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- Siristatidis, Charalampos, et al.
(författare)
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Controlled ovarian hyperstimulation for IVF : impact on ovarian, endometrial and cervical cancer-a systematic review and meta-analysis
- 2013
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Ingår i: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 19:2, s. 105-123
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: In response to the ongoing debate on the long-term effects of assisted reproduction technologies, such as IVF, we systematically reviewed and meta-analyzed available evidence on the association between controlled ovarian hyperstimulation for IVF and risk of ovarian, endometrial and cervical cancer. METHODS: Eligible studies were identified and pooled effect estimates for relative risk (RR) were calculated by cancer type among two reference groups (general population or infertile women), through fixed-or random-effects models as appropriate. RESULTS: Nine cohort studies were synthesized, corresponding to a total size of 109 969 women exposed to IVF, among whom 76 incident cases of ovarian, 18 of endometrial and 207 cases of cervical cancer were studied. The synthesis of studies with general population as the reference group pointed to a statistically significant positive association between IVF and increased risk for ovarian (RR = 1.50, 95% confidence interval (CI): 1.17-1.92) and endometrial (RR = 2.04, 95% CI: 1.22-3.43), but not cervical (RR = 0.86, 95% CI: 0.49-1.49)cancers. On the contrary, when infertile women were used as the reference group, no significant associations with ovarian, endometrial or cervical cancer types were noted (RR=1.26, 95% CI: 0.62-2.55 RR=0.45, 95% CI: 0.18-1.14 and RR= 5.70, 95% CI: 0.28-117.20, respectively). CONCLUSIONS: IVF does not seem to be associated with elevated cervical cancer risk, nor with ovarian or endometrial cancer when the confounding effect of infertility was neutralized in studies allowing such comparisons. Of note, only one study provided follow-up longer than 10 years for the group exposed to IVF. Future cohort studies should preferably use infertile women as the reference group, rely on IVF-registered valid exposure data, adjust for a variety of meaningful confounders and adopt relatively longer follow-up periods before sound conclusions are drawn.
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| 2. |
- Skalkidou, Alkistis, 1977-, et al.
(författare)
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Risk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility
- 2017
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Ingår i: Cochrane Database of Systematic Reviews. - 1469-493X. ; 3
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Medical treatment for subfertility principally involves the use of ovary-stimulating agents, including selective oestrogen receptor modulators (SERMs), such as clomiphene citrate, gonadotropins, gonadotropin-releasing hormone (GnRH) agonists and antagonists, as well as human chorionic gonadotropin. Ovary-stimulating drugs may act directly or indirectly upon the endometrium (lining of the womb). Nulliparity and some causes of subfertility are recognized as risk factors for endometrial cancer.OBJECTIVES: To evaluate the association between the use of ovary-stimulating drugs for the treatment of subfertility and the risk of endometrial cancer.SEARCH METHODS: A search was performed in CENTRAL, MEDLINE (Ovid) and Embase (Ovid) databases up to July 2016, using a predefined search algorithm. A search in OpenGrey, ProQuest, ClinicalTrials.gov, ZETOC and reports of major conferences was also performed. We did not impose language and publication status restrictions.SELECTION CRITERIA: Cohort and case-control studies reporting on the association between endometrial cancer and exposure to ovary-stimulating drugs for subfertility in adult women were deemed eligible.DATA COLLECTION AND ANALYSIS: Study characteristics and findings were extracted by review authors independently working in pairs. Inconsistency between studies was quantified by estimating I(2). Random-effects (RE) models were used to calculate pooled effect estimates. Separate analyses were performed, comparing treated subfertile women versus general population and/or unexposed subfertile women, to address the superimposition of subfertility as an independent risk factor for endometrial cancer.MAIN RESULTS: Nineteen studies were eligible for inclusion (1,937,880 participants). Overall, the quality of evidence was very low, due to serious risk of bias and indirectness (non-randomised studies (NRS), which was reflected on the GRADE assessment.Six eligible studies, including subfertile women, without a general population control group, found that exposure to any ovary-stimulating drug was not associated with an increased risk of endometrial cancer (RR 0.96, 95% CI 0.67 to 1.37; 156,774 participants; very low quality evidence). Fifteen eligible studies, using a general population as the control group, found an increased risk after exposure to any ovary-stimulating drug (RR 1.75, 95% CI 1.18 to 2.61; 1,762,829 participants; very low quality evidence).Five eligible studies, confined to subfertile women (92,849 participants), reported on exposure to clomiphene citrate; the pooled studies indicated a positive association ( RR 1.32; 95% CI 1.01 to 1.71; 88,618 participants; very low quality evidence), although only at high dosage (RR 1.69, 95% CI 1.07 to 2.68; two studies; 12,073 participants) and at a high number of cycles (RR 1.69, 95% CI 1.16 to 2.47; three studies; 13,757 participants). Four studies found an increased risk of endometrial cancer in subfertile women who required clomiphene citrate compared to a general population control group (RR 1.87, 95% CI 1.00 to 3.48; four studies, 19,614 participants; very low quality evidence). These data do not tell us whether the association is due to the underlying conditions requiring clomiphene or the treatment itself.Using unexposed subfertile women as controls, exposure to gonadotropins was associated with an increased risk of endometrial cancer (RR 1.55, 95% CI 1.03 to 2.34; four studies; 17,769 participants; very low quality evidence). The respective analysis of two studies (1595 participants) versus the general population found no difference in risk (RR 2.12, 95% CI 0.79 to 5.64: very low quality evidence).Exposure to a combination of clomiphene citrate and gonadotropins, compared to unexposed subfertile women, produced no difference in risk of endometrial cancer (RR 1.18, 95% CI 0.57 to 2.44; two studies; 6345 participants; very low quality evidence). However, when compared to the general population, an increased risk was found , suggesting that the key factor might be subfertility, rather than treatment (RR 2.99, 95% CI 1.53 to 5.86; three studies; 7789 participants; very low quality evidence).AUTHORS' CONCLUSIONS: The synthesis of the currently available evidence does not allow us to draw robust conclusions, due to the very low quality of evidence. It seems that exposure to clomiphene citrate as an ovary-stimulating drug in subfertile women is associated with increased risk of endometrial cancer, especially at doses greater than 2000 mg and high (more than 7) number of cycles. This may largely be due to underlying risk factors in women who need treatment with clomiphene citrate, such as polycystic ovary syndrome, rather than exposure to the drug itself. The evidence regarding exposure to gonadotropins was inconclusive.
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