Infertility

The widespread availability of Assisted Reproductive Technologies (ART) has led many women with MS to consider pregnancy when unable to conceive in the usual manner. Perhaps no other decision is more difficult and complicated in women with MS, and yet I am surprised by the number of women and reproductive specialists who are unaware of the issues involved.

First, some background information is in order. Almost all assisted reproductive technologies require hormonal manipulation. The most common drugs used to control ovulation are called Gonadotrophin releasing hormone agonists (GHrh agonists) such as clomiphene. This class of drugs is also used to treat endometriosis (think Lupron), and some forms of breast and prostate cancer. Scattered case reports have suggested for many years that the use of these drugs may be associated with an increased risk of relapse in MS patients. I first noticed this issue in patients taking lupron for endometriosis. More recently a study of 16 MS patients undergoing ART reported a 7 fold increase in the risk of relapse and a 9 fold increase in new MRI lesions during the 3 month period following ART. All of the patients in this study were taking GHrh agonists to help them become pregnant and none were taking disease modifying drugs (examples include avonex, betaseron, rebif, copaxone, tecfidera) to help prevent relapses during the ART  period.

So what are you to do with this information if you want a baby and are unable to conceive? First, consider adoption or the use of a surrogate who uses their own eggs fertilized by your partner’s sperm. Neither option will require you to undergo hormonal manipulation. If these options are unacceptable to you, begin a dialogue with your neurologist and reproductive specialists concerning the safest ART option. You will most likely need to educate them about the risks of hormonal manipulation in MS patients. I suggest that you begin by asking them to read the following paper written by Jorge Correale from Argentina, if they have not already done so:

Increase in Multiple Sclerosis Activity after Assisted Reproductive Technology
Annals of Neurology 2012; 72: 682-694

Next you and your neurologist will need to consider if you should be on a MS treatment before, during and after the period of hormonal manipulation and possibly well into pregnancy. This is a very difficult decision but certain features of your MS may suggest a higher risk of relapse during the 3 month period following hormonal manipulation including a high rate of relapses in the past, especially those with incomplete recovery, or a high rate of developing new MRI lesions in the past. Those patients on tysabri are a particular concern since stopping this drug for any reason is associated with a return of prior MS disease activity within 6 months. Strong consideration should be given to continuation of an MS treatment during the ART period to reduce the risk of relapse. The safest option is copaxone which is listed as safe in pregnancy (category B). If this is not acceptable or did not work for you in the past, any interferon treatment (Avonex, betaseron, rebif) is a reasonable option, although they are still listed as pregnancy category C ( Defined as: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks). For those in which both interferons and copaxone are not an option, even less is known about the risks of Tecfidera, Gilenya and Tysabri and all are listed as pregnancy category C. Aubagio, which  is pregnancy category D, should never be used prior to or during pregnancy.  If you and your neurologist decide it is best to take you off your MS treatment during the ART period, I usually recommend an MRI of the brain with and without contrast before stopping your MS drug therapy and 3 months after starting ART, if you are not pregnant by this time. A significant return of MS disease activity 3 months after starting ART would be reason to consider treatment with corticosteroids, starting or restarting an MS drug and possibly stopping the ART.

In addition to consulting your neurologist, the reproductive specialist will need to understand the risks of ART and consider different options to help you successfully become pregnant. For instance, some studies suggest that using newer GHrh antagonists, such as cetrorelix and ganirelix, may not be associated with the increased risk of relapses during the ART period of hormonal manipulation. The reproductive specialist should be made aware of these studies during your initial consultations.