Larry I. Lipshultz, MD, presented “Epigenetic Testing for Male Fertility Management” at the 26th Annual Innovations in Urologic Practice on September 15th, 2022.

How to cite: Lipshultz, Larry I. “Epigenetic Testing for Male Fertility Management” September 2022. Accessed May 2024.

Epigenetic Testing for Male Fertility Management – Summary

Larry I. Lipshultz, MD, Professor of Urology and Chief of the Scott Department of Urology’s Division of Male Reproductive Medicine and Surgery at Baylor College of Medicine in Houston, Texas, discusses epigenetic testing for male fertility management, first explaining the importance of understanding the genetics of male infertility for patient counseling and treatment. He outlines pre-testicular, intrinsic testicular, and post testicular genetic abnormalities and gives examples and causes of each type. He highlights Klinefelter’s Syndrome, a major cause of hypergonadotropic hypogonadism that accounts for two thirds of the chromosomal abnormalities in infertile men. Dr. Lipshultz explains Y chromosome microdeletions and the test used to analyze azoospermia factor regions (AZFa, AZFb, AZFc regions). Dr. Lipshultz then explains post-testicular causes such as mutations in the Cystic Fibrosis Transmembrane Regulator Gene (CFTR) and Young’s syndrome, which is characterized by obstructive azoospermia, chronic sinusitis, bronchiectasis, and azoospermia, and has an unclear cause, though he explains it is likely tied to abnormal ciliary function. He outlines the available genetic tests, including Y chromosome analysis (microdeletions), karyotyping, CFTR and Intron-8 splice variant, sperm deoxyribonucleic acid (DNA) integrity testing, fluorescence in situ hybridization (FISH), and preimplantation genetic diagnosis (PGD). In Y chromosome testing for microdeletions, Dr. Lipschultz explains that if testing results show complete AZFa or AZFb microdeletions, no further interventions are necessary because these men will not have sperm; in contrast, men with AZFc microdeletions have a 56 percent chance of having sperm found on testicular sperm extraction (TESE). He then addresses karyotype testing and emphasizes the importance of high-resolution banding and explains that karyotype abnormalities will be present in 10-15 percent of azoospermic men, five percent of oligospermic men, and even in one percent of men with normal sperm concentration. Dr. Lipshultz again addresses Klinefelter’s syndrome and explains that in many of these patients, sperm can be extracted (data show sperm retrieval in 30-60 percent of patients and, of those, fertilization rates >50 percent). In conclusion, Dr. Lipshultz reviews who should be offered genetic testing, including men with sperm concentration <5-10 million sperm/ml; men with absent vas deferens on examination, idiopathic genital ductal obstruction; and men with known genetic conditions or the clinical features of an undiagnosed genetic condition. 

About The 26th Annual Innovations in Urologic Practice:

Presented by co-chairs Mohit Khera, MD, MBA, MPH, and Michael Coburn, MD, FACS, the Innovations in Urologic Practice conference provides a detailed review and commentary on multiple genitourinary and urologic diseases. Among the featured oncological topics are bladder cancer and immunotherapies, as well as upper tract cancer management, prostate cancer, including state-of-the-art imaging, focal therapy, and MRI. Experts also discuss new tools and techniques for nephrectomy and treating advanced renal cell carcinoma. In terms of general urological approaches, the conference also includes pelvic reconstruction and trauma; men’s health topics like male infertility, andrology, and sexual dysfunction; OAB and voiding dysfunctions; and ways to diagnose and treat infections in the urology patient.

For further educational activities from this conference, visit our collection page.