Assisted Reproduction Therapy in Patients with Multiple Sclerosis: Narrative Review and Practical Recommendations

. 2025 Dec 03 ; 13 (23) : . [epub] 20251203

Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid41373372

Grantová podpora
INTER-COST LUC 23009 Czech Ministry of Education, Youth and Sports
MH CZ - DRO FNBr 65269705 Czech ministry of Health
Andronet COST CA20119 European Cooperation in Science and Technology

Objective: The objective of this study is to present contemporary findings regarding the relationship between the application of assisted reproduction methods and their impact on the incidence of multiple sclerosis. Design: This study adopts a narrative review design. Text: Assisted reproductive technology (ART) is increasingly used to treat human infertility. Due to the massive use of these techniques, it is increasingly important to record not only the course of fertilization and embryonic and fetal development of the individual but also the overall health status of the children born and their mothers. The incidence of autoimmune diseases continues to rise for reasons that remain unclear. One of the factors considered in connection with autoimmune disorders is ART. Opinions on the safety and reliability of ART methods are not consistent. Recently, extensive studies focusing on this issue have been presented and have not found a connection between infertility treatment with assisted reproductive techniques and the development of multiple sclerosis (MS). Conclusions: Current evidence suggests that, in adherence to the principles of evidence-based medicine and modern approaches to multiple sclerosis therapy, assisted reproduction in women with this disease is effective and does not pose a serious health risk. Therefore, it is necessary to always individualize therapy with regard to future pregnancy. Interdisciplinary cooperation on the timing of IVF therapy and minimizing the risk of MS exacerbation is also important.

Zobrazit více v PubMed

World Health Organization 1 in 6 People Globally Affected by Infertility. 2023. [(accessed on 9 October 2025)]. Available online: https://www.who.int/news/item/04-04-2023-1-in-6-people-globally-affected-by-infertility#:~:text=Around%2017.5%25%20of%20the%20adult,prevalence%20of%20infertility%20between%20regions.

Choudhary P., Dogra P., Sharma K. Infertility and lifestyle factors: How habits shape reproductive health. Middle East Fertil. Soc. J. 2025;30:14. doi: 10.1186/s43043-025-00228-7. DOI

Wennerholm U.B., Bergh C. Perinatal outcome in children born after assisted reproductive technologies. Upsala J. Med. Sci. 2020;125:158–166. doi: 10.1080/03009734.2020.1726534. PubMed DOI PMC

Moghadam A.R.E., Moghadam M.T., Hemadi M., Saki G. Oocyte quality and aging. JBRA Assist. Reprod. 2022;26:105–122. doi: 10.5935/1518-0557.20210026. PubMed DOI PMC

GBD 2016 Multiple Sclerosis Collaborators Global, regional, and national burden of multiple sclerosis 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18:269–285. doi: 10.1016/S1474-4422(18)30443-5. PubMed DOI PMC

Rubio-Arias J.Á., Ramos-Campo D.J., Romero-Parra N., Andreu-Caravaca L., Martínez-Rodríguez A., Esteban-García P., López-Liria R., Molina-Torres G., Ventura-Miranda M.I., Martos-Bonilla A., et al. Response to physical activity of females with multiple sclerosis throughout the menstrual cycle: A protocol for a randomised crossover trial (EMMA Project) BMJ Open Sport Exerc. Med. 2023;9:e001797. doi: 10.1136/bmjsem-2023-001797. PubMed DOI PMC

Coyle P.K. Management of women with multiple sclerosis through pregnancy and after childbirth. Ther. Adv. Neurol. Disord. 2016;9:198–210. doi: 10.1177/1756285616631897. PubMed DOI PMC

Kelly V.M., Nelson L.M., Chakravarty E.F. Obstetric outcomes in women with multiple sclerosis and epilepsy. Neurology. 2009;73:1831–1836. doi: 10.1212/WNL.0b013e3181c3f27d. PubMed DOI

Hellwig K., Correale J. Artificial reproductive techniques in multiple sclerosis. Clin. Immunol. 2013;149:219–224. doi: 10.1016/j.clim.2013.02.001. PubMed DOI

World Medical Association World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA. 2013;310:2191–2194. doi: 10.1001/jama.2013.281053. PubMed DOI

Mondschein C.F., Monda C. The EU’s General Data Protection Regulation (GDPR) in a Research Context. In: Kubben P., Dumontier M., Dekker A., editors. Fundamentals of Clinical Data Science. Springer; Cham, Switzerland: 2019. PubMed DOI

Hauser S.L., Cree B.A.C. Treatment of Multiple Sclerosis: A Review. Am. J. Med. 2020;133:1380–1390.e2. doi: 10.1016/j.amjmed.2020.05.049. PubMed DOI PMC

Arneth B. Genes, gene loci, and their impacts on the immune system in the development of multiple sclerosis: A systematic review. Int. J. Mol. Sci. 2024;25:12906. doi: 10.3390/ijms252312906. PubMed DOI PMC

Zarghami A., Li Y., Claflin S.B., van der Mei I., Taylor B.V. Role of environmental factors in multiple sclerosis. Expert. Rev. Neurother. 2021;21:1389–1408. doi: 10.1080/14737175.2021.1978843. PubMed DOI

Portaccio E., Magyari M., Havrdova E.K., Ruet A., Brochet B., Scalfari A., Di Filippo M., Tur C., Montalban X., Amato M.P. Multiple sclerosis: Emerging epidemiological trends and redefining the clinical course. Lancet Reg. Health Eur. 2024;44:100977. doi: 10.1016/j.lanepe.2024.100977. PubMed DOI PMC

Balasooriya N.N., Elliott T.M., Neale R.E., Vasquez P., Comans T., Gordon L.G. The association between vitamin D deficiency and multiple sclerosis: An updated systematic review and meta-analysis. Mult. Scler. Relat. Disord. 2024;90:105804. doi: 10.1016/j.msard.2024.105804. PubMed DOI

Kang T.W., Perez-Gomez A., Lawley K., Young C.R., Welsh C.J., Brinkmeyer-Langford C.L. Comparative analysis of genetic risk for viral-induced axonal loss in genetically diverse mice. Int. J. Mol. Sci. 2025;26:10727. doi: 10.3390/ijms262110727. PubMed DOI PMC

Gianfrancesco M.A., Stridh P., Rhead B., Shao X., Xu E., Graves J.S., Chitnis T., Waldman A., Loetze T., Schreiner T., et al. Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS. Neurology. 2017;88:1623–1629. doi: 10.1212/WNL.0000000000003849. PubMed DOI PMC

van Langelaar J., Rijvers L., Smolders J., van Luijn M.M. B and T Cells driving multiple sclerosis: Identity, mechanisms and potential triggers. Front. Immunol. 2020;11:760. doi: 10.3389/fimmu.2020.00760. PubMed DOI PMC

Lanz T.V., Brewer R.C., Ho P.P., Moon J.-S., Jude K.M., Fernandez D., Fernandes R.A., Gomez A.M., Nadj G.-S., Bartley C.M., et al. Clonally Expanded B Cells in Multiple Sclerosis Bind EBV EBNA1 and GlialCAM. Nature. 2022;603:321–327. doi: 10.1038/s41586-022-04432-7. PubMed DOI PMC

Dias de Sousa M.A., Desidério C.S., da Silva Catarino J., Trevisan R.O., Alves da Silva D.A., Rocha V.F.R., Bovi W.G., Timoteo R.P., Bonatti R.C.F., da Silva A.E., et al. Role of cytokines, chemokines and IFN-γ+ IL-17+ double-positive CD4+ T cells in patients with multiple sclerosis. Biomedicines. 2022;10:2062. PubMed PMC

Oh J., Bar-Or A. Emerging therapies to target CNS pathophysiology in multiple sclerosis. Nat. Rev. Neurol. 2022;18:466–475. doi: 10.1038/s41582-022-00675-0. PubMed DOI

Lassmann H. Pathology and disease mechanisms in different stages of multiple sclerosis. J. Neurol. Sci. 2013;333:1–4. doi: 10.1016/j.jns.2013.05.010. PubMed DOI

Vollmer T.L., Nair K.V., Williams I.M., Alvarez E. Multiple Sclerosis Phenotypes as a Continuum: The Role of Neurologic Reserve. Neurol. Clin. Pract. 2021;11:342–351. PubMed PMC

Lublin F.D., Reingold S.C., Cohen J.A., Cutter G.R., Sørensen P.S., Thompson A.J., Wolinsky J.S., Balcer L.J., Banwell B., Barkhof F., et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology. 2014;83:278–286. doi: 10.1212/WNL.0000000000000560. PubMed DOI PMC

Vicente Escudero J.L. Meta analysis of the efficacy of web based psychological treatments on anxiety, depression, fatigue, and quality of life in patients with multiple sclerosis. J. Technol. Behav. Sci. 2025 doi: 10.1007/s41347-025-00488-0. DOI

Woo M.S., Engler J.B., Friese M.A. The neuropathobiology of multiple sclerosis. Nat. Rev. Neurosci. 2024;25:493–513. doi: 10.1038/s41583-024-00823-z. PubMed DOI

Carbone L., Landi D., Di Girolamo R., Anserini P., Centonze D., Marfia G.A., Alviggi C., Interdisciplinary Group for Fertility in Multiple Sclerosis (IGFMS) Optimizing the “Time to pregnancy” in women with multiple sclerosis: The OPTIMUS Delphi survey. Front. Neurol. 2023;14:1255496. doi: 10.3389/fneur.2023.1255496. PubMed DOI PMC

Mainguy M., Casey R., Vukusic S., Lebrun-Frenay C., Berger E., Kerbrat A., Al Khedr A., Bourre B., Ciron J., Clavelou P., et al. Assessing the risk of relapse after in vitro fertilization in women with multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 2025;12:e200371. doi: 10.1212/NXI.0000000000200371. PubMed DOI PMC

Zaki M.A., Ramzy G., Ali S., Sharaf S.A., Hegazy M.I., Mostafa E., Fawzy I., El-Ghoneimy L. Multiple sclerosis and fecundity: A study of anti-mullerian hormone level in Egyptian patients. Egypt J. Neurol. Psychiatry Neurosurg. 2023;59:141. doi: 10.1186/s41983-023-00748-x. DOI

Roux T., Courtillot C., Debs R., Touraine P., Lubetzki C., Papeix C. Fecundity in women with multiple sclerosis: An observational mono-centric study. J. Neurol. 2015;262:957–960. doi: 10.1007/s00415-015-7663-1. PubMed DOI

Weil S., Vendola K., Zhou J., Bondy C.A. Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development. J. Clin. Endocrinol. Metab. 1999;84:2951–2956. doi: 10.1210/jcem.84.8.5929. PubMed DOI

Houtchens M.K., Kaplan T.B. Seminars in Neurology. Volume 37. Thieme Medical Publishers; New York, NY, USA: 2017. Reproductive Issues in MS; pp. 632–642. PubMed

Lavorgna L., Esposito S., Lanzillo R., Sparaco M., Ippolito D., Cocco E., Fenu G., Borriello G., De Mercanti S., Frau J., et al. Factors interfering with parenthood decision-making in an Italian sample of people with multiple sclerosis: An exploratory online survey. J. Neurol. 2019;266:707–716. doi: 10.1007/s00415-019-09193-4. PubMed DOI

Kawamara K., Kelsey T., Hiraike O. Editorial: Ovarian Ageing: Pathophysiology and recent development of maintaining ovarian reserve. Front. Endocrinol. 2020;11:591764. doi: 10.3389/fendo.2020.591764. PubMed DOI PMC

Amato M.P., Portaccio E. Fertility, pregnancy and childbirth in patients with multiple sclerosis: Impact of disease-modifying drugs. CNS Drugs. 2015;29:207–220. doi: 10.1007/s40263-015-0238-y. PubMed DOI

Cocco E., Sardu C., Gallo P., Capra R., Amato M., Trojano M., Uccelli A., Marrosu M., The FEMIMS Group Frequency and risk factors of mitoxantrone-induced amenorrhea in multiple sclerosis: The FEMIMS study. Mult. Scler. 2008;14:1225–1233. doi: 10.1177/1352458508094882. PubMed DOI

Themmen A.P. Anti-Müllerian hormone: Its role in follicular growth initiation and survival and as an ovarian reserve marker. J. Natl. Cancer Inst. Monogr. 2005;34:18–21. doi: 10.1093/jncimonographs/lgi026. PubMed DOI

Visser J.A., Themmen A.P. Anti-Müllerian hormone and folliculogenesis. Mol. Cell Endocrinol. 2005;234:81–86. doi: 10.1016/j.mce.2004.09.008. PubMed DOI

Durlinger A.L., Visser J.A., Themmen A.P. Regulation of ovarian function: The role of anti-Müllerian hormone. Reproduction. 2002;124:601–609. doi: 10.1530/rep.0.1240601. PubMed DOI

Han Y.-F., Yan Y., Wang H.-Y., Chu M.-Y., Sun K., Feng Z.-W., Feng H. Effect of systemic lupus erythematosus on the ovarian reserve: A systematic review and meta-analysis. Jt. Bone Spine. 2024;91:105728. doi: 10.1016/j.jbspin.2024.105728. PubMed DOI

Mehrpour M., Taherian F., Arfa-Fatollahkhani P., Moghadasi A.N., Mokhtar S., Keivani H. Serum anti-Müllerian hormone levels in multiple sclerosis—A multicentre case-control study. Ces. Slov. Neurol. Neurochir. 2018;81:199–202. doi: 10.14735/amcsnn2018199. DOI

Ismail S.A.A., Zaki M.A., Ramzy G.M., Hegazy M.I., Sharaf S.A.E.A. Anti-mullerian hormone levels in female egyptian multiple sclerosis patients. Mult. Scler. Relat. Disord. 2023;80:105289. doi: 10.1016/j.msard.2023.105289. DOI

Graves J.S., Henry R.G., Cree B.A., Lambert-Messerlian G., Greenblatt R.M., Waubant E., Cedars M.I., Zhu A., Bacchetti P., Hauser S.L., et al. Ovarian aging is associated with gray matter volume and disability in women with MS. Neurology. 2018;90:e254–e260. doi: 10.1212/WNL.0000000000004843. PubMed DOI PMC

Bove R., Healy B., Secor E., Vaughan T., Katic B., Chitnis T., Wicks P., De Jager P. Patients report worse MS symptoms after menopause: Findings from an online cohort. Mult. Scler. Relat. Disord. 2015;4:18–24. doi: 10.1016/j.msard.2014.11.009. PubMed DOI

Bove R., Healy B.C., Musallam A., Glanz B.I., De Jager P.L., Chitnis T. Exploration of changes in disability after menopause in a longitudinal multiple sclerosis cohort. Mult. Scler. 2016;22:935–943. doi: 10.1177/1352458515606211. PubMed DOI PMC

Carbone L., Di Girolamo R., Conforti A., Iorio G.G., Simeon V., Landi D., Marfia G.A., Lanzillo R., Alviggi C. Ovarian reserve in patients with multiple sclerosis: A systematic review and meta-analysis. Int. J. Gynaecol. Obs. 2023;163:11–22. doi: 10.1002/ijgo.14757. PubMed DOI

Thöne J., Kollar S., Nousome D., Ellrichmann G., Kleiter I., Gold R., Hellwig K. Serum anti-Müllerian hormone levels in reproductive-age women with relapsing-remitting multiple sclerosis. Mult. Scler. 2015;21:41–47. doi: 10.1177/1352458514540843. PubMed DOI

Sepúlveda M., Ros C., Martínez-Lapiscina E.H., Solà-Valls N., Hervàs M., Llufriu S., La Puma D., Casals E., Blanco Y., Villoslada P., et al. Pituitary-ovary axis and ovarian reserve in fertile women with multiple sclerosis: A pilot study. Mult. Scler. 2015;22:564–568. doi: 10.1177/1352458515602339. PubMed DOI

Bove R., Chitnis T. The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis. Mult. Scler. 2014;20:520–526. doi: 10.1177/1352458513519181. PubMed DOI

Yuan J., Li J., Huang S.Y., Sun X. Characterization of the subsets of human NKT-like cells and the expression of Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion. J. Reprod. Immunol. 2015;110:81–88. doi: 10.1016/j.jri.2015.05.001. PubMed DOI

Sparaco M., Bonavita S. The role of sex hormones in women with multiple sclerosis: From puberty to assisted reproductive techniques. Front. Neuroendocrinol. 2021;60:100889. doi: 10.1016/j.yfrne.2020.100889. PubMed DOI

Montalban X., Gold R., Thompson A.J., Otero-Romero S., Amato M.P., Chandraratna D., Clanet M., Comi G., Derfuss T., Fazekas F., et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Eur. J. Neurol. 2018;25:215–237. doi: 10.1111/ene.13536. PubMed DOI

Houtchens M.K. Pregnancy and reproductive health in women with multiple sclerosis: An update. Curr. Opin. Neurol. 2024;37:202–211. doi: 10.1097/WCO.0000000000001275. PubMed DOI

Confavreux C., Hutchinson M., Hours M.M., Cortinovis-Tourniaire P., Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N. Engl. J. Med. 1998;339:285–291. doi: 10.1056/NEJM199807303390501. PubMed DOI

Mohr D.C., Hart S.L., Julian L., Cox D., Pelletier D. Association between stressful life events and exacerbation in multiple sclerosis: A meta-analysis. BMJ. 2004;328:731. doi: 10.1136/bmj.38041.724421.55. PubMed DOI PMC

Ladwig A., Dunkl V., Richter N., Schroeter M. Two cases of multiple sclerosis manifesting after in vitro fertilization procedures. J. Neurol. 2016;263:603–605. doi: 10.1007/s00415-016-8041-3. PubMed DOI

Vaknin-Dembinsky A., Bdolah Y., Karussis D., Rosenthal G., Petrou P., Fellig Y., Abramsky O., Lossos A. Tumefactive demyelination following in vitro fertilization (IVF) J. Neurol. Sci. 2015;348:256–258. doi: 10.1016/j.jns.2014.11.016. PubMed DOI

Kopp T.I., Pinborg A., Glazer C.H., Magyari M. Assisted reproductive technology treatment and risk of multiple sclerosis—A Danish cohort study. Fertil. Steril. 2023;119:291–299. doi: 10.1016/j.fertnstert.2022.10.027. PubMed DOI

Hellwig K., Beste C., Brune N., Haghikia A., Muller T., Schimrigk S., Gold R. Increased MS relapse rate during assisted reproduction technique. J. Neurol. 2008;255:592–593. doi: 10.1007/s00415-008-0607-2. PubMed DOI

Michel L., Foucher Y., Vukusic S., Confavreux C., de Sèze J., Brassat D., Clanet M., Clavelou P., Ouallet J.C., Brochet B. Increased risk of multiple sclerosis relapse after in vitro fertilisation. J. Neurol. Neurosurg. Psychiatry. 2012;83:796–802. doi: 10.1136/jnnp-2012-302235. PubMed DOI

Bove R., Rankin K., Lin C., Zhao C., Correale J., Hellwig K., Michel L., Laplaud D.A., Chitnis T. Effect of assisted reproductive technology on multiple sclerosis relapses: Case series and meta-analysis. Mult. Scler. 2020;26:1410–1419. doi: 10.1177/1352458519865118. PubMed DOI

Hoque M. Maintenance of immunomodulatory treatment during assisted reproductive technology reduces relapse risk in multiple sclerosis; Proceedings of the AAN Annual Meeting; Boston, MA, USA. 22–27 April 2023.

Graham E.L., Bakkensen J.B., Anderson A., Lancki N., Davidson A., Perez Giraldo G., Jungheim E.S., Vanderhoff A.C., Ostrem B., Mok-Lin E., et al. Inflammatory activity after diverse fertility treatments: A multicenter analysis in the modern multiple sclerosis treatment Era. Neurol. Neuroimmunol. Neuroinflamm. 2023;10:e200106. doi: 10.1212/NXI.0000000000200106. PubMed DOI PMC

Correale J., Farez M.F., Ysrraelit M.C. Increase in multiple sclerosis activity after assisted reproduction technology. Ann. Neurol. 2012;72:682–694. doi: 10.1002/ana.23745. PubMed DOI

Bove R., Chitnis T. Sexual disparities in the incidence and course of MS. Clin. Immunol. 2013;149:201–210. doi: 10.1016/j.clim.2013.03.005. PubMed DOI

Hemmer B., Kerschensteiner M., Korn T. Role of the innate and adaptive immune responses in the course of multiple sclerosis. Lancet Neurol. 2015;14:406–419. doi: 10.1016/S1474-4422(14)70305-9. PubMed DOI

Sparaco M., Carbone L., Landi D., Ingrasciotta Y., Di Girolamo R., Vitturi G., Marfia G.A., Alviggi C., Bonavita S. Assisted reproductive technology and disease management in infertile women with multiple sclerosis. CNS Drugs. 2023;37:849–866. doi: 10.1007/s40263-023-01036-1. PubMed DOI PMC

Shulga O., Hrytsko M., Romaniuk A., Kotsiuba O. Assisted reproductive technologies in multiple sclerosis: Literature review. Reprod. Endocrinol. 2024;72:60–70. doi: 10.18370/2309-4117.2024.72.60-70. DOI

Torkildsen Ø., Holmøy T., Myhr K.M. Severe multiple sclerosis reactivation after gonadotropin treatment. Mult. Scler. Relat. Disord. 2018;22:38–40. doi: 10.1016/j.msard.2018.02.031. PubMed DOI

Maunula A., Atula S., Laakso S.M., Tienari P.J. Frequency and risk factors of rebound after fingolimod discontinuation—A retrospective study. Mult. Scler. Relat. Disord. 2024;81:105134. doi: 10.1016/j.msard.2023.105134. PubMed DOI

Sakurai K., Shinohara K., Imai T., Yamano Y., Hasegawa Y. Severe multiple sclerosis manifesting upon gnrh agonist therapy for uterine fibroids. Intern. Med. 2020;59:3093–3096. doi: 10.2169/internalmedicine.4839-20. PubMed DOI PMC

Sisková I., Mekiňová L., Hudeček R., Ješeta M., Šimová S. Methods and techniques of fertility preservation in patients with endometriosis. Ces. Gynekol. 2023;88:454–458. doi: 10.48095/cccg2023454. PubMed DOI

The ESHRE Guideline Group on Female Fertility Preservation. Anderson R.A., Amant F., Braat D., D’Angelo A., Chuva de Sousa Lopes S.M., Demeestere I., Dwek S., Frith L., Lambertini M., et al. ESHRE guideline: Female fertility preservation. Hum. Reprod. Open. 2020;2020:hoaa052. PubMed PMC

Ata B., Bosch E., Broer S., Griesinger G., Grynberg M., Kolibianakis E., Kunicki M., Marca A.L., Lainas G., Le Clef N., et al. The ESHRE Guideline Group on Ovarian Stimulation, Update 2025. 2025. [(accessed on 9 October 2025)]. Available online: https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Ovarian-Stimulation-in-IVF-ICSI.

Jølving L.R., Larsen M.D., Fedder J., Nørgård B.M. Live birth in women with multiple sclerosis receiving assisted reproduction. Reprod. Biomed. Online. 2020;40:711–718. doi: 10.1016/j.rbmo.2020.01.013. PubMed DOI

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace

Nahrávání dat ...