Should Patients with Multiple Sclerosis Avoid IVF?
Abstract & Commentary
By Susan Gauthier, MS, DO. Assistant Professor of Neurology, Weill Cornell Medical College. Dr. Gauthier reports she receives research support from EMD Serono, Biogen Idec, and Novartis Pharmaceuticals, and is on the speakers bureau for Biogen Idec and Teva Neurosciences.
Synopsis: Multiple sclerosis (MS) relapse rates were found to increase post in vitro fertilization (IVF) in a small population of MS patients. The risk for relapse was highest in the first 3 months post-IVF.
Source: Michel L, et al. Increased risk of multiple sclerosis relapse after in vitro fertilization. J Neurol Neurosurg Psychiatry 2012;83:796-802.
A hormonal influence over disease activity in patients with multiple sclerosis (MS) has been best demonstrated through a relative protective effect of pregnancy, which is then followed by an increase in relapse rate in the months following delivery. In light of this observation and that assisted reproductive technology (ART), specifically in vitro fertilization (IVF), has become more widely available, the question of how IVF may affect MS is a legitimate concern. Michel et al recently reported on the first comprehensive study to address the potential effect of IVF on MS disease activity.
This retrospective study of 32 women recruited from either the French public hospital database or through private referrals from local neurologists analyzed two main outcomes: 1) the difference between the number of relapses before and after the IVF procedure during two similar time intervals (i.e., 3 months pre-IVF compared to 3 months post-IVF), and 2) the association between IVF and the time between two relapses (i.e., a multivariate analysis to determine the effect of IVF on relapses when controlling for all relapse time intervals experienced throughout the disease course). The two pools of patients were well matched to prevent selection bias and, importantly, the recruitment procedure was controlled for in all statistical models. The majority of the patients had never received treatment for their MS, their mean age was 26.3 years, and disease duration was relatively low, at a mean of 6.6 years. The annualized relapse rate (ARR) was significantly increased to 1.6 at 3 months post-IVF compared to the 3-month pre-IVF period (0.80). For those patients who had a relapse, the mean time to a relapse post-IVF was 42.2 days. If the time was extended to 6 months post-IVF, the ARR was increased as compared to the corresponding time pre-IVF but was no longer significant. Importantly, in the multivariate analysis, when controlling for all relapse time intervals (throughout the course of each patient's disease), there remained a risk of a relapse with IVF (relative risk [RR] = 1.18); however, it was no longer significant. Of the 70 total IVF procedures, 49 failed and 21 resulted in pregnancy. There was a significant risk of post-IVF relapse (RR = 1.67) in patients with a failed outcome; however, these patients had higher pre-IVF ARR (0.98) compared to the pre-IVF ARR in those with success (0.38). Patients who were treated with GnRH agonists had a higher post-IVF ARR (1.6) as compared to those treated with GnRH antagonist (0.84). However, the type of GnRH treatment was not found to be significant in the multivariate analysis.
Commentary
This is the first study to investigate the effect of IVF on MS disease activity. Although there are some obvious methodological limitations to the study, specifically the low patient number and a retrospective analysis, the statistical methods used were well thought out and appropriately applied. As clinicians caring for women with MS, the question of child-bearing is one that is often discussed and is rarely discouraged; however, there are obstacles that must be considered. One such obstacle is breastfeeding vs restarting treatment after delivery and the second obstacle concerns treatment options while attempting to conceive. The majority of women with MS discontinue therapy while attempting to conceive, which, depending on the patient, can be time-sensitive and anxiety provoking. ART, such as IVF, allows patients struggling with infertility to get pregnant and to resume MS treatment more quickly. This study suggests that clinicians should caution their patients regarding the possible risk of relapse associated with IVF. However, these results should be interpreted with caution. The risk of a relapse with IVF exposure was not found to be significant in the multivariate analysis after controlling for all relapse intervals. In addition, the effect of GnRH treatments failed to remain significant in the multivariate analysis; therefore, changing protocols would not be warranted by these data. Interestingly, IVF failures had a much higher pre- and post-IVF ARR, which suggests that active patients are more likely to fail IVF. All of the observations reported in this small study suggest that a larger, prospective study should be organized to further investigate the effects of IVF. In conclusion, MS patients who are stable and without a recent relapse can still safely consider IVF, but those with more active disease should achieve disease stabilization before proceeding.
Multiple sclerosis (MS) relapse rates were found to increase post in vitro fertilization (IVF) in a small population of MS patients. The risk for relapse was highest in the first 3 months post-IVF.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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