I am forty years old and have been through 2 unsuccessful IVF cycles. My fertility specialist is recommending a third cycle, but I’m concerned about the long-term risks from the drugs. What are the risks associated with IVF and do these risks get greater with each additional cycle?

Written by our medical expert, Dr. Steven Hudson.

Thank you for the question – which is a very prudent one.

The first question to ask is whether or not another IVF cycle for you has a reasonable chance of success. I am assuming because your fertility specialist has suggested it, you must have had good IVF cycles – in terms of the response you had to stimulation and the embryo development.

There may be short- and long-term risks related to ovulation induction and IVF. The short-term risks of IVF are likely well known to you and include risks of ovarian hyperstimulation syndrome, deep vein thrombosis, arterial thrombosis and the potential surgical complications from the egg retrieval. Those remain the same for each IVF cycle and are a low risk for most women. The most concerning long-term risk that may be associated with ovulation induction and IVF is the potential increase in the incidence of cancer, particularly breast and ovarian cancer.

Let’s first address the potential risk of breast cancer. Breast cancer is unfortunately very common in the population at large, with an overall incidence of 1 in 8. A number of factors have been identified as potentially increasing a woman’s risk for breast cancer, including a genetic predisposition (a family history of breast cancer or carrying the BRCA 1 or 2 gene), prolonged use of the birth control pill, alcohol consumption, infertility, smoking, obesity, diets high in saturated fats, use of hormone therapies after menopause, number of pregnancies, breast feeding, and socioeconomic status. The current research for many of these factors is correlational, and consequently some of these factors may appear to be related to breast cancer when in fact they are not. As far as IVF and ovulation induction is concerned – the truth is we don’t know if these fertility treatments increase breast cancer risk. There have been conflicting studies – most showing that IVF does not appear to influence the risk of breast cancer. However there was a recent Australian study suggesting that women who do IVF before the age of 24 years may be at increased risk of breast cancer.

Ovarian cancer is much less common than breast cancer, and occurs in about 1 in 75 women in the general population. There is older research data linking the fertility drug clomiphene to an increased risk of ovarian cancer. These studies suggested that more than 12 cycles of clomiphene may increase ovarian cancer risk. However, over the course of the past few years the theory of how ovarian cancer develops has changed. The new theory is that ovarian cancer starts in the fallopian tubes and spreads to the ovary. It is believed that ovarian cancer therefore may be caused by something getting in to the fallopian tubes through the vagina/cervix. The culprit has not yet been identified. If this theory is correct, there would seem no way to link ovarian cancer to fertility drugs.

In summary, there is no clear data linking one or more IVF cycles to a higher risk of breast cancer or ovarian cancer. At the present time studies suggest that there MAY be a link between IVF and a type of ovarian tumour called a borderline tumour (not a true cancer) – but there is no link to ovarian cancer per se. At this time there simply is not enough data to say with certainty that fertility drugs and IVF increase a woman’s risk of getting cancer.

In conclusion, whatever we put in to our bodies can influence our long-term health. Based on the current available research, it is unlikely that doing a third cycle of IVF will make any difference to your long-term risks. Another point to remember is that pregnancy is protective against both breast and ovarian cancer.

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