Moving From Infertility to Possibility for Males With Prune Belly Syndrome

Fertility is an unanswered question for many males with prune belly syndrome. Advances in reproductive medicine are creating new possibilities, but understanding who can benefit — and how — requires more research.

When a child is diagnosed with prune belly syndrome (PBS), the immediate clinical patient priorities are often clear: preserve and maintain kidney function, manage urinary tract abnormalities, and address the undescended testicles characteristic of the condition. However, as these children grow into adolescents and adults, questions about fertility emerge.

I have spent much of my career caring for individuals with PBS and working to better understand this complex condition. One of the most important lessons learned is that we must look beyond the immediate medical needs of childhood to consider the long-term quality of life of our patients in adulthood, including the possibility of parenthood.

For many years, we haven’t been able to give families much encouraging information about reproductive potential. Fortunately, with today’s advances in assisted reproductive technology (ART), the conversation is changing.

Understanding the Barriers to Fertility

Prune belly syndrome is a rare congenital condition characterized by deficient abdominal wall musculature, urinary tract abnormalities, and bilateral undescended testicles. Although the severity of the syndrome varies considerably, reproductive challenges are common.

There are four major threats to male fertility in PBS patients:

• impaired sperm production associated with undescended testicles (also known as cryptorchidism)
• malformed male reproductive tubes (vas and epididymis)
• retrograde ejaculation
• potential genetic factors affecting reproductive function

The first challenge begins at birth. In all males, the testicles form in the belly close to the kidneys and then typically make the journey from the belly, through the groin and into the scrotum.  In males with PBS, both testicles typically remain high within the belly rather than descending into the scrotum. This matters because normal spermatogenesis requires a temperature approximately 1.5 to 2 degrees Celsius below core body temperature. When the testicles remain in the belly, warmer temperatures can damage the self-renewing stem cells in the testicles called Ad spermatogonia, which are the germ cells that differentiate into mature swimming sperm at puberty.  If the number of healthy germ cells decreases, future sperm production can be compromised.

Early orchiopexy, the surgery to bring the testicles from the belly to the scrotum, is vital to mitigating this risk. Ideally, bilateral orchiopexy should occur between 6 and 12 months of age. Early intervention offers the best opportunity to minimize testicular germ cell death and preserve fertility while also reducing the risk associated with undescended testicles, including testicular malignancy after puberty.

However, orchiopexy in PBS is more complicated than in patients with isolated cryptorchidism. The testicles are often located high in the abdomen, and patients may have additional cardiopulmonary or urinary tract conditions that complicate surgical planning. Since both testicles are undescended, most require staged open or laparoscopic orchiopexy surgeries, and the risk of compromising the testicular blood supply must be considered.  To minimize the number of surgeries for the young child, orchiopexy is commonly performed simultaneously with urinary tract reconstruction and abdominoplasty, if needed.

Importantly, successful orchiopexy does not guarantee normal spermatogenesis. Historical data suggest that approximately 50% of males with PBS had no identifiable sperm production, 47% had reduced sperm production and only 3% had normal sperm production. However, in older publications, it is not always known at what age the orchiopexy surgery was performed and there may have been less of a push for early orchiopexy.

While the data appears discouraging at face value, when counseling families today, it’s important to provide context. Much of the available evidence spans decades during which surgical techniques, timing of surgery and reproductive technologies changed substantially.

We do not yet know how accurately these historical findings reflect outcomes for individuals with PBS receiving contemporary care of the 21st century.

Our PBS research group at Nationwide Children’s Hospital is performing a PBS male reproduction study that looks at the entire lifetime, addressing parental and PBS individual reproductive desires, surgeries and outcomes.

Sperm Production Is Only Part of the Challenge

Even when sperm production is preserved, males with PBS may have difficulty delivering sperm out of the testis.  In up to 35% of males with an undescended testis, the epididymis and vas are malformed, preventing sperm flow from the testicles to the seminal vesicles and ejaculatory ducts.

For many males with PBS,  retrograde ejaculation occurs when semen travels backward into the bladder rather than forward out through the urethra. Normally, the bladder neck closes during ejaculation to prevent this backward flow. However, in patients with PBS, a congenitally wide-open bladder neck interferes with that process. Available data show approximately 40% of males with PBS experience retrograde ejaculation.

Although retrograde ejaculation is not inherently harmful to the individual, it can significantly complicate conception. Sperm entering the bladder are exposed to urine, which can rapidly impair sperm viability.

To address this challenge, medications that increase bladder neck resistance may improve antegrade ejaculation, but their effectiveness is limited and potential negative effects on bladder emptying on urination must be considered. Alternatively, sperm may be recovered from the bladder urine after ejaculation using techniques that modify the urine pH and allow prompt sperm collection.

When sperm cannot be recovered through ejaculation or post-ejaculatory urine collection, surgical retrieval, including testicular sperm aspiration (TESA), percutaneous epididymal sperm aspiration (PESA) and surgical testicular sperm extraction (TESE), is another option. More advanced techniques, including microdissection testicular sperm extraction (microTESE), use magnification to identify areas of the testicle that may contain sperm.

When viable sperm are recovered, they may be used in assisted reproductive technologies (ART).

Assisted Reproduction Offers New Possibilities

One of the most encouraging developments in male reproductive medicine is the ability to achieve fertilization with very small numbers of viable sperm. In vitro fertilization (IVF) is often combined with intracytoplasmic sperm injection (ICSI), in which a single sperm is injected directly into an egg.

The first published reports of successful assisted conception involving males with PBS date back more than two decades. Since then, reproductive technology has continued to advance.

While ART makes conception possible for more males with PBS, when counseling patient and families, we also must recognize the considerable financial, physical and emotional demands of fertility treatment. IVF and surgical sperm retrieval can involve substantial out-of-pocket expenses, and treatment may require multiple attempts without guaranteeing pregnancy.

These realities make individualized counseling and collaboration between pediatric urologists, adult male infertility specialists and reproductive endocrinologists particularly important.  Nicholas Tadros, MD, is a urologist specializing in male infertility and PBS; he primarily works at The Ohio State University and is an integral part of our PBS multidisciplinary care team at Nationwide Children’s.

Additionally, families should be counseled on the genetic implications of PBS. The genetics of PBS remain incompletely understood. Although genetic variants have been identified in 10% of affected individuals, we need much more information about inheritance patterns, reproductive outcomes and the potential contribution of specific genetic changes to infertility. For families considering pregnancy, genetic counseling may be appropriate, particularly when a genetic cause has been identified. To better understand the genetics of PBS, our research group has a large research study underway and we invite all individuals with PBS to participate.

Fertility Counseling Should Begin Before Adulthood

One question I frequently hear is, “When should fertility evaluation begin?”

The answer depends on the patient’s age, development and personal goals.

For infants, the most important fertility-preserving intervention is timely orchiopexy. As children approach adolescence, conversations about puberty, sexual function and future reproductive possibilities can become part of longitudinal urologic care. Thoughtful approaches to conversations with teens and families can be tailored to the patient’s interests.

For older adolescents and adults interested in understanding their reproductive potential, semen analysis and consultation with a male infertility specialist may be appropriate.

Unlike certain other conditions associated with progressive loss of sperm production, there is insufficient evidence to suggest that males with PBS routinely benefit from sperm retrieval or cryopreservation immediately after puberty. This remains an area where additional research is needed.

For adults actively attempting conception, early referral is recommended. Although infertility is commonly defined after 12 months of unsuccessful attempts to conceive, men with PBS may benefit from evaluation sooner because of their known reproductive risk factors.

We also must consider the broader health implications of PBS. Chronic kidney disease, kidney failure and dialysis may further impair reproductive function. Kidney transplantation can improve some fertility-related abnormalities associated with renal failure, although it does not eliminate the underlying reproductive challenges of PBS.

Ultimately, reproductive counseling should be integrated into lifelong care rather than treated as an issue that arises only when a patient begins trying to conceive.

Building Evidence for Better Outcomes

Despite decades of clinical experience with PBS, our understanding of male reproductive outcomes remains remarkably limited. To address gaps in knowledge, we are advancing research on male reproduction in PBS through collaboration between Nationwide Children’s and Ohio State.

By learning from adolescents and adults with PBS, including those who have attempted conception and those who have successfully become fathers, we hope to develop a more complete picture of reproductive health across the lifespan.

This research also underscores the importance of multidisciplinary care and thoughtful transition from pediatric to adult specialists.

As pediatric physicians, we have an opportunity to influence reproductive health decades before a patient considers parenthood. Early surgical decisions, long-term follow-up and open conversations about fertility may all shape future possibilities.

For families who have spent years wondering whether biological parenthood is possible, even incremental advances in our understanding can be meaningful.

A Family’s Perspective: From Uncertainty to Parenthood

Tara wrote, “Thank you for the incredible work you do for the PBS community.  Your team’s dedication to research, education, and supporting families truly makes a difference.  We are so grateful for the resources you’ve created and for the hope you’ve given families like ours.  With heartfelt thanks, Tara and Brandon.”

For clinicians and researchers, messages like this remind us that fertility is not simply a measure of sperm production or reproductive anatomy. It is deeply connected to our patients’ hopes for their futures.

And for families living with PBS, knowing that biological parenthood has been achieved can make the future feel a little more hopeful.