Larry I. Lipshultz¹, Jin Ye Yeo²

¹Scott Department of Urology, Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX, USA; ²TAU Editorial Office, AME Publishing Company

Correspondence to: Jin Ye Yeo. TAU Editorial Office, AME Publishing Company. Email: tau@amepc.org

Expert Introduction

Dr. Larry I. Lipshultz (Figure 1) is a male infertility specialist and is recognized as a world-renowned expert in male reproductive medicine and microsurgery. He holds the Smith Chair in Reproductive Medicine and has a research focus on abnormalities of male reproduction, erectile dysfunction, and male hormone therapy. To date, he has performed more than 2000 vasectomy reversals, and his expertise is highly sought after by people from all over the world.

Dr. Lipshultz is a 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, and has trained over 120 fellows. He is a member of the editorial board of more than 20 medical journals and has now published over 440 journal articles. He is also an active member of numerous scientific organizations.

Dr. Lipshultz was the founder of the Society for the Study of Male Reproduction and was previously the President of the American Society for Reproductive Medicine. Dr. Lipshultz, who was the first AUA Research scholar, also served on the FDA Advisory Committee for Reproductive Health Drugs and was awarded the prestigious Hugh Hampton Young Award at the 2005 AUA Annual Meeting held in San Antonio, Texas. Dr. Lipshultz has received numerous clinical awards and honors throughout his career, including the American Association of Genitourinary Surgeons Spence Award and the American Society for Reproductive Medicine Kavoussi Family Outstanding Teacher Award in 2022, and the Androgen Society Dedication to Education Award in 2023.

Figure 1 Dr. Larry I. Lipshultz

Interview

TAU: What drove you into the field of urology?

Dr. Lipshultz: My settling on urology as a subspecialty is an interesting story. I started working while a college student in my senior year at the University of Pennsylvania’s Harrison Department of Surgical Research. As a student, I was assigned to a mentor. By chance, my mentor was a urologist, Dr. Joseph Corriere. I had no idea what urology was but knew it was a surgical subspecialty. Dr. Corriere became not only my mentor but also my role model. I continued to work with him during medical school on various research projects and became more and more interested in the field of urology. By the time I was a third-year student, I was convinced that this was my field of choice. Consequently, I applied to the department and was accepted. This began my journey into the field of urology. My entrance into the subspecialty of infertility is a whole other story.

TAU: As a pioneer in urological microsurgery, could you provide an overview of the current landscape of publications in urological microsurgery? Were there any articles or innovations in recent years that impressed you?

Dr. Lipshultz: The landmark publication of the technique of vasectomy reversals and a review of its success was authored by Belker et al. in 1992 and focused on the vasectomy study group’s review of their over 1,000 completed vasectomy reversal cases. Interestingly, since then there have not been any other landmark groundbreaking studies. The two-layer vasovasostomy technique these authors describe has held up well over the past 25+ years with only slight modifications. Debate has included whether a one-layer versus a two-layer microscopic vasectomy reversal is better, and it would certainly seem that the two-layer microscopic technique has been shown to be superior. The increase in the quality of microsutures, microsurgical instruments, and microscopes has led to increasing success with microscopic reversals. Interestingly, a significant change occurred in 1998 and 2000, when articles describing a new intussusception technique for microscopic epididymovasostomies were described by both Berger and later by Marmar. Most microsurgeons now favor the use of this intussusception technique. Other than modifications of epididymovasostomy techniques, there have been few significant publications on the technique of vasectomy reversal that I find have impacted my practice.

TAU: As a leading expert in male reproductive medicine, what specific areas or aspects of male infertility research do you believe have been overlooked or received insufficient attention?

Dr. Lipshultz: Many of the studies that we have worked on over the years I think received insufficient development. These investigators were excellent ideas initially but should have been further investigated. For example, in 1991 we published a paper focusing on altered receptor binding activity of serum follicle-stimulating hormone (FSH) in infertile men with elevated FSH and luteinizing hormone (LH), i.e., hypergonadotropic hypogonadism. However, while the results were very interesting, we never did more to identify the clinical impact of this type of finding. With the availability of FSH and human chorionic gonadotropin (HCG) as parenteral injections, it would now be possible to increase bioactive FSH in those men who demonstrate decreased FSH bioactivity, as we described in this paper in 1991. However, this area has not been further developed. Another example would be the significance of DNA fragmentation in male infertility. While we think this is an important area of clinical pursuit, many andrologists do not consider DNA fragmentation to be a significant pathophysiologic finding. I still feel that it deserves much more attention and greater scientific study, since it would appear that men with excess DNA fragmentation can initiate pregnancies that may end in increased and recurrent miscarriage or even lack of fertilization itself. Furthermore, current studies would suggest that the use of testicular sperm in these men may lessen the DNA fragmentation index (1). In addition, the introduction and rapid development of artificial intelligence needs to be better focused on male infertility to perhaps identify patterns seen in our patients that might give some direction for further investigation of the man with idiopathic infertility. Certainly, many more areas require more attention and have been somewhat overlooked in the multitude of investigations that have generated single publications without further study.

TAU: The field of male fertility treatments is witnessing rapid advancements. What innovative solutions do you believe hold the most promise for improving outcomes and expanding options for individuals and couples facing fertility challenges?

Dr. Lipshultz: Whole Genome Sequencing (WGS) is an innovative technique that I think holds significant prominence for improving outcomes and expanding options for infertile males. Long-read WGS is a cutting-edge technique that reads very long segments of DNA at once, providing a comprehensive view of an individual’s genetic blueprint. This method significantly improves the ability to detect complex genetic variations that shorter reads might miss, enhancing our understanding of genetic disorders, especially as it pertains to infertile males. Clinically, this technology is pivotal for diagnosing rare genetic conditions, improving personalized medicine, and offering insight into previously unexplained medical conditions such as idiopathic male infertility.

TAU: Moving forward, what do you think should be the direction of male reproduction research?

Dr. Lipshultz: As I explained previously, I feel that whole genome sequencing may open some very important doors to a better understanding of male fertility failure. However, this current technique is expensive, time-consuming, and generates volumes of data. The key is being able to interpret this data and to succinctly collate what is important, which I think is possible with the marriage of artificial intelligence and whole genome sequencing. With properly trained modules, the data can be more rapidly filtered for significant findings and clinically interpreted to aid in the better understanding of unexplained male infertility.

TAU: Reflecting on your journey from initially encountering urology to being one of the world's most renowned urologists, how has your perception of the field evolved and shaped your professional path?

Dr. Lipshultz: My perception of the field of male reproduction has been shaped by much of what has happened around me rather than within my own area of practice. In 1978, with the advent of the first IVF baby, we saw the birth not only of this child but also of the field of reproductive endocrinology and in vitro fertilization (IVF) within the United States. Beginning as a spark and then rapidly becoming a fire and then a blaze, this field steered the direction of men’s fertility management. Initially, while all men, as part of an infertile couple, were seen by urologists while their wives were seen by gynecologists, couples are now being sent directly to the IVF program. Men were detoured and often not referred for a urologic evaluation until much later in the couple’s fertility journey. With the introduction of intracytoplasmic sperm injection (ICSI) in 1994, there was again a second giant leap towards focusing on female factors and putting the male evaluation in the background. Later in the early 2000s, when it was found that sperm extracted from first the epididymis and later the testis itself could be used to effectively initiate a pregnancy, the male evaluation was further defined as a second tier of evaluation after the couple would experience IVF fertility failure. Thus, urologists in the field have been encouraged to develop and become proficient at sperm extraction techniques and even, as in our laboratory, sperm processing. While I think this has been a benefit to infertile couples, I am afraid that males have not received the same evaluation as their female partners. Work by Eisenberg and colleagues at Stanford has clearly shown that male infertility may be a barometer of men’s health and that men with significant infertility may experience increased cancer, increased general morbidity, and even increased mortality. I remain a champion for evaluating the male patient early and as an equal partner in a couple’s journey to fertility success.

TAU: Could you share how you keep yourself motivated despite being a urologist for a long time? What aspects of your work provide the most satisfaction and motivation for you?

Dr. Lipshultz: Throughout these years, it is clear to me that I derived my greatest motivation and satisfaction from seeing the successful results of fertility treatment. I keep two large montages of photographs in my waiting room composed of a collage of baby pictures. Anyone who looks at this is reminded of the fact that there may be no greater gift to a couple than their children. Being able to participate in providing this gift certainly motivates me and gives me unparalleled satisfaction.

TAU: How has your experience been as an Editorial Board Member of TAU?

Dr. Lipshultz: I have thoroughly enjoyed my time on the editorial board of TAU. Dr. Liu has put together a very diverse and clinically experienced group of scholars from around the world. Their combined knowledge has certainly enhanced the quality of the journal over the past 10 years and given it an international focus in both the Eastern and Western hemispheres that is rarely seen in other such publications. I have enjoyed the creative staff of TAU and their innovative projects that focus on interesting and unusual areas of andrology, while at the same time developing a cutting-edge view of the complicated and diverse subject of men’s health.

TAU: As an Editorial Board Member of TAU, what are your expectations for TAU?

Dr. Lipshultz: I expect TAU to grow and become an even more respected journal in the years to come. Because of its international editorial board, I feel that it offers a unique platform for authors to publish a vast array of topics that fall under the broad heading of andrology and urology, incorporating both basic science and clinical advances.

Reference

1. Alvarez JG. 'Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular sperm'. Hum Reprod. 2005;20(7):2031-2032. doi:10.1093/humrep/deh814