Li, Q., Lan, Q. Y., Zhu, W. B., Fan, L. Q., & Huang, C. (2024). Fertility preservation in adult male patients with cancer: a systematic review and meta-analysis. Human reproduction open. https://doi.org/10.1093/hropen/hoae006
Li Q, Lan QY, Zhu WB, Fan LQ, Huang C. Fertility preservation in adult male patients with cancer: a systematic review and meta-analysis. Human reproduction open. 2024. doi:10.1093/hropen/hoae006
Li, Qing, et al. "Fertility preservation in adult male patients with cancer: a systematic review and meta-analysis." Human reproduction open, 2024.
For EndNote, Zotero or Mendeley:
Open access
No open license is recorded for this paper. Reuse terms are set by the publisher.
Open Access
Free full text on PubMed Central (PMC10882264)
RRM Academy Synopsis
Frozen sperm of men with cancer led to pregnancy in 28% of ART cycles
A meta-analysis of 69 non-randomized studies in adult men with cancer found that thawed sperm led to pregnancy in about 3 out of 10 ART cycles. The cycles were IUI, IVF or ICSI, and about 2 out of 10 ended in a delivery. Across the studies, a pooled 9% of men with stored sperm had used it in ART.
Key Findings
Sixty-nine non-randomized studies were pooled. They included 32 234 patients sent for sperm testing, and 23 178 of them cryopreserved at least one sample.
Sperm freezing failed in 10% of patients (95% CI 8–12%). Among men with banked sperm, 23% had it disposed of (95% CI 16–30%) and 9% used it (95% CI 8–10%).
Pooled rates were 28% for pregnancy, 13% for miscarriage and 20% for delivery, with 95% confidence intervals of 22–33%, 10–17% and 15–25%.
Clinical pregnancy per cycle was 34% with ICSI (27–41%), 24% with IVF (14–35%) and 9% with IUI (5–15%). Delivery was 23% with ICSI (17–30%), 18% with IVF (11–26%), 5% with IUI (1–9%).
Across four publication periods, pregnancy rose from 12% to 31% (CIs 4–21% and 25–37%; P = 0.011) and delivery from 5% to 23% (CIs 2–9% and 19–27%; P < 0.001).
Interpretation
The paper is a systematic review and meta-analysis of non-randomized studies. Its main figures are pooled single proportions without a control group. Heterogeneity was high for most outcomes (I2 = 84.0% for pregnancy). The data span 36 years, and many earlier studies had small samples and no control groups. Most studies did not separate tumor types, and almost all did not consider disease severity. In the subgroup comparison, ICSI was numerically highest, and its interval overlaps the IVF interval. The authors conclude that sperm freezing works as a fertility preservation method and may benefit men with cancer. They note that short follow-up may understate the 9% use rate.
RRM Context
Sperm banking stores sperm before cancer treatment, which can lower male fertility. Restorative reproductive medicine includes the male partner in every couple's evaluation because it looks for causes in both partners. The cycle outcomes here come from three ART procedures. IVF and ICSI achieve fertilization outside the body and bypass the body's own process of conception. IUI places thawed sperm directly in the uterus.
Our editorial summary of this paper, not the article's abstract.
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 to 31 December 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 studies did not consider the 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 tumors 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 tumors, 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 Interests
This work was supported by the National Natural Science Foundation of China (grant no. 82001634, 81960550), and the China Postdoctoral Science Foundation (2019M661521). There are no competing interests to declare.
