Female fertility and colorectal cancer

  • Constantine P. Spanos
  • Apostolos Mamopoulos
  • Apostolos Tsapas
  • Theodore Syrakos
  • Dimitris Kiskinis



It is estimated that the incidence of cancer in women aged 40 years or less is 8%. Females under the age of 40 are in their childbearing years. In the Western world, colorectal cancer (CRC) is the most common malignancy of the gastrointestinal tract. It is the third most commonly diagnosed cancer and the second leading cause of cancer-related death in the USA. The incidence of CRC in patients under 40 is 3–6%. Over the past decades, there has been a significant improvement in survival rates due to progress in cancer treatment, including CRC. This has been achieved with advances in adjuvant chemotherapeutic regimens. In the case of locally advanced rectal cancer, radiation therapy is also used. Treatment for CRC may have adverse effects on female fertility. The purpose of this paper is to discuss the effects of treatment of CRC on female fertility as well as the options for fertility preservation.

Materials and methods

A review of relevant English language articles was performed on the basis of a MEDLINE search of the keywords: female, fertility, fecundity, colon, rectal cancer, fertility preservation, chemotherapy, and radiation.


Surgical resection for colon cancer possibly has no effect on female fertility. Resection below the peritoneal reflection may adversely affect fertility, based on lower fertility and fecundity rates associated with pelvic surgery for ulcerative colitis and familial adenomatous polyposis. Standard 5-FU-based chemotherapy may not have significant effects. The advent of oxaliplatin in adjuvant chemotherapy may be more harmful. Adjuvant and neoadjuvant radiation therapy may cause premature ovarian failure using current dosing schedules. The effect of pregnancy and female hormones on the incidence, progression, and recurrence of CRC remains unclear. Established methods for fertility preservation include ovarian transposition and embryo cryopreservation. Oocyte cryopreservation has yielded inferior results. An investigational fertility preservation method is ovarian tissue cryopreservation, with promising results. Ovarian suppression and the use of apoptotic inhibitors are also investigational at present.


Young female patients need to be informed about the effects of treatment on fertility and options for fertility preservation. A multidisciplinary approach for appropriate consultation of these patients is mandatory.


Female Fertility Fecundity Colorectal Cancer 


  1. 1.
    O’Connell JB, Maggard MA, Liu JH et al (2004) Do young colon cancer patients have worse outcomes? World J Surg 28:558–562PubMedCrossRefGoogle Scholar
  2. 2.
    Marhhom E, Cohen I (2007) Fertility preservation options for women with malignancies. Obstet Gynecol Surv 62(1):58–72PubMedCrossRefGoogle Scholar
  3. 3.
    Meyerhardt JA, Mayer RJ (2005) Systemic therapy for colorectal cancer. N Engl J Med 325(5):476–487CrossRefGoogle Scholar
  4. 4.
    Gill S, Blackstock W, Goldberg RM (2007) Colorectal cancer. Mayo Clin Proc 82(1):114–129PubMedGoogle Scholar
  5. 5.
    Strong M, Peche W, Scaife C (2007) Incidence of fertility counselling of women of child-bearing age before treatment of colorectal cancer. Am J Surg 194:765–768PubMedCrossRefGoogle Scholar
  6. 6.
    Davis VJ (2006) Female gamete preservation. Cancer 107(suppl 7):1690–1694PubMedCrossRefGoogle Scholar
  7. 7.
    Maltaris T, Boehm D, Dittrich R et al (2006) Reproduction beyond cancer: a message of hope for young women. Gynecol Oncol 103:1109–1121PubMedCrossRefGoogle Scholar
  8. 8.
    Bleyer A, O’Leary M, Barr R, Ries LAG (eds): Cancer epidemiology in older adolescents and young adults 15 to 29 years of age, including SEER incidence and survival: 1975–2000. National Cancer Institute, NIH Pub. No. 06-5767. Bethesda, MD 2006Google Scholar
  9. 9.
    Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Horner MJ, Howlader N, Eisner MP, Reichman M, Edwards BK (eds). SEER Cancer Statistics Review, 1975–2004, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2004/, based on November 2006 SEER data submission, posted to the SEER web site, 2007
  10. 10.
    O’Connell JB, Maggard MA, Liu JH, Etzioni DA, Ko CY (2004) Are survival rates different for young and old patients with rectal cancer? Dis Colon Rectum 47(12):2064–2069PubMedCrossRefGoogle Scholar
  11. 11.
    Endreseth BH, Romunstad P, Myrvold HE, Hestrik UE, Bjerkeset T, Wibe A (2006) Rectal cancer in the young patient. Dis Colon Rectum 49(7):993–1001PubMedCrossRefGoogle Scholar
  12. 12.
    Saif MW (2005) Management of colorectal cancer in pregnancy: a multimodality approach. Clin Colorectal Cancer 5:247–256PubMedCrossRefGoogle Scholar
  13. 13.
    Bernstein MA, Madoff RD, Caushaj PF (1993) Colon and rectal cancer in pregnancy. Dis Colon Rectum 36:172–178PubMedCrossRefGoogle Scholar
  14. 14.
    Ochshorn Y, Kupfermine MJ, Lessing JB, Pausner D, Gera E, Daniel Y (2000) Rectal carcinoma during pregnancy: a reminder and updated treatment. Eur J Obstet Gynecol Reprod Biol 91:201–202PubMedCrossRefGoogle Scholar
  15. 15.
    Puig-La Calle JP, Ng J, Syn GL, Vuolo MA, Guillem JG (1999) Colorectal cancer recurrence during pregnancy—unique and poorly understood clinical entity. Dis Colon Rectum 42:673–675PubMedCrossRefGoogle Scholar
  16. 16.
    Minter A, Malik R, Ledbetter L et al (2005) Colon cancer in pregnancy. Cancer Control 12(3):196–202PubMedGoogle Scholar
  17. 17.
    Campbell-Thompson M, Lynch IJ, Bhardwaj B (2001) Expression of estrogen receptor (ER) subtypes and ERb isoforms in colon cancer. Cancer Res 61:632–640PubMedGoogle Scholar
  18. 18.
    Wong NACS, Malcomson RDG, Jodrell DI, Groome NP, Harrison DJ, Saunders PTK (2005) ERb isoform expression in colorectal carcinoma: an in vivo and in vitro study of clinicopathological and molecular correlates. J Pathol 207:53–60PubMedCrossRefGoogle Scholar
  19. 19.
    Eberhart CE, Coffey RJ, Radhika A et al (1994) Up-regulation of cyclooxygenase-2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107:1183–1188PubMedGoogle Scholar
  20. 20.
    Lim H, Paria BX, Das SK et al (1997) Multiple female reproductive failures in COX-2 deficient mice. Cell 91:197–208PubMedCrossRefGoogle Scholar
  21. 21.
    Gorgun E, Remzi FH, Goldberg JM, Thornton J, Bast J, Hull TL, Loparo B, Fazio VW (2004) Fertility is reduced after ileal pouch–anal anastomosis: a study of 300 patients. Surgery 136:795–803PubMedCrossRefGoogle Scholar
  22. 22.
    Olsen KO, Joelsson M, Laurberg S, Oresland T (1999) Fertility after ileal pouch–anal anastomosis in women with ulcerative colitis. Br J Surg 86:493–495PubMedCrossRefGoogle Scholar
  23. 23.
    Olsen KO, Svend J, Berndtsson I, Oresland T, Laurberg S (2002) Ulcerative colitis: female fecundity before diagnosis, during disease, after surgery compared with a population sample. Gastroenterology 122:15–19CrossRefGoogle Scholar
  24. 24.
    Olsen KO, Juul S, Buelow S, Järrinen HJ, Bakka A, Björk J, Oresland T, Laurberg S (2003) Female fecundity before and after operation for familial adenomatous polyposis. Br J Surg 90:227–231PubMedCrossRefGoogle Scholar
  25. 25.
    Oresland T, Palmblad S, Ellstrom M et al (1994) Gynecological and sexual function related to anatomical changes in the female pelvis after restorative proctocolectomy. Int J Colorectal Dis 9:77–81PubMedCrossRefGoogle Scholar
  26. 26.
    Bhardwaj R, Parker MC (2007) Impact of adhesions in colorectal surgery. Colorectal Dis 9(suppl II):45–53PubMedCrossRefGoogle Scholar
  27. 27.
    Twelves C, Wong A, Nowacki MP et al (2005) Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 352:2696–704PubMedCrossRefGoogle Scholar
  28. 28.
    Azem F, Amit A, Merimsky O, Lessing J (2004) Successful transfer of frozen–thawed embryos obtained after subtotal colectomy for colorectal cancer and before fluorouracil-based chemotherapy. Gynecol Oncol 93:263–265PubMedCrossRefGoogle Scholar
  29. 29.
    Andre T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil and leucovorin as adjuvant therapy for colon cancer. N Engl J Med 350:2343–2351PubMedCrossRefGoogle Scholar
  30. 30.
    Wallace WHB, Thomson AB, Kelsey TW (2003) The radiosensitivity of the human oocyte. Hum Reprod 18(1):117–121PubMedCrossRefGoogle Scholar
  31. 31.
    Maltaris T, Senfert R, Fischl F et al (2007) The effect of cancer treatment on female fertility and strategies for preserving fertility. Eur J Obstet Gynecol Reprod Biol 130(2):148–155PubMedCrossRefGoogle Scholar
  32. 32.
    Heald RJ, Ryall RD (1986) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1:1479–1482PubMedCrossRefGoogle Scholar
  33. 33.
    Swedish Rectal Cancer Trial (1997) Improved survival with preoperative radiotherapy in resectable rectal cancer [published correction appears in N Engl J Med 1997;336:1539]. N Engl J Med 336:980–987CrossRefGoogle Scholar
  34. 34.
    Kapiteijn E, Marijnen CA, Nagtegaal ID, Dutch Colorectal Cancer Group et al (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638–646PubMedCrossRefGoogle Scholar
  35. 35.
    Bosset JF, Collette L, Calais G et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123PubMedCrossRefGoogle Scholar
  36. 36.
    Sauer R, Becker H, Hohenberger W, German Rectal Cancer Study Group et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740PubMedCrossRefGoogle Scholar
  37. 37.
    Tepper JE, O’Connell M, Niedzwiecki D et al (2002) Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control: final report of intergroup 0114. J Clin Oncol 20:1744–1750PubMedCrossRefGoogle Scholar
  38. 38.
    Morice P, Juncker L, Rey A et al (2000) Ovarian transposition for patients with cervical carcinoma treated by radiosurgical combination. Fertil Steril 74:743–748PubMedCrossRefGoogle Scholar
  39. 39.
    Bisharak M, Tulandi T (2003) Laparoscopic preservation of ovarian function: an underused procedure. Am J Obstet Gynecol 188:367–370CrossRefGoogle Scholar
  40. 40.
    Morice P, Haie-Meder C, Pautier P et al (2001) Ovarian metastasis on transposed ovary in patients treated for squamous cell carcinoma of the uterine cervix: report of two cases and surgical implications. Gynecol Oncol 83:605–607PubMedCrossRefGoogle Scholar
  41. 41.
    Oktay K, Cil AR et al (2006) Efficiency of oocyte cryopreservation: a meta-analysis. Fertil Steril 86:70–80PubMedCrossRefGoogle Scholar
  42. 42.
    American Society of Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology Practice Committee (2006) Ovarian tissue and oocyte cryopreservation. Fertil Steril 86(suppl 4):S142–S147Google Scholar
  43. 43.
    Oktay K, Buyuk E, Veek L et al (2004) Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet 363:837–840PubMedCrossRefGoogle Scholar
  44. 44.
    Oktay K, Sonmezer M (2004) Ovarian tissue banking for cancer patients. Fertility preservation, not just ovarian cryopreservation. Hum Reprod 19(3):477–480PubMedCrossRefGoogle Scholar
  45. 45.
    Meirow D, Levron J, Eldar-Geva T (2005) Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med 353(3):318–320PubMedCrossRefGoogle Scholar
  46. 46.
    Blumenfeld Z (2003) Gynaecologic concerns for young women exposed to gonadotoxic chemotherapy. Curr Opin Obstet Gynecol 15(5):359–370 ReviewPubMedCrossRefGoogle Scholar
  47. 47.
    Meirow D (2000) Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol 169(1–2):123–131 Nov 27PubMedCrossRefGoogle Scholar
  48. 48.
    Pal L, Leykin L, Schifren JL et al (1998) Malignancy may adversely influence the quality and behaviour of oocytes. Hum Reprod 13(7):1837–1840PubMedCrossRefGoogle Scholar
  49. 49.
    Morice P, Pautier P, Fanchin R et al (2007) Therapy insight: fertility in women after cancer treatment. Nat Clin Pract Endocrinol Metab 3:819–826PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Constantine P. Spanos
    • 1
  • Apostolos Mamopoulos
    • 1
  • Apostolos Tsapas
    • 1
  • Theodore Syrakos
    • 1
  • Dimitris Kiskinis
    • 1
  1. 1.Department of SurgeryAristotelian UniversityThessalonikiGreece

Personalised recommendations