The Effect of Assisted Reproductive Technologies on Gynecological Cancer: Report of Our Experiences and Literature Review

Introduction: Infertility is as an important and common problem in couples necessitating assisted reproductive technology (ART) or drug therapy. Infertility is known as a risk factor for ovarian, breast and endometrial cancer. We aimed on evaluation of the history of primary infertility and previous ART in patients with the above-mentioned cancers. Material and method: In this retrospective study we evaluated all of the risk factors in patients with breast cancer, ovarian cancer and endometrial cancers who referred to the Gynecological Oncology Clinic in Shahid Sadoughi Hospital in Yazd, Iran from 2002 to 2012. We also investigated the history of primary infertility and ART in these patients before diagnosis of cancers. Results: We gathered data from 92 patients with endometrial cancer, 84 patients with advanced epithelial ovarian cancer and 113 patients with breast cancer. There was history of infertility in 39.1% of patients with endometrial cancer who were obese (body mass index, BMI>29) and in 18.8% of patients with endometrial cancer and normal body mass index (BMI=25-29). ART had been performed in 7.3% of all patients with endometrial cancer. In patients with epithelial ovarian cancer, infertility was diagnosed in 28.4% and ART applied in 14.1%. Clomiphene with or without HCG and HMG was the most common drug used for patients with ovarian cancer. In patients with breast cancer, there was infertility in 16.5% and ART performed in 7.3%. Conclusion: Although infertility was present as an important and fairly common risk factor in some patients with endometrial, ovarian and breast cancer, but some other factors may be more important, including age, BMI and the etiology of infertility. Finding the association between ART and gynecological cancers needs long cohort studies with follow-up of infertile women who get the ART or drug therapy for over 15-20 years. We think BMI and age (in addition to infertility and ART) are contributing factors for development of gynecological cancers.

[1]  R. Marci,et al.  Fertility-sparing treatment of endometrial cancer precursors among young women: a reproductive point of view. , 2012, European review for medical and pharmacological sciences.

[2]  S. Kōzuma,et al.  The Influence of Infertility Treatment on the Prognosis of Endometrial Cancer and Atypical Complex Endometrial Hyperplasia , 2012, International Journal of Gynecologic Cancer.

[3]  J. Weissfeld,et al.  Use of Fertility Drugs and Risk of Ovarian Cancer: Results from a U.S.-Based Case–Control Study , 2012, Cancer Epidemiology, Biomarkers & Prevention.

[4]  J. Litton Breast Cancer and Fertility , 2012, Current Treatment Options in Oncology.

[5]  J. Jeruss,et al.  Effect of infertility treatment and pregnancy-related hormones on breast cell proliferation in vitro. , 2012, Human reproduction.

[6]  B. Källén,et al.  Malignancies among women who gave birth after in vitro fertilization. , 2011, Human reproduction.

[7]  M. Gilani,et al.  Fertility sparing treatments in young patients with gynecological cancers: Iranian experience and literature review. , 2011, Asian Pacific journal of cancer prevention : APJCP.

[8]  E. Petru Fertility preservation and infertility treatment in breast cancer patients , 2010, Wiener Medizinische Wochenschrift.

[9]  Christine F. Wogan,et al.  Fertility drugs and the risk of breast cancer: a meta-analysis and review , 2010, Breast Cancer Research and Treatment.

[10]  S. Inoue,et al.  Clomiphene citrate elicits estrogen agonistic/antagonistic effects differentially via estrogen receptors αand β , 2010 .

[11]  K. Oktay,et al.  GnRH agonist trigger for women with breast cancer undergoing fertility preservation by aromatase inhibitor/FSH stimulation. , 2010, Reproductive biomedicine online.

[12]  N. Paneth,et al.  Pregnancy characteristics and maternal breast cancer risk: a review of the epidemiologic literature , 2010, Cancer Causes & Control.

[13]  N. Vlahos,et al.  Endometriosis, in vitro fertilisation and the risk of gynaecological malignancies, including ovarian and breast cancer. , 2010, Best practice & research. Clinical obstetrics & gynaecology.

[14]  S. Inoue,et al.  Clomiphene citrate elicits estrogen agonistic/antagonistic effects differentially via estrogen receptors alpha and beta. , 2010, Endocrine journal.

[15]  M. Carney,et al.  Current Understanding of Risk Factors for Ovarian Cancer , 2009, Current treatment options in oncology.

[16]  R. Hiatt,et al.  The Breast Cancer and the Environment Research Centers: Transdisciplinary Research on the Role of the Environment in Breast Cancer Etiology , 2009, Environmental health perspectives.

[17]  P. Dickman,et al.  Ovarian epithelial neoplasia after hormonal infertility treatment: long-term follow-up of a historical cohort in Sweden. , 2009, Fertility and sterility.

[18]  K. Czene,et al.  Breast cancer incidence after hormonal infertility treatment in Sweden: a cohort study. , 2009, American journal of obstetrics and gynecology.

[19]  T. Peretz,et al.  Beginning IVF Treatments After Age 30 Increases the Risk of Breast Cancer: Results of a Case–Control Study , 2008, The breast journal.

[20]  I. Cetin,et al.  Infertility as a cancer risk factor - a review. , 2008, Placenta.

[21]  J. Olsen,et al.  Risk of breast cancer and gynecologic cancers in a large population of nearly 50,000 infertile Danish women. , 2008, American journal of epidemiology.

[22]  K. P. Phillips,et al.  Risk Factors for Ovarian Cancer: An Overview with Emphasis on Hormonal Factors , 2008, Journal of toxicology and environmental health. Part B, Critical reviews.

[23]  Fahimeh Ghotbizadeh,et al.  Ovarian carcinoma associated with pregnancy: A clinicopathologic analysis of 23 cases and review of the literature , 2008, BMC pregnancy and childbirth.

[24]  A. Halevy,et al.  The Possible Association between IVF and Breast Cancer Incidence , 2008, Annals of Surgical Oncology.

[25]  K. Frederiksen,et al.  Risk of Breast Cancer After Exposure to Fertility Drugs: Results from a Large Danish Cohort Study , 2007, Cancer Epidemiology Biomarkers & Prevention.

[26]  S. Kjaer,et al.  Different Risk Factor Profiles for Mucinous and Nonmucinous Ovarian Cancer: Results from the Danish MALOVA Study , 2007, Cancer Epidemiology Biomarkers & Prevention.

[27]  S. Ku,et al.  Use of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles: a pilot study. , 2006, Fertility and sterility.

[28]  J. Schenker,et al.  Infertility, Ovulation Induction Treatments and the Incidence of Breast Cancer—a Historical Prospective Cohort of Israeli Women , 2006, Breast Cancer Research and Treatment.

[29]  C. Trial Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial , 2006 .

[30]  J. Manson,et al.  Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. , 2006, JAMA.

[31]  J. Manson,et al.  Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. , 2006, JAMA.

[32]  B. Källén,et al.  In vitro fertilisation in Sweden: obstetric characteristics, maternal morbidity and mortality , 2005, BJOG : an international journal of obstetrics and gynaecology.

[33]  K. Mokbel,et al.  In vitro fertilization and breast cancer risk: a review. , 2005, International journal of fertility and women's medicine.

[34]  U. Menon,et al.  Epithelial ovarian cancer and induction of ovulation , 2005 .

[35]  M. Gultekin,et al.  Association between fertility drugs and gynecologic cancers, breast cancer, and childhood cancers , 2004, Acta obstetricia et gynecologica Scandinavica.

[36]  L. Brinton,et al.  Breast cancer risk associated with ovulation-stimulating drugs. , 2004, Human reproduction.

[37]  S. Manna,et al.  Human Chorionic Gonadotropin Decreases Proliferation and Invasion of Breast Cancer MCF-7 Cells by Inhibiting NF-κB and AP-1 Activation* , 2004, Journal of Biological Chemistry.

[38]  B. Strom,et al.  Infertility drugs and the risk of breast cancer: findings from the National Institute of Child Health and Human Development Women's Contraceptive and Reproductive Experiences Study. , 2003, Fertility and sterility.

[39]  A. Chetrit,et al.  The possible association between in vitro fertilization treatments and cancer development , 2002, International Journal of Gynecologic Cancer.

[40]  B. Modan,et al.  Cancer incidence in a cohort of infertile women who underwent in vitro fertilization. , 2002, Fertility and sterility.

[41]  P. Goss,et al.  Estrogen and the risk of breast cancer. , 2001, The New England journal of medicine.

[42]  A. Venn,et al.  Risk of cancer after use of fertility drugs with in-vitro fertilisation , 1999, The Lancet.

[43]  C. la Vecchia,et al.  Fertility drugs and the risk of breast cancer. , 1999, Human reproduction.

[44]  A. Chetrit,et al.  Fertility drugs and the risk of breast and ovarian cancers: results of a long-term follow-up study. , 1999, Fertility and sterility.

[45]  C. la Vecchia,et al.  Fertility treatment and risk of breast cancer. , 1996, Human reproduction.

[46]  S. Self,et al.  Risk of breast cancer in a cohort of infertile women. , 1996, Gynecologic oncology.

[47]  A. Venn,et al.  Breast and ovarian cancer incidence after infertility and in vitro fertilisation , 1995, The Lancet.

[48]  S. Self,et al.  Ovarian tumors in a cohort of infertile women. , 1994, The New England journal of medicine.

[49]  C. Runowicz,et al.  Lymph node sampling in patients with epithelial ovarian carcinoma. , 1992, Gynecologic oncology.

[50]  J. Baak,et al.  Borderline malignancy of the ovary and controlled hyperstimulation, a report of 2 cases. , 1992, European journal of cancer.

[51]  J. J. Li,et al.  Hormonal Carcinogenesis , 2020, Springer New York.

[52]  W. Thompson,et al.  Infertility and breast cancer: a population-based case-control study. , 1990, American journal of epidemiology.

[53]  R. Sutherland,et al.  Points of action of estrogen antagonists and a calmodulin antagonist within the MCF-7 human breast cancer cell cycle. , 1989, Cancer research.

[54]  J. Menczer,et al.  Massive Hyperstimulation and Borderline Carcinoma of the Ovary , 1982, Acta obstetricia et gynecologica Scandinavica.