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. 2001 Apr;84(4):355–359. doi: 10.1136/adc.84.4.355

Fertility preservation for children treated for cancer (1): scientific advances and research dilemmas

R Grundy 1, R Gosden 1, M Hewitt 1, V Larcher 1, A Leiper 1, H Spoudeas 1, D Walker 1, W Wallace 1
PMCID: PMC1718722  PMID: 11259242

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Selected References

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  1. Andersen B. L. Surviving cancer: the importance of sexual self-concept. Med Pediatr Oncol. 1999 Jul;33(1):15–23. doi: 10.1002/(sici)1096-911x(199907)33:1<15::aid-mpo4>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  2. Ashwood-Smith M. J., Edwards R. G. DNA repair by oocytes. Mol Hum Reprod. 1996 Jan;2(1):46–51. doi: 10.1093/molehr/2.1.46. [DOI] [PubMed] [Google Scholar]
  3. Avarbock M. R., Brinster C. J., Brinster R. L. Reconstitution of spermatogenesis from frozen spermatogonial stem cells. Nat Med. 1996 Jun;2(6):693–696. doi: 10.1038/nm0696-693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baird D. T., Webb R., Campbell B. K., Harkness L. M., Gosden R. G. Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at -196 C. Endocrinology. 1999 Jan;140(1):462–471. doi: 10.1210/endo.140.1.6453. [DOI] [PubMed] [Google Scholar]
  5. Bernabeu R., Cremades N., Takahashi K., Sousa M. Successful pregnancy after spermatid injection. Hum Reprod. 1998 Jul;13(7):1898–1900. doi: 10.1093/humrep/13.7.1898. [DOI] [PubMed] [Google Scholar]
  6. Brinster R. L., Avarbock M. R. Germline transmission of donor haplotype following spermatogonial transplantation. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11303–11307. doi: 10.1073/pnas.91.24.11303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brinster R. L., Zimmermann J. W. Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11298–11302. doi: 10.1073/pnas.91.24.11298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Byrne J. Infertility and premature menopause in childhood cancer survivors. Med Pediatr Oncol. 1999 Jul;33(1):24–28. doi: 10.1002/(sici)1096-911x(199907)33:1<24::aid-mpo5>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  9. Castillo L. A., Craft A. W., Kernahan J., Evans R. G., Aynsley-Green A. Gonadal function after 12-Gy testicular irradiation in childhood acute lymphoblastic leukaemia. Med Pediatr Oncol. 1990;18(3):185–189. doi: 10.1002/mpo.2950180304. [DOI] [PubMed] [Google Scholar]
  10. Clayton P. E., Shalet S. M., Price D. A., Campbell R. H. Testicular damage after chemotherapy for childhood brain tumors. J Pediatr. 1988 Jun;112(6):922–926. doi: 10.1016/s0022-3476(88)80218-x. [DOI] [PubMed] [Google Scholar]
  11. Clayton P. E., Shalet S. M., Price D. A., Jones P. H. Ovarian function following chemotherapy for childhood brain tumours. Med Pediatr Oncol. 1989;17(2):92–96. doi: 10.1002/mpo.2950170204. [DOI] [PubMed] [Google Scholar]
  12. Clouthier D. E., Avarbock M. R., Maika S. D., Hammer R. E., Brinster R. L. Rat spermatogenesis in mouse testis. Nature. 1996 May 30;381(6581):418–421. doi: 10.1038/381418a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Critchley H. O. Factors of importance for implantation and problems after treatment for childhood cancer. Med Pediatr Oncol. 1999 Jul;33(1):9–14. doi: 10.1002/(sici)1096-911x(199907)33:1<9::aid-mpo3>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  14. Danan C., Sternberg D., Van Steirteghem A., Cazeneuve C., Duquesnoy P., Besmond C., Goossens M., Lissens W., Amselem S. Evaluation of parental mitochondrial inheritance in neonates born after intracytoplasmic sperm injection. Am J Hum Genet. 1999 Aug;65(2):463–473. doi: 10.1086/302484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eppig J. J., O'Brien M. J. Development in vitro of mouse oocytes from primordial follicles. Biol Reprod. 1996 Jan;54(1):197–207. doi: 10.1095/biolreprod54.1.197. [DOI] [PubMed] [Google Scholar]
  16. Genescà A., Caballín M. R., Miró R., Benet J., Germà J. R., Egozcue J. Repair of human sperm chromosome aberrations in the hamster egg. Hum Genet. 1992 May;89(2):181–186. doi: 10.1007/BF00217120. [DOI] [PubMed] [Google Scholar]
  17. Gosden R. G., Baird D. T., Wade J. C., Webb R. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at -196 degrees C. Hum Reprod. 1994 Apr;9(4):597–603. doi: 10.1093/oxfordjournals.humrep.a138556. [DOI] [PubMed] [Google Scholar]
  18. Hall J. G. Genomic imprinting: review and relevance to human diseases. Am J Hum Genet. 1990 May;46(5):857–873. [PMC free article] [PubMed] [Google Scholar]
  19. Hallak J., Kolettis P. N., Sekhon V. S., Thomas A. J., Jr, Agarwal A. Cryopreservation of sperm from patients with leukemia: is it worth the effort? Cancer. 1999 May 1;85(9):1973–1978. [PubMed] [Google Scholar]
  20. Hawkins M. M., Draper G. J., Smith R. A. Cancer among 1,348 offspring of survivors of childhood cancer. Int J Cancer. 1989 Jun 15;43(6):975–978. doi: 10.1002/ijc.2910430604. [DOI] [PubMed] [Google Scholar]
  21. Hawkins M. M., Smith R. A. Pregnancy outcomes in childhood cancer survivors: probable effects of abdominal irradiation. Int J Cancer. 1989 Mar 15;43(3):399–402. doi: 10.1002/ijc.2910430309. [DOI] [PubMed] [Google Scholar]
  22. Hovatta O., Silye R., Krausz T., Abir R., Margara R., Trew G., Lass A., Winston R. M. Cryopreservation of human ovarian tissue using dimethylsulphoxide and propanediol-sucrose as cryoprotectants. Hum Reprod. 1996 Jun;11(6):1268–1272. doi: 10.1093/oxfordjournals.humrep.a019370. [DOI] [PubMed] [Google Scholar]
  23. Kulin H. E., Frontera M. A., Demers L. M., Bartholomew M. J., Lloyd T. A. The onset of sperm production in pubertal boys. Relationship to gonadotropin excretion. Am J Dis Child. 1989 Feb;143(2):190–193. [PubMed] [Google Scholar]
  24. Lerner-Geva L., Toren A., Chetrit A., Modan B., Mandel M., Rechavi G., Dor J. The risk for cancer among children of women who underwent in vitro fertilization. Cancer. 2000 Jun 15;88(12):2845–2847. doi: 10.1002/1097-0142(20000615)88:12<2845::aid-cncr26>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  25. Li F. P., Fine W., Jaffe N., Holmes G. E., Holmes F. F. Offspring of patients treated for cancer in childhood. J Natl Cancer Inst. 1979 May;62(5):1193–1197. [PubMed] [Google Scholar]
  26. Malkin D., Portwine C. The genetics of childhood cancer. Eur J Cancer. 1994;30A(13):1942–1946. doi: 10.1016/0959-8049(94)00384-h. [DOI] [PubMed] [Google Scholar]
  27. Meistrich M. L., Wilson G., Brown B. W., da Cunha M. F., Lipshultz L. I. Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer. 1992 Dec 1;70(11):2703–2712. doi: 10.1002/1097-0142(19921201)70:11<2703::aid-cncr2820701123>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  28. Müller J., Skakkebaek N. E. Quantification of germ cells and seminiferous tubules by stereological examination of testicles from 50 boys who suffered from sudden death. Int J Androl. 1983 Apr;6(2):143–156. doi: 10.1111/j.1365-2605.1983.tb00333.x. [DOI] [PubMed] [Google Scholar]
  29. Müller J., Sønksen J., Sommer P., Schmiegelow M., Petersen P. M., Heilman C., Schmiegelow K. Cryopreservation of semen from pubertal boys with cancer. Med Pediatr Oncol. 2000 Mar;34(3):191–194. doi: 10.1002/(sici)1096-911x(200003)34:3<191::aid-mpo5>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  30. Newton H., Aubard Y., Rutherford A., Sharma V., Gosden R. Low temperature storage and grafting of human ovarian tissue. Hum Reprod. 1996 Jul;11(7):1487–1491. doi: 10.1093/oxfordjournals.humrep.a019423. [DOI] [PubMed] [Google Scholar]
  31. Nicholls R. D. The impact of genomic imprinting for neurobehavioral and developmental disorders. J Clin Invest. 2000 Feb;105(4):413–418. doi: 10.1172/JCI9460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nichols K. E., Li F. P., Haber D. A., Diller L. Childhood cancer predisposition: applications of molecular testing and future implications. J Pediatr. 1998 Mar;132(3 Pt 1):389–397. doi: 10.1016/s0022-3476(98)70007-1. [DOI] [PubMed] [Google Scholar]
  33. Nicholson H. S., Byrne J. Fertility and pregnancy after treatment for cancer during childhood or adolescence. Cancer. 1993 May 15;71(10 Suppl):3392–3399. doi: 10.1002/1097-0142(19930515)71:10+<3392::aid-cncr2820711743>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  34. Nielsen C. T., Skakkebaek N. E., Richardson D. W., Darling J. A., Hunter W. M., Jørgensen M., Nielsen A., Ingerslev O., Keiding N., Müller J. Onset of the release of spermatozoa (spermarche) in boys in relation to age, testicular growth, pubic hair, and height. J Clin Endocrinol Metab. 1986 Mar;62(3):532–535. doi: 10.1210/jcem-62-3-532. [DOI] [PubMed] [Google Scholar]
  35. Nistal M., Paniagua R. Occurrence of primary spermatocytes in the infant and child testis. Andrologia. 1984 Nov-Dec;16(6):532–536. doi: 10.1111/j.1439-0272.1984.tb00409.x. [DOI] [PubMed] [Google Scholar]
  36. Ogawa O., Becroft D. M., Morison I. M., Eccles M. R., Skeen J. E., Mauger D. C., Reeve A. E. Constitutional relaxation of insulin-like growth factor II gene imprinting associated with Wilms' tumour and gigantism. Nat Genet. 1993 Dec;5(4):408–412. doi: 10.1038/ng1293-408. [DOI] [PubMed] [Google Scholar]
  37. Ogilvy-Stuart A. L., Clark D. J., Wallace W. H., Gibson B. E., Stevens R. F., Shalet S. M., Donaldson M. D. Endocrine deficit after fractionated total body irradiation. Arch Dis Child. 1992 Sep;67(9):1107–1110. doi: 10.1136/adc.67.9.1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Oktay K., Nugent D., Newton H., Salha O., Chatterjee P., Gosden R. G. Isolation and characterization of primordial follicles from fresh and cryopreserved human ovarian tissue. Fertil Steril. 1997 Mar;67(3):481–486. doi: 10.1016/s0015-0282(97)80073-8. [DOI] [PubMed] [Google Scholar]
  39. Palermo G., Joris H., Devroey P., Van Steirteghem A. C. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992 Jul 4;340(8810):17–18. doi: 10.1016/0140-6736(92)92425-f. [DOI] [PubMed] [Google Scholar]
  40. Palermo G., Munné S., Cohen J. The human zygote inherits its mitotic potential from the male gamete. Hum Reprod. 1994 Jul;9(7):1220–1225. doi: 10.1093/oxfordjournals.humrep.a138682. [DOI] [PubMed] [Google Scholar]
  41. Quigley C., Cowell C., Jimenez M., Burger H., Kirk J., Bergin M., Stevens M., Simpson J., Silink M. Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia. N Engl J Med. 1989 Jul 20;321(3):143–151. doi: 10.1056/NEJM198907203210303. [DOI] [PubMed] [Google Scholar]
  42. Rademaker A., Spriggs E., Ko E., Martin R. Reliability of estimates of diploid human spermatozoa using multicolour fluorescence in-situ hybridization. Hum Reprod. 1997 Jan;12(1):77–79. doi: 10.1093/humrep/12.1.77. [DOI] [PubMed] [Google Scholar]
  43. Rainier S., Johnson L. A., Dobry C. J., Ping A. J., Grundy P. E., Feinberg A. P. Relaxation of imprinted genes in human cancer. Nature. 1993 Apr 22;362(6422):747–749. doi: 10.1038/362747a0. [DOI] [PubMed] [Google Scholar]
  44. Rivkees S. A., Crawford J. D. The relationship of gonadal activity and chemotherapy-induced gonadal damage. JAMA. 1988 Apr 8;259(14):2123–2125. [PubMed] [Google Scholar]
  45. Sanders J. E., Hawley J., Levy W., Gooley T., Buckner C. D., Deeg H. J., Doney K., Storb R., Sullivan K., Witherspoon R. Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood. 1996 Apr 1;87(7):3045–3052. [PubMed] [Google Scholar]
  46. Sathananthan A. H., Kola I., Osborne J., Trounson A., Ng S. C., Bongso A., Ratnam S. S. Centrioles in the beginning of human development. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4806–4810. doi: 10.1073/pnas.88.11.4806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Schlegel P. N., Su L. M. Physiological consequences of testicular sperm extraction. Hum Reprod. 1997 Aug;12(8):1688–1692. doi: 10.1093/humrep/12.8.1688. [DOI] [PubMed] [Google Scholar]
  48. Schover L. R., Agarwal A., Thomas A. J., Jr Cryopreservation of gametes in young patients with cancer. J Pediatr Hematol Oncol. 1998 Sep-Oct;20(5):426–428. doi: 10.1097/00043426-199809000-00003. [DOI] [PubMed] [Google Scholar]
  49. Schover L. R. Psychosocial aspects of infertility and decisions about reproduction in young cancer survivors: a review. Med Pediatr Oncol. 1999 Jul;33(1):53–59. doi: 10.1002/(sici)1096-911x(199907)33:1<53::aid-mpo10>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  50. Scrable H., Cavenee W., Ghavimi F., Lovell M., Morgan K., Sapienza C. A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7480–7484. doi: 10.1073/pnas.86.19.7480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Shalet S. M., Tsatsoulis A., Whitehead E., Read G. Vulnerability of the human Leydig cell to radiation damage is dependent upon age. J Endocrinol. 1989 Jan;120(1):161–165. doi: 10.1677/joe.0.1200161. [DOI] [PubMed] [Google Scholar]
  52. Shaw J. M., Bowles J., Koopman P., Wood E. C., Trounson A. O. Fresh and cryopreserved ovarian tissue samples from donors with lymphoma transmit the cancer to graft recipients. Hum Reprod. 1996 Aug;11(8):1668–1673. doi: 10.1093/oxfordjournals.humrep.a019467. [DOI] [PubMed] [Google Scholar]
  53. Shaw J., Trounson A. Oncological implications in the replacement of ovarian tissue. Hum Reprod. 1997 Mar;12(3):403–405. [PubMed] [Google Scholar]
  54. Shields P. G., Harris C. C. Cancer risk and low-penetrance susceptibility genes in gene-environment interactions. J Clin Oncol. 2000 Jun;18(11):2309–2315. doi: 10.1200/JCO.2000.18.11.2309. [DOI] [PubMed] [Google Scholar]
  55. Simerly C., Wu G. J., Zoran S., Ord T., Rawlins R., Jones J., Navara C., Gerrity M., Rinehart J., Binor Z. The paternal inheritance of the centrosome, the cell's microtubule-organizing center, in humans, and the implications for infertility. Nat Med. 1995 Jan;1(1):47–52. doi: 10.1038/nm0195-47. [DOI] [PubMed] [Google Scholar]
  56. Sklar C. Reproductive physiology and treatment-related loss of sex hormone production. Med Pediatr Oncol. 1999 Jul;33(1):2–8. doi: 10.1002/(sici)1096-911x(199907)33:1<2::aid-mpo2>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  57. Sofikitis N., Mantzavinos T., Loutradis D., Yamamoto Y., Tarlatzis V., Miyagawa I. Ooplasmic injections of secondary spermatocytes for non-obstructive azoospermia. Lancet. 1998 Apr 18;351(9110):1177–1178. doi: 10.1016/S0140-6736(05)79121-2. [DOI] [PubMed] [Google Scholar]
  58. Sousa M., Mendoza C., Barros A., Tesarik J. Calcium responses of human oocytes after intracytoplasmic injection of leukocytes, spermatocytes and round spermatids. Mol Hum Reprod. 1996 Nov;2(11):853–857. doi: 10.1093/molehr/2.11.853. [DOI] [PubMed] [Google Scholar]
  59. Surani M. A., Barton S. C., Norris M. L. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature. 1984 Apr 5;308(5959):548–550. doi: 10.1038/308548a0. [DOI] [PubMed] [Google Scholar]
  60. Sutcliffe A. G. Intracytoplasmic sperm injection and other aspects of new reproductive technologies. Arch Dis Child. 2000 Aug;83(2):98–101. doi: 10.1136/adc.83.2.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Tesarik J., Mendoza C. Spermatid injection into human oocytes. I. Laboratory techniques and special features of zygote development. Hum Reprod. 1996 Apr;11(4):772–779. doi: 10.1093/oxfordjournals.humrep.a019253. [DOI] [PubMed] [Google Scholar]
  62. Tesarik J., Mendoza C., Testart J. Viable embryos from injection of round spermatids into oocytes. N Engl J Med. 1995 Aug 24;333(8):525–525. doi: 10.1056/NEJM199508243330819. [DOI] [PubMed] [Google Scholar]
  63. Vanderzwalmen P., Zech H., Birkenfeld A., Yemini M., Bertin G., Lejeune B., Nijs M., Segal L., Stecher A., Vandamme B. Intracytoplasmic injection of spermatids retrieved from testicular tissue: influence of testicular pathology, type of selected spermatids and oocyte activation. Hum Reprod. 1997 Jun;12(6):1203–1213. doi: 10.1093/humrep/12.6.1203. [DOI] [PubMed] [Google Scholar]
  64. Wallace W. H., Shalet S. M., Crowne E. C., Morris-Jones P. H., Gattamaneni H. R., Price D. A. Gonadal dysfunction due to cis-platinum. Med Pediatr Oncol. 1989;17(5):409–413. doi: 10.1002/mpo.2950170510. [DOI] [PubMed] [Google Scholar]
  65. Wallace W. H., Shalet S. M., Hendry J. H., Morris-Jones P. H., Gattamaneni H. R. Ovarian failure following abdominal irradiation in childhood: the radiosensitivity of the human oocyte. Br J Radiol. 1989 Nov;62(743):995–998. doi: 10.1259/0007-1285-62-743-995. [DOI] [PubMed] [Google Scholar]
  66. Waring A. B., Wallace W. H. Subfertility following treatment for childhood cancer. Hosp Med. 2000 Aug;61(8):550–557. doi: 10.12968/hosp.2000.61.8.1398. [DOI] [PubMed] [Google Scholar]
  67. Zhang J., Liu J., Xu K. P., Liu B., DiMattina M. Extracorporeal development and ultrarapid freezing of human fetal ova. J Assist Reprod Genet. 1995 Jul;12(6):361–368. doi: 10.1007/BF02215727. [DOI] [PubMed] [Google Scholar]

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