Fertility and Assisted Reproductive Techniques in Women with MS

  • Kerstin Hellwig
  • Barabra Brzosko
  • Laura Airas
  • Emma K. Smith


Although substantive research is lacking in the field of fertility and multiple sclerosis (MS), available data suggest that fertility might be slightly impaired in women with MS, and unsuccessful assisted reproductive techniques (ARTs) may be associated with increased relapses.

In this chapter, we will briefly elucidate the physiology of fertility. We will also review possible mechanisms of infertility and discuss recently available data on fertility and MS, as well as discussing whether or not ARTs may have an effect on MS disease activity.


Multiple Sclerosis Luteinizing Hormone Multiple Sclerosis Patient Corpus Luteum GnRH Agonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Anderson SE, Dallal GE, Must A. Relative weight and race influence average age at menarche: results from two nationally representative surveys of US girls studied 25 years apart. Pediatrics. 2003;111:844–50.CrossRefPubMedGoogle Scholar
  2. 2.
    Brodin T, Bergh T, Berglund L, Hadziosmanovic N, Holte J. Menstrual cycle length is an age-independent marker of female fertility: results from 6271 treatment cycles of in vitro fertilization. Fertil Steril. 2008;90:1656–61.CrossRefPubMedGoogle Scholar
  3. 3.
    Broom TJ, Matthews CD, Cooke ID, Ralph MM, Seamark RF, Cox LW. Endocrine profiles and fertility status of human menstrual cycles of varying follicular phase length. Fertil Steril. 1981;36:194–200.CrossRefPubMedGoogle Scholar
  4. 4.
    Haag P. Hanhart N, Müller M. Gynäkologie und Urologie. 2008/2009. p. 20–2.Google Scholar
  5. 5.
    Haag P, Hanhart N, Müller M. Gynäkologie und Urologie. 4. Auflage. 2009. p. 230–1.Google Scholar
  6. 6.
    Kamel HM, Amin AH, Al-Adawy AR. Basal serum anti-Mullerian hormone (AMH) is a promising test in prediction of occurrence of pregnancy rate in infertile women undergoing ICSI cycles. Clin Lab. 2014;60:1717–23.Google Scholar
  7. 7.
    Kloss JD, Perlis ML, Zamzow JA, Culnan EJ, Gracia CR. Sleep, sleep disturbance, and fertility in women. Sleep Med Rev. 2014;22:78–87.Google Scholar
  8. 8.
    Losos JBR, Peter H, Johnson GB, Singer SR. Biology. New York: McGraw-Hill; 2002. p. 1207–9.Google Scholar
  9. 9.
    Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007;370:685–97.CrossRefPubMedGoogle Scholar
  10. 10.
    Silverthorn DU. Human physiology: an integrated approach. 6th ed. 2013. p. 850–90. ISBN-13: 978-0321814838 or ISBN-10: 0321814835 [Pearson]Google Scholar
  11. 11.
    Vassena R, Vidal R, Coll O, Vernaeve V. Menstrual cycle length in reproductive age women is an indicator of oocyte quality and a candidate marker of ovarian reserve. Eur J Obstet Gynecol Reprod Biol. 2014;177:130–4.Google Scholar
  12. 12.
  13. 13.
    Widmaier EPR, Hershel R, Strang KT. Vander’s human physiology: the mechanism of body function. 12th ed. 2010. p. 555–631. ISBN-13: 978-0073378305 or ISBN-10: 0073378305 [McGraw-Hill Education]Google Scholar
  14. 14.
    Yasuzumi G, Yabumoto N, Saito K, Tsubo I. In vivo production of nucleolar channel system in human endocervical secretory cells. J Submicrosc Cytol. 1981;13:639–47.PubMedGoogle Scholar
  15. 15.
    Niedziela N, Adamczyk-Sowa M, Pierzchala K. Epidemiology and clinical record of multiple sclerosis in selected countries: a systematic review. Int J Neurosci. 2013;124:322–30.CrossRefPubMedGoogle Scholar
  16. 16.
    Runmarker B, Andersen O. Pregnancy is associated with a lower risk of onset and a better prognosis in multiple sclerosis. Brain. 1995;118:253–61.CrossRefPubMedGoogle Scholar
  17. 17.
    Cavalla P, Rovei V, Masera S, et al. Fertility in patients with multiple sclerosis: current knowledge and future perspectives. Neurol Sci. 2006;27:231–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Lombardi G, Celso M, Bartelli M, Cilotti A, Del Popolo G. Female sexual dysfunction and hormonal status in multiple sclerosis patients. J Sex Med. 2011;8:1138–46.CrossRefPubMedGoogle Scholar
  19. 19.
    Ghezzi A. Sexual dysfunction in multiple sclerosis. Int MS J. 1999;5:44–53.Google Scholar
  20. 20.
    Nielsen NM, Jorgensen KT, Stenager E, et al. Reproductive history and risk of multiple sclerosis. Epidemiology. 2011;22:546–22.CrossRefPubMedGoogle Scholar
  21. 21.
    Jalkanen A, Alanen A, Airas L. Pregnancy outcome in women with multiple sclerosis: results from a prospective nationwide study in Finland. Mult Scler. 2010;16:950–5.CrossRefPubMedGoogle Scholar
  22. 22.
    Grinsted L, Heltberg A, Hagen C, Djursing H. Serum sex hormone and gonadotropin concentrations in premenopausal women with multiple sclerosis. J Intern Med. 1989;226:241–4.CrossRefPubMedGoogle Scholar
  23. 23.
    Cil AP, Leventoglu A, Sonmezer M, et al. Assessment of ovarian reserve and Doppler characteristics in patients with multiple sclerosis using immunomodulating drugs. J Turk Ger Gynecol Assoc. 2009;10:213–9.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Thone J, Kollar S, Nousome D, et al. Serum anti- Mullerian hormone levels in reproductive-age women with relapsing remitting multiple sclerosis. Mult Scler. 2015;21:41–7.CrossRefPubMedGoogle Scholar
  25. 25.
    McCombe PA, Stenager E. Female infertility and multiple sclerosis: is this an issue? Mult Scler. 2015;21:5–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Patti F, Messina S, D’Amico E, Lo Fermo S, Zappia M. Pregnancy outcomes in multiple sclerosis patients previously treated with cyclophosphamide. Acta Neurol Scand. 2014;130:41–4.CrossRefGoogle Scholar
  27. 27.
    Paladini D, Vassallo M, D’Armiento MR, Cianciaruso B, Martinelli P. Prenatal detection of multiple fetal anomalies following inadvertent exposure to cyclophosphamide in the first trimester of pregnancy. Birth Defects Res A Clin Mol Teratol. 2004;70:99–100.CrossRefPubMedGoogle Scholar
  28. 28.
    Amato MP, Portaccio E. Fertility. Pregnancy and childbirth in patients with multiple sclerosis: impact of disease-modifying drugs. CNS Drugs. 2015;29:207–20.CrossRefPubMedGoogle Scholar
  29. 29.
    Sen A, Kushnir VA, Barad DH, Gleicher N. Endocrine autoimmune diseases and female infertility. Nat Rev Endocrinol. 2014;10:37–50.CrossRefPubMedGoogle Scholar
  30. 30.
    Hellwig K, Beste C, Brune N, et al. Increased MS relapse rate during assisted reproduction technique. J Neurol. 2008;255(4):592–3.CrossRefPubMedGoogle Scholar
  31. 31.
    Hellwig K, Schimrigk S, Beste C, Muller T, Gold R. Increase in relapse rate during assisted reproduction technique in patients with multiple sclerosis. Eur Neurol. 2009;61(2):65–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Laplaud DA, Leray E, Barriere P, Wiertlewski S, Moreau T. Increase in multiple sclerosis relapse rate following in vitro fertilization. Neurology. 2006;66(8):1280–1.CrossRefPubMedGoogle Scholar
  33. 33.
    Michel L, Foucher Y, Vukusic S, et al. Increased risk of multiple sclerosis relapse after in vitro fertilisation. J Neurol Neurosurg Psychiatry. 2012;83(8):796–802.CrossRefPubMedGoogle Scholar
  34. 34.
    Correale J, Farez MF, Ysrraelit MC. Increase in multiple sclerosis activity after assisted reproduction technology. Ann Neurol. 2012;72(5):682–94.Google Scholar
  35. 35.
    Hellwig K, Correale J. Artificial reproductive techniques in multiple sclerosis. Clin Immunol. 2013;149(2):219–24.CrossRefPubMedGoogle Scholar
  36. 36.
    Voskuhl RR, Palaszynski K. Sex hormones in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. Neuroscientist. 2001;7(3):258–70.CrossRefPubMedGoogle Scholar
  37. 37.
    Voskuhl RR, Gold SM. Sex-related factors in multiple sclerosis susceptibility and progression. Nature Reviews. Neurology. 2012;8(5):255–63.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998;339(5):285–91.CrossRefPubMedGoogle Scholar
  39. 39.
    Heesen C, Gold SM, Huitinga I, Reul JM. Stress and hypothalamic-pituitary-adrenal axis function in experimental autoimmune encephalomyelitis and multiple sclerosis – a review. Psychoneuroendocrinology. 2007;32(6):604–18.CrossRefPubMedGoogle Scholar
  40. 40.
    Gold SM, Mohr DC, Huitinga I, Flachenecker P, Sternberg EM, Heesen C. The role of stress-response systems for the pathogenesis and progression of MS. Trends Immunol. 2005;26(12):644–52.CrossRefPubMedGoogle Scholar
  41. 41.
    Pasch LA, Gregorich SE, Katz PK, Millstein SG, Nachtigall RD, Bleil ME, et al. Psychological distress and in vitro fertilization outcome. Fertil Steril. 2012;98(2):459–64.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Gonzalez DA, Diaz BB, Rodriguez Perez Mdel C, Hernandez AG, Chico BN, de Leon AC. Sex hormones and autoimmunity. Immunol Lett. 2010;133(1):6–13.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  • Kerstin Hellwig
    • 1
  • Barabra Brzosko
    • 1
  • Laura Airas
    • 2
  • Emma K. Smith
    • 2
  1. 1.Department of NeurologySt. Josef Hospital, Klinikum der Ruhr-UniversitätBochumGermany
  2. 2.Division of Clinical NeurosciencesTurku University HospitalTurkuFinland

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