Strong evidences of the ovarian carcinoma risk in women after ivf treatment

Shaghayegh Zokaei,1 Dariush d. farhud,2,* Marjan zarif yeganeh,3

1. School of Advanced Medical Sciences, Islamic Azad University, Tehran Medical Branch, Tehran, Iran
2. School of Public Health, Tehran University of Medical sciences, Tehran, Iran
3. Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Med



Every year, around 239,000 new cases of women in the world are diagnosed with ovarian cancer, with only below 45% survival rates, and according to the death toll of (152,000 deaths),it has become the 8th deadly(fatal) cause of cancer death among women. it is also diagnosed that serous ovarian tumors can be originated from the fallopian tube instead of the ovary itself. among all gynecological malignancies, ovarian cancer is recognized as the worst cancer in prognosis (the worst prognosis), which, as a medical term includes several types of tumors with different phenotypes, molecular biology, tumor progression, etiology, and even different prognosis. there are many factors which can increase the risk of ovarian cancer such as a family history of the patient or heredity, mutation status, age, number of pregnancies, breastfeeding, physical activity, alcohol consumption and, in general, life style. overall, it should be noted that there is a well-established association with a high proportion of hereditary between ovarian cancer risk and mutations, furthermore, these mutations are also prevalent among patients with ovarian cancer who do not have a family history of ovarian cancer. according to the appearance of the epithelium ovarian tumors are classified into these subtypes: serous, mucinous, clear cell, endometrioid, squamous, transitional, mixed and undifferentiated. these subtypes are also divided into two groups of high-grade and low-grade tumors, based on morphology and genetic alternation. low-grade ones, including serous carcinoma, mucinous, endometrioid, and clear cell carcinomas, likely to arise stepwise in an adenoma (borderline tumor) carcinoma sequence from typical to micropapillary borderline tumors to low-grade invasive serous carcinoma, with a lower rate of progression, and be caused by mutation in different genes including kras, braf, pten, and beta-catenin, and kras or braf mutations lead to the effective activation of the mapk signaling in low-grade serous carcinoma cells. contrary to the previous type, the high-grade type, consist of high-grade serous carcinoma, malignant mixed mesodermal tumors (carcinosarcomas) and undifferentiated carcinomas, grows rapidly and aggressively, with a high levels of genetic stability characterized by tp53 mutations and brca1 and / or brca2 dysfunction.


Our paper is a review article and we studied more than 70 articles to evaluate the future risk of ovarian carcinoma in women treated with ivf.


It is evidence that women who had a long period of treatments with high doses of fertility drugs can develop ovarian cysts which can lead to ovarian cancer. therefore, it is recommended that women be checked for "personalized medicine" before conducting ivf.


In summary, ivf, which has been highly regarded as a method of treatment for infertility, can carry risks like any other method. studies in this field give us different results, so that in some studies with a small sample size, no significant results have been achieved. however, other studies with a large sample size in this field clearly show the risk of developing ovarian cysts and cancer of the ovary. the drugs used in this method, like clomiphene citrate and gonadotropins, greatly hyper stimulate the ovary, leading to twin or multiple pregnancy, increased ovarian cyst and risk of ovarian cancer. it should be noted that the failure of each cycle compel the couples to try subsequent cycles, in which the dose and duration of drug intake are increased, and so the risk of this cancer also increases. altogether, different aspects of ivf courses should be considered. initially, the couple should completely apprehend the risks associated with this treatment. each couple should enter these therapies with regard to their “personalized medicine” in order to avoid long-term infertility treatment in the event of an inherited risk of ovarian cancer. every patient, especially susceptible patients, should be monitored closely by the doctor and appropriate tests.


Ovarian cancer, ivf,clomiphene citrate, anovulatory, infertility