Figure. Human cannabis users vs THC-exposed rhesus. A, Overlap of genes annotated to pre- vs high-THC differentially methylated regions (DMRs) with genes annotated cannabis user vs nonuser differentially methylated cytosines (DMCs). B, Overlap of genes annotated to pre- vs post-THC DMRs with genes annotated cannabis user vs abstinent-user DMCs. C, Enrichment for autism-spectrum disorder candidate genes. D, DMRs restored with THC discontinuation; E, DMRs nonrestored (persistent) with THC discontinuation. Adapted with permission from Hedges et al, J Urol. 2023;209(Suppl 4):e3-e4.¹

Once again, the annual AUA meeting delivered outstanding research and innovation in the field of male infertility. The program included multiple poster and podium sessions, courses, seminars, and plenary sessions covering a broad range of clinical and basic science topics.

Multiple studies utilized a translational approach to examine the impact of certain exposures on bulk semen parameters and sperm quality. Hedges et al (MP01-06) studied the impact of cannabis on the sperm epigenome using a rhesus macaque model with chronic δ-9-tetrahydrocannabinol (THC) exposure.¹ The authors performed whole genome bisulfite sequencing of sperm DNA collected from rhesus macaques at baseline, during high-THC exposure, and 140 days after THC discontinuation. They found significant overlap of genes annotated to differentially methylated regions (DMRs) in the monkeys and those of human cannabis users (Figure). Importantly, they found that high-THC DMRs had significant overlap with those associated with autism spectrum disorder, and many of these methylation changes persisted even after cessation of THC exposure, raising concern that chronic THC may alter the sperm epigenome in regions that can impact nervous system development and function.

Another study similarly sought to characterize the impact of e-cigarette vapor on bulk semen parameters and sperm DNA quality. Pelzman et al (MP01-13) used a mouse model, exposing mice to prolonged periods of e-cigarette vapor or simply the vaping vehicle and assessing the impact on sperm when compared to wild type mice.² They found that both the vaping and vehicle-only exposed groups had significantly decreased sperm concentrations compared to the wild type. Likewise, both groups showed impaired DNA repair mechanisms and significant increase in the number of apoptotic cells per seminiferous tubule. Collectively, these studies offer cautionary data to suggest that e-cigarette and cannabis exposure may have deleterious effects on sperm and reproductive health.

A number of groups reported their experiences with fertility preservation among transgender patients. Ralph et al (MP43-10) studied 122 adolescent patients referred for fertility preservation prior to initiation of gender-affirming hormone therapy.³ While 78 (65%) successfully masturbated and cryopreserved an average of 6.6 straws, a significant proportion of these patients had azoospermia (12%) or oligospermia (36%). Parikh et al (MP43-09) presented their single institutional experience in performing testicular tissue cryopreservation (TTC) in younger pre- and peripubertal patients (median age 12 years, range 10-16 years) prior to initiation of gender-affirming hormone therapy.⁴ Among 20 patients who underwent TTC, 100% were found to have spermatogonial stem cells that were successfully cryopreserved for future patient use. While this approach remains experimental, these results offer great promise for future reproductive technologies in these patients.

Health policy featured prominently throughout the meeting. Sandozi et al (PD20-12) characterized the landscape of state mandates addressing coverage for fertility care.⁵ Dupree et al (PD18-11) examined the downstream effects of these mandates on care utilization.⁶ The authors found that utilization of both in vitro fertilization and male fertility procedures (varicocelectomy, testicular and epididymal procedures) were highest in states with mandates for both in vitro fertilization and male-factor infertility coverage, indicating that these mandates do seem to improve access to fertility care.

There was a significant focus throughout the meeting on the condition of nonobstructive azoospermia (NOA). Campbell et al (MP01-07) found that men with NOA had a significantly less diverse microbiome, enriched for known pathogens, compared to fertile controls.⁷ Multiple groups sought to optimize predictors and prediction models for successful sperm retrieval in men with NOA using sperm-specific DNA methylation ratios (Jenkins et al, MP30-06⁸), artificial neural networks (Kobayashi et al, MP30-02⁹), and seminal cell-free DNA (Barney et al, MP01-01¹⁰).

An initial, single-arm trial demonstrated exciting potential for a new nonhormonal male contraceptive agent. Anderson et al (PD42-08) studied a degradable hydrogel contraceptive agent that was administered to a very small group of men (N=6) through a no-scalpel vasectomy approach to the vas deferens using a novel vasal injector device.¹¹ The procedure was well-tolerated by most with a total of 23 adverse events reported within the first month, mostly mild (78.3%) and consistent with typical postvasectomy bruising and discomfort. No severe adverse events were reported. Importantly, all 6 participants reached azoospermia by day 30. While larger studies and longer follow-up are needed to determine long-term safety and efficacy, and to identify the ideal candidate for this procedure, the trial provides encouraging preliminary data for the effectiveness of this new male contraceptive agent.

Beyond the primary research efforts, courses, and plenary sessions, the Sunday meeting of the Society for the Study of Male Reproduction also spanned a wide variety of themes in male infertility. Drs Ryan Flannigan and Joseph Gabrielsen discussed translational research exploring RNA, exosomes, epigenetics, and future therapies for spermatogenic failure. Subsequent speakers addressed office-based microsurgery, direct-to-consumer technologies in andrology, access to care for underserved populations, and the recent revamping of the Andrology Fellowship Match. After a robust discussion of health policy and the ability of research to effect change, the session concluded with outstanding talks from Drs Smith and Pierorazio about wellness, burnout, and efficiency in the busy life of a practicing andrologist.