1%). In patients with a history of varicocele, there were only 10 (27.8%) patients with SCOS (p=0.378). There was no association between SCOS and the history of varicocele. Patients without SCOS have mean FSH levels of 14.1± 8.6IU/L and patients with SCOS have mean FSH of 21.3±7.5IU/L. There was significant difference mean of FSH level (paired t test, p<0,05), which is 7,247 in SCOS group and non-SCOS. There were 36 testes with the Johnson criteria of 2 and 157 testes having values above 2. The SCOS and non-SCOS group testicular volumes were significantly different (Mann-Whitney test, p=0.018). Varicocele could not be used as an indicator of SCOS, however high levels of FSH may indicate SCOS in azoospermic patients

Association of FSH Level with Spermatogenic Histology Based on Johnson Criteria in Azoospermic Patients

The aims of this study is to know the association FSH level with spermatogenic histology on testical biopsy and to evaluate the use of FSH level as predictor of the succes of testical biopsy on azoospermic patient using Johnson criteria.  This is a cross-sectional study, comparing two groups, i.e. spermatogenic histology pattern using Johnson criteria and FSH level (IU/L). Age, FSH level, spermatogenic histology pattern are collected from medical record. Population of this study were azoospermic patients in the Deparment of Urology Cipto Mangunkusumo hospital and Morula Clinic Bunda Hospital between 2011 – 2015. Descriptive study was calculate, followed by one way ANOVA comparative test with post-hoc test Duncan and ROC curve analysis to determined the AUC and cut-off value. The age of the patients were 21-51 years old and the most frequent were 31-40 years old (67%). The most frequent histology pattern and Johnson criteraia were maturation arrest (41%) and 5 (27.8%) respectively.  Mean level of FSH was 15.83 IU/L with minimum level was 2.35 IU/L and maximaum 41.3 IU/L. There was association between FSH level and spermatogensis histology pattern using Johnsosn criteria, however the validity to predict the outcome of sperm in biopsy in azoospermic patients using FSH level was still low

Antisperm Antibody Testing: A Comprehensive Review of Its Role in the Management of Immunological Male Infertility and Results of a Global Survey of Clinical Practices

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility

Post-Vasectomy Semen Analysis: Optimizing Laboratory Procedures and Test Interpretation through a Clinical Audit and Global Survey of Practices

Purpose: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. Materials and methods: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. Results: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. Conclusions: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy

Controversy and consensus on indications for sperm DNA fragmentation testing in male infertility: a global survey, current guidelines, and expert recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians

Controversy and consensus on the management of elevated sperm DNA fragmentation in male infertility: a global survey, current guidelines, and expert recommendations

PURPOSE: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. MATERIALS AND METHODS: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. RESULTS: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. CONCLUSIONS: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians

Technical aspects and clinical limitations of sperm DNA fragmentation testing in male infertility: a global survey, current guidelines, and expert recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial