Induction of ovulation and ovarian cancer: A critical review of the literature

Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai School of Medicine, New York, New York, USA.
Fertility and sterility (Impact Factor: 4.59). 05/2006; 85(4):819-26. DOI: 10.1016/j.fertnstert.2005.08.061
Source: PubMed


To critically examine the possible association between ovulation-inducing drugs and ovarian cancer.
Medline literature review and cross-reference of published data.
The studies that have adjusted for the effects of confounding factors such as duration of oral contraceptive use and number of pregnancies have noted an increased risk of ovarian cancer among infertile women who remain childless despite long periods of unprotected intercourse. Whether such women are at risk due to the primary basis for their infertility or factors such as ovulation-inducing drugs, has been the subject of several studies. Overall, the findings on ovarian cancer (especially invasive epithelial and non-epithelial) risk associated with fertility drug treatment are reassuring. However, a stronger association between fertility drug use and borderline tumors of the ovary has been observed.
Despite the overall reassuring findings of the available studies, there is a need for well-designed clinical trials to understand the possible carcinogenic effects of the ovulation-inducing drugs.

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Available from: Tanja Pejovic
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    • "Ovarian-stimulation drugs have been widely used in infertility-treatment regimes for nearly 40 years. Limited studies, mainly case reports and retrospective studies, have investigated the safety of these drugs and the associated risks (Whittemore et al., 1992;Rossing et al., 1994;Mahdavi et al., 2006;Vlahos et al., 2010), and have reported that treatments may be associated with the increased risk of some specific cancers. However, most research into the long-term effects of ovarianstimulation medications on the risk of cancer have had their shortcomings as many cohort studies have short follow-up periods. "
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    ABSTRACT: Background: The trend toward late childbearing has made fertility preservation a major issue for women who face gynecological cancer. New techniques in assisted reproductive medicine enable conception after primary treatment of these cancers. Here, we aimed to review the efficacy and safety of assisted reproductive techniques (ART) after fertility-preserving treatment of gynaecological cancers. Methods: We conducted a systematic literature review of both prospective and retrospective studies in the PubMed, EMBASE, CENTRAL and SciSearch databases. In the retrieved studies, we evaluated live births, clinical pregnancies, overall survival and disease-free survival. Results: We identified many prospective and retrospective studies on this topic, but no relevant randomized clinical trials. Fertility-sparing treatments with safe oncological outcomes are feasible in endometrial, cervical and ovarian cancer cases. After cancer treatment, ART seem safe and show variable obstetrical outcomes. Conclusions: After fertility-preserving treatment for gynaecological cancers, ART can enable pregnancy to be achieved with apparent oncological safety. The success of such procedures should directly impact clinical practice and management of those patients who require fertility-sparing treatment.
    Full-text · Article · Jan 2016 · Human Reproduction Update
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    • "Our previous studies confirmed these results (mean dysplasia score 7.64) and ovarian dysplasia seemed to be linked to the intensity and number of stimulations (dose-effect) and after a sufficient lapse of time (time-effect).13 However, the long term evolution is unknown.14,22 Animal experiments have given some interesting conclusions. "
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    ABSTRACT: Ovarian epithelial dysplasia was initially described in material from prophylactic oophorectomies for BReast CAncer gene (BRCA) mutation. Similar histopathological abnormalities have been revealed after ovulation stimulation. Given that tamoxifen (TAM) has a clomid-like effect and is sometimes used to induce ovulation, we studied the morphological features and immunohistochemical expression patterns of neoplasia-associated markers in adnexectomies previously exposed to TAM for breast cancer. We blindly reviewed 173 histopathological slides of adnexectomies according to three groups – oophorectomies associated with TAM exposure (n=42), oophorectomies associated with clomiphene exposure (n=15) and a spontaneously fertile non cancerous control group (n=116). Morphological features (with an ovarian and tubal dysplasia scoring system) and immunohistochemical expression patterns of Ki-67, p53 and Aldehyde dehydrogenase 1 (ALDH1 is an enzyme significantly associated with earlystage ovarian cancer) were evaluated and correlated. Mean tubal dysplasia score was significantly higher in the TAM group and clomiphen group than in controls (respectively 7.8 vs 3.5, P<0.007 and 6.8 vs 3.5, P=0.008). There is no statistical difference for the ovarian score in TAM group in comparison with the control group whereas we found a significant score for clomiphen group (6.5, P=0.009). Increased ALDH1 expression was observed in the two exposed group whereas expression patterns of Ki67 and p53 were moderate. Interestingly, ALDH1 expression was low in non-dysplastic epithelium, high in dysplasia, and constantly low in the two carcinoma. Furthemore, we confirm our previous results showing that ALDH1 may be a useful tissue biomarker in the subtle histopathological diagnosis of tubo-ovarian dysplasia.
    Full-text · Article · Apr 2014 · European journal of histochemistry: EJH
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    • "Moreover, the risk of cancer has been shown to be similar in children conceived by artificial reproductive therapies and those conceived naturally [27]. It should also be noted that, due to close medical surveillance, malignancies are overdiagnosed in the female population; this may also augment the early detection of cancers [28]. "
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    Full-text · Article · Sep 2013 · Reproductive Biology and Endocrinology
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