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Journal of Assisted Reproduction and Genetics

, Volume 32, Issue 8, pp 1179–1186 | Cite as

Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study

  • Wei Gao
  • Jin-Xiao Liang
  • Qiu Yan
Fertility Preservation

Abstract

Background and aims

Many epidemiological studies have revealed a positive correlation between medical radiation exposure and the reproductive health in female childhood cancer survivors. However, because of variations in the samples size, such studies showed partly inconsistent conclusions. The aim of this meta-analysis was to clarify the association between radiotherapy and the risk of reproductive health impairment for female who survived from childhood cancer.

Methods

Fourteen cohort studies involving childhood radiotherapy were selected as the exposure of interest and the impaired reproductive health condition during the childbearing age as the outcome. Among meta-analysis of observational studies found in Pubmed and Embase from 1900 to 2014, we evaluated those relevant observational studies which surveyed the association of medical radiation and reproductive health in female childhood cancer survivors. Review Manager 5.2 and STATA 12.0 software were used to perform the meta-analysis. Study-specific estimations for each outcome were combined into a pooled relative risk (RR) with 95 % confidence interval (CI) by a meta-analytic approach.

Results

Based on a random-effects meta-analysis, significant association between infertility (RR = 1.28, 95 % CI = 1.16–1.42), acute ovarian failure (AOF) (RR = 9.51, 95 % CI = 5.03–17.96), low level of anti mullerian hormone (AMH) (<1 ng/mL) (RR = 14.79, 95 % CI = 3.36–66.64), stillbirth (RR = 1.19, 95 % CI = 1.02–1.39) and low birth weight (RR = 2.22, 95 % CI = 1.55–3.17) were identified. Conversely, no significant results were found in abortion and congenital malformations.

Conclusions

To the best of our knowledge, this is the first meta-analysis assessing the effect of medical radiation on female childhood cancer survivors’ reproductive capability and pregnancy outcomes. Although there were some limitations, our meta-analysis further supported that radiotherapy was a risk factor for reproductive health problems of female who survived from childhood cancer.

Keywords

Radiotherapy Infertility Reproductive capability Pregnancy outcomes Meta-analysis 

Notes

Acknowledgments

The project was supported by National Natural Science Foundation of China Research grants no. 30672753 and 31270866.

The quality of eligible studies was estimated by two authors (W.G and J.L), and the disagreements were discussed and resolved by the reviewer (Q.Y).

References

  1. 1.
    Groen RS, Bae JY, Lim KJ. Fear of the unknown: ionizing radiation exposure during pregnancy. Am J Obstet Gynecol. 2012;206(6):456–62.PubMedCrossRefGoogle Scholar
  2. 2.
    Kaatsch P. Epidemiology of childhood cancer. Cancer Treat Rev. 2010;36(4):277–85.PubMedCrossRefGoogle Scholar
  3. 3.
    Reinmuth S, Hohmann C, Rendtorff R, Balcerek M, Holzhausen S, Muller A, et al. Impact of chemotherapy and radiotherapy in childhood on fertility in adulthood: the FeCt-survey of childhood cancer survivors in Germany. J Cancer Res Clin Oncol. 2013;139(12):2071–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Lunsford AJ, Whelan K, McCormick K, McLaren JF. Antimullerian hormone as a measure of reproductive function in female childhood cancer survivors. Fertil Steril. 2014;101(1):227–31.PubMedCrossRefGoogle Scholar
  5. 5.
    Mahran YF, El-Demerdash E, Nada AS, et al. Insights into the protective mechanisms of tamoxifen in radiotherapy-induced ovarian follicular loss: impact on insulin-like growth factor 1. Endocrinology. 2013;154(10):3888–99.PubMedCrossRefGoogle Scholar
  6. 6.
    Chiarelli AM, Marrett LD, Darlington G. Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964–1988 in Ontario, Canada. Am J Epidemiol. 1999;150(3):245–54.PubMedCrossRefGoogle Scholar
  7. 7.
    Chiarelli AM, Marrett LD, Darlington GA. Pregnancy outcomes in females after treatment for childhood cancer. Epidemiology. 2000;11(2):161–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Green DM, Whitton JA, Stovall M, Mertens AC, Donaldson SS, Ruymann FB, et al. Pregnancy outcome of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Am J Obstet Gynecol. 2002;187(4):1070–80.PubMedCrossRefGoogle Scholar
  9. 9.
    Ronckers CM, Land CE, Hayes RB, Verduijn PG, Stovall M, van Leeuwen FE. Late health effects of childhood nasopharyngeal radium irradiation: nonmelanoma skin cancers, benign tumors, and hormonal disorders. Pediatr Res. 2002;52(6):850–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Chemaitilly W, Mertens AC, Mitby P, Whitton J, Stovall M, Yasui Y, et al. Acute ovarian failure in the childhood cancer survivor study. J Clin Endocrinol Metab. 2006;91(5):1723–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Signorello LB, Cohen SS, Bosetti C, Stovall M, Kasper CE, Weathers RE, et al. Female survivors of childhood cancer: preterm birth and low birth weight among their children. J Natl Cancer Inst. 2006;98(20):1453–61.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Winther JF, Boice JJ, Svendsen AL, Frederiksen K, Stovall M, Olsen JH. Spontaneous abortion in a Danish population-based cohort of childhood cancer survivors. J Clin Oncol. 2008;26(26):4340–6.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Signorello LB, Mulvihill JJ, Green DM, Munro HM, Stovall M, Weathers RE, et al. Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study. Lancet. 2010;376(9741):624–30.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Green DM, Nolan VG, Kawashima T, Stovall M, Donaldson SS, Srivastava D, et al. Decreased fertility among female childhood cancer survivors who received 22–27 Gy hypothalamic/pituitary irradiation: a report from the Childhood Cancer Survivor Study. Fertil Steril. 2011;95(6):1922–7. 1921–1927.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Signorello LB, Mulvihill JJ, Green DM, Munro HM, Stovall M, Weathers RE, et al. Congenital anomalies in the children of cancer survivors: a report from the childhood cancer survivor study. J Clin Oncol. 2012;30(3):239–45.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Thomas-Teinturier C, Fayech C, El Oberlin O, De Vathaire F. Acute ovarian failure in survivors of childhood cancer: major influence of surgery and radiotherapy. Horm Res Paediatr. 2012;78:201.CrossRefGoogle Scholar
  17. 17.
    van Dorp W, van den Heuvel-Eibrink MM, Stolk L, Pieters R, Uitterlinden AG, Visser JA, et al. Genetic variation may modify ovarian reserve in female childhood cancer survivors. Hum Reprod. 2013;28(4):1069–76.PubMedCrossRefGoogle Scholar
  18. 18.
    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;14(9):873–81.PubMedCrossRefGoogle Scholar
  19. 19.
    Thomas-Teinturier C, Fayech C, El Oberlin O, Pacquement H, Haddy N, Labbe M, et al. Age at menopause and its influencing factors in a cohort of survivors of childhood cancer: earlier but rarely premature. Hum Reprod. 2013;28(2):488–95.PubMedCrossRefGoogle Scholar
  20. 20.
    Edelmann MN, Krull KR, Liu W, Glass JO, Ji Q, Ogg RJ, et al. Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia. Brain. 2014;137(Pt 11):2973–83.Google Scholar
  21. 21.
    Ford JS, Kawashima T, Whitton J, Leisenring W, Laverdiere C, Stovall M, et al. Psychosexual functioning among adult female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol. 2014;32(28):3126–36.Google Scholar
  22. 22.
    Gnaneswaran S, Deans R, Cohn RJ. Reproductive late effects in female survivors of childhood cancer. Obstet Gynecol Int. 2012;2012:564794.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Xing ZW, Jiang EH, Du JY, et al. Long-term follow-up of the genital organs and eye lenses in three cases of acute radiation sickness from a 60Co radiation accident in China. Health Phys. 2015;108(1):1–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Styne D, Grumbach M. Puberty: ontogeny, neuroendocrinology, physiology, and disorders. In: H. Kronenberg, editor, Williams textbook of endocrinology. 2008. pp. 969–1166.Google Scholar
  25. 25.
    Wallace WH, Shalet SM, Crowne EC, Morris-Jones PH, Gattamaneni HR. Ovarian failure following abdominal irradiation in childhood: natural history and prognosis. Clin Oncol (R Coll Radiol). 1989;1(2):75–9.CrossRefGoogle Scholar
  26. 26.
    Viswanathan AN. Childhood cancer survivors: stillbirth and neonatal death. Lancet. 2010;376(9741):570–2.PubMedCrossRefGoogle Scholar
  27. 27.
    Nakamura N, Suyama A, Noda A, Kodama Y. Radiation effects on human heredity. Annu Rev Genet. 2013;47:33–50.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, Liaoning Provincial Core Lab of Glycobiology and GlycoengineeringDalian Medical UniversityDalianPeople’s Republic of China
  2. 2.Department of Thoracic SurgeryZhejiang Cancer HospitalHangzhouPeople’s Republic of China

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