Off Label Drugs and IVF

Episode: 
104

Do you remember the DES scare of a generation ago? DES was a drug given to pregnant women to prevent miscarriage. Even without clinical evidence to prove it would work that way, DES was prescribed “off-label” for over 30 years. DES exposure in the womb caused infertility and cancer in some of the offspring.[1]

Now, there’s another drug—“Dex”—that is being used in a similar pattern. Dex is the nickname for Dexamethasone, a drug given to women who undergo IVF. According to one well-known clinic,[2] a patient is put on Dex one to two days before egg retrieval and is kept on it until the first ultrasound, about 6 weeks after pregnancy.[3] Dex is not FDA-approved for IVF, making this an “off-label” use of a drug.[4] (Now, off-label use of drugs is not illegal, and can be quite useful, but in some cases, off-label use could be unethical.)

In many IVF clinics, giving Dex is standard procedure.. However, IVF—including the use of Dex—is  largely unregulated in the United States.

The theory behind Dex is that some infertile women have immune responses to pregnancy. Dex may suppress the woman’s immune system, preventing miscarriage. While it is approved for autoimmune conditions after birth, Dex has been used off-label for many years by women who run a genetic risk of having a daughter with CAH, which affects development of her sex organs.[5] So doctors know that Dex crosses the placental barrier and can affect the child’s development.

The only clinical study involving the use of Dex during pregnancy was in Sweden in 2012. Scientists investigated whether Dex should be used to prevent CAH. Researchers shut down the trial because there were too many “severe adverse events,” such as mental retardation and growth disorders, that might bhave been due to Dex. They advised against using Dex as standard procedure until more studies could be done.[6] What’s more, they pointed out that it was “unacceptable” not to do follow-up on children already exposed to Dex.

Some studies have shown a possible correlation between Dex and improved embryo implantation.[7] However, these studies were not FDA clinical trials which test for safety, efficacy, dosage, and long-term effects. With every drug, one must weigh the risks with the benefits. If a drug is being used off-label, then the risks are largely unknown, and in the case of Dex, the benefits are not confirmed either. Infertile couples who are willing to try anything to have children may be too fragile to question the medical regimen, including the use of Dex.[8] Combined with the lack of accurate information, they are not able to give truly informed consent.

People who are paying attention are concerned about the potential harmful effects of Dex on the embryos being exposed to it. At the very least, better clinical trials and follow-up studies should be required. In the meantime, I’d advise extreme caution.



[3] Alice Dreger, “IVF on Steroids: The Dangerous Off-Label Use of ‘Dex’ During Pregnancy.” The Atlantic. January 16, 2013, http://www.theatlantic.com/health/archive/2013/01/ivf-on-steroids-the-dangerous-off-label-use-of-dex-during-pregnancy/267187/ (accessed 02/27/13).

[4] Doctors can prescribe drugs for an “off-label” use if they believe it to be medically efficacious to the patient. Informed consent is problematic in these cases because doctors cannot give information for the particular non-FDA approved situation.

[5] CAH - Congenital Adrenal Hyperplasia (female fetuses born with ambiguous genitalia). See this article on the dangers of using Dex for CAH: Susan Donaldson James, “Intersex Experts: Protect Pregnant Moms from Off-label Drug.” ABC Good Morning America, August 22, 2012, http://abcnews.go.com/Health/intersex-experts-protect-pregnant-moms-off-label-drug/story?id=17052075 (accessed 02/27/13).

[6] Dreger.

[7] S.D. Keay et al., “Low-dose dexamethasone augments the ovarian response to exogenous gonadotropins leading to a reduction in cycle cancellation rate in standard IVF programme.”  Human Reproduction, 16(9), 2001, http://humrep.oxfordjournals.org/content/16/9/1861.long (accessed 02/27/13).

[8] Argument for the use of low-dosage IVF: Jacqueline Mroz, “High doses of hormones faulted in fertility care.” New York Times, July 16, 2012, http://www.nytimes.com/2012/07/17/health/research/high-doses-of-hormones-add-to-ivf-complications.html?pagewanted=all&_r=0 (accessed 02/27/13).

 

 

 

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