Influence of substance use on male reproductive health and offspring outcomes.

The prevalence of substance use globally is rising and is highest among men of reproductive age. In Africa, and South and Central America, cannabis use disorder is most prevalent and in Eastern and South-Eastern Europe, Central America, Canada and the USA, opioid use disorder predominates. Substance use might be contributing to the ongoing global decline in male fertility, and emerging evidence has linked paternal substance use with short-term and long-term adverse effects on offspring development and outcomes. This trend is concerning given that substance use is increasing, including during the COVID-19 pandemic. Preclinical studies have shown that male preconception substance use can influence offspring brain development and neurobehaviour through epigenetic mechanisms. Additionally, human studies investigating paternal health behaviours during the prenatal period suggest that paternal tobacco, opioid, cannabis and alcohol use is associated with reduced offspring mental health, in particular hyperactivity and attention-deficit hyperactivity disorder. The potential effects of paternal substance use are areas in which to focus public health efforts and health-care provider counselling of couples or individuals interested in conceiving.

Cannabis Use and Perinatal Health Research.

This Viewpoint examines the significant gap in knowledge regarding the effects of cannabis use on perinatal health outcomes.

Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes.

BACKGROUND: With the growing availability of cannabis and the popularization of additional routes of cannabis use beyond smoking, including edibles, the prevalence of cannabis use in pregnancy is rapidly increasing. However, the potential effects of prenatal cannabis use on fetal developmental programming remain unknown. RESULTS: We designed this study to determine whether the use of edible cannabis during pregnancy is deleterious to the fetal and placental epigenome. Pregnant rhesus macaques consumed a daily edible containing either delta-9-tetrahydrocannabinol (THC) (2.5 mg/7 kg/day) or placebo. DNA methylation was measured in 5 tissues collected at cesarean delivery (placenta, lung, cerebellum, prefrontal cortex, and right ventricle of the heart) using the Illumina MethylationEPIC platform and filtering for probes previously validated in rhesus macaque. In utero exposure to THC was associated with differential methylation at 581 CpGs, with 573 (98%) identified in placenta. Loci differentially methylated with THC were enriched for candidate autism spectrum disorder (ASD) genes from the Simons Foundation Autism Research Initiative (SFARI) database in all tissues. The placenta demonstrated greatest SFARI gene enrichment, including genes differentially methylated in placentas from a prospective ASD study. CONCLUSIONS: Overall, our findings reveal that prenatal THC exposure alters placental and fetal DNA methylation at genes involved in neurobehavioral development that may influence longer-term offspring outcomes. The data from this study add to the limited existing literature to help guide patient counseling and public health polices focused on prenatal cannabis use in the future.

Cessation of chronic delta-9-tetrahydrocannabinol use partially reverses impacts on male fertility and the sperm epigenome in rhesus macaques.

OBJECTIVE: To determine whether discontinuation of delta-9-tetrahydrocannabinol (THC) use mitigates THC-associated changes in male reproductive health using a rhesus macaque model of daily THC edible consumption. DESIGN: Research animal study. SETTING: Research institute environment. PATIENT(S): Adult male rhesus macaques (age, 8-10 years; n = 6). INTERVENTION(S): Chronic daily THC edible administration at medically and recreationally relevant contemporary doses followed by cessation of THC use. MAIN OUTCOME MEASURE(S): Testicular volume, serum male hormones, semen parameters, sperm deoxyribonucleic acid (DNA) fragmentation, seminal fluid proteomics, and whole genome bisulfite sequencing of sperm DNA. RESULT(S): Chronic THC use resulted in significant testicular atrophy, increased gonadotropin levels, decreased serum sex steroid levels, changes in seminal fluid proteome, and increased DNA fragmentation with partial recovery after discontinuation of THC use. For every increase of 1 mg/7 kg/day in THC dosing, there was a significant decrease in the total testicular volume bilaterally by 12.6 cm3 (95% confidence interval [CI], 10.6-14.5), resulting in a 59% decrease in volume. With THC abstinence, the total testicular volume increased to 73% of its original volume. Similarly, with THC exposure, there were significant decreases in the mean total testosterone and estradiol levels and a significant increase in the follicle-stimulating hormone level. With increasing THC dose, there was a significant decrease in the liquid semen ejaculate volume and weight of coagulum; however, no other significant changes in the other semen parameters were noted. After discontinuing THC use, there was a significant increase in the total serum testosterone level by 1.3 ng/mL (95% CI, 0.1-2.4) and estradiol level by 2.9 pg/mL (95% CI, 0.4-5.4), and the follicle-stimulating hormone level significantly decreased by 0.06 ng/mL (95% CI, 0.01-0.11). Seminal fluid proteome analysis revealed differential expression of proteins enriched for processes related to cellular secretion, immune response, and fibrinolysis. Whole genome bisulfite sequencing identified 23,558 CpGs differentially methylated in heavy-THC vs. pre-THC sperm, with partial restoration of methylation after discontinuation of THC use. Genes associated with altered differentially methylated regions were enriched for those involved in the development and function of the nervous system. CONCLUSION(S): This is the first study demonstrating that discontinuation of chronic THC use in rhesus macaques partially restores adverse impacts to male reproductive health, THC-associated sperm differentially methylated regions in genes important for development, and expression of proteins important for male fertility.

Vasectomy reversal outcomes in men after testosterone therapy.

The prevalence of males on testosterone therapy (TT) seeking vasectomy reversal (VR) is rising. As medical therapy (MT) to recover spermatogenesis after TT has been previously described, our study's objective is to present our institution's management and outcomes of VR in men previously on TT. We performed a retrospective case series of vasectomy patients on TT with subsequent VR by a single microsurgeon between March, 2010 and March, 2022. 14 men undergoing VR during the study period met inclusion criteria. The median age at VR was 43 years with a median obstructive interval of 11 years. Median time from MT to VR was 5 months. Post-operative semen analysis was performed in 10 men and all demonstrated patency. 2 patients had very low sperm counts secondary to continuing TT following VR contrary to medical advice and 5 men with patency achieved pregnancy. Our study noted a high rate of vasovasostomy (VV) (96%) and sustained patency despite a 12-year median obstructive interval. Our findings support favorable outcomes with less stringent VV indications after MT in patients previously on TT that desire VR. The use of MT reduces the recommended wait times for VR after TT discontinuation by more than half.

Impact of cannabinoids on pregnancy, reproductive health, and offspring outcomes.

Cannabis is the most commonly used federally illegal drug in the United States and the world, especially among people of reproductive age. In addition, the potency of cannabis products has increased significantly in the past decade. This is concerning because the available evidence suggests an adverse effect of cannabis exposure on male and female reproductive health. Exposure to cannabinoids may have differential impacts on female reproductive health across a woman's lifespan, from preconception to pregnancy, throughout lactation, and during menopause. Moreover, cannabis use has been associated with adverse effects on fetal outcomes and longer-term offspring health and developmental trajectories. Despite the prevalence of cannabis use, there is limited available evidence regarding its safety, especially in regard to reproductive health, pregnancy, and lactation. The biological effects of cannabis are mediated by the endocannabinoid system, and studies have reported the presence of cannabinoid receptors in the male and female reproductive tract, on sperm and the placenta, suggesting that the endocannabinoid system plays a role in regulating reproduction. Cannabis use can affect male and female fertility and has been associated with altered reproductive hormones, menstrual cyclicity, and semen parameters. Use of cannabis in male patients has also been associated with erectile dysfunction, abnormal spermatogenesis, and testicular atrophy. In female patients, cannabis use has been associated with infertility and abnormal embryo implantation and development. The main psychoactive component of cannabis, the delta-9-tetrahydrocannabinol, can also cross the placenta and has been detected in breast milk. Maternal cannabis use during pregnancy and lactation has been associated with adverse effects, including small-for-gestational-age infants, preterm birth, fetal neurodevelopmental consequences, and impaired offspring sociobehavioral and cognitive development. The prevalence of cannabis use for alleviating menopausal symptoms has also increased despite the limited information on its benefits and safety. Given that cannabis use is on the rise, it is critical to understand its impact on reproductive health and offspring developmental outcomes. This is an understudied but timely subject requiring much further information to guide healthcare providers and those interested in conceiving or who are pregnant and lactating, and those at the end of their reproductive time span.

Development of a Hemostatic Urinary Catheter for Transurethral Prostatic Surgical Applications.

OBJECTIVE: To investigate a novel transurethral hemostatic catheter device with an integrated chitosan endoluminal hemostatic dressing (CEHD). Development and implementation of this technology may help address bleeding following surgery such as transurethral resection of prostate (TURP). Bleeding remains the most common complication following TURP, leading to increased morbidity and hospitalization. METHODS: Investigation of hemostasis, delivery, safety and efficacy of the CEHD device is conducted using Female Yorkshire swine (N = 23). Hemostatic efficacy of the CEHD (N = 12) is investigated against a control of gauze (N = 12) in a splenic injury model (3 swine). The delivery, safety, and efficacy of the CEHD device (N = 10) are investigated against Foley-catheter control (N = 10) for 7 days using a swine bladder-neck-injury model. RESULTS: In the splenic injury study, 9/12 CEHD dressings successfully achieved hemostasis within 150 seconds (mean 83 seconds) vs success of 6/12 (mean 150 seconds) for gauze (P = .04). In the 7-day study, the CEHD was successfully deployed in 10/10 animals and all dressings were tolerated without histologic or clinical adverse effect. Hemostasis of the CEHD device was found to be noninferior to control catheters. Noninferiority is attributed to low bleeding rates in the swine bladder neck injury model. CONCLUSION: This investigation successfully demonstrated the feasibility of transurethral deployment of the CEHD in vivo. Routine use of safe and slowly dissolvable CEHDs could reduce the rate of complications and hospitalizations associated with bleeding and blood loss in TURP procedures. Further investigation is warranted.

Chronic exposure to delta-9-tetrahydrocannabinol impacts testicular volume and male reproductive health in rhesus macaques.

OBJECTIVE: To determine the dose-dependent effect of delta-9-tetrahydrocannabinol (THC) exposure on male testes and reproductive health in a nonhuman primate model. DESIGN: Research animal study. SETTING: Research institute. ANIMAL(S): Adult male rhesus macaques 8-10 years of age (n = 6). INTERVENTION(S): Daily edible THC at medically and recreationally relevant doses. MAIN OUTCOME MEASURE(S): Testicular volume and epididymal head width, serum levels of inhibin B, albumin, total testosterone, prolactin, follicle-stimulating hormone, estradiol, and luteinizing hormone; semen volume; and sperm motility, morphology, and concentration. RESULT(S): For each 1 mg/7 kg/day increase in THC dosing, there was a marked loss in total bilateral testicular volume of 11.8 cm3 (95% confidence interval [CI]: 8.3-15.4). In total, average bilateral testicular volume decreased by 58%. Significant dose-response decreases in mean total testosterone level by 1.49 ng/mL (95% CI: 0.83-2.15) and in estradiol level by 3.8 pg/mL (95% CI: 2.2-5.4) were observed, but significant increases in the levels of follicle-stimulating hormone by 0.06 ng/mL (95% CI: 0.02-0.10), luteinizing hormone by 0.16 ng/mL (95% CI: 0.08-0.25), and prolactin by 7.4 ng/mL (95% CI: 3.4-11.3) were observed. There were no statistically significant changes in semen parameters. CONCLUSION(S): In rhesus macaques, chronic exposure to THC resulted in significant dose-response testicular atrophy, increased serum gonadotropin levels, and decreased serum sex steroids, suggestive of primary testicular failure. Further studies are needed to determine if reversal of these observed adverse effects would occur if THC was discontinued and for validation of thefindings in a human cohort.

The effects of delta-9-tetrahydrocannabinol exposure on female menstrual cyclicity and reproductive health in rhesus macaques.

OBJECTIVE: To determine the dose-dependent effect of contemporary marijuana exposure on female menstrual cyclicity and reproductive endocrine physiology in a nonhuman primate model. DESIGN: Research animal study. SETTING: Research institute environment. ANIMALS: Adult female rhesus macaques (6-12 years of age; n = 8). INTERVENTIONS: Daily delta-9-tetrahydrocannabinol (THC) edible at medically and recreationally relevant contemporary doses. MAIN OUTCOME MEASURES: Menstrual cycle length (MCL), anti-Müllerian hormone, prolactin, basal follicle-stimulating hormone (FSH), estradiol (E2) and progesterone, luteinizing hormone (LH), and thyroid-stimulating hormone. RESULTS: The average before THC weight was 6.9 kg (standard deviation, 0.8), and at the highest THC dosing, the average weight was 7.2 kg (standard deviation, 0.8). With increasing THC dosing, MCL and FSH concentrations increased, while basal E2 concentration was stable. The average MCL concentration increased 4.0 days for each mg/7 kg/day of THC (95% CI, 1.4-6.6 days). Follicle-stimulating hormone concentration increased significantly with increasing THC dose, 0.34 ng/mL for each mg/7 kg/day of THC (95% CI, 0.14-0.57 ng/mL). No significant trends were observed between THC dosing and average basal progesterone, anti-Müllerian hormone, prolactin, LH, or thyroid-stimulating hormone concentrations. CONCLUSIONS: In rhesus macaques, a dose response toward increased MCL and basal FSH concentrations but plateau of basal E2 and LH concentrations was observed with increasing THC dosing, suggesting ovulatory dysfunction. Further studies are needed to determine the effects of a longer duration of exposure and whether the significant increase in MCL and FSH concentrations results in reduced fecundity.

Effects of marijuana on reproductive health: preconception and gestational effects.

PURPOSE OF REVIEW: Recent widespread legalization changes have promoted the availability of marijuana and its increased potency and perceived safety. The limited evidence on reproductive and perinatal outcomes from marijuana exposure is enough to warrant concern and action. The objective of this review is to provide a current and relevant summary of the recent literature surrounding this topic. RECENT FINDINGS: The available published studies on the effect of marijuana exposure on reproductive health and pregnancy outcomes are conflicting. Human studies are often observational or retrospective and confounded by self-report and polysubstance use. However, the current, limited evidence suggests that marijuana use adversely affects male and female reproductive health. Additionally, prenatal marijuana exposure has been reported to be associated with an increased risk of preterm birth and small for gestational age infants. SUMMARY: With the increasing prevalence of marijuana use, there is an urgent need for evidence-driven recommendations and guidelines for couples interested in conception, affected by infertility or who are expecting. At this time, no amount of marijuana use during conception or pregnancy is known to be well tolerated and the limited available evidence suggests that the safest choice is to abstain.

Educational value of the transplant experience in urology residency.

INTRODUCTION To evaluate the educational value of transplant rotation in urology residency. In the United States, exposure to kidney transplantation during urology residency has declined significantly over the past few decades. At our institution, transplantation has been a core component of urology residency since its inception in 1959. MATERIALS AND METHODS: A 15-question anonymous survey was developed. The first 8 questions queried demographics and the last 7 were a set of questions with a Likert Scale response. The survey was electronic- mailed to past and current urology residents who had completed the transplant rotation, dating back to 1972. RESULTS: A total of 61 out of 98 (62%) individuals responded. The majority (59%) were general urologists, and one (2%) had completed a transplant fellowship. In their practices, 17% performed kidney transplants and 28% performed donor nephrectomies. Overall, 100% responded that the skills learned on the transplant rotation were beneficial for urology training, 100% had learned valuable vascular surgical techniques, and 93% felt that urology residents should have clinical transplant experience during their training. There was no statistical difference between the younger and older graduates in Likert scale responses. CONCLUSION: The majority of graduates did not perform transplants in their practice, yet, all of responders agreed that the skills learned on the transplant rotation were beneficial and 93% expressed that urology residents should have clinical transplant experience during residency. Kidney transplantation should be an integral part of urology residency training.

One size does not fit all: variations by ethnicity in demographic characteristics of men seeking fertility treatment across North America.

OBJECTIVE: To compare racial differences in male fertility history and treatment. DESIGN: Retrospective review of prospectively collected data. SETTING: North American reproductive urology centers. PATIENT(S): Males undergoing urologist fertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Demographic and reproductive Andrology Research Consortium data. RESULT(S): The racial breakdown of 6,462 men was: 51% White, 20% Asian/Indo-Canadian/Indo-American, 6% Black, 1% Indian/Native, <1% Native Hawaiian/Other Pacific Islander, and 21% "Other". White males sought evaluation sooner (3.5 ± 4.7 vs. 3.8 ± 4.2 years), had older partners (33.3 ± 4.9 vs. 32.9 ± 5.2 years), and more had undergone vasectomy (8.4% vs. 2.9%) vs. all other races. Black males were older (38.0 ± 8.1 vs. 36.5 ± 7.4 years), sought fertility evaluation later (4.8 ± 5.1 vs. 3.6 ± 4.4 years), fewer had undergone vasectomy (3.3% vs. 5.9%), and fewer had partners who underwent intrauterine insemination (8.2% vs. 12.6%) compared with all other races. Asian/Indo-Canadian/Indo-American patients were younger (36.1 ± 7.2 vs. 36.7 ± 7.6 years), fewer had undergone vasectomy (1.2% vs. 6.9%), and more had partners who underwent intrauterine insemination (14.2% vs. 11.9%). Indian/Native males sought evaluation later (5.1 ± 6.8 vs. 3.6 ± 4.4 years) and more had undergone vasectomy (13.4% vs. 5.7%). CONCLUSION(S): Racial differences exist for males undergoing fertility evaluation by a reproductive urologist. Better understanding of these differences in history in conjunction with societal and biologic factors can guide personalized care, as well as help to better understand and address disparities in access to fertility evaluation and treatment.

Perioperative stroke and myocardial infarction in urologic surgery.

INTRODUCTION Perioperative stroke and myocardial infarction are uncommon but devastating thromboembolic complications. There is no comprehensive study detailing these complications for urologic procedures. The primary aim of this study is to determine which urologic procedures and patients carry the highest risk of perioperative stroke and myocardial infarction. MATERIALS AND METHODS: The National Surgical Quality Improvement Program data set was reviewed from 2008-2017. Procedures coded under the urology specialty were included and patients who had a perioperative stroke or myocardial infarction were identified. CPTs were stratified into clinically relevant procedure groups. Two multivariable logistic regression analyses were performed to determine preoperative and procedural risk factors for developing perioperative stroke or myocardial infarction. A multivariable logistic regression analysis was performed to determine the association between these complications and 30-day mortality. RESULTS: A total of 281,744 cases were included, identifying 392 strokes (0.14%) and 1,016 myocardial infarctions (0.36%). Age ≥ 70, hypertension, and disseminated cancer were the strongest preoperative risk factors for perioperative stroke or myocardial infarction. Cystectomy was the highest risk urologic procedure (stroke: OR 3.3, 95%CI 2.3-4.8; MI: OR 7.2, 95%CI 5.6-9.1). Thirty-day mortality was dramatically worse for patients who had a perioperative stroke or myocardial infarction. CONCLUSIONS: Perioperative stroke and myocardial infarction were confirmed to be uncommon but devastating complications of urologic surgery, with incidence of 0.14% and 0.36%, respectively. Cystectomy was the highest risk urologic procedure. Perioperative stroke and myocardial infarction were strongly associated with age ≥ 70, hypertension, and disseminated cancer.

Misaligned Incentives in Benign Prostatic Enlargement Surgery: More Complex and Efficacious Procedures Are Earning Fewer Relative Value Units.

Background: Relative value units (RVUs) are the measure of value used in US Medicare reimbursement. Medicare determines physician work RVUs (wRVUs) from the Relative Value Update Committee (RUC) for a procedure based on operative time, technical skill and effort, mental effort and judgment, and stress. In theory, work RVUs should account for the complexity and operative time involved in a procedure. The aim of this study was to assess whether major procedures for treatment of benign prostatic enlargement (BPE) are fairly compensated based on complexity and operative time in the RVU system and compare them with the intended reimbursement. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database and the Centers for Medicare and Medicaid Services (CMS) Medicare Physician Fee Schedule were queried from 2015 to 2017. Single, current, procedural terminology codes associated with BPE treatments were included: transurethral resection of the prostate (TURP), photovaporization of the prostate (PVP), holmium laser enucleation of the prostate (HoLEP), retropubic simple prostatectomy (RSP), and suprapubic simple prostatectomy (SSP). The CMS operative times and the NSQIP real data were used in turn to calculate separate values for wRVUs per hour (wRVUs/hr) of operative time. The wRVUs/hr derived from CMS operative times represent RUC-estimated wRVUs/hr and wRVUs/hr derived from NSQIP represent actual wRVUs/hr. Results: A total of 27,664 cases were included from the NSQIP dataset. Median wRVU was 15.3 (interquartile range [IQR] 12.2-15.3), median operative time 50 minutes (IQR 33-74), and median wRVUs/hr 17.0 (IQR 11.6-26.2). RUC-estimated wRVUs/hr were TURP 12.2, PVP 12.2, RSP 9, SSP 9.3, and HoLEP 7.3. The actual wRVUs/hr were TURP 19.1, PVP 15.5, RSP 10.2, HoLEP 9.4, and SSP 7.6. Conclusions: Laser enucleation and simple prostatectomy are highly complex and efficacious procedures for treating BPE, yet the current payment schedule assigns these procedures the least amount of wRVUs/hr. Financial incentives for performing BPE surgeries are clearly misaligned.

The vasal fluid proteomic profile and microscopic sperm presence at time of vasectomy reversal.

BACKGROUND: The microscopic characteristics of vasal fluid at time of vasectomy reversal (VR) guide operative decision making and predict fertility outcomes. The proteomic profile of this vasal fluid has not been described or correlated with the microscopic fluid appearance. To characterize the vasal fluid proteome at time of VR and evaluate the variation of the vasal fluid proteome with respect to microscopic presence of sperm. METHODS: A prospective cohort study was conducted enrolling twenty-five men undergoing VR for infertility and/or pain at a University-affiliated hospital. Vasal fluid samples obtained at time of VR were grouped based on presence of sperm on light microscopy at time of VR. Proteomic profiles were generated using liquid chromatography/ tandem mass spectrometry, and MS/MS protein spectral counts compared between individuals and treatment groups, controlling for less than 5% protein false discovery rate (FDR). Proteins were matched with the human swissprot database using the Comet search engine, and categorized by Gene Ontology (GO) terms. RESULTS: There was large variability between the 46 vasal fluid samples collected, with 1,692 unique proteins detected. The three most abundant proteins were Lactotransferrin, Cysteine-rich secretory protein 1, A-kinase anchor protein 4. There was no correlation between the proteome and microscopic sperm presence. Prevalent GO terms included viral process, signal transduction, innate immune response, protein folding and spermatogenesis. CONCLUSIONS: We describe the proteome and the most common proteins in vasal fluid at time of VR. Numerable sperm, testis and epididymis specific proteins were present even in the absence of sperm on microscopy. Further evaluation is needed to determine if a protein biomarker may better guide operative decision making and predict VR fertility outcomes.

Effects of Estrogen on Spermatogenesis in Transgender Women.

OBJECTIVE: To characterize spermatogenesis in the estrogenized transgender patient. MATERIALS AND METHODS: This is a retrospective, single-center, cross-sectional study. Seventy-two transgender women underwent gender-affirming orchiectomy between May 2015 and January 2017. All were on long-term (>1 year) cross-sex hormonal therapy prior to orchiectomy. Patient data were obtained via chart review. Histologic analysis was performed by a pathology resident under the supervision of a genitourinary pathologist. The main outcome is histologic presence of germ cells and presence of spermatids (a proxy for preserved spermatogenesis) in orchiectomy specimens. RESULTS: There were 141 pathologic specimens available for analysis. Germ cells were present in 114 out of 141 (81%) testicles. Spermatids were present in 57 (40%) testicles. Presence of germ cells was associated with older age (43 vs 35 years, P = .007) and increased testicular weight (28.6 g vs 19.3 g, P <.001). Presence of spermatids was associated with increased weight (31.5 g vs 23.3 g, P <.001) and volume (20.3 mL vs 12.6 mL, P <.001). There was a linear correlation between testis volume and preserved spermatogenesis (Pearson's r = 0.448, P <.001). CONCLUSION: Despite long-term hormone therapy, the majority (80%) of transgender women have germ cells present in the testicle. Spermatogenesis is preserved in approximately 40% of these individuals. Duration of hormonal therapy did not affect the degree of preservation of germ cells or spermatogenesis but starting hormonal treatment at a younger age may be associated with decreased germ cells in the testicle. Volume of testicles predict presence of preserved spermatogenesis.

Reproductive endocrinologists are the gatekeepers for male infertility care in North America: results of a North American survey on the referral patterns and characteristics of men presenting to male infertility specialists for infertility investigations.

OBJECTIVE: To characterize the referral patterns and characteristics of men presenting for infertility evaluation using data obtained from the Andrology Research Consortium. DESIGN: Standardized male infertility questionnaire. SETTING: Male infertility centers. PATIENT(S): Men presenting for fertility evaluation. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Demographic, infertility history, and referral data. RESULT(S): The questionnaires were completed by 4,287 men, with a mean male age of 40 years ± 7.4 years and female partners age of 37 years ± 4.9 years. Most were Caucasian (54%) with other races being less commonly represented (Asian 18.6%, and African American 5.5%). The majority (59.7%) were referred by a reproductive gynecologist, 19.4% were referred by their primary care physician, 4.2% were self-referred, and 621 (14.5%) were referred by "other." Before the male infertility investigation, 12.1% of couples had undergone intrauterine insemination, and 4.9% of couples had undergone in vitro fertilization (up to six cycles). Among the male participants, 0.9% reported using finasteride (5α-reductase inhibitor) at a dose used for androgenic alopecia, and 1.6% reported exogenous testosterone use. CONCLUSION(S): This broad North American patient survey shows that reproductive gynecologists are the de facto gateway for most male infertility referrals, with most men being assessed in the male infertility service being referred by reproductive endocrinologists. Some of the couples with apparent male factor infertility are treated with assisted reproductive technologies before a male factor investigation. The survey also identified potentially reversible causes for the male infertility including lifestyle factors such as testosterone and 5α-reductase inhibitor use.

Reconsidering vasectomy reversal over assisted reproduction in older couples.

OBJECTIVE: To provide pregnancy and live birth rates from a contemporary series of vasectomy reversals in men with female partners aged ≥35 years and to correlate the results with IVF. SETTING: Tertiary academic referral center. DESIGN: Retrospective comparative study of prospectively collected database. PATIENT(S): Two hundred forty-six men who underwent vasectomy reversal for fertility with female partner aged ≥35 years. INTERVENTION(S): Vasovasostomy or vasoepididymostomy. MAIN OUTCOME MEASURE(S): Correlation of pregnancy and live birth rate of this cohort by age groups with most recently published pregnancy and live birth rate per IVF cycle. RESULT(S): One hundred thirty-six men who underwent vasectomy reversal between 2006 and 2014 met our inclusion criteria. Overall pregnancy and live birth rates were 35% and 30%, respectively. Subgroup analysis by female age groups (35-37, 38-40, >40 years) demonstrated pregnancy and live birth rates comparable to those per IVF cycle by age groups according to a recently published (2015) national report. CONCLUSION(S): Vasectomy reversal should be strongly considered in men with a partner aged ≤40 years. Additionally, vasectomy reversal can be considered in carefully selected patients even with a partner aged >40 years.