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Risk of prostate cancer for men fathering through assisted reproduction: nationwide population based register study

BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l5214 (Published 25 September 2019) Cite this as: BMJ 2019;366:l5214

Linked editorial

Male infertility linked to risk of prostate cancer

Linked opinion

Assisted reproduction and risk of prostate cancer for men

  1. Yahia Al-Jebari, doctoral student researcher1,
  2. Angel Elenkov, postdoctoral research scholar1 2 3,
  3. Elin Wirestrand, medical student researcher1,
  4. Indra Schütz, medical student researcher1,
  5. Aleksander Giwercman, professor1 3,
  6. Yvonne Lundberg Giwercman, professor1
  1. 1Department of Translational Medicine, Lund University, Malmö, Sweden
  2. 2Department of Urology, Medical University Sofia, Sofia, Bulgaria
  3. 3Reproductive Medicine Center, Skåne University Hospital Malmö, Malmö, Sweden
  1. Correspondence to: Y Al-Jebari yahia.al-jebari{at}med.lu.se or @YahiaAlJebari on Twitter
  • Accepted 26 July 2019

Abstract

Objective To compare the risk and severity of prostate cancer between men achieving fatherhood by assisted reproduction and men conceiving naturally.

Design National register based cohort study.

Setting Sweden from January 1994 to December 2014.

Participants 1 181 490 children born alive in Sweden during 1994-2014 to the same number of fathers. Fathers were grouped according to fertility status by mode of conception: 20 618 by in vitro fertilisation (IVF), 14 882 by intra-cytoplasmic sperm injection (ICSI), and 1 145 990 by natural conception.

Main outcome measures Prostate cancer diagnosis, age of onset, and androgen deprivation therapy (serving as proxy for advanced or metastatic malignancy).

Results Among men achieving fatherhood by IVF, by ICSI, and by non-assisted means, 77 (0.37%), 63 (0.42%), and 3244 (0.28%), respectively, were diagnosed as having prostate cancer. Mean age at onset was 55.9, 55.1, and 57.1 years, respectively. Men who became fathers through assisted reproduction had a statistically significantly increased risk of prostate cancer compared with men who conceived naturally (hazard ratio 1.64, 95% confidence interval 1.25 to 2.15, for ICSI; 1.33, 1.06 to 1.66, for IVF). They also had an increased risk of early onset disease (that is, diagnosis before age 55 years) (hazard ratio 1.86, 1.25 to 2.77, for ICSI; 1.51, 1.09 to 2.08, for IVF). Fathers who conceived through ICSI and developed prostate cancer received androgen deprivation therapy to at least the same extent as the reference group (odds ratio 1.91; P=0.07).

Conclusions Men who achieved fatherhood through assisted reproduction techniques, particularly through ICSI, are at increased risk for early onset prostate cancer and thus constitute a risk group in which testing and careful long term follow-up for prostate cancer may be beneficial.

Footnotes

  • Contributors: YLG and AG designed and supervised the study. YA, AE, EW, and IS analysed the data. All authors had access to the raw data, interpreted the analysed data, discussed and revised the manuscript, and approved the final version of the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. YLG is the guarantor.

  • Funding: The study was funded by the Swedish Cancer Foundation (CAN 2014/360 and 2017/392), an ALF government grant (F2014/354), the Malmö University Hospital Cancer Research Fund, the Swedish Prostate Cancer Federation, and the European Association of Urology (scholarship EUSP/REPRO-02-2017). Funders had no role in study design, results, or write-up or manuscript submission decisions other than to provide funding. The researchers were independent of the funders.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support for the submitted work as detailed above; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The Regional Ethical Board in Lund, Sweden, approved the study (No 2015/670).

  • Transparency: The lead author (the manuscript’s guarantor) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Data sharing: Medical researchers can, if conditions are met under Swedish law, obtain de-identified data by contacting the corresponding author.

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