Paternity through use of assisted reproduction technology in male adult and childhood cancer survivors: a nationwide register study
Authors: Kitlinski Michael , Giwercman Aleksander , Elenkov Angel 
Published: February 2023

Abstract

STUDY QUESTION
How does a history of cancer affect the likelihood of using assisted reproduction in order to achieve paternity?

SUMMARY ANSWER
As compared to men with no history of cancer, use of assisted reproduction to achieve paternity was more frequent in fathers with a history of cancer, mainly those with testicular, prostate, and hematological and lymphatic malignancies.

WHAT IS KNOWN ALREADY
Although it is well known that different types of cancer and their treatment may have a negative impact on fertility, there is a lack of data regarding the use of IVF and ICSI among male cancer survivors.

STUDY DESIGN, SIZE, DURATION
In this population-based nation-wide study using the Swedish Medical Birth Register, we identified all men who fathered their first-born child in Sweden between 1994 and 2014. Using personal identification numbers, anonymized data from the Swedish National Quality of Assisted Reproduction Register, Swedish Cancer Register, Swedish Multi-generation Register, and Swedish Education Register were linked with the Swedish Medical Birth Register.

PARTICIPANTS/MATERIALS, SETTING, METHODS
During the study period, a total of 1 181 488 men fathering their first-born child were identified. Of these, 26 901 fathers had a cancer diagnosis. Fathers diagnosed with cancer with &lt;12 months from offspring conception, or with a cancer diagnosis after offspring conception, were excluded (n = 21 529). The remaining fathers who had a history of cancer (n = 5372) were divided into three groups based on age at cancer diagnosis (&lt;15, ≥15 and &lt;24, or ≥24 years). For subgroup analyses, they were also grouped according to the cancer location using ICD-7 codes. The fathers with no cancer diagnosis (n = 1 154 587), were included as controls. In total, 1 159 959 men were included. Associations between IVF/ICSI use and history of cancer were evaluated using logistic regression models, unadjusted and adjusted for paternal education, fathers age at childbirth, and year of conception, yielding crude and adjusted odds ratio (aOR), respectively, with a 95% CI.

MAIN RESULTS AND THE ROLE OF CHANCE
As compared to controls, childhood cancer survivors were only more likely to achieve paternity through ICSI (aOR 3.52, 95% CI 2.52–4.93; P &lt; 0.001) but not through IVF treatment (aOR 1.02, 95% CI 0.61–1.70; P = 0.955). Similarly, teenage and young adult cancer survivors were more likely to father through ICSI treatment (aOR 6.84, 95% CI 5.64–8.30; P &lt; 0.001) but not using IVF (aOR 1.27, 95% CI 0.90–1.80; P = 0.17). However, adult cancer survivors were more likely to conceive through either ICSI (aOR 5.52, 95% CI 4.86–6.27; P &lt; 0.001) or IVF treatment (aOR 1.32, 95% CI 1.09–1.60; P = 0.004). In subgroup analyses, childhood survivors of testicular cancer (aOR 5.15, 95% CI 1.20–22.0; P = 0.027), soft tissue and bone cancers (aOR 4.70, 2.13–10.4; P &lt; 0.001), hematological and lymphatic cancers (aOR 4.49, 95% CI 2.72–7.40; P &lt; 0.001), or central nervous system (CNS) and eye cancers (aOR 2.64, 95% CI 1.23–5.67; P = 0.012), were at an increased likelihood of fathering through ICSI. Teenage and young adult survivors of testicular cancer (aOR 15.4, 95% CI 11.5–20.7; P &lt; 0.001), hematological and lymphatic cancers (aOR 9.84, 95% CI 6.93–14.0; P &lt; 0.001), or soft tissue and bone cancers (aOR 6.83, 95% CI 3.53–13.2; P &lt; 0.001) were more likely to father through ICSI treatment. Adult survivors of prostate cancer (aOR 15.7, 95% CI 6.70–36.9; P &lt; 0.001), testicular cancer (aOR 9.54, 95% CI 7.81–11.7; P &lt; 0.001), hematological and lymphatic cancers (aOR 11.3, 95% CI 8.63–14.9; P &lt; 0.001), digestive, respiratory, and urogenital tract cancers (aOR 2.62, 95% CI 1.75–3.92; P &lt; 0.001), CNS and eye cancers (aOR 2.74, 95% CI 1.48–5.08; P = 0.001), or skin cancer (aOR 1.68, 95% CI 1.08–2.62; P = 0.022) were more likely to father through ICSI treatment. Only teenage and young adult survivors of hematological and lymphatic cancers (aOR 1.98, 95% CI 1.10–3.56; P = 0.022) and adult survivors of testicular cancer (aOR 1.88, 95% CI 1.37–2.58; P &lt; 0.001) were significantly more likely to achieve fatherhood using IVF treatment.

LIMITATIONS, REASONS FOR CAUTION
Information on men failing to father children was not available, and thus our results cannot estimate the risk of infertility in men with a history of cancer.

WIDER IMPLICATIONS OF THE FINDINGS
Use of ART, in particular ICSI, was significantly more frequent in fathers with malignancies of the male reproductive tract or hematological and lymphatic systems. Our findings highlight which groups of male cancer survivors would benefit from access to fertility care, thereby improving future fertility treatment policies.

STUDY FUNDING/COMPETING INTEREST(S)
The study received funding from the Swedish Cancer Society, Swedish Childhood Cancer Society, and the Swedish Government Fund for Clinical Research. There are no competing interest.

TRIAL REGISTRATION NUMBER
N/A.