P-461 “15 years of cryopreservation of semen and testicular tissue samples and outcomes of fertility treatments – a single centre experience at Charité-Universitätsmedizin Berlin”
Authors: Fernández González M.J , Wilkemeyer I , Radauer-Plank A.C , Borgmann-Staudt A , Geiger W , Goranova I , Stelzer C , Balcerek M 
Published: June 2022

Abstract

Study question
To explore practices of cryopreservation among male cancer patients and describe outcomes of fertility treatments with samples collected before and after cancer treatment.

Summary answer
Only 9.1% of cancer patients used their samples for fertility treatment (ART). Patients underwent ART mostly within the first two years and following high-risk treatment.

What is known already
Fertility preservation has become an important issue, due to the potential gonadotoxicity of oncological therapies. Most cancer patients who undergo gonadotoxic treatment desire to have children. Yet, cancer patients may suffer impaired spermatogenesis in more than a third to over two thirds of cases following standard or high dose cancer treatments, respectively. Identifying risk factors of infertility is therefore fundamental for individual and risk adapted patient counseling. Current guidelines recommend fertility preservation, especially cryopreservation of sperm/testicular tissue, in cancer patients who require gonadotoxic treatment. Rates of utilisation of cryopreserved samples for fertility treatment are low (often &lt;10%).

Study design, size, duration
In our retrospective study, we collected data from 506 cancer patients who cryopreserved semen/testicular tissue samples between 2004 and 2019 in our centre and for who oncological treatment data was available. Additionally, former patients who had used their previously cryopreserved samples were asked for informed consent to collect information on fertility treatment from the respective fertility centre in which they were treated.

Participants/materials, setting, methods
We collected oncologic and cryopreservation data from medical records, and fertility treatment data from external clinics. Patients were stratified according to age at diagnosis (&lt;18 or ≥ 18 years old), diagnosis (brain, testicular or solid tumors in other locations or hematologic malignancy) and time-point of cryopreservation (before or after gonadotoxic treatment). We assessed the following fertility outcomes: fertilisation, pregnancy, miscarriage and live birth rate as well as perinatal outcomes (gestational age, weight and height at delivery).

Main results and the role of chance
The majority of the 506 cancer patients (including 10.5% adolescents) had suffered from a testicular or hematological malignancy. The number of patients that underwent cryopreservation annually in our centre had increased over time. On average, patients collected one sample (1.2±0.4, range:1-3). The majority of samples were collected before oncologic treatment (460/600, 76.7%) and were semen samples (554/601, 92.2%). The rate of cryopreserved tissue was higher in adolescents compared to adults. At the time-point of our study, only 46 patients (9.1%) had used their samples (15,2% tissue samples) for fertility treatment after a median of 18 months following cryopreservation (IQR:7.25±27.5). We received fertility cycle information on 21 patients. Eleven couples (55.0%) had only required one cycle to achieve a pregnancy (range:1-3 cycles, n = 38). Between 70-80% of couples, depending on the cancer diagnosis, achieved at least one pregnancy. Out of 16 patients who had successfully achieved a pregnancy, thirteen succeeded using cryopreserved sperm, one patient required to change from fresh to cryopreserved sperm in the third cycle and two patients used fresh sperm. Rate of pregnancy per e mbryo transfer (ET) was 51.4% (19/37), including eleven singletons, three twin pairs, four miscarriages (in two patients) and one pregnancy with unknown outcome.

Limitations, reasons for caution
Bias might be caused by the restrospective study design and the fact that recommendations for clinical practice have changed over time. We could not collect information on patients who would have been eligible but did not perform cryopreservation, whose partners conceived spontaneously or who used tissue samples for ART.

Wider implications of the findings
This study supports sperm and tissue cryopreservation as effective methods for fertility preservation. The rate of ART utilisation is still low, however results from ART cycles are reassuring, also when cryopreserved semen samples are used. Upcoming high-risk treatment is a predictor for ART utilisation, whereas follow-up time is not.

Trial registration number
Our study was approved by the ethics committee of Charité-Universitätsmedizin Berlin (EA4/158/19).