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Originally published as JCO Early Release 10.1200/JCO.2008.19.7749 on December 15 2008 © 2009 American Society of Clinical Oncology.
Rates of Postcancer Parenthood
The University of Texas M. D. Anderson Cancer Center, Houston, TX The wish to have a biologic child is rooted deeply in human evolution.1 Although our drive to reproduce is moderated by conscious attitudes and emotions, we are programmed to mate, just like other mammals. It is not surprising that young men and women who survive cancer still want children, especially if they were childless at diagnosis.2-6 Parents of children and teenagers diagnosed with cancer are also concerned about potential treatment-related infertility and endorse fertility preservation, as long as it does not delay cancer treatment7 or remove so much gonadal tissue that recovery of natural fertility might be compromised.8 Although many cancer survivors have exaggerated worries that children will have birth defects linked to the parent's cancer treatment or will have a heightened lifetime risk of cancer, few want to give up having children.2,3,5 Other populations exposed to environmental or genetic risk react in a similar way. In a long-term study of 2,345 women exposed to atomic bomb radiation in Hiroshima and Nagasaki, only 10 said they avoided getting pregnant out of fear of having unhealthy children.9 Their fecundity was comparable to that of unexposed Japanese women. When in vitro fertilization (IVF) using intracytoplasmic injection of one sperm into an oocyte became available to treat severe male infertility, couples who could previously become parents only through adoption or donor insemination could have a biologic child. Despite being informed that their sons or grandsons might inherit genetically linked male infertility, those who could afford the costs of IVF preferred that option,10 an observation confirmed by a subsequent survey of subfertile men with known Y-chromosome microdeletions.11 Couples’ choices about giving up childbearing or terminating a pregnancy to avoid a risk to a child's health depend on the perceived severity of the condition and the degree to which the child's quality of life will be affected.12 In our surveys of young adult cancer survivors, less than 10% of men and women would choose adoption or gamete donation to have a child because of concerns about the health of their biologic offspring.2,3 Women concerned about inherited cancer report they would be more likely to consider preimplantation genetic diagnosis (ie, creating embryos through IVF and discarding those harboring a known mutation), than to conceive a pregnancy and plan elective termination of an affected fetus.2,13 Familial adenomatous polyposis (FAP) is a hereditary cancer syndrome in which colon polyps proliferate and typically become malignant in late adolescence or young adulthood. Almost all men and women with FAP in a recent survey desired prenatal testing in planning future pregnancies.13 In contrast, only 36% of women affected by hereditary breast and ovarian cancer said they intended to use preimplantation genetic diagnosis in a future conception.14 Of course, inherited breast and ovarian cancer has a later age of onset and less complete penetrance than FAP. The psychosocial literature confirms the strong desire to have children after cancer and the distress that infertility brings.2-6 Thus, biologic limitations on fertility are probably the major cause of decreased birth rates in young cancer survivors. Until now, estimates of birth rates after cancer have been based on relatively small samples of patients who had a specific type of malignancy15,16 or fertility-sparing treatment.17 The notable exceptions are recent publications from the Childhood Cancer Survivor Study,18,19 from analysis of a large Finnish cohort of patients diagnosed from childhood to young adulthood,20 and from a previous analysis21 of a subset of the same registry data used by Cvancarovaet al.22 The Childhood Cancer Survivor Study pediatric cancer survivors were diagnosed between 1970 and 1986, corresponding to the earlier patient cases in the study by Cvancarova et al.19,20 Among 1,915 female survivors, those currently age 15 to 30 years were significantly less likely to have live births compared with their sisters, with relative ratios ranging from 0.64 to 0.74.19 Similarly, 1,227 male survivors of cancer fathered significantly fewer live-born infants than their 1,139 brothers (relative risk 0.77).20 Exposure to pelvic irradiation was associated with higher rates of miscarriage and low birth weight infants in women, but for men, no type of cancer treatment had a clear negative impact. The previous report based on patients treated at one tertiary referral center in Norway only included 463 male and 284 female cancer survivors and did not distinguish between children conceived before, compared with after, cancer treatment.21 When data for children born to cancer survivors were compared with data for the general Norwegian population born in the same period (1945 to 1982), no discrepancy in rates of children fathered was observed in men, but only 66% of women with cancer became parents, compared with 79% of controls.21 Cvancarova et al22 used the same registries, but they had detailed information on 6,071 patients diagnosed between age 15 and 44 years and treated from 1971 to 1997, each matched in age to five controls drawn from the Norwegian birth registry. Their estimate of a 50% reduction in postcancer births for women and 30% for men is somewhat more severe than that in other studies, but also probably more accurate. It is important to have long-term follow-up because of the risk of premature ovarian failure in young women, which may not be apparent in the years just after cancer treatment.23 Estimates of postcancer fecundity from Cvancarova et al22 agree well with another recent analysis based on 25,784 cancer survivors and 44,811 siblings from Finland's cancer and birth registries.20 The Finnish cohort included patients diagnosed in childhood, adolescence, and young adulthood. Overall, the relative probability of having a first child was 0.46 for women and 0.57 for men. However, men were more likely to remain childless if treated before age 14 years, whereas women were most severely affected when treated as young adults (age 20 to 34 years), which could account for the small discrepancies in reproductive rates between these two large case-control studies. Although fertility-sparing treatment is allowing more patients to have children after cancer, the gains are minimal compared with the elevated rates of childlessness among cancer survivors.22 As Cvancarova et al point out, the need for more effective fertility preservation for girls and young women is particularly pressing. Even with the availability of sperm banking for men, however, many oncologists neglect to discuss the option or make a referral.24-26 Epidemiologic studies such as the present one remind us that controlling cancer is necessary but not sufficient to ensure a satisfying quality of life for our patients. AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. NOTES published online ahead of print at www.jco.org on December 15, 2008 REFERENCES 1. Fisher HE, Aron A, Mashek D, et al: Defining the brain systems of lust, romantic attraction, and attachment. Arch Sex Behav 31:413-419, 2002[CrossRef][Medline] 2. Schover LR, Rybicki LA, Martin BA, et al: Having children after cancer: A pilot survey of survivors’ attitudes and experiences. Cancer 86:697-709, 1999[CrossRef][Medline] 3. Schover LR, Brey K, Lichtin A, et al: Knowledge and experience regarding cancer, infertility, and sperm banking in younger male survivors. J Clin Oncol 20:1880-1889, 2002 4. Zebrack BJ, Casillas J, Nohr L, et al: Fertility issues for young adult survivors of childhood cancer. Psychooncology 13:689-699, 2004[CrossRef][Medline] 5. Reinmuth S, Liebeskind AK, Wickmann L, et al: Having children after surviving cancer in childhood or adolescence: Results of a Berlin survey. Klin Padiatr 220:159-165, 2008[CrossRef][Medline] 6. Hammond C, Abrams JR, Syrjala KL: Fertility and risk factors for elevated infertility concern in 10-year hematopoietic cell transplant survivors and case-matched controls. J Clin Oncol 25:3511-3517, 2007 7. Oosterhuis EB, Goodwin T, Kiernan M, et al: Concerns about infertility risks among pediatric oncology patients and their parents. Pediatr Blood Cancer 50:85-89, 2008[CrossRef][Medline] 8. van den Berg H, Repping S, van der Veen F: Parental desire and acceptability of spermatogonial stem cell cryopreservation in boys with cancer. Hum Reprod 22:594-597, 2007 9. Blot WJ, Sawada H: Fertility among female survivors of the atomic bombs of Hiroshima and Nagasaki. Am J Hum Genet 24:613-622, 1972[Medline] 10. Schover LR, Thomas AJ, Miller KF, et al: Preferences for intracytoplasmic sperm injection versus donor insemination in severe male factor infertility: A preliminary report. Hum Reprod 11:2461-2464, 1996 11. Nap AW, Van Golde RJ, Tuerlings JH, et al: Reproductive decisions of men with microdeletions of the Y chromosome: The role of genetic counseling. Hum Reprod 14:2166-2169, 1999 12. García E, Timmermans DR, van Leeuwen E: The impact of ethical beliefs on decisions about prenatal screening tests: Searching for justification. Soc Sci Med 66:753-764, 2008[CrossRef][Medline] 13. Kastrinos F, Stoffel EM, Balmaña J, et al: Attitudes toward prenatal genetic testing in patients with familial adenomatous polyposis. Am J Gastroenterol 102:1284-1290, 2007[CrossRef][Medline] 14. Quinn G, Vadaparampil S, Wilson C, et al: Attitudes of high-risk women toward preimplantation genetic diagnosis. Fertil Steril doi:10.1016/j.fertnstert.2008.03.019 [epub ahead of print on April 26, 2008] 15. Magelssen H, Haugen TB, von During V, et al: Twenty years experience with semen cryopreservation in testicular cancer patients: Who needs it? Eur Urol 48:779-785, 2005[CrossRef][Medline] 16. Zanagnolo V, Sartori E, Trussardi E, et al: Preservation of ovarian function, reproductive ability and emotional attitudes in patients with malignant ovarian tumors. Eur J Obstet Gynecol Reprod Biol 123:235-243, 2005[CrossRef][Medline] 17. Ramirez PT, Schmeler KM, Soliman PT, et al: Fertility preservation in patients with early cervical cancer: Radical trachelectomy. Gynecol Oncol 110:S25-S28, 2008 (suppl 2)[CrossRef][Medline] 18. Green DM, Whitton JA, Stovall M, et al: Pregnancy outcome of partners of male survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. J Clin Oncol 21:716-721, 2003 19. Green DM, Whitton JA, Stovall M, et al: Pregnancy outcome of female survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Am J Obstet Gynecol 187:1070-1080, 2002[CrossRef][Medline] 20. Madanat L-MS, Malila N, Dyba T, et al: Probability of parenthood after early onset cancer: A population-based study. Int J Cancer 123:2891-2898, 2008[CrossRef][Medline] 21. Magelssen H, Melve KK, Skj\jrven R, et al: Parenthood probability and pregnancy outcome in patients with a cancer diagnosis during adolescence and young adulthood. Hum Reprod 23:178-186, 2008 22. Cvancarova M, Samuelsen SO, Magelssen H, et al: Reproduction rates after cancer treatment: Experience from the Norwegian Radium Hospital. J Clin Oncol doi:10.1200/JCO.2007.15.3130 [epub ahead of print on December 15, 2008] 23. Lutchman Singh K, Muttukrishna S, Stein RC, et al: Predictors of ovarian reserve in young women with breast cancer. Br J Cancer 96:1808-1816, 2007[CrossRef][Medline] 24. Schover LR, Brey K, Lichtin A, et al: Oncologists’ attitudes and practices regarding banking sperm before cancer treatment. J Clin Oncol 20:1890-1897, 2002 25. Glaser AW, Phelan L, Crawshaw M, et al: Fertility preservation in adolescent males with cancer in the United Kingdom: A survey of practice. Arch Dis Child 89:736-737, 2004 26. Heath JA, Stern CJ: Fertility preservation in children newly diagnosed with cancer: Existing standards of practice in Australia and New Zealand. Med J Austr 185:538-541, 2006
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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