Sperm morphology: Evaluating its clinical relevance in contemporary fertility practice.

Background: The World Health Organization (WHO) recommends reporting sperm morphology in a standard semen analysis. However, the clinical utility and prognostic value of morphology is often debated. Methods: We reviewed and summarized studies that assessed both the benefits and limitations of sperm morphology in the context of natural fertility, assisted reproductive technologies, and recurrent pregnancy loss. We additionally describe possible environmental and anatomical etiologies of teratozoospermia. Results: Sperm morphology evaluation has continuously evolved since the release of the first WHO manual in 1980. Initially, several large studies reported significant inverse associations between fertility outcomes and teratozoospermia. Most recent studies, however, fail to show an association between sperm morphology and natural or assisted fertility outcomes. Conclusion: Sperm morphology analysis may have limited diagnostic and prognostic value. Providers should be aware of these limitations when counseling or managing infertile patients.

Decision regret among couples experiencing infertility: a mixed methods longitudinal cohort study.

BACKGROUND: Decisions for how to resolve infertility are complex and may lead to regret. We examined whether couples and individuals who sought a consultation from a reproductive specialist for infertility later expressed decisional regret about their family-building choices and whether regret was associated with parental role, family-building paths, or outcomes. METHODS: This longitudinal mixed methods study included women and their partners who completed a questionnaire prior to their initial consultation with a reproductive specialist and 6 years later. The six-year questionnaire included the Ottawa Decision Regret Scale referencing "the decisions you made about how to add a child to your family." A score of 25+ indicates moderate-to-severe regret. Additional items invited reflections on family-building decisions, treatments, and costs. A systematic content analysis assessed qualitative themes. RESULTS: Forty-five couples and 34 individuals participated in the six-year questionnaire (76% retention rate), Half (n = 61) of participants expressed no regret, which was similar by role (median 0 for women and supporting partners, F = .08; p = .77). One in 5 women and 1 in 7 partners expressed moderate-to-severe regret. Women who did not pursue any treatment had significantly higher regret (median 15; F = 5.6, p < 0.01) compared to those who pursued IVF (median 0) or other treatments (median 0). Women who did not add a child to their family had significantly higher regret (median 35; F = 10.1, p < 0.001) than those who added a child through treatment (median 0), through fostering/adoption (median 0), or naturally (median 5). Among partners, regret scores were not associated with family-building paths or outcomes. More than one-quarter of participants wished they had spent less money trying to add a child to their family. Qualitative themes included gratitude for parenthood despite the burdensome process of family-building as well as dissatisfaction or regret about the process. Results should be confirmed in other settings to increase generalizability. CONCLUSION: This longitudinal study provides new insight into the burden of infertility. For women seeking parenthood, any of the multiple paths to parenthood may prevent future decision regret. Greater psychosocial, financial, and decision support is needed to help patients and their partners navigate family-building with minimal regret.

When people experience infertility, there are many decisions that can be challenging, such as whether to seek fertility treatments, to pursue fostering/adoption, and how to manage costs. With each decision, there is an opportunity for regret. The goal of this study was to look at whether people who were experiencing infertility and made an appointment with a doctor who specializes in infertility felt any regret about their decisions 6 years later. We also looked at whether different roles (that is, women seeking pregnancy or their supporting partners), different family-building paths (that is, medical treatments or not), or different outcomes (that is, adding a child to their family or not) were associated with different levels of regret. Results showed that half of the 120 people in the study did not have any regret 6 years after meeting with a specialty doctor. However, some patients did have regret, including 20% of women and 14% of partners who expressed moderate-to-severe regret. Women who did not add a child to their family in the six years during the study reported higher regret compared to women who did add a child to their family. There were no such differences among partners. About 25% of participants wished they had tried more, fewer, or different treatments. More than 25% wished they spent less money to try to add a child to their family. For people who want to add a child to their family, there are multiple ways to become a parent, any of which may be linked to lower decision regret. Decision regret is experienced differently between women seeking to add a child to their family and their partners. Would-be parents need more emotional, financial, and decision making support to help them navigate family-building with minimal regret.

Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline Part I.

PURPOSE: The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.

Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

Prednisone after vasectomy reversal may improve semen parameters: one institution's experience.

INTRODUCTION: Patients with suboptimal semen parameters following vasectomy reversal represent a diagnostic and therapeutic challenge. This may be caused by either partial or complete anastomotic obstruction. Despite the relatively common clinical use of corticosteroids in this patient population, data remain sparse. Thus, we set out to evaluate the safety and efficacy of prednisone after vasectomy reversal. MATERIALS AND METHODS: A chart review was performed from January 1, 2008 to September 30, 2018 to identify men in which prednisone was used for suspected anastomotic obstruction after vasectomy reversal. Obstruction was based on sub-optimal or decreasing semen parameters and physical exam findings. A course consisted of 2 weeks of 20 mg PO daily followed by 2 weeks of 10 mg PO daily. RESULTS: A total of 89 patients were identified in which prednisone was used postoperatively. Total motile sperm counts were found to increase in the overall cohort by 10.5 million (p < 0.0002) after a course of prednisone. On sub-group analysis, men who had a bilateral vasovasostomy (VV) or VV/vasoepididymostomy experienced an increase in total motile sperm counts by 13.4 million (p < 0.0012) and 6.2 million (p < 0.014), respectively. Patients who were patent at the time of prednisone treatment were more likely to see an improvement in total motile sperm counts (76.9% versus 33.3%, p < 0.003). CONCLUSIONS: Prednisone seems to be safe and potentially efficacious in men with suspected anastomotic obstruction following vasectomy reversals. Further studies are needed to more conclusively determine the treatment's effectiveness in this patient cohort.

Time to improvement of semen parameters after microscopic varicocelectomy: When it occurs and its effects on fertility.

While ligation of clinical varicoceles has been clearly shown to improve semen parameters in subfertile men, evidence describing when to expect improvement and the potential effects on fertility following surgery are sparse. A chart review was undertaken to identify men who had undergone a microscopic subinguinal varicocelectomy from January 1, 2006, to June 30, 2018. Semen analyses were reviewed to determine if a significant improvement occurred post-operatively and when the improvement was seen. Pregnancy data were reviewed to determine if fecundity rates were affected by semen parameter improvement or the interval at which improvement occurred. A total of 170 men met criteria for inclusion, including pregnancy data on 140. 69.4% of patients experienced a significant improvement in total progressive sperm count (TPSC), 78.8% of which occurred after 3 months. The overall pregnancy rate was 40.7%. When comparing men whose TPSC improved to those who did not, there was an odds ratio (OR) of 5.89 (2.28-15.28, 0.0003) for achieving pregnancy, while an OR of 2.05 (0.80-5.28, 0.13) was found when comparing pregnancy rates between early and late improvement in semen parameters. Pregnancy rates were not affected by time to improvement, but were higher in men who had a significant improvement in TPSC after surgery.

Sperm agglutination: Prevalence and contributory factors.

Agglutination is a finding noted in semen analyses (SAs) that often causes confusion as to its significance. While some have attributed agglutination to antisperm antibodies (ASAs), there are other causes as well, such as genital tract infection and ascorbic acid deficiency. Additionally, it is known that patients with ASAs often have risk factors such as a history of scrotal trauma or surgery. Therefore, we sought to determine the prevalence of agglutination in our patient population and correlate it with these risk factors, regardless of the presence/absence of ASAs. A retrospective study was conducted on the SAs of men seen at a single academic Reproductive Center. Of the 1,095 SAs identified, 133 (12.1%) patients experienced agglutination (61.7% scant, 21.8% moderate and 16.5% excessive). Of patients who underwent multiple SAs, 24 (12.2%) showed variability. Furthermore, patients who underwent scrotal surgery carried 3.4 times the risk of agglutination (X2 p < 0.01) and 5.5 times the risk of variability (X2 p < 0.01) as compared to those patients without a history significant for scrotal surgery. Agglutination is a relatively common finding in men presenting to a reproductive clinic with little intrapatient variability. Scrotal surgery confers a higher risk of agglutination and variability.

Priorities for family building among patients and partners seeking treatment for infertility.

BACKGROUND: Infertility treatment decisions require people to balance multiple priorities. Within couples, partners must also negotiate priorities with one another. In this study, we assessed the family-building priorities of couples prior to their first consultations with a reproductive specialist. METHODS: Participants were couples who had upcoming first consultations with a reproductive specialist (N = 59 couples (59 women; 59 men)). Prior to the consultation, couples separately completed the Family-Building Priorities Tool, which tasked them with ranking from least to most important 10 factors associated with family building. We describe the highest (top three) and lowest (bottom three) priorities, the alignment of priorities within couples, and test for differences in prioritization between men and women within couples (Wilcoxon signed rank test). RESULTS: Maintaining a close and satisfying relationship with one's partner was ranked as a high priority by majorities of men and women, and in 25% of couples, both partners ranked this factor as their most important priority for family building. Majorities of men and women also ranked building a family in a way that does not make infertility obvious to others as a low priority, and in 27% of couples, both partners ranked this factor as the least important priority for family building. There were also differences within couples that involved either men or women ranking a particular goal more highly than their partners. More women ranked two factors higher than did their partners: 1) that I become a parent one way or another (p = 0.015) and 2) that I have a child in the next year or two (p < 0.001), whereas more men ranked 4 factors higher than their partners: 1) that our child has [woman's] genes (p = 0.025), 2) that our child has [man's] genes (p < 0.001), 3) that I maintain a close relationship with my partner (p = 0.034), and 4) that I avoid side effects from treatment (p < 0.001). CONCLUSIONS: Clinicians who support patients in assessing available family-building paths should be aware that: (1) patients balance multiple priorities as a part of, or beside, becoming a parent; and (2) patients and their partners may not be aligned in their prioritization of achieving parenthood. For infertility patients who are in relationships, clinicians should encourage the active participation of both partners as well as frank discussions about each partner's priorities for building their family.

A conceptual framework for patient-centered fertility treatment.

BACKGROUND: Patient-centered care is a pillar of quality health care and is important to patients experiencing infertility. In this study we used empirical, in-depth data on couples' experiences of infertility treatment decision making to inform and revise a conceptual framework for patient-centered fertility treatment that was developed based on health care professionals' conceptualizations of fertility treatment, covering effectiveness, burden, safety, and costs. METHODS: In this prospective, longitudinal mixed methods study, we collected data from both members (separately) of 37 couples who scheduled an initial consult with a reproductive specialist. Data collection occurred 1 week before the initial consultation, 1 week after the initial consultation, and then roughly 2, 4, 8, and 12 months later. Data collection included semi-structured qualitative interviews, self-reported questionnaires, and medical record review. Interviews were recorded, transcribed, and content analyzed in NVivo. A single coder analyzed all transcripts, with > 25% of transcripts coded by a second coder to ensure quality control and consistency. RESULTS: Content analysis of the interview transcripts revealed 6 treatment dimensions: effectiveness, physical and emotional burden, time, cost, potential risks, and genetic parentage. Thus, the revised framework for patient-centered fertility treatment retains much from the original framework, with modification to one dimension (from safety to potential risks) and the addition of two dimensions (time and genetic parentage). For patients and their partners making fertility treatment decisions, tradeoffs are explicitly considered across dimensions as opposed to each dimension being considered on its own. CONCLUSIONS: Patient-centered fertility treatment should account for the dimensions of treatment that patients and their partners weigh when making decisions about how to add a child to their family. Based on the lived experiences of couples seeking specialist medical care for infertility, this revised conceptual framework can be used to inform patient-centered treatment and research on infertility and to develop decision support tools for patients and providers.

Relating economic conditions to vasectomy and vasectomy reversal frequencies: a multi-institutional study.

PURPOSE: It was theorized that the use of permanent contraceptive methods may vary with economic conditions. We evaluated the relationship between vasectomy/vasectomy reversal frequencies at several large referral centers and national economic indicators during 2 recessions spanning 2001 to 2011. MATERIALS AND METHODS: We performed an institutional review board approved, retrospective chart review to identify the number of vasectomies/vasectomy reversals per month at several large referral centers from January 2001 to July 2011. The rates of these procedures were pooled, correlated with national economic data and analyzed in a multivariate linear regression model. RESULTS: A total of 4,599 vasectomies and 1,549 vasectomy reversals were performed at our institutions during the study period. The number of vasectomies per month positively correlated with the unemployment rate (r=0.556, p<0.001) and personal income per capita (r=0.276, p=0.002). The number of reversals per month negatively correlated with the unemployment rate (r=-0.399, p<0.001) and personal income per capita (r=-0.305, p<0.001). Neither vasectomy nor vasectomy reversal frequency significantly correlated with the inflation rate or the S&P 500®. Regression models confirmed that the unemployment rate explained more of the variance in vasectomy/vasectomy reversal frequencies than other indicators. CONCLUSIONS: We noted a correlation between the number of vasectomies/vasectomy reversals performed at our institutions and national economic indicators. The strongest association was with the unemployment rate. This points to the importance of financial pressure on family planning decisions.

Comparative review of vasectomy guidelines and novel vasal occlusion techniques.

Vasectomy is the most commonly performed urologic procedure in the United States and is a highly effective form of male contraception. The introduction of guidelines by urological societies has standardized vasectomy care. Providers should be awadre of the rationale behind these guidelines, as well as key differences among them. While few major changes to vasectomy technique have been adopted over the past 40 years, new, reversible vasal occlusive technologies may affect delivery of male contraceptive care in the future. Here, we perform a comparative review of vasectomy guidelines from six urological societies worldwide. In addition, we report on the status of several experimental vasal occlusion methods that may be available in the next decade.

Vasectomy Regret Among Childless Men.

OBJECTIVE: To address historical concerns surrounding vasectomy in childless men, we sought to evaluate for the level of regret in this unique cohort. METHODS: The records of patients who underwent vasectomy via single surgeon between 2006 and 2021 were retrospectively reviewed and those who had not fathered children in any capacity at time of vasectomy were selected. We devised a 6-question survey inquiring about regret and thoughts on vasectomy reversal and assisted reproductive technology (ART). The questions are listed in Table 1. Patients were queried via a telephone call to rate their level of regret, both immediately after vasectomy and present day. The cohort was analyzed via age at time of vasectomy, time since vasectomy and marital status. RESULTS: There were 4812 overall patients who underwent vasectomy in this interval, with 205 (4.3%) who were childless. The response rate was 33.2% (68/205). Average age was 36.6 years with average time since vasectomy at time of phone call was 5.51 years. Regret rate was 4.4% immediately following vasectomy and 7.4% at time of telephone interview. A confirmatory, second consultation before vasectomy was present in 6.8% (14/205). The majority of patients 150/205 (73.1%) were married. When patients were stratified by marital status, there was no significant difference in any of the questions. The majority of patients were satisfied with their decision, with few contemplating or pursuing reversal or ART (Table 1). CONCLUSION: Regret in childless patients who undergo vasectomy is very rare, with the majority of patients feeling that their life was improved.

An Online Investigation Into Direct-to-Consumer Men's Health Clinics: The Who, What, and Where.

OBJECTIVE: To characterize direct-to-consumer (DTC) men's health clinics by reviewing their online content. Increasing numbers of patients are seeking treatment for erectile dysfunction (ED) and hypogonadism from DTC "men's health" clinics. Treatments are often used off-label, with lack of transparency of provider credentials and qualifications. METHODS: We identified DTC Men's Health Clinics in the United States by internet search by state using the terms, "Men's Health Clinic," and "Low T Center." All stand-alone clinics were reviewed. RESULTS: Two hundred and twenty-three clinics were reviewed, with 147 (65.9%) offered ED treatments and 196 (87.9%) offering testosterone replacement, and 120 (53.8%) offering both ED treatment and testosterone replacement. Of those clinics offering ED treatments, 93 (63.3%) advertised shockwave therapy and 84 (57.1%) PRP therapy. There were 56 (38%) who offered shockwave therapy and PRP. ICI was significantly more likely to be offered if there was a urologist on staff (p <.001). Clinic providers represented 20 different medical and alternative medicine specialties. Internal medicine was most common (17.4%), followed by family medicine (11.1%). A nonphysician (nurse practitioner or physician assistant) was listed as the primary provider in 10 clinics (4.5%) and 45 clinics (20.1%) did not list their providers. Urologists were listed as the primary provider in 10.3% of clinics. A naturopathic provider was listed as a staff member in 22 (11.6%) of clinics. CONCLUSION: There is significant heterogeneity and misinformation available to the public regarding men's health. Familiarity with and insight into practice patterns of "men's health" clinics will help provide informed patient care and counseling.

Practice and development of male contraception: European Academy of Andrology and American Society of Andrology guidelines.

BACKGROUNDS: Despite a wide spectrum of contraceptive methods for women, the unintended pregnancy rate remains high (45% in the US), with 50% resulting in abortion. Currently, 20% of global contraceptive use is male-directed, with a wide variation among countries due to limited availability and lack of efficacy. Worldwide studies indicate that >50% of men would opt to use a reversible method, and 90% of women would rely on their partner to use a contraceptive. Additional reasons for novel male contraceptive methods to be available include the increased life expectancy, sharing the reproductive risks among partners, social issues, the lack of pharma industry involvement and the lack of opinion makers advocating for male contraception. AIM: The present guidelines aim to review the status regarding male contraception, the current state of the art to support the clinical practice, recommend minimal requirements for new male contraceptive development and provide and grade updated, evidence-based recommendations from the European Society of Andrology (EAA) and the American Society of Andrology (ASA). METHODS: An expert panel of academicians appointed by the EAA and the ASA generated a consensus guideline according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. RESULTS: Sixty evidence-based and graded recommendations were produced on couple-centered communication, behaviors, barrier methods, semen analysis and contraceptive efficacy, physical agents, surgical methods, actions before initiating male contraception, hormonal methods, non-hormonal methods, vaccines, and social and ethical considerations. CONCLUSION: As gender roles transform and gender equity is established in relationships, the male contribution to family planning must be facilitated. Efficient and safe male-directed methods must be evaluated and introduced into clinical practice, preferably reversible, either hormonal or non-hormonal. From a future perspective, identifying new hormonal combinations, suitable testicular targets, and emerging vas occlusion methods will produce novel molecules and products for male contraception.

The effect of body mass index on the outcomes of varicocelectomy.

PURPOSE: Obesity is recognized as a potential contributor to male factor infertility. There are no studies to date to our knowledge that have examined the success of varicocelectomy in obese men. We determined if body mass index significantly affects the outcome of varicocelectomy. MATERIALS AND METHODS: Retrospective chart review was performed for all patients who underwent varicocelectomy from September 2003 to December 2009. Patients were placed into 3 groups based on body mass index, and categorized as normal weight (group 1-38 patients, body mass index 18.5 to 24.9), overweight (group 2-59 patients, body mass index 25 to 29.9) or obese (group 3-46 patients, body mass index 30 or greater). Significant improvement was defined as a greater than 50% increase in the total motile per ejaculate parameter on postoperative semen analysis. RESULTS: A total of 143 patients were available for analysis. There were no significant differences among patients in the 3 groups except for body mass index. Significant improvement in total motile/ejaculate on semen analyses was 71.1% (group 1), 61.0% (group 2) and 58.7% (group 3). Pregnancy rates were 43.8% (group 1), 43.5% (group 2) and 46.3% (group 3). There were no significant differences in improvement in total motile per ejaculate (p = 0.21, p = 0.17) or pregnancy rate (p = 0.60, p = 0.51) between the normal body mass index group, and the overweight and obese groups. CONCLUSIONS: Varicocelectomy for men with clinically palpable varicoceles has a significant chance of improving semen parameters and pregnancy rates regardless of preoperative body mass index. The outcomes of varicocelectomy in overweight and obese patients were similar to those of normal weight men. Therefore, varicocelectomy can be performed effectively and safely in overweight and obese men.

Vasectomy: AUA guideline.

PURPOSE: The purpose of this guideline is to provide guidance to clinicians who offer vasectomy services. MATERIALS AND METHODS: A systematic review of the literature using the search dates January 1949-August 2011 was conducted to identify peer-reviewed publications relevant to vasectomy. The search identified almost 2,000 titles and abstracts. Application of inclusion/exclusion criteria yielded an evidence base of 275 articles. Evidence-based practices for vasectomy were defined when evidence was available. When evidence was insufficient or absent, expert opinion-based practices were defined by Panel consensus. The Panel sought to define the minimum and necessary concepts for pre-vasectomy counseling; optimum methods for anesthesia, vas isolation, vas occlusion and post-vasectomy follow up; and rates of complications of vasectomy. This guideline was peer reviewed by 55 independent experts during the guideline development process. RESULTS: Vas isolation should be performed using a minimally-invasive vasectomy technique such as the no-scalpel vasectomy technique. Vas occlusion should be performed by any one of four techniques that are associated with occlusive failure rates consistently below 1%. These are mucosal cautery of both ends of the divided vas without ligation or clips (1) with or (2) without fascial interposition; (3) open testicular end of the divided vas with MC of abdominal end with FI and without ligation or clips; and (4) non-divisional extended electrocautery. Patients may stop using other methods of contraception when one uncentrifuged fresh semen specimen shows azoospermia or ≤ 100,000 non-motile sperm/mL. CONCLUSIONS: Vasectomy should be considered for permanent contraception much more frequently than is the current practice in the U.S. and many other nations. The full text of this guideline is available to the public at http://www.auanet.org/content/media/vasectomy.pdf.

Varicocelectomy in the treatment of testicular pain: a review.

PURPOSE OF REVIEW: Varicoceles are a common finding in adolescent boys and men. Most are asymptomatic, although up to 10% may cause testicular pain. This study will review the use of varicocelectomy in the treatment of testicular pain in men with clinical varicoceles, as well as provide prognostic indicators for successful outcome. RECENT FINDINGS: Recent studies that examined the impact of varix ligation on preoperative testicular pain were reviewed. Most studies are retrospective and uncontrolled; although objective outcome measures were used in the majority. Varicocele grade, duration of discomfort, and the quality of pain tended to predict outcome but have not been universally supported. SUMMARY: On the basis of the majority of the recently published studies, varicocelectomy, in the properly chosen patients, results in significant improvement or resolution of testicular pain.

Testosterone-Mediated Aggression in Angelman Syndrome Treated With Leuprolide and Orchiectomy.

Angelman syndrome (AS) is a rare genetic imprinting disorder characterized by a maternal microdeletion of the 15q11q13 locus. It is traditionally associated with intellectual disability, inappropriate laughing, and a happy demeanor. Here, we report a patient with AS who presented with aggression and hypersexuality and was successfully treated with leuprolide injections for nine years until a definitive orchiectomy was performed. To the best of our knowledge, this is the first report of castration as a treatment for refractory behavioral symptoms in a patient with AS.

Diverse monogenic subforms of human spermatogenic failure.

Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven challenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes in a 2-stage burden test with 2072 cases and 11,587 fertile controls. The disrupted genes are primarily on the autosomes, enriched for undescribed human "knockouts", and, for the most part, have yet to be linked to a Mendelian trait. Integration with single-cell RNA sequencing data shows that azoospermia genes can be grouped into molecular subforms with synchronized expression patterns, and analogs of these subforms exist in mice. This analysis framework identifies groups of genes with known roles in spermatogenesis but also reveals unrecognized subforms, such as a set of genes expressed across mitotic divisions of differentiating spermatogonia. Our findings highlight NOA as an understudied Mendelian disorder and provide a conceptual structure for organizing the complex genetics of male infertility, which may provide a rational basis for disease classification.