Dr. Sher Blog

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Are Injectable Fertility Drugs Safe?

by Dr. Geoffrey Sher on November 28, 2016

I have all too often heard it said that medical providers knowingly place unsuspecting infertile women at risk of developing cancer through the fertility injectable drugs and treatment they administer and that we knowingly place patients at risk by understating medical risks associated with the use of fertility treatments. To me this is both offensive and untrue.

It is true that the indiscriminate use of gonadotropin therapy to stimulate follicle and egg development is not without risk. For example, women with very high ovarian reserve, those with polycystic ovarian syndrome-PCOS, and non-ovulating women are highly sensitive to ovarian stimulation and are at risk of developing too many ovarian follicles with inordinately raised blood estrogen levels resulting in Severe Ovarian Hyperstimulation Syndrome (OHSS) with serious and even life-endangering complications. It also a fact that such women often experience multiple ovulations that result in high order multiple pregnancies (triplets or greater) that places the mother at increased risk of pregnancy-induced complications and the newborn at risk from premature delivery. However, it is possible to identify such  cases well in advance of ovarian stimulation and so mitigate or avoid their occurrence through judicious and individualized approaches to the  prescription and implementation of ovarian stimulation protocols.

However the assertion that gonadotropin stimulation increases the risk of cancer is in my opinion baseless. To illustrate my point, let us together trace how that the use of gonadotropin fertility agents (e.g. Follistim/Gonal F/ Puregon/ Menopur, GnRH agonists (e.g. Lupron/Superfact/Supercur and GnRH antagonists (e.g. Ganirelix/ Cetrotide/Orgalutron) significantly increase the risk of ovarian cancer, came about.

About 3 decades ago, a Saturday Night Live celebrity, Gilda Radner, who had previously undergone ovarian stimulation with gonadotropins was diagnosed with, and then tragically succumbed to ovarian cancer. This was quickly reported in a lay press article that highlighted the fact that Ms. Radner had previously undergone ovarian stimulation with gonadotropins. This rapidly led to panic and pandemonium in the infertile community as well among medical providers of infertility treatment, leading to a retrospective report in a highly prestigious medical journal that gave credence to the assertion that such a ling indeed did exist. This ill-conceived article only fanned the flames further leading a frenzy of media-driven reports that almost led to withdrawing gonadotropin therapy from the fertility therapeutic armamentarium. Fortunately however, it also prompted the launching of several evidence-based well controlled prospective studies tamed at examining the matter further. When the results were reported, all these studies refuted the assertion.

So how did we get it so wrong at first?  Well, firstly, the original study that caused all the fuss was a retrospective one. That means that, that id took a hindsight look at women with infertility that had received treatment with fertility drugs and retrospective studies, while helping to identify problems that need investigation are hardly ever conclusive. To do this requires a controlled prospective undertaking. Second, the original study  was strongly biased towards women who had been taking a (non-gonadotropin) oral synthetic fertility drug, clomiphene citrate where based on animal studies there is a  suggested link  between  prolonged use and the subsequent risk of malignant disease. Third, the reported study failed to take into consideration the fact that infertility itself predisposes women to an increased risk of ovarian cancer. In fact childless women who have never used gonadotropins develop ovarian cancer with the same frequency as those that have been treated with these agents. Finally, there is the  fact that ovarian cancer cells do not even have follicle stimulating hormone (FSH) surface receptors makes it highly unlikely that gonadotropins that contain FSH would promote growth and proliferation of ovarian cancer cells.

When it comes to GnRH agonists and antagonists, while prolonged usage can indeed lead to estrogen deprivation and osteoporosis (bone loss). However, this is hardly likely to happen when such agents are used for relatively short periods of time, as is the case with assisted reproduction.

Any intervention carries with it both an upside and a downside….whether it is driving a car, discharging a fire arm or taking medication. Obviously the level of such risk is directly proportionate to competency, skill and intent It follows that when it comes to fertility treatments, it is incumbent upon the doctor and patient to discuss the cost-benefit ratio, and in so doing to base their judgment on fact rather than emotion.

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