Fertility treatments like IVF help thousands of women achieve their dream of motherhood each year, but what are the long-term health implications? Dr Srdjan Saso, Honorary Clinical Senior Lecturer in the Department of Metabolism, Digestion and Reproduction and Consultant Gynaecologist and Gynaecological Cancer Surgeon at Imperial College Healthcare NHS Trust, explores what the data reveals, and how clinics can improve long-term health monitoring.
As a gynaecological cancer surgeon, I see many women diagnosed with cancers who I know are also concerned about protecting their fertility. Societal pressures, evolving gender roles, financial insecurities, but most importantly, in my opinion, a declining cultural emphasis of motherhood are leading to delayed childbearing and lower fertility rates.
Fertility treatments, such as in vitro fertilization (IVF), help many thousands of women conceive every year. With colleagues from Imperial and KU Leuven, I set out on a collaborative research project to explore an important question: could undergoing fertility treatment influence the risk of developing certain gynaecological cancers?
Investigating the link between fertility treatment and cancer
Focusing solely on ovarian, endometrial, breast and cervical cancers, we embarked on what is known as an ‘umbrella review’ – an analysis of meta-analyses and systematic reviews. We searched databases including Cochrane, EMBASE, Google Scholar and PubMed for all studies comparing the incidence of any of these four cancers in infertility patients who had undergone fertility treatment (controlled stimulation to their ovaries and/or (IVF), to those who had not had any treatment.
We initially identified 3,129 publications and after a screening process, 284 studies met the criteria for a thorough review. Eventually 11 meta-analyses were eligible for inclusion. Within these 11 meta-analyses, 188 studies were included which covered many types of fertility treatment – not solely IVF, but also Intracytoplasmic sperm injection (ICSI), live egg donation and frozen egg donation. Some studies also compared the different drug regimens used within IVF.
What we found
After all our results were assessed, we found no association at all between endometrial, cervical or breast cancers and fertility treatment. But we did find some correlation between fertility treatment and ovarian cancer. The incidence of ovarian cancer was highest overall following fertility treatment and IVF specifically, with a modest increase of approximately 0.13%, (or 1.3 additional cases per 1000 women).
Meanwhile, the incidence of borderline ovarian tumours – precancerous growths – was higher not only with fertility treatment and IVF, but also according to the fertility drug regimen applied. Here there was a smaller rise in the absolute risk, amounting to a 0.031% rise (or 0.31 additional cases per 1,000 women).
Understanding the context
However, it is important to say that we did not prove causation. It is very difficult to retrospectively isolate the effect of fertility treatment from underlying treatment in this group of women. Infertility itself is already an established risk factor for ovarian, endometrial and breast cancer. We acknowledge that there are limitations to this study and like all reviews we relied on the data of previous work and meta-analyses.
So, we believe that, while women should not be overly concerned following our study, it is key that they have all the necessary information about the IVF process. Women cannot take steps to protect themselves from associated risks of fertility treatment; but both they and fertility clinics should be aware that increased vigilance after treatment would be wise. In particular, being aware of abdominal bloating and pain, changes in bowel habits, issues with the menstrual periods and sudden loss of weight and/or appetite.
The case for long-term monitoring
What we would ideally like is for every centre offering IVF to subscribe to a centralised monitoring system to keep a close eye on their patients when they leave the clinics and have a duty to report long-term health consequences. At present the focus is on whether pregnancies result, but we would also like closer attention to the health of the women themselves in the years to come, especially cancer occurrence as explained.
Publication
An umbrella review of meta-analyses regarding the incidence of female-specific malignancies after fertility treatment by Saso S., Barcroft J., Kasaven L., Bourne T., Ghaem-Maghami S., Verbakel J., et al. is published in Fertility and Sterility.