Akanksha Mehta

Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor.

OBJECTIVEnTo evaluate surgical sperm retrieval rates in adolescents with Klinefelter syndrome and testosterone replacement therapy (TRT).nnnDESIGNnCase series.nnnSETTINGnAcademic medical center.nnnPATIENT(S)nTen patients with Klinefelter syndrome, aged 14-22 years, treated with testosterone replacement and aromatase inhibitor therapy for a period of 1-5 years before surgical sperm retrieval.nnnINTERVENTION(S)nMicrosurgical testis sperm extraction with cryopreservation of harvested tissue.nnnMAIN OUTCOME MEASURE(S)nPresence of spermatozoa within testis tissue.nnnRESULT(S)nSuccessful sperm retrieval in 7/10 patients (70%).nnnCONCLUSION(S)nUse of topical TRT did not appear to suppress spermatogenesis in adolescents with KS. It is uncertain whether sperm retrieval rates would be higher or lower without testosterone replacement in these young males. Sperm cryopreservation should be discussed in all KS adolescents who are either receiving or considering initiating TRT.

Klinefelter syndrome: an argument for early aggressive hormonal and fertility management

OBJECTIVEnTo investigate the impact of early hormone replacement therapy (HT) on sperm retrieval rates in patients with Klinefelter syndrome (KS).nnnDESIGNnA systematic review of the relevant literature using the PubMed NLM database.nnnRESULT(S)nThere are no randomized controlled trials evaluating the impact of HT on sperm retrieval or reproductive outcomes in men with KS. On average, surgical sperm retrieval rates in men with KS are around 51%, with a range of 28%-69%. Young patient age is the most consistent positive predictor of sperm retrieval. Lower retrieval rates have been reported in a small subset of KS adults who previously received exogenous T, although the nature, duration, and reason for such therapy in these patient subsets are unknown.nnnCONCLUSION(S)nEarly HT is recommended in patients with KS, but its effect on fertility potential has not been definitively studied. Larger studies are needed to better answer this question. Cryopreservation of sperm-containing semen or testicular tissue from a significant proportion of affected adolescents is possible, even when containing very low numbers of spermatozoa, and should be considered to maximize future fertility potential.

Activation of GPER-1 Estradiol Receptor Downregulates Production of Testosterone in Isolated Rat Leydig Cells and Adult Human Testis

Purpose Estradiol (E2) modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30), a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis. Materials and Methods Isolated Leydig cells (LC) from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH) -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist), and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Results GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20–30% as compared to estradiol-naïve LC. The exposure to G-1 does not affect viability of isolated LCs. Conclusions Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men.

Higher pregnancy rates using testicular sperm in men with severe oligospermia

OBJECTIVEnTo evaluate assisted reproductive technology (ART) outcomes using testicular sperm in oligospermic men who previously failed to achieve paternity using TUNEL-positive ejaculated sperm.nnnDESIGNnRetrospective cohort.nnnSETTINGnAcademic medical center.nnnPATIENT(S)nTwenty-four oligospermic men who failed one or more ART cycles using ejaculated sperm with TUNEL-positive proportion >7%, and subsequently underwent microsurgical testicular sperm extraction (TESE).nnnINTERVENTION(S)nTESE followed by intracytoplasmic sperm injection (ICSI).nnnMAIN OUTCOME MEASURE(S)nTUNEL-positive level in ejaculated and testicular sperm; clinical pregnancy.nnnRESULT(S)nThe mean TUNEL-positive level was 24.5% for ejaculated sperm, and 4.6% for testicular sperm. Clinical pregnancy was achieved in the first ART cycle with testicular sperm in 12 (50%) out of 24 couples. There was no statistically significant difference in maternal and paternal age, maternal gravity and parity, number of previous ART attempts, concentration or motility of retrieved sperm, number of oocytes retrieved, fertilization rate, or number of embryos transferred between couples who did and did not achieve pregnancy. No miscarriages occurred. All 12 pregnancies resulted in the delivery of healthy children.nnnCONCLUSION(S)nThe percentage of TUNEL-positive cells is lower in testicular sperm for oligospermic men who have abnormal ejaculated sperm DNA fragmentation. The use of testicular sperm for ICSI was associated with a 50% pregnancy and live-birth rate for couples who had previously failed one or more IVF-ICSI cycles with ejaculated sperm. No other clinical predictors of successful pregnancies after the use of surgically retrieved sperm could be identified. In men with elevated TUNEL-positive ejaculated sperm and failed ART, TESE may be considered.

Efficacy of a penile variable tension loop for improving climacturia after radical prostatectomy.

Climacturia is present in ∼20–40% of men after radical prostatectomy, and adversely affects sexual satisfaction. Although several strategies have been proposed for the treatment of climacturia, none have been systematically studied to date. This observational study shows that use of a penile variable tension loop can significantly reduce the degree and frequency of orgasm‐associated incontinence, and the associated distress experienced by patients and partners. Climacturia resolves completely in half the patients, and occurs occasionally or rarely in the remainder.

Safety and Efficacy of Testosterone Replacement Therapy in Adolescents with Klinefelter Syndrome

PURPOSEnWe investigated the safety and tolerability of testosterone replacement therapy in adolescents with Klinefelter syndrome.nnnMATERIALS AND METHODSnWe reviewed the medical records of all consecutive adolescents with Klinefelter syndrome evaluated between 2007 and 2012. Patients receiving testosterone replacement and aromatase inhibitor therapy were identified. Data on demographics, physical characteristics, medical history and serum hormone concentrations were collected for each patient. We evaluated longitudinal changes in serum testosterone, luteinizing hormone and follicle-stimulating hormone as well as changes in body mass index after the initiation of testosterone replacement therapy.nnnRESULTSnWe identified 151 adolescents with Klinefelter syndrome. Mean age at presentation was 11.6 years. Testosterone replacement therapy and aromatase inhibitors were initiated in 110 and 75 patients, respectively, at an average age of 13 to 14 years. Topical testosterone replacement therapy was used in 95% of patients with good clinical efficacy and compliance based on serial serum testosterone values. After the initiation of testosterone replacement therapy average serum testosterone improved from 240 to 650 ng/ml. Serum luteinizing hormone and follicle-stimulating hormone increased with the progression of puberty from 2.6 to 16.6 and 7 to 42 mIU/ml, respectively. No adverse outcomes related to testosterone replacement therapy were reported.nnnCONCLUSIONSnHormone supplementation with testosterone and aromatase inhibitors in adolescents with Klinefelter syndrome appears to be safe and effective for maintaining serum testosterone within the normal range. Compliance with topical formulations is high. Topical testosterone replacement therapy is not associated with the suppression of endogenous serum luteinizing hormone or follicle-stimulating hormone.

Perioperative Celecoxib Decreases Opioid Use in Patients Undergoing Testicular Surgery: A Randomized, Double-Blind, Placebo Controlled Trial

PURPOSEnWe evaluated the effect of daily perioperative celecoxib on patient reported pain control and opioid use after testicular surgery.nnnMATERIALS AND METHODSnMen scheduled to undergo elective outpatient microsurgical testicular sperm extraction were prospectively randomized to receive 200 mg celecoxib or placebo twice daily, which was initiated the night before surgery and continued for 6 days thereafter. Using an 11-point visual analog scale, participants self-reported the postoperative pain level and acetaminophen/hydrocodone use for supplemental pain control. We compared differences in pain scores and opioid use between the 2 patient groups using the Student t test with p<0.05 considered significant.nnnRESULTSnAt 1-year interim analysis 35 of 78 eligible participants (45%) had returned the study questionnaire, of whom 34 were included in the final analysis. Of the 34 patients the 16 who received celecoxib had significantly lower postoperative opioid use than those on placebo (6 vs 16 pills, p=0.02). We noted a statistically significant difference in postoperative day 1 and 2 patient reported pain scores (4 vs 6, p<0.05 and 3 vs 5, p=0.03) and opioid use (1 vs 5 pills, p<0.01 and 2 vs 4, p=0.02) seen between the celecoxib and placebo groups, respectively. No study complications were identified. The trial was terminated early based on the results of interim analysis.nnnCONCLUSIONSnTwice daily celecoxib use started preoperatively significantly decreased patient reported postoperative pain and opioid use, especially in the early postoperative period. A short course of celecoxib is well tolerated and may be effective as part of multimodal postoperative analgesia in patients who undergo testicular surgery for sperm retrieval.

Defining the aetiology of erectile dysfunction in men with chronic pelvic pain syndrome.

Men presenting with chronic pelvic pain syndrome (CPPS) frequently report concomitant erectile dysfunction (ED), but the underlying cause of ED in this patient population has not been previously studied. This study prospectively investigated the aetiology of ED in men with CPPS. The study population comprised 46 men with penile pain or dysorgasmia, and concomitant ED. All participants completed the NIH‐CPSI and international index of erectile function‐ erectile function domain (IIEF‐EFD) questionnaires, and underwent penile duplex Doppler ultrasonography (DUS), following intracavernosal trimix injection, to evaluate erectile hemodynamic parameters. Pearsons correlation between NIH‐CPSI and IIEF‐EFD scores, and between NIH‐CPSI score and the erectile response to trimix injections was investigated. The prevalence of mild, moderate and severe CPPS symptoms was 26, 48 and 26% respectively. The severity of ED was mild, moderate or severe in 15, 61 and 24% of men respectively. NIH‐CPSI and IIEF‐EFD scores were negatively correlated (r = −0.32, p = 0.002). Peak systolic velocity (PSV) and end‐diastolic velocity (EDV) were normal in 96 and 100% of men respectively. The majority of men (78%) required ≥2 trimix injections to attain an adequate erection for DUS. NIH‐CPSI scores and the number of trimix injections needed were positively correlated (r = 0.22, p = 0.035). The aetiology of erectile dysfunction in men who present with CPPS and concomitant ED is almost always psychogenic. Penile DUS in this population of men is fraught with the potential for error, and frequently necessitates more than one dose of a vasoactive agent.

Noninfertility Scrotal Microsurgery

The use of microsurgical techniques for noninfertility urologic surgery is growing. Urologic literature published over the past three decades describes the use of microsurgery for a variety of penile, scrotal, and upper urinary tract reconstructive procedures, testicular autotransplantation for cryptorchidism, testis-sparing surgery for testis tumors, spermatic cord denervation for chronic pain, as well as routine urologic procedures such as hernia repair, hydrocelectomy, spermatocelectomy. In the hands of skilled microsurgeons, superior outcomes have been reported following these procedures. With further improvements in microsurgical technology, and training of dedicated microsurgeons, the role for microsurgery will only continue to grow.

Treatment of Hypogonadism in Men

The goal of testosterone replacement therapy (TRT) is to alleviate the symptoms of hypogonadism while minimizing potential adverse affects associated with testosterone replacement. There are several approved options available for the treatment of androgen deficiency, including oral, transdermal, injectable, and implantable formulations of testosterone, as well as emerging therapies such as selective androgen receptor modulators (SARMs), each associated with specific advantages, disadvantages, and side effects. In men with an identifiable etiology of hypogonadism, the underlying pathology should be addressed first. For men interested in fertility, androgen deficiency may be treated with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropin therapy using human chorionic gonadotropin (hCG), purified or recombinant luteinizing hormone (LH) and follicle-stimulating hormone (FSH) preparations. The empiric use of selective estrogen receptor modulators (SERMs) and aromatase inhibitors for the treatment of men with primary hypogonadism is associated with variable outcomes, depending on the severity of the underlying defect. The choice of therapy should be guided by consideration of the formulation-specific pharmacokinetics and adverse effects, cost, and patient preference. All patients on any form of TRT should be evaluated on a regular basis.