Despite the challenges of the virtual AUA, this year’s conference delivered spectacular research and innovation in the field of male infertility. The program included multiple poster (MP-21, MP-31) and podium (PD-29, PD-39) sessions, along with plenary panel discussions covering a broad range of clinical topics, including a review of the new AUA Guideline on the Diagnosis and Treatment of Infertility in Men.

In the basic and translational science arena, multiple investigators developed novel approaches towards the study and understanding of spermatogenesis. One group used both whole testes and testicular organoids to identify 133 unique miRNAs present along various stages of spermatogenesis, providing new insight into the role of miRNA in regulation of spermatogenesis (PD39-05). Another group used sorted cells from human testicular biopsies in a bioprinted microfiber, demonstrating high cell viability and an intrinsic ability for cell organization after bioprinting (PD39-09; see figure). This model shows significant promise as a platform for future studies of spermatogenesis and regenerative therapies.

Figure. Three-dimensional bioprinted hollow tubules similarly sized to seminiferous tubules. Contained within concentric rings are human Sertoli cells, Leydig cells, myoid cells and spermatogonial stem cells. These constructs were then cultured in media conditions to promote in vitro spermatogenesis.

A large number of studies focused on the condition of nonobstructive azoospermia (NOA). Single-cell transcriptome analysis of spermatogonia from men with NOA due to early maturation arrest (25) and obstructive azoospermia (12) were compared in order to determine differences in gene expression between men with impaired versus normal spermatogenesis (PD39-02). Over 5,000 differentially expressed genes were upregulated and over 12,000 differentially expressed genes were downregulated in spermatogonia of men with NOA, indicating that impaired spermatogenesis is likely the result of a large number of alterations in gene expression working in concert across functional areas pertaining to DNA synthesis, cell cycle, stress response and glucose metabolism.

A randomized trial compared the success of testicular sperm aspiration (TESA) and microdissection testicular sperm extraction (microTESE) in men with NOA (MP31-03). After randomization, men who underwent TESA with negative sperm retrieval went on to a subsequent “salvage” microTESE. Only 22% of TESA patients had successful retrieval compared to 43% of microTESE patients (p=0.02). Interestingly, even with salvage microTESE, successful retrieval in the TESA + salvage group was seen in only 29% of men; while the study was underpowered to compare the salvage protocol to conventional microTESE, these data support the role of microTESE as a gold standard approach for NOA.

Lastly, a deep learning artificial intelligence approach was used for automated sperm identification in men with NOA (PD39-12), showing great promise for convolutional neural networks to support andrological evaluation of semen specimens that may harbor rare sperm.

Two studies examined the relationship between reproductive urologists and reproductive endocrinologists and its impact on access to care for male infertility. Interviews with 477 assisted reproductive technology clinics revealed that higher number of in vitro fertilization cycles, urban location, presence of fertility fellowship program in-state and affiliation with an academic center were all associated with a higher likelihood of urology referral for male-factor infertility (PD29-04). Institutional data from a single, high-volume center found that overall urology referral rates for men with semen parameter abnormalities was quite low at just 20.5% (PD29-03). There was also significant variability in referral rates across individual reproductive endocrinologist providers. Together, these data suggest an important role for further interdisciplinary communication and collaboration to increase the proportion of men who undergo reproductive urology evaluation.

Klinefelter syndrome (KS) was the focus of multiple abstracts throughout the meeting (MP31-08, MP31-09, MP31-12, PD39-06, MP47-01), and 2 studies specifically examined the use of testosterone replacement therapy (TRT) in men with KS. Among 290 men with KS who underwent microTESE, men without current or recent TRT use had significantly higher sperm retrieval rates (85.7%) compared to those on short-acting (40.0%) and long-acting (0.0%) TRT medications, suggesting a negative impact of TRT upon sperm retrieval in these patients (MP31-08). The risks of TRT in men with KS were also examined among 235 men across a national-access database (MP31-09). Men receiving TRT had significantly higher rates of thromboembolic events compared to those not receiving TRT (30.4% vs 10.9%, p <0.001). While limited by small sample size and retrospective design, these studies demonstrate important risks of TRT in the KS population, which physicians should discuss with patients and consider before initiation of TRT.

As the COVID-19 pandemic ushered in the era of telemedicine, multiple abstracts throughout the meeting explored the use of telemedicine for health care delivery. One retrospective study examined the use of telemedicine versus in-person visits for the initial consultation prior to vasectomy (PD25-12). A very high proportion of men (97.4%) who had initial telemedicine consultation went on to successfully complete a vasectomy, which was similar to those who underwent in-person consultation (98.7%, p=0.68). While 3 (2.6%) procedures were aborted due to anatomical considerations on the day of the procedure, these data provide reassurance that the overwhelming majority of men are good candidates for telemedicine consultation prior to this procedure.

The program concluded with an excellent overview of the new 2-part AUA Guideline on the Diagnosis and Treatment of Infertility in Men from Dr. Peter Schlegel, Chair of the guideline panel.^1,2 The updated guidelines emphasize the importance of the male partner evaluation in parallel to the female evaluation. Other notable changes include more extensive statements in the realm of fertility preservation, critical assessment of the role of lifestyle factors and medical therapy in male infertility, and restriction of criteria for retroperitoneal evaluation in the setting of an isolated right varicocele.