Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate versus Subcutaneous Testosterone Enanthate.

PURPOSE: Intramuscular testosterone cypionate (IM-TC) is known to cause significant rises in estradiol (E2), hematocrit (HCT), and prostate specific antigen (PSA) due to its supraphysiological testosterone peaks, whereas a novel subcutaneous testosterone enanthate autoinjector (SCTE-AI) was designed with a lower testosterone peak-to-trough ratio to mitigate these reactions. We compare the total testosterone (TT), E2, HCT and PSA response to treatment with IM-TC versus SCTE-AI. MATERIALS AND METHODS: A total of 234 hypogonadal men were treated with testosterone replacement therapy (TRT) via IM-TC 100 mg weekly or SCTE-AI 100 mg weekly. TT, E2, HCT and PSA levels were obtained at baseline and 12 weeks post-treatment. Significant differences in baseline and post-treatment levels were identified by univariate analysis. Linear regression models determined whether treatment modality was independently associated with post-TRT levels of TT, E2, HCT and PSA. RESULTS: Post-TRT, both cohorts had significant increases in trough TT compared to their baseline levels (IM-TC: 313.6 ng/dL to 536.4 ng/dL, p <0.001; SCTE-AI: 246.6 ng/dL to 552.8 ng/dL, p <0.001). After linear regression, type of TRT modality was not found to be associated with TT levels (p=0.057). SCTE-AI was independently associated with lower post-therapy E2 (p <0.001) and HCT (p <0.001). Neither TRT modality was associated with significant post-therapy elevation of PSA (p=0.965). CONCLUSIONS: While IM-TC and SCTE-AI provide a significant increase in TT levels, SCTE-AI is associated with lower levels of post-therapy HCT and E2 compared to IM-TC after adjusting for significant covariates. SCTE-AI is an effective testosterone delivery system with a potentially preferable safety profile over IM-TC.

Vasocutaneous fistula formation and repair following inguinal hernia repair in a rhesus monkey (Macaca mulatta).

A 6-year-old adult male rhesus macaque (Macaca mulatta) developed a vasocutaneous fistula following an anatomic inguinal hernia repair years earlier. The vasocutaneous fistula was surgically repaired, the vas deferens was ligated, and the wound was closed in layers with non-overlapping suture lines with no further adverse sequalae of events.

Direct conversion from long-acting testosterone replacement therapy to Natesto allows for spermatogenesis resumption: Proof of concept.

Long-acting testosterone replacement therapy (TRT) suppresses spermatogenesis. A short-acting TRT, Natesto, maintains spermatogenesis in some men. This study evaluated hormonal and semen parameters converting men from long-acting TRT to Natesto. Baseline hormones, again on long-acting TRT and 1 month after converting to Natesto, as well as semen parameters 3 months after converting to Natesto were assessed. Twenty-seven men were directly converted from long-acting forms of TRT to Natesto. Mean duration on long-acting TRT was 24.3 ± 19 months. Testosterone levels were similar on long-acting forms of TRT and Natesto, however; E2 levels were significantly lower on Natesto. Ten men had semen analyses demonstrating azoospermia while on long-acting TRT, the remainder were presumed to be azoospermic or severely oligospermic which has been well established as an effect of long-acting TRT. All 27 men had resumption of spermatogenesis with a mean sperm concentration of 50.7 million/ml after converting to Natesto, considered within the fertile range. One couple achieved a pregnancy 4 months after converting to Natesto. Hypogonadal men on long-acting TRT interested in resumption of spermatogenesis may convert directly to Natesto for an opportunity to do so while remaining on a form of TRT and achieving lower E2 levels.

The expression of pregnancy-associated plasma protein-A (PAPP-A) in human blastocoel fluid-conditioned media: a proof of concept study.

PURPOSE: The aim of this study was to determine if pregnancy-associated plasma protein-A (PAPP-A), typically measured in maternal serum and a potential predictor of adverse maternal and fetal outcomes such as spontaneous miscarriage, pre-eclampsia, and stillbirth, is expressed in blastocoel fluid-conditioned media (BFCM) at the embryonic blastocyst stage. DESIGN: This is an in vitro study. METHODS: BFCM samples from trophectoderm-tested euploid blastocysts (n = 80) from in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients were analyzed for PAPP-A mRNA. BFCM was obtained from blastocyst stage embryos in 20 uL drops. Blastocysts underwent trophectoderm biopsy for preimplantation genetic testing for aneuploidy prior to blastocyst vitrification and BFCM collection for snap freezing. cfDNA was synthesized using BFCM collected from 80 individual euploid blastocysts. Next, real-time qPCR was performed to detect expression of PAPP-A with GAPDH for normalization of expression in each sample. RESULTS: PAPP-A mRNA was detected in 45 of 80 BFCM samples (56.3%), with varying levels of expression across samples. CONCLUSION: Our study demonstrates the expression of PAPP-A in BFCM. To our knowledge, this is the first study to report detection of PAPP-A mRNA in BFCM. Further studies are required and underway to investigate a greater number of BFCM samples as well as the possible correlation of PAPP-A expression with pregnancy outcomes of transferred euploid blastocysts. If found to predict IVF and obstetric outcomes, PAPP-A may provide additional information along with embryonic euploidy for the selection of the optimal blastocyst for embryo transfer.

FSH levels and testicular volumes are associated with the severity of testicular histopathology in men with non-obstructive azoospermia.

PURPOSE: The purpose of this study is to assess a potential association between FSH levels and testicular volumes with the severity of testicular histopathology on testicular biopsy in men with non-obstructive azoospermia (NOA) undergoing microdissection testicular sperm extraction (microTESE). METHODS: A retrospective chart review was performed from the electronic health records of men who underwent microTESE with NOA. RESULTS: Eighty-six men with NOA underwent microTESE with concomitant testicular biopsy for permanent section to assess the testicular cellular architecture. The histopathological patterns were categorized by severity indicating the odds of sperm retrieval into 2 categories. The unfavorable category included Sertoli cell only pattern and early maturation arrest (n = 50) and the favorable category included late maturation arrest and hypospermatogenesis patterns (n = 36). In the men with unfavorable histopathologic patterns, the mean FSH level was 22.9 ± 16.6 IU/L, and the mean testicular volume was 10.4 ± 6.0 cc. This was in comparison to men with favorable histopathologic patterns revealing a mean FSH level of FSH 13.3 ± 12.0 with a mean testicular volume of 13.3 ± 5.9 cc. There was a statistically significant higher FSH level in men with unfavorable histopathology than favorable (p = 0.004) as well as a significant smaller mean testicular volume in men with unfavorable histopathology (p = 0.029). CONCLUSIONS: Higher serum FSH levels and smaller testicular volumes are associated with more severe testicular histopathological patterns in men with NOA.

A comprehensive assessment of predictors of fertility outcomes in men with non-obstructive azoospermia undergoing microdissection testicular sperm extraction.

BACKGROUND: Microdissection testicular sperm extraction (microTESE) in men with non-obstructive azoospermia (NOA) is the procedure that results in the highest number of sperm cells retrieved for in vitro fertilization (IVF). This study presents a novel assessment of predictors of sperm retrieval as well as downstream embryology and pregnancy outcomes in cases of men with NOA undergoing microTESE. METHODS: A retrospective chart review of 72 men who underwent microTESE for predictors of fertility outcomes including sperm retrieved at microTESE, embryology progression to embryo transfer (ET), clinical pregnancy, live birth, and surplus sperm retrieved for additional IVF/intracytoplasmic injection cycles beyond one initial cycle. Statistical models for each of these outcomes were fitted, with a p-value of < 0.05 considered significant for the parameters estimated in each model. RESULTS: Seventy-two men underwent microTESE, and 51/72 (70.8%) had sperm retrieved. Of those, 29/43 (67.4%) reached ET. Of the couples who underwent ET, 21/29 (72.4%) achieved pregnancy and 18/29 (62.1%) resulted in live birth. Of the men with sperm retrieved, 38/51 (74.5%) had surplus sperm cryopreserved beyond the initial IVF cycle. Age, testicular volume, FSH, and testicular histopathology were assessed as predictors for sperm retrieved at microTESE, progression to ET, pregnancy, live birth, and surplus sperm. There were no preoperative predictors of sperm retrieval, clinical pregnancy, or live birth. Age predicted reaching ET, with older men having increased odds. FSH level had a negative relationship with surplus sperm retrieved. Men with hypospermatogenesis histology had higher rates of sperm retrieval, clinical pregnancy, live birth, and having surplus sperm. CONCLUSIONS: Men who underwent microTESE with a hypospermatogenesis histopathology had better outcomes, including higher rates of sperm retrieval, clinical pregnancy, live birth, and having surplus sperm retrieved. Increasing male partner age increased the odds of reaching ET. No other clinical factors were predictive for the outcomes considered.

Microsurgical subinguinal cremaster muscle release for chronic orchialgia secondary to hyperactive cremaster muscle reflex in adults.

A careful history and evaluation of men with chronic orchialgia elucidates the aetiology in some men to be a hyperactive cremaster muscle reflex with testicular retraction as the cause. The objective is to evaluate outcomes in men who underwent microsurgical subinguinal cremaster muscle release (MSCMR) with a retrospective chart review between September 2011 and April 2019. Nineteen men with hyperactive cremaster muscle reflex in 25 spermatic cord units underwent MSCMR, six bilateral and thirteen unilateral. Candidacy for MSCMR included answering yes to the question: "at times of testicular pain, does the testicle retract up in the groin to the extent that you have to milk it back down to the scrotum?", normal digital rectal examinations, negative urinalyses, negative scrotal Doppler ultrasounds, vigorous retraction of testis with Valsalva on examination and pain without an anatomic or pathologically identifiable aetiology except testicular retraction. Of the men who underwent MSCMR, 100% (25/25) of spermatic cord units had resolution of testicular retraction and 92% (23/25) of spermatic cord units had complete resolution of orchialgia. There was one complication, a small scrotal hematoma which resolved. MSCMR is an effective option for men with orchialgia secondary to testicular retraction due to a hyperactive cremaster muscle reflex.

Factors associated with subchorionic hematoma formation in pregnancies achieved via assisted reproductive technologies.

PURPOSE: To determine if certain clinical and/or embryologic factors are independently associated with the increased prevalence of subchorionic hematoma (SCH) among pregnancies achieved via in vitro fertilization (IVF) with fresh embryo transfer (ET). DESIGN: Retrospective chart review. METHODS: In this retrospective study, data were abstracted from 210 autologous oocyte IVF clinical pregnancies that resulted from fresh ET at a single fertility center from January 2012 through December 2016. Clinical and embryology laboratory variables were analyzed as possible factors associated with the presence or absence of SCH in IVF pregnancies via bivariate associations and multivariable logistic regression analyses. Independent variables included prior uterine surgery versus no uterine surgery, peak estradiol, and progesterone levels, day 3 (n = 92) versus day 5 (n = 118) ET, and assisted hatching versus no assisted hatching. Among the day 5 ET subgroup of 118 patients, 117 had data for the variables inner cell mass (ICM) grading and trophectoderm (TE) because one day 5 ET was at the morula stage. RESULTS: We found a significant bivariate association between TE grading and SCH, where cases with TE grade "A" were significantly less likely to have SCH compared with cases with grades "B" or "C." This significant difference remained when adjusting for the other factors considered in a multivariable logistic regression model for the probability of SCH. CONCLUSIONS: The data analyzed here suggest that a less-advanced trophectoderm grade may be a potential factor that is associated with the presence of SCH in pregnancies achieved via IVF.

Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism.

PURPOSE: Clomiphene citrate may be used as an off label treatment of hypogonadism. There are few long-term data on clomiphene citrate efficacy and safety when administered for more than 3 years. We assessed improvements in testosterone and hypogonadal symptoms while on clomiphene citrate for extended periods. MATERIALS AND METHODS: We performed a retrospective review to identify patients treated with clomiphene citrate for hypogonadism (baseline testosterone less than 300 ng/dl) at a total of 2 institutions from 2010 to 2018. We assessed the duration of clomiphene citrate therapy, serum testosterone levels, symptom improvement and clomiphene citrate side effects. RESULTS: A total of 400 patients underwent clomiphene citrate treatment for a mean ± SD of 25.5 ± 20.48 months (range 0 to 84). Of the patients 280 received clomiphene citrate for 3 years or less (mean 12.75 ± 9.52 months) and 120 received it for more than 3 years (mean 51.93 ± 10.52 months). Of men on clomiphene citrate for more than 3 years 88% achieved eugonadism, 77% reported improved symptoms and 8% reported side effects. Estradiol was significantly increased following clomiphene citrate treatment. Results did not significantly differ between patients treated for more than 3, or 3 or fewer years. The most common side effects reported by patients treated more than 3 years included changes in mood in 5, blurred vision in 3 and breast tenderness in 2. There was no significant adverse event in any patient treated with clomiphene citrate. CONCLUSIONS: Clomiphene citrate is not typically offered as primary treatment of hypogonadism in men who do not desire fertility preservation. These data demonstrate that clomiphene citrate is safe and effective with few side effects when used as long-term treatment of hypogonadism.

Serum Antimüllerian hormone does not predict elevated progesterone levels among women who undergo controlled ovarian hyperstimulation for in vitro fertilization.

Serum Antimüllerian hormone (AMH) has been shown to predict various in vitro fertilization (IVF) outcomes. AMH and progesterone (P) are products of granulosa cells of the ovary. Since overall granulosa cell number directly correlates with oocyte number and AMH production, the aim of this study is to evaluate whether or not serum AMH is associated with elevated P during controlled ovarian hyperstimulation (COH) for IVF. For this retrospective study, data were abstracted from charts of first IVF cycles of women (n = 201) who had undergone COH between May 2014 and May 2017. Groups were as follows: (A) AMH < 1 ng/mL (n = 32), (B) AMH 1-3.99 ng/mL (n = 109), (C), AMH ≥ 4 ng/mL (n = 60). The primary outcome measure was serum P level at trigger prior to oocyte retrieval. Mean serum P levels among groups A, B, and C were 0.92 ng/mL, 0.96 ng/mL, and 0.84 ng/mL, respectively. One-way ANOVA showed that there was no difference in mean serum P level among groups A, B, and C (p-value = 0.28). Multivariable linear regression with P as the dependent variable showed that total gonadotropin dose and peak estradiol level on day of trigger each had a significant positive relationship with P, and clinical pregnancy had a significant negative relationship. Although AMH is a predictor of certain IVF outcomes, AMH is not a predictor of elevated serum P level at trigger among women who undergo COH for IVF.

Ibuprofen does not have an adverse impact on semen parameters.

PURPOSE: A recent study suggested that ibuprofen may alter testicular physiology in a state of compensated hypogonadism, but only evaluated spermatogenic cells in a laboratory ex-vivo model with no significant effect, and found no significant change in follicle stimulating hormone (FSH) in men treated with ibuprofen. The study did not evaluate the impact of ibuprofen use on clinical semen parameters, which has not been assessed to date. The purpose of this study was to evaluate the impact of ibuprofen on semen parameters. METHODS: In a retrospective chart review from October 2012 to February 2018, 64 men had semen analyses revealing leukocytospermia and were treated with a 3-week course of ibuprofen 600 mg every 8 hours (1800 mg per day) and had a repeat semen analyses 3 weeks later. RESULTS: Of the 64 men diagnosed with leukocytospermia, 51 returned for post-treatment semen analyses. Parameters included semen volume, sperm concentration, motility, TMC, and forward progression. Morphology was excluded as it could not be standardized between assessments with strict Kruger criteria versus WHO fourth edition criteria depending on the lab in which it was performed. The mean age of these men was 35 (SD 4.6). There was no difference in mean abstinence intervals prior to semen analyses for the pre-treatment and post-treatment data. There was no significant difference in pre-treatment and post-treatment semen volumes, sperm concentrations, motility, TMC, or forward progression. CONCLUSIONS: Among men with leukocytospermia, the treatment with a 3-week course of ibuprofen at 1800 mg per day did not demonstrate a significant adverse impact on semen volume, sperm concentration, motility, TMC, or forward progressive motility when compared to pre-treatment semen analyses parameters.

A Comparison of Secondary Polycythemia in Hypogonadal Men Treated with Clomiphene Citrate versus Testosterone Replacement: A Multi-Institutional Study.

PURPOSE: We evaluated the relative prevalence of secondary polycythemia in hypogonadal men treated with clomiphene citrate or testosterone replacement therapy. MATERIALS AND METHODS: In this retrospective, multi-institutional study, we included 188 men who received clomiphene citrate and 175 who received testosterone replacement therapy with symptomatic hypogonadism. The overall prevalence and ORs of secondary polycythemia for clomiphene citrate treatment vs testosterone replacement were primarily measured, as were baseline characteristics. Subset analysis included polycythemia rates for different types of testosterone replacement therapy. RESULTS: Overall, men on testosterone replacement therapy were older than clomiphene citrate treated men (age 51.5 vs 38 years). Men on testosterone replacement had longer treatment duration than clomiphene citrate treated men (19.6 vs 9.2 months). For testosterone replacement therapy and clomiphene citrate the mean change in hematocrit was 3.0% and 0.6%, and the mean change in serum testosterone was 333.1 and 367.6 ng/dl, respectively. The prevalence of polycythemia in men on testosterone replacement was 11.2% vs 1.7% in men on clomiphene citrate (p = 0.0003). This significance remained on logistic regression after correcting for age, site, smoking history and pretreatment hematocrit. CONCLUSIONS: The prevalence of polycythemia in men treated with clomiphene citrate was markedly lower than that in men on testosterone replacement therapy. The improvement in absolute serum testosterone levels was similar to that in men on testosterone replacement. There is no significant risk of polycythemia in men treated with clomiphene citrate for hypogonadism.

Sperm retrieval and concomitant tumor resection in azoospermic men with congenital adrenal hyperplasia and bilateral testicular adrenal rest tumors: a case report.

PURPOSE: The objective of this study was to offer a new treatment approach for sperm retrieval simultaneously with tumor resection in azoospermic men with congenital adrenal hyperplasia (CAH), orchialgia, and bilateral testicular adrenal rest tumors (TARTs) who fail to respond to medical treatment. METHODS: This is a retrospective chart review from a couple's fertility center. RESULTS: Between May 2013 and May 2015, two azoospermic men with CAH and bilateral TARTs, with orchialgia, and desire to conceive underwent bilateral TART resection in the same surgical setting as sperm retrieval after remaining azoospermic with normalization of gonadotropins with treatment with human chorionic gonadotropin (hCG). Both men had adequate sperm retrieved for in vitro fertilization/intracytoplasmic sperm retrieval (IVF/ICSI) at the time of bilateral TART resections. They had complete TART resections with resolution of orchialgia. The wife of one patient had a successful pregnancy with use of retrieved sperm resulting in a live birth, and the sperm from the other man is cryopreserved for future use. CONCLUSIONS: It is feasible to perform successful sperm retrieval simultaneously with TART resection in azoospermic men with CAH after medical treatments with persistent azoospermia, rather than subjecting these men to multiple invasive procedures.

Alterations in microRNA expression in a murine model of diet-induced vasculogenic erectile dysfunction.

INTRODUCTION: MicroRNAs (miRs) are noncoding, endogenous RNA molecules that regulate gene expression and play roles in response to vascular injury. AIM: The aim of this study was to identify miRs expressed in corporal tissue (CT) and to determine whether miRs demonstrate differential expression in a mouse model of diet-induced erectile dysfunction (ED). METHODS: RNA was isolated from the CT from control mice and mice with diet-induced ED. A quantifiable miR profiling technique (NanoString) was used to determine the expression of over 600 miRs. MAIN OUTCOME MEASURES: Differential expression analysis was performed using a negative binomial regression model for count-based data. Mean expression levels, fold change, and false discovery-corrected P values were determined. Candidate miRs were validated via quantitative polymerase chain reaction (Q-PCR). RESULTS: In control mice, NanoString analysis revealed that 181 miRs were expressed above background levels and 5 miRs were expressed at high levels. Diet-induced ED resulted in the up-regulation of 6 miRs and the down-regulation of 65 miRs in the CT compared with mice on control diet. Focusing on the upregulated miRs, we chose five for Q-PCR validation. Of these five, two (miR-151-5p and miR-1937c) demonstrated significance via Q-PCR, whereas the other three (miR-720, miR-1937a, miR-205) trended in the correct direction. CONCLUSIONS: MiRs may play a significant role in mRNA regulation in CT and specific miRs may be involved in diet-induced vasculogenic ED. Future studies are aimed at determining the mRNA targets of these miRs.

Live birth following IVF/ICSI using oocytes from donor who was conceived via IVF: a case report.

PURPOSE: The purpose of the study was to report a case of live birth following donor oocyte in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in which the oocyte donor herself was conceived via IVF. To our knowledge, such a case has not been previously reported. METHODS: Retrospective chart review; this case is reported after chart review of a successful outcome. RESULTS: A 42 year-old woman, with diminished ovarian reserve, and her husband desired to conceive. She underwent a fresh IVF/ICSI cycle with her own oocytes, which unfortunately was not fruitful in terms of pregnancy or cryopreserved embryos. The couple was counseled regarding the option of donor oocytes, and they elected to proceed with a fresh cycle of donor oocyte IVF/ICSI. The couple selected an anonymous oocyte donor from a donor agency who was a first-time oocyte donor and, interestingly, was conceived via IVF herself. The fresh donor oocyte/IVF/ICSI cycle did not result in pregnancy; however, two supernumerary blastocysts were cryopreserved for future cycles. The recipient's subsequent frozen-thawed embryo transfer (FET) resulted in a singleton gestation and live birth. CONCLUSIONS: An oocyte donor who was conceived via IVF had good ovarian response to stimulation, a good number of oocytes retrieved, and the formation and cryopreservation of blastocysts which, in a subsequent FET cycle, resulted in pregnancy and live birth for a recipient couple. To our knowledge, this is the first case reported of live birth with the use of donor oocytes from an oocyte donor who herself was conceived via IVF.

The role of regulatory proteins and S-nitrosylation of endothelial nitric oxide synthase in the human clitoris: implications for female sexual function.

INTRODUCTION: During female sexual arousal, clitoral blood flow is controlled by endothelial nitric oxide synthase (eNOS) and its product, nitric oxide (NO). The mechanisms regulating eNOS activity and NO bioavailability in the clitoris are largely unknown. AIM: To identify proteins involved in regulation of eNOS activity within the clitoris and to evaluate the effects of S-nitrosoglutathione reductase (GSNO-R) and eNOS nitrosylation/denitrosylation on clitoral blood flow. METHODS: Immunohistochemistry for eNOS, caveolin-1 (Cav1), heat shock protein-90 (Hsp90), phosphodiesterase type 5 (PDE5), GSNO-R, and soluble guanylate cyclase (sGC) was performed on human and murine clitoral tissue. Western blot analysis was performed for eNOS, phosphorylated eNOS (phospho-eNOS, Ser1177), Cav1, Hsp90, sGC, PDE5, phosphoinositide 3-kinase (PI3K), Akt (protein kinase B), and GSNO-R on protein from human clitoral tissue. A biotin switch assay was used to analyze the S-nitrosylation of eNOS, nNOS, and GSNO-R. Clitoral blood flow was measured in wild-type and GSNO-R(-/-) mice at baseline and during cavernous nerve electrical stimulation (CNES). MAIN OUTCOME MEASURES: Localization of eNOS regulatory proteins and clitoral blood flow. RESULTS: eNOS and GSNO-R co-localized to the vascular endothelium and sinusoids of human clitoral tissue. Immunohistochemistry also localized Cav1 and Hsp90 to the endothelium and PDE5 and sGC to the trabecular smooth muscle. Expression of S-nitrosylated (SNO)-eNOS and SNO-GSNO-R was detected by biotin switch assays. Wild-type control mice exhibited increased clitoral blood flow with CNES whereas GSNO-R(-/-) animals failed to show an increase in blood flow. CONCLUSIONS: Several key eNOS regulatory proteins are present in the clitoral tissue in a cellular specific pattern. S-nitrosylation of eNOS may also represent a key regulatory mechanism governing eNOS activation/deactivation since mice deficient in GSNO-R failed to increase clitoral blood flow. Additional studies are necessary to define the role of S-nitrosylation in the genital vascular response and its subsequent impact on female sexual function.

Varicocele and nonobstructive azoospermia.

Approximately 15% of men in the general population have varicoceles, and varicoceles are diagnosed in 40% of men presenting for fertility evaluations. One percent of men in the general population are azoospermic, and 15% of men presenting for fertility evaluations are diagnosed with azoospermia. This article aims to review the impact of varicoceles on testicular function in men with azoospermia, the impact of varicocele repair on the semen parameters of azoospermic men, and the impact of varicocele repair on sperm retrieval and pregnancy outcomes when the male partner remains azoospermic after varicocele repair.

Technologies to improve sperm retrieval in men undergoing micro-TESE for NOA.

Nonobstructive azoospermia (NOA) is considered the most challenging clinical scenario for infertile men and current treatments leave many men unsuccessful at being able to achieve a pregnancy with their partner using their own sperm. Microdissection testicular sperm extraction (micro-TESE) is the choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection. With suboptimal micro-TESE success rates of sperm retrieval and then pregnancy and live birth using the retrieved sperm with in vitro fertilization/intracytoplasmic sperm injection, advances to improve outcomes are necessary. This article comprehensively reviews the technologies investigated to date to improve the outcomes for men undergoing micro-TESE.

Clinical predictors of successful outcomes for couples with nonobstructive azoospermic male partners undergoing micro-TESE.

ABSTRACT: Nonobstructive azoospermia (NOA) is the most challenging and complex clinical scenario for infertile men. Besides circumstances such as hypogonadotropic hypogonadism, surgical sperm retrieval is typically necessary, and microdissection testicular sperm extraction (micro-TESE) is the procedure of choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection (ICSI) in comparison to all other techniques for surgical sperm retrieval in men with NOA. Several factors may affect sperm retrieval rate and ICSI outcomes, including the patient's age, testicular volume, histopathological and genetic profile, and serum hormone levels. This article aims to review the medical literature describing predictors of successful micro-TESE and the outcomes of ICSI in men with NOA.

Increased phosphodiesterase type 5 levels in a mouse model of type 2 diabetes mellitus.

INTRODUCTION: Diabetes mellitus (DM) is a major risk factor for developing erectile dysfunction (ED) and men with DM are often less responsive to phosphodiesterase type 5 (PDE5) inhibitors than ED due to other causes. AIMS: The aim of this study was to explore potential mechanisms whereby PDE5 inhibitors may have reduced efficacy in type 2 DM. METHODS: At 4 weeks of age, mice were either fed a high-fat diet (HFD) for 22-36 weeks or fed regular chow (control). An additional group of mice in the same genetic background had a genetic form of type 1 DM. MAIN OUTCOME MEASURES: Glucose tolerance testing, intracorporal pressures (ICPs), oxidative stress (OS), apoptotic cell death (active caspase-3 and apostain), PDE5, p53, and cyclic guanosine monophosphate (cGMP) levels, and histological examination of inflow arteries were performed in mice fed a HFD and control mice. A group of mice with type 1 DM were studied for PDE5 expression levels. RESULTS: All mice fed a HFD had impaired glucose tolerance compared with the age-matched mice fed on standard chow diet (control). HFD fed mice had reduced maximum ICPs following in vivo cavernous nerve electrical stimulation and increased apoptotic cell death, OS, and p53 levels in the corporal tissue. Interestingly, PDE5 levels were increased and cGMP levels were decreased. In contrast, mice with type 1 DM did not have increases in PDE5. CONCLUSIONS: Taken together, our results suggest that type 2 DM-induced ED is associated with findings that could lead to reduced cGMP and may account for reduced efficacy of PDE5 inhibitors.