Fertility preservation in adult male patients with cancer: a systematic review and meta-analysis

Abstract

STUDY QUESTION Does sperm cryopreservation serve as a feasible and effective method for preserving fertility in adult male patients with cancer? SUMMARY ANSWER Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer. WHAT IS KNOWN ALREADY Sperm cryopreservation is the only way to efficiently preserve male fertility. It is an important procedure in ART. Recently, due to remarkable advances in cancer treatment, an increasing number of studies have reported the outcomes of sperm cryopreservation in patients with cancer. STUDY DESIGN, SIZE, DURATION We conducted an extensive literature search for relevant studies published through December 31, 2021, in the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science. The search terms used were “(cryopreservation OR freeze OR freezing OR banking OR cryostorage OR storage) AND (sperm OR semen OR spermatozoon) AND (cancer OR tumor OR malignancy OR neoplasm). PARTICIPANTS/MATERIALS, SETTING, METHODS We included all studies that reported offering or attempting to cryopreserve sperm before or during cancer treatment in male patients considered at risk of treatment-related fertility impairment. We evaluated the eligibility of all data in each study. The major exclusion criteria were as follows: non-cancer patients; pediatric and adolescent cancer patients; not reporting the use of cryopreserved sperm; use of fresh semen for ART; not reporting the number of patients with cancer offered sperm cryopreservation or attempting to do so before or during treatment; using an experimental fertility preservation technique such as preservation of testicular tissue or spermatogonial stem cells; duplicate data; abstracts, case report, comments, reviews, or editorials; insufficient data reported. The quality of the included studies was assessed using the Newcastle–Ottawa scale and the Methodological Index for Non-Randomized Studies. MAIN RESULTS AND THE ROLE OF CHANCE This meta-analysis included 69 non-randomized studies, with 32,234 patients referred for sperm analysis and 23,178 patients cryopreserving at least one sperm sample. The pooled failed-to-cryopreserve rate was 10% (95% CI, 8–12%), and the sperm disposal and sperm use rates were 23% (95% CI, 16–30%) and 9% (95% CI, 8–10%), respectively. The pregnancy, miscarriage, and delivery rates were 28% (95% CI, 22–33%), 13% (95% CI, 10–17%), and 20% (95% CI, 15–25%), respectively. Subgroup analysis showed higher pregnancy and delivery rates, as well as a lower failed-to-cryopreserve rate, in recent studies compared to those released a decade ago. The studies from Asia reported higher sperm disposal and pregnancy rates than in other continents. Our analysis showed clinical pregnancy rates per cycle of 34% (27–41%), 24% (14–35%), and 9% (5–15%) and delivery rates per cycle of 23% (17–30%), 18% (11–26%), and 5% (1–9%) for ICSI, IVF, and IUI, respectively. LIMITATIONS, REASONS FOR CAUTION As with all meta-analyses, some limitations should be considered. The first limitation of our study is that the data span 36 years. During this time, the World Health Organization has revised its sperm analysis standards, and other important changes have been made. There is also a limitation in that the outcome does not analyze the correlation between the type of cancer and sperm quality. Many of the earlier studies were limited by small sample sizes and a lack of control groups. Furthermore, almost all of studies did not consider severity of the disease, which could potentially have a substantial impact on the results. Consequently, further research should evaluate the effect of the type of cancer and, in particular, the severity of the condition on sperm quality in order to draw more precise conclusions. Similarly, it is inappropriate that most studies failed to differentiate between patients with different types of tumor and instead drew generalized conclusions that are presumed to apply to all patients with cancer. In the present analysis we did not have in-depth information on patients’ disease, and although extensive efforts were made to conduct a thorough systematic review and meta-analysis of the outcomes for patients with various types of tumor, the results must be acknowledged as being subject to bias. However, the use of average results obtained in each study, without the patient-level data, might also represent a source of bias. WIDER IMPLICATIONS OF THE FINDINGS Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer. The observed utilization rate of frozen sperm at 9% may underestimate the actual usage, as the short follow-up period is inadequate for obtaining comprehensive data on the use of frozen sperm in young cancer survivors. ART plays an important role in fertility preservation and the achievement of pregnancy, with this meta-analysis showing that ICSI delivers better clinical outcomes than IVF or IUI in patients with cancer undergoing fertility preservation. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (Grand No. 82001634), and the China Postdoctoral Science Foundation (2019M661521). There are no competing interests to declare. REGISTRATION NUMBER CRID 42022314460

An Assessment of Cryopreserved Semen and Testicular Tissue Collected Before and After Cancer Treatment Initiation

“… 40 Samples may be used for in-vitro fertilization (IVF) or – with better clinical outcomes than IVF or intrauterine insemination (IUI) – for intracytoplasmic sperm infection (ICSI). 41 The success rates of assisted reproductive techniques (ART) with fresh oocytes are comparable for couples where the male partner has a history of cancer treatment, regardless of whether fresh or cryopreserved semen is utilized with fresh oocytes. 42 The outcome of embryo transfers is significantly higher when cryopreserved semen is used, but live birth rates remain similar to those using fresh sperm.…”