Increased risk of multiple sclerosis relapse after in vitro fertilisation
- Laure Michel1,2,
- Yohann Foucher2,3,
- Sandra Vukusic4,
- Christian Confavreux4,
- Jérome de Sèze5,
- David Brassat6,
- Michel Clanet6,
- Pierre Clavelou7,
- Jean-Christophe Ouallet8,
- Bruno Brochet8,
- Jean Pelletier9,
- Pierre Labauge10,
- Christine Lebrun11,
- Emmanuelle Lepage12,
- Fabienne Le Frere13,
- Marylène Jacq-Foucher13,
- Paul Barriere14,
- Sandrine Wiertlewski1,13,
- David-Axel Laplaud1,2,13,
- on behalf of the Club Francophone de la Sclérose En Plaques (CFSEP)
- 1Service de Neurologie, Centre Hospitalier Universitaire de Nantes, Hôpital Laennec, Nantes Cedex, France
- 2Institut de Transplantation Et de Recherche en Transplantation, Inserm UMR643, Nantes, France
- 3EA 4275 ‘Biostatistique, Recherche clinique et Mesures Subjectives en Santé’, Université de Nantes, Nantes, France
- 4Service de Neurologie A and EDMUS Coordinating Centre for Multiple Sclerosis, Hôpital Neurologique Pierre-Wertheimer, Hospices Civils de Lyon, Université Lyon I, Lyon, France
- 5Service de Neurologie, University Hospital of Strasbourg, Strasbourg, France
- 6Service de Neurologie, CHU de Toulouse, France
- 7Service de Neurologie, CHU Gabriel Montpied, Clermont-Ferrand, France
- 8CHU Pellegrin, groupe hospitalier Pellegrin-Tripode, Bordeaux cedex, France
- 9Service de Neurologie, CHU Timone, Marseille cedex, France
- 10Service de Neurologie, Centre Hospitalier Universitaire de Nîmes, Hôpital Caremeau, Nîmes CEDEX, France
- 11Service de Neurologie, CHU de Nice, Nice cedex, France
- 12Service de Neurologie, Hôpital Pontchaillou, Rennes, France
- 13CIC Inserm 004, Centre Hospitalier Universitaire de Nantes, Hôpital Laennec, Nantes Cedex, France
- 14Service de Biologie de la reproduction, Centre Hospitalier Universitaire de Nantes, Nantes Cedex, France
- Correspondence to Dr D-A Laplaud, INSERM U643, 30 Bd J Monnet, Nantes Cedex 44093, France;
Contributors LM analysed the data and wrote the manuscript; YF checked the non-parametrical statistical analyses, planned the statistical analyses and performed the multivariate analyses; SV helped write the manuscript and the general strategy; LM, MJ-F and FL went on site and checked the medical files; CC, JDS, DB, MC, PC, J-CO, BB, JP, PL, CL, EL and PB discussed the results and corrected the manuscript; SW helped in the general strategy, and writing and corrections of the manuscript; D-AL designed the general strategy and corrected the manuscript. D-AL takes full responsibility for the data, the analyses and interpretation, and the conduct of the research. He had full access to all of the data and has the right to publish any and all data separate and apart from any sponsor. As indicated in the methods section, a National Review Board gave authorisation to conduct this study.
- Received 9 January 2012
- Revised 10 April 2012
- Accepted 12 April 2012
- Published Online First 11 June 2012
Background Exogenous sexual steroids together with pregnancy have been shown to influence the risk of relapses in multiple sclerosis (MS). Treatments used during assisted reproductive techniques may consequently influence the short term evolution of MS by modifying the hormonal status of the patient. The objective of this study was to determine if there was an increased risk of developing exacerbations in women with MS after in vitro fertilisation (IVF).
Methods MS and IVF data were either automatically extracted from 13 French university hospital databases or obtained from referring neurologists. After matching databases, patient clinical files were systematically reviewed to collect information about MS and the treatments used for IVF. The association between IVF and the occurrence of MS relapses was analysed in detail using univariate and multivariate statistical tests.
Findings During the 11 year study period, 32 women with MS had undergone 70 IVF treatments, 48 using gonadotrophin releasing hormone (GnRH) agonists and 19 using GnRH antagonists. A significant increase in the annualised relapse rate (ARR) was observed during the 3 month period following IVF (mean ARR 1.60, median ARR 0) compared with the same period just before IVF (mean ARR 0.80, median ARR 0) and to a control period 1 year before IVF (mean ARR 0.68, median ARR 0). The significant increase in relapses was associated with the use of GnRH agonists (Wilcoxon paired test, p=0.025) as well as IVF failure (Wilcoxon paired test, p=0.019).
Interpretation An increased relapse rate was observed in this study after IVF in patients with MS and may be partly related both to IVF failure and the use of GnRH agonists.
Funding This work was supported by a grant from the PHRC Inter-régional 2005 (French Ministry of Health).
Competing interest None.
Ethics approval Ethics approval was provided by the National Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.