Sperm Cryopreservation Prior to Gonadotoxic Treatment

Experience of a Single Academic Centre Over 4 Decades

Nandini Shankara-Narayana; Irene Di Pierro; Carolyn Fennell; Lam P. Ly; Fay Bacha; Ljubica Vrga; Sasha Savkovic; Leo Turner; Veena Jayadev; Ann J. Conway; David J. Handelsman

Disclosures

Hum Reprod. 2019;34(5):795-803. 

In This Article

Abstract and Introduction

Abstract

Study Question: What is the natural history of outcomes of sperm cryostorage at an Australian tertiary academic centre?

Summary Answer: Cryostorage is feasible in virtually all men facing gonadotoxic therapy but the timing of sperm disposal varies according to the reason for it.

What is Known Already: Gonadotoxic treatment for cancer or non-cancer diseases damages spermatogenesis and impairs male fertility. Sperm cryopreservation is an established technique to preserve male fertility prior to gonadotoxic treatment.

Study Design, Size, Duration: A retrospective review of clinical, anthropometric, semen analysis and hormonal data from 1978 to 2017 involving 2717 men comprising 2085 men with cancer, 234 non-cancer disease and 398 healthy controls, in a single tertiary academic centre with the same clinic and laboratory staff.

Participants/Materials, Setting and Methods: Sperm output was analysed according to diseases, the feasibility of sperm cryostorage notably for adolescents, regional access to an urban cryostorage facility, the determinants of sperm output and time-dependent disposal of cryostored sperm. Semen samples were assessed by contemporaneous WHO methods.

Main Results and the Role of Chance: Of 2085 men with cancer, 904 (43%) had haematological malignancies, 680 (33%) testicular cancers and 136 (6.5%) were adolescents. Most men (89%) and adolescents (80%) could collect sperm. Sperm output for all cancers and non-cancer diseases was lower than controls. Sperm output correlated positively with total testicular volume (r = 0.44, P < 0.0001) and negatively with serum FSH and LH (r = −0.24, −0.12, respectively, both P < 0.0001) but not testosterone. For all stored samples, the median time in cryostorage was 8.5 years, 7% were transferred for use to induce pregnancy (median time 2.5 years) and 62.2% were discarded as no longer needed (return of fertility, 35.9% median 3.5 years; death, 26.3%, median 6.5 years), the high disposal rate reflecting regular annual follow-up to establish ongoing need for continued cryostorage. Cryostorage facilities are not available in remote and rural areas of the State and the proportion of outer regional and remote area residents cryostoring sperm was only about half that compared with urban residents.

Limitations, Reasons for Caution: This study does not report the pregnancy outcomes of the patients who used the cryostored sperm, due to recent limitations on health data privacy.

Wider Implications of the Findings: Sperm cryostorage is feasible for virtually all men, including sufficiently mature adolescents, who can collect semen to insure future paternity as well as making positive psychological preparation for the patient's survival. Disposal of cryostored material when no longer required is efficient with regular follow-up. Sperm cryopreservation should be an integral part of comprehensive treatment plan in men receiving gonadotoxic treatment but remains underutilized.

Study Funding/Competing Interest(s): There was no external funding for this study and there were no relevant conflicts of interest.

Introduction

Major improvement in survival from cancers over recent decades (Gatta et al., 2009; Fidler et al., 2017) has led comprehensive cancer care programs to focus on survivor experience of complications from effective oncology treatment (Fossa et al., 2008; Edgar et al., 2009). Prominent among these is at least transient fertility impairment as reproductive dysfunction is a virtually universal consequence of gonadotoxic (chemo- and/or radiotherapy) regimens or surgery leading to gamete loss such as orchidectomy. These cause spermatogenic damage resulting from temporary or permanent gamete loss causing male infertility (Meistrich, 2013). Following the proof in 1953 that human sperm freezing can preserve fertilizing capacity (Bunge and Sherman, 1953), sperm banking was developed in the 1960s using donor sperm for untreatable male infertility (Sherman, 1973). By the 1970s, this was extended as prospective fertility insurance for men embarking on potentially sterilizing cancer treatments (Saunders and Medcalf, 1978; Rothman, 1980).

The most frequent cancers affecting young men are testicular cancer and haematological diseases including lymphomas, leukaemia and bone marrow transplantation. However, many other cancers and non-cancer disease requiring gonadotoxic treatment may require sperm cryostorage to protect against lack of timely recovery of male fertility following iatrogenic spermatogenic damage.

This study describes an effective sperm cryostorage program in New South Wales, operating over 4 decades from the late 1970s in a single academic centre with the same clinical and laboratory staff providing comprehensive in clinical, reproductive, semen analysis and hormonal data. We report the feasibility of sperm cryostorage especially at young age, regional access to the urban cryostorage facility, the impact on sperm output at the time of cryostorage of underlying reproductive, malignant and non-malignant disease as well as systemic symptoms.

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