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Fertility preservation for people with cancer

Pregnancy and live birth

Clinical Question

Are people who received cancer treatment less likely to conceive or give birth?

The effects of cancer and cancer treatment on the ability to conceive and give birth are important concerns for many people with cancer.[1] With five-year disease-free survival rates now surpassing 80% for young people,[2] health care providers need to provide information about the risks of infertility to patients with cancer. In order to discuss fertility with patients, it is important to understand the impact of cancer treatment on fertility and the chance of conceiving a child naturally.

One of the challenges in answering this question is the lack of routinely collected data that can be used to determine the impact of cancer treatment on fertility. This continues to be an issue for understanding effects of new anti-cancer therapies such as immunotherapy, CDK4/6 inhibitors and PARP inhibitors on fertility. Better understanding of the impact of cancer treatment on fertility through routine collection of data in clinical trials will enable health professionals to better inform people with cancer of the likely impact of their cancer treatment on their future fertility.

The strongest evidence available comes from a number of comprehensive systematic reviews and meta-analyses which indicate a trend of lower birth rates for people who received cancer treatment. The pregnancy rate for women treated for breast cancer is on average 40% lower than the general population.[3] Women treated for haematological cancer,[4] gynecological malignancy[5] and cancer diagnosed during childhood or adolescence[6] also experience lower birth rates. Similarly, female partners of men treated for testicular cancer experience lower pregnancy and live birth rates.[7] These systematic reviews report mainly retrospective cohort studies (Level III evidence) but together provide good evidence that people treated for cancer are less likely to conceive and give birth.

Further evidence for lower conception and birth rates for people diagnosed with cancer comes from sub-studies of the Childhood Cancer Survivors Cohort. These retrospective cohort studies involve large numbers of childhood cancer survivors and their siblings. Women treated for cancer in childhood have an increased risk of infertility[8][9] and an increased time to pregnancy compared with their siblings.[9] Men treated for cancer in childhood have a decreased likelihood of their female partners falling pregnant[10][11][12] or their female partners having a live birth compared to their siblings.[11][13]

It important to acknowledge that reduced fertility is not the only reason for lower pregnancy rates after cancer – there are a number of psychological moderators which mean some people treated for cancer may choose not to become parents. Some of the studies mentioned in this section have taken this in to account.

Evidence Summary

Evidence summaryLevelReferences
The treatment of cancer in pre-menopausal women of child bearing age is associated with decreased pregnancy and live birth rates. The treatment of cancer in men, especially those treated in childhood, is associated with decreased pregnancy and live birth rates for their female partners.III-3[7], [6], [3], [4], [5]

Recommendation

Evidence-based recommendationGrade
It is recommended that health professionals inform all people diagnosed with cancer (or their parents in the case of children) that there is potential for cancer treatment to impact their fertility.B

References

  1. Levine J, Canada A, Stern CJ. Fertility preservation in adolescents and young adults with cancer. J Clin Oncol 2010 Nov 10;28(32):4831-41 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20458029.
  2. Australian Institute of Health and Welfare (AIHW). Reports and data: Health conditions, disability & deaths (Cancer). [homepage on the internet] Australian Government; 2019 [cited 2019 Aug 16; updated 2019 Jan 9]. Available from: https://www.aihw.gov.au/reports-data/health-conditions-disability-deaths/cancer/overview.
  3. Gerstl B, Sullivan E, Ives A, Saunders C, Wand H, Anazodo A. Pregnancy Outcomes After a Breast Cancer Diagnosis: A Systematic Review and Meta-analysis. Clin Breast Cancer 2018 Feb;18(1):e79-e88 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28797766.
  4. Gerstl B, Sullivan E, Koch J, Wand H, Ives A, Mitchell R, et al. Reproductive outcomes following a stem cell transplant for a haematological malignancy in female cancer survivors: a systematic review and meta-analysis. Support Care Cancer 2019 Dec;27(12):4451-4460 Available from: http://www.ncbi.nlm.nih.gov/pubmed/31541306.
  5. Gerstl B, Sullivan E, Vallejo M, Koch J, Johnson M, Wand H, et al. Reproductive outcomes following treatment for a gynecological cancer diagnosis: a systematic review. J Cancer Surviv 2019 Apr;13(2):269-281 Available from: http://www.ncbi.nlm.nih.gov/pubmed/30997658.
  6. Gerstl B, Sullivan E, Chong S, Chia D, Wand H, Anazodo A. Reproductive Outcomes After a Childhood and Adolescent Young Adult Cancer Diagnosis in Female Cancer Survivors: A Systematic Review and Meta-analysis. J Adolesc Young Adult Oncol 2018 Nov 16 Available from: http://www.ncbi.nlm.nih.gov/pubmed/30452301.
  7. Gerstl B, Bertoldo MJ, Sullivan E, Volckmar X, Kerr A, Wand H, et al. Fatherhood Following Treatment for Testicular Cancer: A Systematic Review and Meta-Analyses. J Adolesc Young Adult Oncol 2020 Jun;9(3):341-353 Available from: http://www.ncbi.nlm.nih.gov/pubmed/32255696.
  8. Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 2009 Jun 1;27(16):2677-85 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19364965.
  9. Barton SE, Najita JS, Ginsburg ES, Leisenring WM, Stovall M, Weathers RE, et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 2013 Aug;14(9):873-81 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23856401.
  10. Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2010 Jan 10;28(2):332-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19949008.
  11. Chow EJ, Stratton KL, Leisenring WM, Oeffinger KC, Sklar CA, Donaldson SS, et al. Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 2016 May;17(5):567-76 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27020005.
  12. Wasilewski-Masker K, Seidel KD, Leisenring W, Mertens AC, Shnorhavorian M, Ritenour CW, et al. Male infertility in long-term survivors of pediatric cancer: a report from the childhood cancer survivor study. J Cancer Surviv 2014 Sep;8(3):437-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24711092.
  13. Green DM, Whitton JA, Stovall M, Mertens AC, Donaldson SS, Ruymann FB, et al. Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2003 Feb 15;21(4):716-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12586811.

Body of Evidence

CitationLevel of EvidenceQuality of EvidenceSize of EffectNumber of PatientsRelevance of Evidence
Anderson RA, Brewster DH, Wood R, Nowell S, Fischbacher C, Kelsey TW, et al. The impact of cancer on subsequent chance of pregnancy: a population-based analysis. Hum Reprod 2018 Jul 1;33(7):1281-1290 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29912328.III-3LowN/A23,201N/A
Armuand G, Skoog-Svanberg A, Bladh M, Sydsjö G. Reproductive Patterns Among Childhood and Adolescent Cancer Survivors in Sweden: A Population-Based Matched-Cohort Study. J Clin Oncol 2017 May 10;35(14):1577-1583 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28350518.III-3LowN/A1,206N/A
Barton SE, Najita JS, Ginsburg ES, Leisenring WM, Stovall M, Weathers RE, et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 2013 Aug;14(9):873-81 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23856401.III-3HighN/A4,897N/A
Baxter NN, Sutradhar R, DelGuidice ME, Forbes S, Paszat LF, Wilton AS, et al. A population-based study of rates of childbirth in recurrence-free female young adult survivors of non-gynecologic malignancies. BMC Cancer 2013 Jan 23;13:30 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23343211.III-3MediumN/AN/AN/A
Byrne J, Mulvihill JJ, Myers MH, Connelly RR, Naughton MD, Krauss MR, et al. Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer. N Engl J Med 1987 Nov 19;317(21):1315-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3683460.III-3MediumN/AN/AN/A
Chow EJ, Stratton KL, Leisenring WM, Oeffinger KC, Sklar CA, Donaldson SS, et al. Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 2016 May;17(5):567-76 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27020005.III-3MediumN/A10,938N/A
Dillon KE, Sammel MD, Ginsberg JP, Lechtenberg L, Prewitt M, Gracia CR. Pregnancy after cancer: results from a prospective cohort study of cancer survivors. Pediatr Blood Cancer 2013 Dec;60(12):2001-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24038829.IIMediumN/A200N/A
Gerstl B, Sullivan E, Ives A, Saunders C, Wand H, Anazodo A. Pregnancy Outcomes After a Breast Cancer Diagnosis: A Systematic Review and Meta-analysis. Clin Breast Cancer 2018 Feb;18(1):e79-e88 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28797766.III-3HighN/AN/AN/A
Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 2009 Jun 1;27(16):2677-85 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19364965.III-3MediumN/A6,590N/A
Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2010 Jan 10;28(2):332-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19949008.III-3MediumN/A7,516N/A
Green DM, Whitton JA, Stovall M, Mertens AC, Donaldson SS, Ruymann FB, et al. Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2003 Feb 15;21(4):716-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12586811.III-3MediumN/A8,405N/A
Hartman M, Liu J, Czene K, Miao H, Chia KS, Salim A, et al. Birth rates among female cancer survivors: a population-based cohort study in Sweden. Cancer 2013 May 15;119(10):1892-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23436251.III-3LowN/A3,907,708N/A
Lee HM, Kim BW, Park S, Park S, Lee JE, Choi YJ, et al. Childbirth in young Korean women with previously treated breast cancer: The SMARTSHIP study. Breast Cancer Res Treat 2019 Jul;176(2):419-427 Available from: http://www.ncbi.nlm.nih.gov/pubmed/31020470.III-3HighN/A18,000N/A
Magelssen H, Melve KK, Skjaerven R, Fosså SD. Parenthood probability and pregnancy outcome in patients with a cancer diagnosis during adolescence and young adulthood. Hum Reprod 2008 Jan;23(1):178-86 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18024486.III-3MediumN/AN/AN/A
Reulen RC, Zeegers MP, Wallace WH, Frobisher C, Taylor AJ, Lancashire ER, et al. Pregnancy outcomes among adult survivors of childhood cancer in the British Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 2009 Aug;18(8):2239-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19661083.III-3LowN/A10,483N/A
Tang SW, Liu J, Juay L, Czene K, Miao H, Salim A, et al. Birth rates among male cancer survivors and mortality rates among their offspring: a population-based study from Sweden. BMC Cancer 2016 Mar 8;16:196 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26955945.III-3LowN/A3,145,998N/A
Wasilewski-Masker K, Seidel KD, Leisenring W, Mertens AC, Shnorhavorian M, Ritenour CW, et al. Male infertility in long-term survivors of pediatric cancer: a report from the childhood cancer survivor study. J Cancer Surviv 2014 Sep;8(3):437-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24711092.III-3MediumN/A1,622N/A
Winther JF, Boice JD Jr, Svendsen AL, Frederiksen K, Stovall M, Olsen JH. Spontaneous abortion in a Danish population-based cohort of childhood cancer survivors. J Clin Oncol 2008 Sep 10;26(26):4340-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18779621.III-3HighN/A1,688N/A


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