Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

The Renaissance of Male Infertility Management in the Golden Age of Andrology.

Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with an increasing prevalence of male infertility. This suggests an urgent need to implement further basic and clinical research in Andrology. Andrology developed as a branch of urology, gynecology, endocrinology, and, dermatology. The first scientific journal devoted to andrological sciences was founded in 1969. Since then, despite great advancements, andrology has encountered several obstacles in its growth. In fact, for cultural reasons, the male partner has often been neglected in the diagnostic and therapeutic workup of the infertile couple. Furthermore, the development of assisted reproductive techniques (ART) has driven a strong impression that this biotechnology can overcome all forms of infertility, with a common belief that having a spermatozoon from a male partner (a sort of sperm donor) is all that is needed to achieve pregnancy. However, clinical practice has shown that the quality of the male gamete is important for a successful ART outcome. Furthermore, the safety of ART has been questioned because of the high prevalence of comorbidities in the offspring of ART conceptions compared to spontaneous conceptions. These issues have paved the way for more research and a greater understanding of the mechanisms of spermatogenesis and male infertility. Consequently, numerous discoveries have been made in the field of andrology, ranging from genetics to several "omics" technologies, oxidative stress and sperm DNA fragmentation, the sixth edition of the WHO manual, artificial intelligence, management of azoospermia, fertility in cancers survivors, artificial testis, 3D printing, gene engineering, stem cells therapy for spermatogenesis, and reconstructive microsurgery and seminal microbiome. Nevertheless, as many cases of male infertility remain idiopathic, further studies are required to improve the clinical management of infertile males. A multidisciplinary strategy involving both clinicians and scientists in basic, translational, and clinical research is the core principle that will allow andrology to overcome its limits and reach further goals. This state-of-the-art article aims to present a historical review of andrology, and, particularly, male infertility, from its "Middle Ages" to its "Renaissance", a golden age of andrology.

Cremaster muscle thickening: the anatomic difference in men with testicular retraction due to hyperactive cremaster muscle reflex.

The objective was to assess whether men suffering from testicular retraction secondary to hyperactive cremaster muscle reflex have an anatomic difference in the thickness of the cremaster muscle in comparison to men who do not have retraction. From March 2021 to December 2021, 21 men underwent microsurgical subinguinal cremaster muscle release (MSCMR) on 33 spermatic cord units, as 12 of them had bilateral surgery, at Surgicare of South Austin Ambulatory Surgery Center in Austin, TX, USA. During that same time frame, 36 men underwent subinguinal microsurgical varicocele repair on 41 spermatic cord units, as 5 were bilateral for infertility. The thickness of cremaster muscles was measured by the operating surgeon in men undergoing MSCMR and varicocele repair. Comparison was made between the cremaster muscle thickness in men with testicular retraction due to a hyperactive cremaster muscle reflex undergoing MSCMR and the cremaster muscle thickness in men undergoing varicocele repair for infertility with no history of testicular retraction, which served as an anatomic control. The mean cremaster muscle thickness in men who underwent MSCMR was significantly greater than those undergoing varicocele repair for infertility, with a mean cremaster muscle thickness of 3.9 (standard deviation [s.d.]: 1.2) mm vs 1.0 (s.d.: 0.4) mm, respectively. Men with testicular retraction secondary to a hyperactive cremaster muscle reflex demonstrate thicker cremaster muscles than controls, those undergoing varicocele repair. An anatomic difference may be a beginning to understanding the pathology in men who struggle with testicular retraction.

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.

Post-market safety and efficacy profile of subcutaneous testosterone enanthate-autoinjector: a cohort analysis.

A subcutaneous testosterone enanthate-autoinjector (SCTE-AI) was recently approved by the Food and Drug Administration for patient-administered weekly testosterone replacement therapy (TRT). From January 2019 to October 2019, 110 hypogonadal men were treated with SCTE-AI at two institutions. Patients were assessed in a pretherapy visit prior to receiving SCTE-AI and re-assessed 6 weeks after treatment initiation. Patients with a history of prostate cancer were excluded. Trough serum total testosterone (TT), estradiol (E2), prostate-specific antigen (PSA), and hematocrit (HCT) levels were collected at clinic visits. Therapeutic phlebotomy was recommended for HCT > 54%, and treatment was discontinued for significant increases in PSA as well as for significant treatment-related adverse events. Values from each visit were compared with univariate analysis. 110 patients completed the 6 weeks of observation with a mean age of 40.3 (SD: 10.5). TT significantly rose from 246.6 ng/dL (SD:113.3) pretherapy to 538.4 ng/dL (SD: 209.3) at 6 weeks (p < 0.001). Post-therapy, 101/110 (91.8%) of patients had TT > 300 ng/dL. No patients had HCT > 54%. 74 patients (70.5%) had PSA increase with only 3 (2.9%) experiencing an increase >1.0 ng/dL. There was a significant increase in mean PSA from 1.07 ng/dL (SD: 0.8) pretherapy to 1.18 ng/dL (SD: 0.9) at 6 weeks (p = 0.01). One patient had immediate treatment cessation following diagnosis of prostate cancer. This is the largest non-industry sponsored safety and efficacy profile of SCTE-AI application in urology clinics. After 6 weeks of observation, TT levels increased significantly without any reports of adverse events. SCTE-AI is a safe and effective alternative delivery system of TRT.

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.

The effects of hysteroscopic morcellation of endometrial polyps on frozen embryo transfer outcomes.

OBJECTIVE(S): To determine if hysteroscopic removal of endometrial polyps, specifically via morcellation of polyps, affects implantation rate (IR), clinical pregnancy rate (CPR), spontaneous abortion (SAB) rate, and live birth rate (LBR) in first frozen embryo transfer (FET) cycles. STUDY DESIGN: Retrospective chart review, with data abstracted from the charts of all first autologous oocyte frozen embryo transfer (FET) cases (n = 135) at a single fertility center from January 2018 through June 2020. Subjects were grouped into (A) hysteroscopic polypectomy prior to first FET (n = 25) or (B) no hysteroscopic polypectomy prior to first FET (n = 110). The primary outcome was live birth rate (LBR). Secondary outcomes were implantation rate (IR), clinical pregnancy rate (CPR), and spontaneous abortion (SAB) rate. RESULTS: We found no difference between the groups in terms of the primary outcome (LBR) or the secondary outcomes IR, CPR, and SAB rate. CONCLUSION(S): The data analyzed here suggest that hysteroscopic morcellation of endometrial polyps has no adverse effect on IR, SAB rate, CPR, or LBR among first FET cases after this type of polypectomy.

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.

The impact of ipsilateral testicular atrophy on semen quality and sperm DNA fragmentation response to varicocele repair.

Varicoceles adversely impact semen quality and sperm DNA fragmentation, which typically improve with surgical repair. Some men with varicoceles have ipsilateral testicular atrophy due to damage from the varicocele. This study assessed semen quality and the sperm DNA fragmentation index (DFI) response to varicocele repair in men with ipsilateral testicular atrophy (TA) versus men with no testicular atrophy (NTA). Semen parameter values and DFI in both groups were compared preoperatively and postoperatively. The Mann-Whitney U test and the Wilcoxon signed-rank test were used where appropriate. There were 20 men in the TA group and 121 men in the NTA group with no difference in age, varicocele grade, or preoperative semen parameter values between the two groups. The NTA group had a higher preoperative DFI than the TA group. Both groups showed improvement in semen quality postoperatively, only the TA group showed a significant improvement in DFI, whereas the NTA group showed significant improvements in several parameter values and DFI. The change from preoperative to postoperative parameter values when comparing the two groups revealed a difference in total sperm motile count and DFI, with a larger mean improvement in the NTA group than in the TA group. Both TA and NTA groups showed improved semen quality and DFI after varicocele repair, but the NTA group had more improvement than the TA group. However, only total motile count (TMC) and DFI had a significantly greater mean change in preoperative to postoperative response in the NTA group than in the TA group.

Preoperative Predictors of Failure of Microsurgical Spermatic Cord Denervation for Men With Chronic Orchialgia.

OBJECTIVE: To evaluate predictors of failure of microsurgical spermatic cord denervation (MSCD) for men with chronic orchialgia. METHODS: Retrospective chart review of men who underwent MSCD. Outcomes were recorded with potential preoperative predictors of failure. RESULTS: One hundred and five men underwent MSCD, and of those, 38 were bilateral for a total of 143 testicular units. Overall, 97 of 143 (67.8%) had complete resolution of pain, 27 of 143 (18.9%) had improvement of pain, and 19 of 143 (13.3%) were considered failures with either no improvement or less than 50% improvement in pain after MSCD with a 1-year follow-up period. Overall, 59 of 143 (41%) presented with intermittent orchialgia while 84 of 143 (59%) presented with constant pain. The mean preoperative visual analog scale was 6.8 ± 2 and the mean duration of pain prior to MSCD was 62.5 ± 100 months. Potential etiologies of pain per testicular unit included previous scrotal/inguinal surgery 17 of 143 (11.9%), postvasectomy pain syndrome (PVPS) 30 of 143 (21%), infectious epididymitis 9 of 143 (6.3%), trauma 15/143 (10.5%), and idiopathic 72/143 (50.3%). The only pre-operative predictor having an association with predicting failure was the etiology of orchialgia. Relative to men who had idiopathic orchialgia or prior scrotal/inguinal surgery inciting orchialgia, men with PVPS had increased odds of failure with MSCD. CONCLUSION: PVPS is an etiology associated with a higher risk of failure to respond to MSCD than idiopathic chronic orchialgia or chronic orchialgia subsequent to scrotal/inguinal surgery.

Converting Men From Clomiphene Citrate to Natesto for Hypogonadism Improves Libido, Maintains Semen Parameters, and Reduces Estradiol.

OBJECTIVE: To evaluate outcomes including libido, semen parameters, testosterone, estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone when converting men with low libido on Clomiphene Citrate (CC) to Natesto. METHODS: A retrospective chart review was performed. Baseline hormones prior to treatment, and again on CC and Natesto, as well as semen parameters on CC and on Natesto were assessed. RESULTS: In 41 men, there was no difference in serum testosterone levels on CC vs Natesto, however; there was a significantly higher E2 on CC than on Natesto. Although FSH levels were significantly lower on Natesto than at baseline, the mean FSH level on Natesto remained in the normal reference range. There was no difference in luteinizing hormone levels at baseline vs on Natesto. There was not a significant difference in semen parameter values when men were on CC vs when they were on Natesto for 3 months. At 3 months after changing to Natesto, 38 of 41 (92.7%) men reported significantly improved libido on Natesto when compared to CC. CONCLUSION: Men on CC and Natesto reach eugonadal testosterone levels, however; on CC the E2 level nearly doubled from baseline, and converting men from CC to Natesto returned E2 to nearly baseline levels. There was not a detrimental effect on semen parameters, and there was subjective reporting of improved libido after converting from CC to Natesto in this cohort, but further long-term studies are needed prior to Natesto being established as a definitive treatment for hypogonadism for men desiring to maintain fertility.

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.

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.

Sertoli cell only syndrome induced by a varicocele.

A case is reported which describes the severity of testicular histological damage that can be induced by a high-grade varicocele in a male with secondary infertility. A chart review of a patient's case was performed. A 34-year-old male with a three-and-a-half-year-old son who was conceived spontaneously with timed intercourse, with a grade three left varicocele, who's semen parameters progressed to non-obstructive azoospermia (NOA). He did not regain sperm in the ejaculate three or six months post left subinguinal microsurgical varicocele repair. He underwent bilateral microdissection testicular sperm extraction (microTESE) without identification of sperm in the testicular samples. A testicular biopsy from the time of microTESE revealed a Sertoli cell only pattern. A high-grade varicocele has the potential to induce sufficient testicular damage to result in the most severe testicular histological architecture associated with non-obstructive azoospermia (NOA), Sertoli cell only syndrome (SCOS).

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.

Validation of targeted microsurgical spermatic cord denervation: comparison of outcomes to traditional complete microsurgical spermatic cord denervation.

The aim of this study was to validate the effectiveness of targeted microsurgical spermatic cord denervation (MSCD) of the trifecta nerve complex in comparison to traditional full MSCD with complete skeletonization of the spermatic cord in men with chronic orchialgia. Retrospective chart review was performed by a single fellowship-trained microsurgeon between 2011 and 2016. Patients had follow-ups at 6 weeks, 6 months, and 1 year postoperatively. Thirty-nine men with chronic orchialgia underwent full MSCD between 2011 and 2013. In July 2013, after the publication of an anatomic study with identification of Wallerian degeneration of the trifecta nerve complex in men with chronic orchialgia, the technique was changed to targeted MSCD. From July 2013 to March 2016, 43 men underwent targeted MSCD. When comparing the full MSCD group to the targeted MSCD group, there was no significant difference in resolution of pain (66.7% vs 69.8%, P = 0.88), no difference in partial relief of pain (17.9% vs 23.3%, P = 0.55), and no difference in failure to respond rates (15.4% vs 7.0%, P = 0.22) between the two groups. There was no difference in mean change of visual analog pain scale scores between the two groups (P = 0.27). Targeted MSCD had a shorter operative time (53 min vs 21 min, P = 0.0001). Targeted MSCD offers patients comparable outcomes to traditional full MSCD, with a shorter operative time, a less technically challenging surgery, and potentially less risk to cord structures which should be preserved.

Clomiphene Citrate for the Treatment of Hypogonadism.

INTRODUCTION: Clomiphene citrate (CC) is a selective estrogen receptor modulator that has been used for the treatment of hypogonadism in men since the 1970s. It acts centrally to increase secretion of luteinizing hormone and follicle-stimulating hormone, thereby increasing testosterone production and serum levels. Unlike testosterone replacement therapy, CC does not suppress the hypothalamic-pituitary-gonadal axis, preserving intratesticular testosterone production and spermatogenesis. This is especially useful in treating hypogonadal men who are interested in fertility. AIM: To review the literature regarding the use of CC in the setting of hypogonadism. METHODS: A review of the relevant literature through September 2018 was performed via PubMed. MAIN OUTCOME MEASURE: The data regarding the efficacy and safety of CC when used in the setting of hypogonadism is summarized. RESULTS: Although results are mixed, many studies show CC reduces symptoms in hypogonadal men. Studies have also shown improvement in erectile function and bone mineral density, as well as a reduction in body mass index. There have been few studies investigating fertility rates in hypogonadal men treated with CC, but a metaanalysis of these shows significant improvement in fertility rates. Several studies show improvement in semen parameters. Few studies have investigated adverse effects of the drug. Reports include headache, dizziness, gynecomastia, and exacerbation of psychiatric illnesses. Despite these reports, CC is generally considered to be safe and well tolerated. CONCLUSION: CC is safe and effective and should remain in the armament of urologists treating hypogonadal men, especially men interested in preservation of fertility. Wheeler KM, Sharma D, Kavoussi PK, et al. Clomiphene citrate for the treatment of hypogonadism. Sex Med Rev 2019;7:272-276.