With the intensified direct marketing of sex medicine treatments to men, recent legislative changes in reproductive rights and their unknown long-term impact on the availability of assisted reproduction for infertile men, and the explosion of telemedicine, the practice of male sex medicine is evolving at a breakneck pace. Specialists in male sexual and reproductive medicine were commissioned to process the evolving literature and produce evidence-based treatment guidelines for men with erectile dysfunction, Peyronie’s disease, infertility, and a host of other conditions. Compared to other areas of urology and medicine in general, male sexual and reproductive medicine has a disappointingly small number of well-designed prospective studies, along with a significant funding gap for male reproductive health compared to female reproductive health. Several manuscripts published in 2022 began to fill this gap and provide valuable Level 1 evidence that supports (or disregards) key areas in sexual medicine and infertility.
In men with severe male infertility and non-obstructive azoospermia, surgery to obtain sperm is often indicated. Testicular sperm aspiration (TESA) and microdissection of testicular sperm extraction (mTESE) are two commonly used approaches. A recent study by Jensen et al. compared the effectiveness of these two approaches in one of the few prospective randomized controlled trials on male infertility.1 In the study, 49 patients were randomized to mTESE with a sperm recovery rate of 43% and 51 patients were randomized to TESA with a sperm recovery rate of 22%. Men with failed TESA then proceeded to rescue mTESE with a combined sperm recovery rate of 29%. However, participants in the mTESE arm had decreased postoperative testosterone levels and 24% of participants experienced de novo hypogonadism at 6 months. Previous literature has suggested that the drop in testosterone is transient and likely to recover after 12 months. In summary, the study results indicated that mTESE remains the gold standard for the treatment of non-obstructive azoospermia, but patients should be educated about the risk of de novo hypogonadism.
Despite this, mTESE success rates remain modest and depend on the expertise and skill of the laboratory and andrologist processing the tissue. Several hours can be spent trying to find the few viable sperm hidden in a sea of distractors. A recent study by Lee et al. investigated the power of artificial intelligence to detect human sperm in semen and mTESE samples using brightfield microscopy for patients with non-obstructive azoospermia (NOA).2 First, they trained the program to identify sperm from semen samples from fertile patients. After validating the effectiveness of their algorithm, they retrained it to identify sperm in tissues from NOA patients spiked with large amounts of sperm. When tested on samples containing 3,000 to 6,000 sperm along with other cell types, they achieved a positive predictive value of 84.0% and a sensitivity of 72.7%. Finally, without retraining their algorithm, they tested it on samples containing 10 to 200 sperm, replicating the “rare sperm” phenomenon seen in patients with NOA. Their model was able to recognize 2969 out of a total of 3517 sperm with a sensitivity of 84.4% PPV and 86.1%. The clinical applications of artificial intelligence and machine learning in medicine continue to grow and have found their way to male infertility. While this is not yet ready for immediate clinical use, it underscores the need for further work to harness the power of the technology to improve andrologist workflow and thereby increase the success of infertility treatment for patients.
As the population ages and the number of comorbidities increases, the need for male sexual health and reproductive health specialists has increased rapidly, although certain disease processes falling within this specialty may potentially be managed by a general urologist. In an analysis of the current educational landscape, Asanad et al. drawing attention to the need for a structured educational curriculum in male infertility residency.3 In a survey of urologists, 54 out of 72 respondents (75%) said male infertility was less than 10% of their education. Compared with residents who did not learn from an infertility-trained professional, residents exposed to an infertility-trained professional were 14.4 times more likely to feel safe performing infertility procedures (P < 0.001) and felt more comfortable performing post-residency fertility procedures (P = 0.001).3 For trainees, their career depends on what they are exposed to. Smaller subdisciplines within urology may be more difficult to teach consistently, and perhaps there are opportunities for motivated physicians to increase exposure to these areas (e.g., by attending other programs).
One disease process within male sexual health that all urologists should be able to diagnose and treat initially is erectile dysfunction (ED). With studies reporting ED prevalence as high as 52%, demand for ED treatment providers remains sky-high. Current treatment options include phosphodiesterase type 5 inhibitors (PDE5is), intracavernous injections, vacuum erection devices, and penile prostheses. A newcomer to the field is shock wave therapy, which uses controlled energy to induce angiogenesis.
The short-term efficacy of focused shockwave therapy in patients with moderate ED was evaluated in a double-blind, randomized, sham-controlled study.4 In this study of 70 patients with moderate ED, 35 were randomly assigned to low-intensity shock wave therapy (LiST) and the other 35 were randomly assigned to sham therapy. After a 4-week washout of PDE5i, patients underwent LiST or sham treatment twice weekly for 6 weeks. One month after completion of treatment, 59% of patients in the LiST group experienced at least a 5 point improvement in the International Index of Erectile Function (IIEF) compared to 1 patient (2.9%) in the sham group (P < 0.001). This effect persisted 3 months after treatment. Therefore, the short-term data for LiST are compelling and suggest that it could be a viable option in treating vasculogenic ED for men with mild/moderate ED. More studies are urgently needed to validate these findings, and urologists have an obligation to provide patients with an honest assessment of the data and only recommend treatments where the risks (including the financial burden) outweigh the benefits.
In stark contrast to focused therapy, radial shockwave therapy uses low-pressure radial shockwaves to treat ED. To characterize its effectiveness, 80 men with mild to moderate ED were enrolled in a randomized, double-blind, sham-controlled clinical trial.5 Patients were treated weekly for 6 weeks with either radial wave therapy or sham therapy, and the primary outcome measured was the change in IIEF score between baseline and post-treatment. The study results showed that there was no significant difference in IIEF scores between the groups at 6 weeks or 10 weeks after randomization. The study results revealed the lack of evidence supporting the use of radial wave therapy.
Despite the evidence of its ineffectiveness in treating ED, shock wave therapy, and radial wave therapy in particular, have been heavily marketed directly to consumers in the United States. A recent article using a “secret shopper” method found troubling marketing and practice trends in the US. The authors noted that patients are often not adequately informed about the different types of treatments and may not know if the administrator is a licensed physician.6 With average treatment costs between $2,600 and $3,900 per cycle, clinics offering radial wave therapy have an obvious financial incentive to continue marketing it despite a lack of evidence of its effectiveness.
Recent advances in the field of male sexual health and reproduction present a bright future for the field with new diagnostic and therapeutic options on the horizon. However, it is evident that the demand for specialized men’s health treatments still exceeds supply. Urologists must work diligently to fill this gap, not only to improve patient access to evidence-based care, but also to prevent men from falling victim to practices looking to exploit this unmet demand and a vulnerable patient population.
references
1. Jensen CFS, Ohl DA, Fode M, et al. Microdissection of testicular sperm extraction versus multi-needle percutaneous testicular sperm aspiration in men with nonobstructive azoospermia: a randomized clinical trial. EUR Urol. Published online May 19, 2022. doi:10.1016/j.eururo.2022.04.030
2. Lee R, Witherspoon L, Robinson M et al. Automated identification of rare sperm from low-magnification microscopy images of dissociated microsurgical testicular sperm extraction specimens using deep learning. Fertile Sterile. 2022;118(1):90-99. doi:10.1016/j.fertnstert.2022.03.011
3. Asanad K, Nusbaum D, Fuchs G, Rodman JCS, Samplaski MK. The impact of male infertility on urology residency training. andrology. 2022;54(8):e14457. doi:10.1111/ and.14457
4. Kalyvianakis D, Mykoniatis I, Pyrgidis N, et al. The effect of low-intensity shockwave therapy on moderate erectile dysfunction: a double-blind, randomized, sham-controlled clinical trial. J Urol. 2022;208(2):388-395. doi:10.1097/JU.0000000000002684
5. Sandoval-Salinas C, Saffon JP, Martínez JM, Corredor HA, Gallego A. Are radial pressure waves effective for the treatment of moderate or mild to moderate erectile dysfunction? A randomized sham therapy-controlled clinical trial. J Sexmed. 2022;19(5):738-744. doi:10.1016/j.jsxm.2022.02.010
6. Weinberger JM, Shahinyan GK, Yang SC, et al. Shockwave therapy for erectile dysfunction: marketing and practice trends in major metropolitan areas in the United States. Urol practice. 2022;9(3):212-219. doi:10.1097/UPJ.0000000000000299
