Abstract
Abstract Study question To investigate the validity of the association between the development of female specific malignancies, including ovarian, endometrial, breast and cervical cancer following fertility treatment. Summary answer There is a statistically significant increase in the incidence of ovarian cancer and borderline ovarian tumours associated with fertility treatment. What is known already Approximately 1.3 million IVF cycles have been performed since 1991. The association between fertility treatment (FT) and female-specific cancers however, remains contentious, largely due to the conflicting outcomes published in various meta-analyses. Study design, size, duration A thorough literature search of the Cochrane Database of Systematic Review, EMBASE, Google Scholar and Pubmed was carried out to identify relevant systematic reviews and meta-analyses, from inception up until April 2022. Participants/materials, setting, methods The inclusion criteria included original studies stating the incidence of cancer in FT and control groups (non-FT). The principal outcome of interest was the incidence of cancer (breast, endometrial, cervical, and ovarian) in FT and non-FT groups. The effect estimates, Hazard Ratios and Odds Ratios (OR) were extracted, or calculated de novo. The strength of evidence and extent of potential biases were summarised. Main results and the role of chance In total, 3129 publications were identified, and 11 meta-analytical reviews were included. This umbrella review synthesised 324 meta-analyses, including data from over 20 million patients. The incidence of ovarian cancer (OR 1·21;95% CI 1·00-1·45) and BOTs (OR 1.87;95%CI 1·18-2.97) was higher in the FT compared to non-FT group. The meta-analyses related to ovarian cancer was statistically significant (p < 0.05), using a random-effects model. There was no significant association demonstrated between FT and the incidence of cervical, breast or endometrial cancer. Limitations, reasons for caution Although it has been demonstrated that exposure to fertility treatment does significantly increase the risk of ovarian cancer and BOTs, further studies are required in order to draw accurate conclusions. Wider implications of the findings Understanding the potential long-term sequelae of FT is fundamental to guide counselling and enable individuals to make informed decisions about their reproductive future. Clinicians should engage in appropriate patient selection, with those deemed to be at a higher risk, selected for more personalised fertility treatment and careful preventative follow-up. Trial registration number NA
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