AUA 2019: European Urological Association (EAU) Lecture: Fertility Preservation in Cancer Patients

Chicago, IL ( Dr. Sønksen gave a comprehensive, focused talk on fertility preservation in cancer patients (adult and pediatric) as part of the EAU lecture at the AUA.

Some basic demographics and statistics:

  • 1,735,000 new cancer diagnoses in the United States each year
  • 135,000 cases in patients in their reproductive years (20-44 years old)
  • 17,000 cases in patients below 20 years old
Given this and the fact that 80% of current childhood cancer patients survive, the concept of fertility preservation is going to become more and more relevant!

We know that both cancer and cancer treatments have a negative impact on fertility. Therefore, fertility preservation is defined as the saving of oocytes (females) and spermatozoa (males) or reproductive tissue (both) with the aim of future parenthood.

Dr. Sønksen broke this down into 3 groups:

  • Females (pre- and post-puberty): Cryopreservation of ovarian tissue, specifically the primordial follicles from the ovarian cortex
  • Males (post-puberty): Cryopreservation of ejaculated spermatozoa
  • Males (pre-puberty): Cryopreservation of spermatogonial stem cells (SSCs) from testicular tissue
The first two are well established. The last has been the most difficult to achieve.

He then briefly touched on each of these techniques, primarily with anecdotes, but also with some data.

Females (pre- and post-puberty): Cryopreservation of ovarian tissue, specifically the primordial follicles from the ovarian cortex

This is a well-established procedure. Ovaries are harvested and primordial follicles in the cortex are sectioned, separated and frozen. Then, when the time is appropriate for reimplantation, this is done through autotransplantation through either laparoscopy or mini-laparotomy. It can be placed orthotopically, or as demonstrated more recently, heterotopically (sub-peritoneal, anterior abdominal wall, or lateral pelvic wall). The precipitous drop in FSH demonstrates ovarian tissue activity after reimplantation.

Anecdotally, the first baby ever born after autotransplantation of ovarian tissue was to a woman with thalassemia in the UK. Ovarian tissue was frozen at the age of 9 in 2001, and then she underwent bone marrow transplantation. Ovarian tissue was brought to Denmark and was autotransplanted in 2015. The patient conceived after IVF treatment in the UK and gave birth in December of 2016.

The numbers have since been increasing internationally, with the most in Denmark, Germany, Israel, and the US.

Males (post-puberty): Cryopreservation of ejaculated spermatozoa

This is also already well established. In adult males, masturbation and collection of semen is the optimal method for collection and storage of sperm for future fertility.

Dr. Sønksen focused much of this session on how to optimize collection from post-pubertal pediatric patients aged 12-18 years old. As he notes, this isn’t always a comfortable topic for the patients at this age, and collection becomes the biggest issue. He also noted that at a younger age, the volume and concentration of sperm are lower than older patients.

Options for assisted ejaculation for these patients include:

  • Perineal stimulation – a tool has been developed that provides perineum stimulation to the patient and an easy collection device. This may work for some patients and allow them the opportunity to obtain a sample without too much discomfort.
  • Electroejaculation – another established method to occur under anesthesia 
Between these two methods, he notes that his group has never had to go to surgery for sperm retrieval.

However, sperm retrieval via TESE or TESA are options (testicular sperm aspiration or extraction) as a last resort.

Males (pre-puberty): Cryopreservation of spermatogonial stem cells (SSCs) from testicular tissue

Cryopreservation in pre-pubertal boys has been the most difficult, as they have not yet begun to produce sperm. There are 2 strategies: 1) In vitro maturation of SSCs and 2) transplantation of SSCs.

In the first method, SSCs are identified from testicular tissue and then developed in vitro. However, identification of SSCs in testicular tissue is not easy! The goal is then to grow these in vitro and mature them in vitro, to eventually obtain spermatozoa that can be used for IVF (ICSI specifically).

In the second method, which has demonstrated some recent success in rhesus monkey models, donor SSCs are transplanted back into infertile recipients. They have found in these monkey models that spermatogenesis was restored with both adult and pre-pubertal donors. In some models, the SSCs were injected into the infertile specimen’s testis, but in a recent study, success was seen with injection into the subcutaneous space in the scrotum and back. They observed testosterone production resumption and complete spermatogenesis with mature spermatozoa in all specimens.

As of now, there are no registered studies in human patients yet – but there will be in the near future. There is now some hope for pre-pubertal males currently being diagnosed with cancer. However, the protocol needs to be optimized, and the jump from animals to humans may not be easy!

His final take-home slide was the following:
AUA 2019 Take Home Message

Presented by: Jens Sønksen, MD, PhD, DMSci, Chair Professor of Urology, Department of Urology, Herlev & gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, Twitter: @tchandra_uromd, @JEFFUrology at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois
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