Combination clomiphene citrate and anastrozole duotherapy improves semen parameters in a multi-institutional, retrospective cohort of infertile men.

In men with impaired semen parameters, empiric medical therapies such as clomiphene citrate, a selective estrogen receptor modulator (SERM), and anastrozole, a selective aromatase inhibitor, are often employed. The effects of jointly administering these agents on semen parameters are not well understood. Here, we describe the findings of our multi-center, retrospective cohort study of men with idiopathic primary or secondary infertility. Twenty-one men were treated with combination therapy (anastrozole and clomiphene) and 69 men were treated with monotherapy (anastrozole). Patients with pre-treatment normozoospermia and recent or current exogenous testosterone therapy were excluded. Baseline and post-treatment semen and sex hormone parameters were compared among groups. The median follow-up duration was 91 days [interquartile range (IQR), 64-117 days]. Following treatment, 43% of men in the combination therapy group demonstrated normozoospermia, compared to 25% in the monotherapy group. Furthermore, men in the combined group demonstrated marked improvements in total motile sperm count (TMSC) [11.3 vs. 2.1 million (M), P=0.03]. There were no significant differences in hormone levels among the two groups following treatment. Combination therapy with clomiphene citrate and anastrozole was associated with modest benefits in post-treatment semen parameters, when compared to anastrozole monotherapy. These benefits may contribute to improvements in pregnancy outcomes with less invasive assisted reproductive technologies, such as intrauterine insemination (IUI). Future investigations with larger sample sizes and prospective study designs are necessary.

The effect of red blood cell disorders on male fertility and reproductive health.

Male infertility is defined as a failure to conceive after 12 months of unprotected intercourse owing to suspected male reproductive factors. Non-malignant red blood cell disorders are systemic conditions that have been associated with male infertility with varying severity and strength of evidence. Hereditary haemoglobinopathies and bone marrow failure syndromes have been associated with hypothalamic-pituitary-gonadal axis dysfunction, hypogonadism, and abnormal sperm parameters. Bone marrow transplantation is a potential cure for these conditions, but exposes patients to potentially gonadotoxic chemotherapy and/or radiation that could further impair fertility. Iron imbalance might also reduce male fertility. Thus, disorders of hereditary iron overload can cause iron deposition in tissues that might result in hypogonadism and impaired spermatogenesis, whereas severe iron deficiency can propagate anaemias that decrease gonadotropin release and sperm counts. Reproductive urologists should be included in the comprehensive care of patients with red blood cell disorders, especially when gonadotoxic treatments are being considered, to ensure fertility concerns are appropriately evaluated and managed.

Robotic-assisted seminal vesiculectomy for treatment of refractory hematospermia.

Hematospermia is a common, but anxiety-provoking genitourinary condition. In instances without spontaneous resolution, pharmacologic intervention with a 5-alpha reductase inhibitor has been shown to be successful. In cases of refractory hematospermia, robotic-assisted laparoscopic seminal vesiculectomy may provide a definitive treatment option. A robotic-assisted bilateral seminal vesiculectomy was performed on a 42-year-old male with refractory painless hematospermia after failing conservative management. Three months post-operatively, the patient reported resolution of hematospermia after six ejaculations with no impact on erectile function. The robotic-assisted approach is safe and feasible with good functional outcomes and reduced morbidity.

Testosterone and luteinizing hormone predict semen parameter improvement in infertile men treated with anastrozole.

OBJECTIVE: To identify patient factors associated with a clinically significant improvement in semen parameters among infertile men treated with the aromatase inhibitor anastrozole. DESIGN: Multi-institutional retrospective cohort study. SETTING: Two Tertiary Academic Medical Centers. PATIENTS: A total of 90 infertile men treated at 2 tertiary academic medical centers who met inclusion criteria and obtained pretreatment and posttreatment semen analyses. INTERVENTION: Prescription of anastrozole (median 3 mg/wk). MAIN OUTCOME MEASURES: Upgrade in the World Health Organization sperm concentration category (WHO-SCC). Univariate logistic regression, multivariable logistic regression, and partitioning analyses were performed to identify statistically significant patient factors capable of predicting treatment response. RESULTS: With anastrozole treatment, 46% (n = 41/90) of men responded favorably with a WHO-SCC upgrade, and 12% (n = 11/90) experienced a downgrade. Responders exhibited lower pretreatment levels of luteinizing hormone (LH, 4.7 vs. 8.3 IU/L) and follicle-stimulating hormone (4.7 vs. 6.7 IU/mL), higher pretreatment levels of testosterone (T, 356 vs. 265 ng/dL), and similar baseline level of estradiol (E2, 73% vs. 70% with detectible level). Baseline semen parameters differed, with anastrozole responders demonstrating higher baseline semen concentration (3.6 vs. 0.3 M/mL) and higher total motile sperm counts (3.7 vs. 0.1 M). Anastrozole therapy converted 29% (n = 26/90) of the cohort to normozoospermia and enabled intrauterine insemination access in 31% (n = 20/64) of previously ineligible patients. Interestingly, neither body mass index nor the baseline E2 level or E2-T ratio was associated with WHO-SCC upgrade. Multivariable logistic regression revealed the T-LH ratio (odds ratio: 1.02, 95% confidence interval: 1.00-1.03) and baseline nonazoospermia (odds ratio: 9.4, 95% confidence interval: 1.1-78.9) to be statistically significant predictors of WHO-SCC upgrade (area under receiver operating characteristic curve: 0.77). The final user-friendly partitioning model consisting of the T-LH ratio ≥100 and baseline non-azoospermia was 98% sensitive and 33% specific for WHO-SCC upgrades (area under the curve: 0.77). CONCLUSION: Anastrozole therapy decreases serum E2 levels, increases serum gonadotropins, and clinically improves semen parameters in half of men with idiopathic infertility. Nonazoospermic infertile men with T-LH ratios ≥100 are likely to benefit from anastrozole treatment irrespective of baseline E2 level or E2-T ratio. Men with azoospermia rarely respond to anastrozole and should be counseled on alternative treatments.

Discordant Bilateral Testicular Pathology Does not Affect Sperm Retrieval Rate in Bilateral Microdissection Testicular Sperm Extraction (mTESE).

OBJECTIVE: To assess the incidence of discordant testicular pathology in men undergoing bilateral microdissection testicular sperm extraction (mTESE) and association with sperm retrieval rate. METHODS: We performed a retrospective single-institutional review of all patients undergoing mTESE from 2007 to 2021 and aggregated clinical history, physical exam, semen analysis, and operative findings. Specimens with discordant pathology were re-reviewed by an experienced genitourinary.ßpathologist and categorized in a standardized fashion. Data were analyzed using SPSS. RESULTS: One hundred fourteen non-obstructive azoospermia.ßmen undergoing 132 mTESEs were identified within the study period. Eighty-five percent (112/132) of cases had pathology specimens available, and within this specific cohort the success rate was 41.9% (47/112). A total of 206 pathological reports resulted including 52.4% Sertoli cell only, 4.9% Leydig cell hyperplasia, 8.7% fibrosis, 16.5% maturation arrest, and 17.5% hypospermatogenesis. Twelve percent of testicles had more than 1 pathologic diagnosis. Sixty-six men had synchronous bilateral testicular pathology, and 11/66 (16.6%) had at least partially discordant pathology on initial review. Focused re-review by a genitourinary pathologist confirmed exclusively discordant pathology in 7/66 (10.6%) cases, with a sperm retrieval rate of 57% (4/7). The sperm retrieval rate.ßin men with discordant pathology was not significantly different from those with concordant pathology. CONCLUSION: Over 1 in 10 men undergoing mTESE may have discordant pathology between testicles, though this may not affect sperm retrieval rate.ßat the time of procedure. Clinicians should consider submitting bilateral testicular specimens for pathology to (1) clarify their outcomes data, and (2) assist with clinical decision-making and surgical planning if a repeat mTESE is indicated.

The Role of Natural Flavonoids as Telomerase Inhibitors in Suppressing Cancer Growth.

Cancer is a complex and multifaceted group of diseases characterized by the uncontrolled growth and spread of abnormal cells. While cancer can be challenging and life-altering, advances in research and development have led to the identification of new promising anti-cancer targets. Telomerase is one such target that is overexpressed in almost all cancer cells and plays a critical role in maintaining telomere length, which is essential for cell proliferation and survival. Inhibiting telomerase activity can lead to telomere shortening and eventual cell death, thus presenting itself as a potential target for cancer therapy. Naturally occurring flavonoids are a class of compounds that have already been shown to possess different biological properties, including the anti-cancer property. They are present in various everyday food sources and richly present in fruits, nuts, soybeans, vegetables, tea, wine, and berries, to name a few. Thus, these flavonoids could inhibit or deactivate telomerase expression in cancer cells by different mechanisms, which include inhibiting the expression of hTERT, mRNA, protein, and nuclear translocation, inhibiting the binding of transcription factors to hTERT promoters, and even telomere shortening. Numerous cell line studies and in vivo experiments have supported this hypothesis, and this development could serve as a vital and innovative therapeutic option for cancer. In this light, we aim to elucidate the role of telomerase as a potential anti-cancer target. Subsequently, we have illustrated that how commonly found natural flavonoids demonstrate their anti-cancer activity via telomerase inactivation in different cancer types, thus proving the potential of these naturally occurring flavonoids as useful therapeutic agents.

Rising vasectomy volume following reversal of federal protections for abortion rights in the United States.

In June 2022 the United States Supreme Court issued a ruling in the case Dobbs v. Jackson that overturned Roe v. Wade, the 1973 ruling establishing a federally protected right to abortion in the United States. Anecdotal reports suggested increased vasectomy volume following this event; however, no published data exist. We sought to describe trends in vasectomy consultation before and after the Dobbs v. Jackson ruling (referred to as pre- and post-Dobbs herein). Following IRB approval, we reviewed charts of all adults seeking vasectomy consultation in July-August 2021 and July-August 2022 at a large healthcare organization. We then aggregated vasectomy procedural billing data from 2018 to present. The primary outcome was volume of vasectomy consultation appointments and the secondary outcome was number of vasectomies performed. In July-August 2021 (Pre-Dobbs), 116 men attended vasectomy consultation versus 142 men in July-August 2022 (Post-Dobbs). Median age Post-Dobbs was significantly younger than Pre-Dobbs (35 vs 38 years, respectively, p = 0.01) with a significant increase in Post-Dobbs men under 30 seeking vasectomy (p = 0.005). A total of 16.9% (24/142) of Post-Dobbs men were childless, compared to 8.6% (10/116) of Pre-Dobbs men (p = 0.05). Of those with children, median number of offspring was unchanged at 2. Billing data showed a significant increase in vasectomy procedural volumes Post-Dobbs. While overturning Roe v Wade directly impacted female reproductive rights, number of vasectomy consultations and procedures increased significantly following this decision. Younger men, especially those under 30, as well as childless men were significantly more likely to seek consultation Post-Dobbs compared to the prior reproductive legal climate. While longer-term data are needed, findings indicate that men are invested in maintaining reproductive autonomy for themselves and their partners.

The Diversity of Vasectomy Reversal Providers and Their Web-based Advertising Habits in the United States.

OBJECTIVE: To better understand the internet advertising material published on clinician websites for the 30,000 men who undergo evaluation for vasectomy reversal (VR), which is a technically demanding procedure requiring microsurgical expertise. METHODS: Internet search trends for "vasectomy" and "vasectomy reversal" from 2004 to 2022 were assessed using Google Trends. Search engines were then queried on a state-by-state basis for physicians performing VR and the available information aggregated and analyzed using standard statistical approaches. RESULTS: VR search volume consistently represented roughly one-tenth of the search volume for vasectomy. One hundred and ninety reversal clinics were identified in 44 of 50 states with the highest number identified in the southeast region and an overall median price of $6500. Ninety percent of physicians were male and completed residencies in urology. Other specialties included obstetrics and gynecology, general surgery, family medicine and orthopedic surgery. Forty-two percent of urologists had completed infertility fellowships. Sixty percent of physicians utilized a microscope, and 4.7% of physicians explicitly stated they did not perform vasoepididymostomy even when indicated. Fifty two percent of clinics reported VR success rates as high as 100%, and 34% of clinics reported pregnancy outcomes. Twenty-five percent of clinics reported out-of-pocket VR pricing and 26% discussed possible complications. CONCLUSION: VR is a technically demanding cash-pay procedure being performed by physicians with a wide array of backgrounds and outcomes. Urologists should strive to lead by example and report their training, personal experiences, and expected outcomes to enable optimal medical decision making for each patient.

Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations.

PURPOSE: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. MATERIALS AND METHODS: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. RESULTS: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. CONCLUSIONS: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Robotic Adrenalectomy: A 10-Year Clinical Experience at a Tertiary Medical Center.

Background and Objective: Laparoscopic adrenalectomy is now the preferred approach for most adrenal tumors. As minimally invasive surgery departments gain familiarity with the robotic platform, the safety profiles and efficacy of robotic adrenalectomy has been an area of continued discussion. The objective of this study is to outline our experience with transitioning to the robotic platform and determining the effectiveness and safety of transperitoneal robotic adrenalectomy. Methods: We performed a single-center, retrospective review of 37 patients who underwent transperitoneal robotic adrenalectomy between August 1, 2010 and August 31, 2020. Outcomes included patient morbidity, hospital length of stay, operative time, estimated blood loss, gland volume, pathology, and postoperative complications. Results: Sixty-five percent of the total robotic adrenalectomies were of the left adrenal gland. The average operating room time was 213 minutes. The average gland volume was 71 cm3, estimated blood loss was 74 mL and length of stay was 1.4 days. There were no significant differences in outcomes between the right and left total robotic adrenalectomies. Approximately one-third of our cohort had an adrenal cortical adenoma, while only one patient had adrenal cortical carcinoma. Four patients experienced postoperative complications that resulted in unplanned hospital readmissions and there was one mortality. Conclusions: Although the standard of care for most adrenal tumors is laparoscopic resection, our 10-year experience has shown that robotic adrenalectomy is highly effective and can be a valuable tool in the community and academic setting.

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.

Sperm Vitality and Necrozoospermia: Diagnosis, Management, and Results of a Global Survey of Clinical Practice.

Sperm vitality testing is a basic semen examination that has been described in the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen from its primary edition, 40 years ago. Several methods can be used to test sperm vitality, such as the eosin-nigrosin (E-N) stain or the hypoosmotic swelling (HOS) test. In the 6th (2021) edition of the WHO Laboratory Manual, sperm vitality assessment is mainly recommended if the total motility is less than 40%. Hence, a motile spermatozoon is considered alive, however, in certain conditions an immotile spermatozoon can also be alive. Therefore, the differentiation between asthenozoospermia (pathological decrease in sperm motility) and necrozoospermia (pathological decrease in sperm vitality) is important in directing further investigation and management of infertile patients. The causes leading to necrozoospermia are diverse and can either be local or general, testicular or extra-testicular. The andrological management of necrozoospermia depends on its etiology. However, there is no standardized treatment available presently and practice varies among clinicians. In this study, we report the results of a global survey to understand current practices regarding the physician order of sperm vitality tests as well as the management practices for necrozoospermia. Laboratory and clinical scenarios are presented to guide the reader in the management of necrozoospermia with the overall objective of establishing a benchmark ranging from the diagnosis of necrozoospermia by sperm vitality testing to its clinical management.

A Comprehensive Guide to Sperm Recovery in Infertile Men with Retrograde Ejaculation.

Retrograde ejaculation (RE) is a condition defined as the backward flow of the semen during ejaculation, and when present can result in male infertility. RE may be partial or complete, resulting in either low seminal volume or complete absence of the ejaculate (dry ejaculate). RE can result from anatomic, neurological or pharmacological conditions. The treatment approaches outlined are determined by the cause. Alkalinizing urinary pH with oral medications or by adding sperm wash media into the bladder prior to ejaculation may preserve the viability of the sperm. This article provides a step-by-step guide to diagnose RE and the optimal techniques to retrieve sperm.

Relevance of Leukocytospermia and Semen Culture and Its True Place in Diagnosing and Treating Male Infertility.

The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×106/mL of semen. Granular leukocytes when activated are capable of generating high levels of reactive oxygen species in semen resulting in oxidative stress. Oxidative stress has been correlated with poor sperm quality, increased level of sperm DNA fragmentation and low fertility potential. The presence of leukocytes and pathogens in the semen may be a sign of infection and/or localized inflammatory response in the male genital tract and the accessory glands. Common uro-pathogens including Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, Mycoplasma hominis, and Escherichia coli can cause epididymitis, epididymo-orchitis, or prostatitis. The relationship between leukocytospermia and infection is unclear. Therefore, we describe the pathogens responsible for male genital tract infections and their association with leukocytospermia. The review also examines the diagnostic tests available to identify seminal leukocytes. The role of leukocytospermia in male infertility and its management is also discussed.

Sperm Morphology Assessment in the Era of Intracytoplasmic Sperm Injection: Reliable Results Require Focus on Standardization, Quality Control, and Training.

Semen analysis is the first, and frequently, the only step in the evaluation of male fertility. Although the laboratory procedures are conducted according to the World Health Organization (WHO) guidelines, semen analysis and especially sperm morphology assessment is very difficult to standardize and obtain reproducible results. This is mainly due to the highly subjective nature of their evaluation. ICSI is the choice of treatment when sperm morphology is severely abnormal (teratozoospermic). Hence, the standardization of laboratory protocols for sperm morphology evaluation represents a fundamental step to ensure reliable, accurate and consistent laboratory results that avoid misdiagnoses and inadequate treatment of the infertile patient. This article aims to promote standardized laboratory procedures for an accurate evaluation of sperm morphology, including the establishment of quality control and quality assurance policies. Additionally, the clinical importance of sperm morphology results in assisted reproductive outcomes is discussed, along with the clinical management of teratozoospermic patients.

Standardized Laboratory Procedures, Quality Control and Quality Assurance Are Key Requirements for Accurate Semen Analysis in the Evaluation of Infertile Male.

Semen analysis is a basic test for evaluating male fertility potential, as it plays an essential role in driving the future management and treatment of infertility in couples. Manual semen analysis includes the evaluation of both macroscopic and microscopic parameters, whereas automated semen analysis is conducted through a computer-aided sperm analysis system and can include additional parameters that are not evaluated by manual analysis. Both quality control (QC) and quality assurance (QA) are important to ensure reproducible results for semen analysis, and represent fundamental checks and balances of all stages (pre-analytical, analytical, and post-analytical) of semen analysis. To ensure accuracy and precision, the laboratory technicians' performance should be evaluated biannually. This narrative review aims to describe standardized laboratory procedures for an accurate assessment of semen parameters that incorporate both QC and QA practices.

Sperm DNA Fragmentation: A Critical Assessment of Clinical Practice Guidelines.

Sperm DNA fragmentation (SDF) is implicated in male infertility and adverse reproductive outcomes. With the publication of many studies regarding the etiologies and contributors to SDF, as well as the effects of SDF, guidelines are necessary to aid clinicians in the application of SDF for male fertility evaluation. Two recent clinical practice guidelines were published by Agarwal et al and Esteves et al. In this article, we have evaluated and compared both guidelines. We have found fairly similar recommendations between the two guidelines and have also highlighted the differences between them. Finally, we have summarized and combined the best practice recommendations from both guidelines.

A case of Fournier's gangrene following a large-volume hydrocelectomy in a diabetic patient managed with SGLT-2 inhibitor therapy.

Dapagliflozin (Farxiga), is an SGLT-2 inhibitor commonly indicated for the treatment of diabetes mellitus type 2 (DM 2), heart failure, and chronic kidney disease. One rare side effect associated with SGLT-2 inhibitors is bacterial infection of the genitalia. There are several case reports highlighting the incidence of Fournier's gangrene (FG) in patients who take medications within this drug class. We report a case of FG in a diabetic patient on dapagliflozin who presented following scrotal hydrocelectomy for a large-volume hydrocele. The patient was urgently taken to the operating room for scrotal debridement and recovered well in the post-operative period.

Malignant Priapism as a Result of Metastatic Thyroid Cancer: A Hard Reality.

Metastasis to the penis is an extremely rare entity. Malignant priapism is defined as a persistent, nonsexual erection that is refractory to pharmacologic treatment, corporal aspiration, and surgical shunts. Furthermore, it is typically a hallmark of an advanced cancer that has metastasized, most commonly from regional organs like the prostate or bladder. We report an unusual case of malignant priapism in the setting of metastatic follicular thyroid carcinoma. To date, this is the second reported case of penile metastasis due to thyroid carcinoma and the first incidence of priapism secondary to follicular thyroid carcinoma metastasis.