Kyle Orwig

We are excited to introduce you to Kyle Orwig, Professor of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh School of Medicine. He directs a research lab at Magee-Womens Research Institute and a clinical center at Magee-Womens Hospital, where his work bridges innovative reproductive research and clinical care.

How did you find your way into the field of fertility preservation?

I have always worked in reproductive sciences, including research on ovary, placenta and testis function across multiple species, including mice, rats, cows, sheep, pigs, monkeys and humans. My second postdoctoral experience was in Ralph Brinster’s laboratory at the University of Pennsylvania who pioneered a method for transplanting spermatogonial stem cells (SSCs) into the testes of infertile males to restore sperm production and fertility. His group also demonstrated that SSCs could be frozen and thawed prior to transplantation without compromising their regenerative potential. We thought that technology might application for prepubertal boys who were at risk of infertility due to their diseases or medical treatments. Prepubertal boys are not yet producing sperm, but they do have SSCs in their testes that could potentially be cryopreserved prior to gonadotoxic treatment and thawed in the future to produce sperm using one of several technologies in the research pipeline. In 2012 we reported that SSCs could be frozen, thawed and transplanted to restore spermatogenesis in chemotherapy treated monkeys. This demonstrated safety and feasibility higher primates that justified approval of our initial TTC and OTC protocols in 2011. Our fertility preservation program now resides in the UPMC Magee Center for Reproduction and Transplantation that opened in 2020 and houses a dedicated andrology and fertility preservation clinical laboratory. Our center provides gonadal tissue cryopreservation services to over 60 institutions around the US, with a current volume of about 350 tissues cryopreserved each year. In addition to cryopreservation services, our center is also approved for SSC or testicular tissue transplantation and ovarian tissue transplantation.

 

If you had to choose a different field than fertility preservation, which field would you choose and why?

In addition to fertility preservation, our lab also conducts research on genetic causes of infertility and developing targeted gene therapies. It is believed that half of infertility is due to genetic causes but we still need to discover the causative genes in order to develop therapies. Gene therapy in and around the germline is controversial because transgenes or genetic edits can be passed to offspring with unknown consequences. Also, germline gene editing technologies could be used or abused to enable enhancements (e.g., intelligence, body characteristics, etc) in offspring.

We have a new project discovering stem cells in the vagina. This project is exciting because 100% of women will experience vaginal dysfunction at the time of menopause, if not before, and treatment options are limited. Little is know about the role of stem cells in the maintenance and regeneration of vaginal tissues after injury, so discoveries in this area could lead to new targets for treatment.

If not science, I think I would enjoy farming.

 

What moment in your career had the biggest impact on you? Or which achievement are you most proud of?

I am proud of our work in monkeys demonstrating that SSC transplantation and testicular tissue transplantation can produce sperm and offspring.

I am proud of our efforts to translate lab bench discoveries into clinical practice.

I am proud of our trainees who do the work and carry it forward.

 

What do you enjoy most about your job?

Every day is a different experience. I enjoy seeing our lab bench discoveries being translated into clinical care.

 

What advice would you give to your younger self (or to early-career researchers/clinicians)?

Don’t be afraid to fail. You will fail a lot but persistence pays off in the end.