Ranjith Ramasamy

Successful Fertility Treatment for Klinefelter's Syndrome

PURPOSE We examined preoperative factors that could predict successful microdissection testicular sperm extraction in men with azoospermia and nonmosaic Klinefelters syndrome. We also analyzed the influence of preoperative hormonal therapy on the sperm retrieval rate. MATERIALS AND METHODS A total of 91 microdissection testicular sperm extraction attempts were done in 68 men with nonmosaic Klinefelters syndrome. Men with serum testosterone less than 300 ng/dl received medical therapy with aromatase inhibitors, clomiphene or human chorionic gonadotropin before microdissection testicular sperm extraction. Preoperative factors of patient age and endocrinological data were compared in those in whom the procedure was and was not successful. The sperm retrieval rate was the main outcome. Clinical pregnancy (pregnancy with heartbeat) and the live birth rate were also calculated. RESULTS Testicular spermatozoa were successfully retrieved in 45 men (66%), representing 62 (68%) attempts. Increasing male age was associated with a trend toward a lower sperm retrieval rate (p = 0.05). The various types of preoperative hormonal therapies did not have different sperm retrieval rates but men with normal baseline testosterone had the best sperm retrieval rate of 86%. Patients who required medical therapy and responded to that treatment with a resultant testosterone of 250 ng/dl or higher had a higher sperm retrieval rate than men in whom posttreatment testosterone was less than 250 ng/dl (77% vs 55%). For in vitro fertilization attempts in which sperm were retrieved the clinical pregnancy and live birth rates were 57% and 45%, respectively. CONCLUSIONS Microdissection testicular sperm extraction is an effective sperm retrieval technique in men with Klinefelters syndrome. Men with hypogonadism who respond to medical therapy may have a better chance of sperm retrieval.

High serum FSH levels in men with nonobstructive azoospermia does not affect success of microdissection testicular sperm extraction

OBJECTIVE To evaluate the outcomes of microdissection testicular sperm extraction (micro-TESE) in patients with high FSH. DESIGN Clinical retrospective study. SETTING Department of urology at a tertiary university hospital. PATIENT(S) Seven hundred ninety-two men with nonobstructive azoospermia. INTERVENTION(S) Micro-TESE followed by intracytoplasmic sperm injection was performed. The men were classified into four groups based on serum FSH levels: <15, 15-30, 31-45, and >45 IU/mL. MAIN OUTCOME MEASURE(S) Sperm retrieval, clinical pregnancy, and live birth rates. RESULT(S) Testicular sperm were successfully retrieved in 60% of the men. Sperm retrieval rates in the groups of men with FSH values 15-30, 31-45, and >45 IU/mL was 60%, 67%, and 60% respectively; this was higher than the group of men with FSH < 15 (51%). Of those men who had sperm retrieved, clinical pregnancy and live birth rates were similar in the four groups (46%, 50%, 52%, 46% and 38%, 45%, 44%, 36%, respectively). CONCLUSION(S) The chances of sperm retrieval using micro-TESE is just as common, if not better for men with elevated FSH levels than for men with lower FSH. Micro-TESE results appear to differ from earlier series that report low retrieval rates with random biopsies for men with elevated FSH. High FSH is not a contraindication for micro-TESE.

Role of Optimizing Testosterone Before Microdissection Testicular Sperm Extraction in Men with Nonobstructive Azoospermia

PURPOSE Although optimizing endogenous testosterone production before testicular sperm extraction is commonly practiced, whether improved preoperative testosterone levels enhance sperm retrieval remains unclear. We evaluated the influence of preoperative medical therapy in men with nonobstructive azoospermia before microdissection testicular sperm extraction. MATERIALS AND METHODS A total of 1,054 men underwent microdissection testicular sperm extraction from 1999 to 2010. Patients with preoperative testosterone levels less than 300 ng/dl were treated with aromatase inhibitors, clomiphene citrate or human chorionic gonadotropin before microdissection testicular sperm extraction with the goal of optimizing testosterone levels. Patient demographics, preoperative testosterone levels, sperm retrieval rate and pregnancy outcomes were recorded and compared in men with different baseline testosterone levels. RESULTS Of the 736 men who had preoperative hormonal data 388 (53%) had baseline testosterone levels greater than 300 ng/dl. The sperm retrieval rate in these men was 56%. In the remaining 348 men with pretreatment testosterone levels less than 300 ng/dl, the sperm retrieval rate was similar (52%, p = 0.29). In addition, the sperm retrieval, clinical pregnancy and live birth rates were similar between men who responded to hormonal therapy and those who did not. CONCLUSIONS Men with nonobstructive azoospermia and hypogonadism often respond to hormonal therapy with an increase in testosterone levels, but neither baseline testosterone level nor response to hormonal therapy appears to affect overall sperm retrieval, clinical pregnancy or live birth rates.

The role of estradiol in male reproductive function

Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone′s effects on erectile function, spermatogenesis, and libido.

Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: a systematic review and meta-analysis

OBJECTIVE To investigate the relative differences in outcomes among microdissection testicular sperm extraction (micro-TESE), conventional testicular sperm extraction (cTESE), and testicular sperm aspiration (TESA) in men with nonobstructive azoospermia. DESIGN Systematic review and meta-analysis. SETTING Outpatient academic and private urology clinics. PATIENTS(S) Men with nonobstructive azoospermia. INTERVENTION(S) Micro-TESE, cTESE, or TESA. MAIN OUTCOME MEASURE(S) Sperm retrieval (SR). RESULT(S) Fifteen studies with a total of 1,890 patients were identified. The weighted average age of the patients was 34.4 years, the follicular stimulating hormone level was 20.5 mIU/mL, the T was 373 ng/dL, and the testicular volume was 13.5 mL. In a direct comparison, performance of micro-TESE was 1.5 times more likely (95% confidence interval 1.4-1.6) to result in successful SR as compared with cTESE. Similarly, in a direct comparison, performance of cTESE was 2.0 times more likely (95% confidence interval 1.8-2.2) to result in successful SR as compared with TESA. Because of inconsistent reporting, evaluation of other procedural characteristics and pregnancy outcomes was not possible. CONCLUSION(S) Sperm retrieval was higher for micro-TESE compared with cTESE and for cTESE compared with TESA. Standardization of reported outcomes as well as combining all available SR data would help to further elucidate the SRs of these procedures.

Severe Testicular Atrophy does not Affect the Success of Microdissection Testicular Sperm Extraction

PURPOSE Men with azoospermia and severe testicular atrophy may be counseled to avoid sperm retrieval due to perceived limited success. We evaluated the outcomes of microdissection testicular sperm extraction in men with severe testicular atrophy (volume 2 ml or less). MATERIALS AND METHODS We reviewed the records of 1,127 men with nonobstructive azoospermia who underwent microdissection testicular sperm extraction followed by intracytoplasmic sperm injection. They were classified into 3 groups based on average testicular volume, including 2 ml or less, greater than 2 to less than 10 and 10 or greater. Sperm retrieval, clinical pregnancy and live birth rates were calculated. Clinical features evaluated included age, follicle-stimulating hormone level, cryptorchidism history, Klinefelter syndrome, varicocele and testicular histology on diagnostic biopsy. RESULTS Testicular sperm were successfully retrieved in 56% of the men. The sperm retrieval rate in those with a testicular volume of 2 ml or less, greater than 2 to less than 10 and 10 or greater was 55%, 56% and 55%, respectively. Clinical pregnancy and live birth rates were similar in men in the 3 groups who underwent sperm retrieval (55.2%, 50.0% and 47.0%, and 47.2%, 43.0% and 42.2%, respectively). Of the 106 men with an average testis volume of 2 ml or less those from whom sperm were retrieved were younger (31.1 vs 35.2 years) and more likely to have a history of Klinefelter syndrome (82.2% vs 55.6%) than men in whom sperm were not found (p <0.05). Men in this group had a higher prevalence of Klinefelter syndrome than men with a testis volume of greater than 2 ml (72.6% vs 5.3%, p <0.0001). Men younger than 30 years with Klinefelter syndrome had a higher sperm retrieval rate than men older than 30 years without Klinefelter syndrome (81.8% vs 33%, p <0.01). There was no cutoff point for age beyond which sperm could not be retrieved in men with small testes. On multivariable analysis younger age was the only preoperative factor associated with successful sperm retrieval in men with small testes (2 ml or less). CONCLUSIONS Testicular volume does not affect the sperm retrieval rate at our center for microdissection testicular sperm extraction. Of men with the smallest volume testes those who were younger with Klinefelter syndrome had the highest sperm retrieval rate. Severe testicular atrophy should not be a contraindication to microdissection testicular sperm extraction.

A comparison of models for predicting sperm retrieval before microdissection testicular sperm extraction in men with nonobstructive azoospermia.

PURPOSE We developed an artificial neural network and nomogram using readily available clinical features to model the chance of identifying sperm with microdissection testicular sperm extraction by readily available preoperative clinical parameters for men with nonobstructive azoospermia. MATERIALS AND METHODS We reviewed the records of 1,026 men who underwent microdissection testicular sperm extraction. Patient age, follicle-stimulating hormone level, testicular volume, history of cryptorchidism, Klinefelter syndrome and presence of varicocele were included in the models. For the artificial neural network the data set was divided randomly into a training set (75%) and a test set (25%) with n1/n2 cross validation used to evaluate model accuracy, and then modeled with a neural computational system. In addition, a nomogram with calibration plots was developed to predict sperm retrieval with microdissection testicular sperm extraction. We compared these models to logistic regression. RESULTS The ROC area for the neural computational system in the test set was 0.641. The neural network correctly predicted the outcome in 152 of the 256 test set patients (59.4%). The nomogram AUC was 0.59 and adequately calibrated. Multivariable logistic regression demonstrated patient age, history of Klinefelter syndrome and cryptorchidism to be significant predictors of sperm retrieval (p <0.05). However, follicle-stimulating hormone and testicular volume were not significant by internal validation. CONCLUSIONS We modeled a combination of well described preoperative clinical parameters to predict sperm retrieval using a neural computational system and nomogram with acceptable predictive values. The generalizability of these findings requires external validation.

Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios

Sperm DNA fragmentation (SDF) has been generally acknowledged as a valuable tool for male fertility evaluation. While its detrimental implications on sperm function were extensively investigated, little is known about the actual indications for performing SDF analysis. This review delivers practice based recommendations on commonly encountered scenarios in the clinic. An illustrative description of the different SDF measurement techniques is presented. SDF testing is recommended in patients with clinical varicocele and borderline to normal semen parameters as it can better select varicocelectomy candidates. High SDF is also linked with recurrent spontaneous abortion (RSA) and can influence outcomes of different assisted reproductive techniques. Several studies have shown some benefit in using testicular sperm rather than ejaculated sperm in men with high SDF, oligozoospermia or recurrent in vitro fertilization (IVF) failure. Infertile men with evidence of exposure to pollutants can benefit from sperm DNA testing as it can help reinforce the importance of lifestyle modification (e.g., cessation of cigarette smoking, antioxidant therapy), predict fertility and monitor the patient’s response to intervention.

Duration of Microdissection Testicular Sperm Extraction Procedures: Relationship to Sperm Retrieval Success

PURPOSE We evaluated the operative time of microdissection testicular sperm extraction in successful and failed procedures to identify the chance of sperm retrieval during longer microsurgical procedures. MATERIALS AND METHODS A total of 793 men with nonobstructive azoospermia underwent a first attempt at microdissection testicular sperm extraction from January 2000 to September 2009. Clinical factors were analyzed, including age, testicular volume, endocrinological data and histology. Operative time was calculated from incision until the procedure was terminated. RESULTS Testicular sperm were successfully retrieved in 57% of the men. Sperm were found within 2, 2 to 4 and 4 to 7 hours in 89%, 30% and 37% of the men, respectively. There were no differences in preoperative clinical characteristics, age, follicle-stimulating hormone, testicular volume, incidence of a Klinefelters syndrome diagnosis and distribution of most advanced histopathology in patients in the 3 operative time groups. In men in whom sperm were retrieved the clinical pregnancy and live birth rates were 48%, 45% and 29%, and 37%, 30% and 29% for operative times up to 2, 2 to 4 and 4 to 7 hours, respectively (p >0.05). ROC curve analysis of the different operative times for detecting sperm showed that 125 minutes was the most accurate time (AUC 0.81) with 84% sensitivity and 95% specificity. CONCLUSIONS The chance of sperm retrieval during microdissection testicular sperm extraction was best during the first 2 hours of the operation. However, sperm were still found in up to 37% of men who required greater than 4 hours of microdissection. Retrospective analysis of our data indicated no cutoff point after which sperm retrieval was uniformly unsuccessful.

Comparison of Complications of Laparoscopic Versus Laparoendoscopic Single Site Donor Nephrectomy Using the Modified Clavien Grading System

PURPOSE We compared postoperative complications of laparoendoscopic single site and standard laparoscopic living donor nephrectomy using a standardized complication reporting system. MATERIALS AND METHODS We retrospectively analyzed the records of consecutive patients who underwent a total of 663 laparoscopic living donor nephrectomies and 101 laparoendoscopic single site donor nephrectomies. All data were recorded retrospectively. The 30-day complication rate was compiled and graded using the modified Clavien complication scale. Multivariate binary logistic regression was used to determine independent predictors of complications. RESULTS Baseline demographics were comparable between the groups. Compared to those with laparoscopic living donor nephrectomy patients who underwent laparoendoscopic single site donor nephrectomy had a shorter hospital stay and less estimated blood loss but longer operative time (p <0.05) as well as higher oral but lower intravenous in hospital analgesic requirements (p <0.05). Mean warm ischemia time was marginally lower in the laparoendoscopic single site donor nephrectomy group (3.9 vs 4 minutes, p = 0.03). At 30 days there was no difference in the overall complication rate between the laparoscopic living and laparoendoscopic single site donor nephrectomy groups (7.1% vs 7.9%, p >0.05). There were 8 major complications (grade 3 to 5) in the laparoscopic living donor nephrectomy group but only 1 in the laparoendoscopic single site group. Multivariate binary logistic regression analysis revealed that estimated blood loss was a predictor of fewer complications at 30 days. CONCLUSIONS With appropriate patient selection and operative experience laparoendoscopic single site donor nephrectomy may be a safe procedure associated with postoperative outcomes similar to those of laparoscopic living donor nephrectomy as well as low morbidity. Using a standardized complication system can aid in counseling potential donors in the future.