Multiple Sclerosis, Infertility and its Treatment

Authors: I. Šrotová 1,2;  I. Crha 3;  E. Vlčková 1,2;  M. Svobodová 1,2;  E. Nekvapilová 2;  P. Štourač 1,2;  J. Bednařík 1,2
Authors‘ workplace: Neurologická klinika LF MU a FN Brno 1;  CEITEC – Středoevropský technologický institut, MU, Brno 2;  Gynekologicko-porodnická klinika LF MU a FN Brno 3
Published in: Cesk Slov Neurol N 2015; 78/111(6): 655-660
Category: Review Article


Multiple sclerosis is a common autoimmune disease affecting young people, with onset usually at the age of 20– 40 years. During these decades patients are usually planning pregnancy. In patients with multiple sclerosis fertility seems to be slightly impaired. Several factors might contribute to this condition. It is mainly sexual dysfunctions, which belong to comparatively common symptoms of the disease, hormonal alteration, concomitant (autoimmune) disease and specific therapy of multiple sclerosis. Psychosocial factors have an influence on fertility and its therapy. The aim of this review is description of factors potentially interfering with fertility in multiple, the current applications of assisted reproductive techniques and its influence on course of multiple sclerosis.

Key words:
multiple sclerosis – infertility – in vitro fertilisation – endometriosis – sexual dysfunctions – sexual hormons

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.


1. Vachová M. Epidemie roztroušené sklerózy ve světě? Cesk Slov Neurol N 2012; 75/ 108(6): 701– 706.

2. Duquette P, Pleines J, Girard M, Charest L, Senecal‑ Quevil­lon M, Mas­se C. The increased susceptibility of women to multiple sclerosis. Can J Neurol Sci 1992; 19(4): 466– 471.

3. Compston A, Coles A. Multiple sclerosis. Lancet 2002; 359(9313): 1221– 1231.

4. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M et al. Dia­gnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69(2): 292– 302. doi: 10.1002/ ana.22366.

5. Alwan S, Chambers CD, Armenti VT, Sadovnick AD. The need for a disease‑ specific prospective pregnancy registry for multiple sclerosis (MS). Mult Scler Relat Disord 2015; 4(1): 6– 17. doi: 10.1016/ j.msard.2014.10.001.

6. Meluzínová E. Těhotenství a roztroušená skleróza. Neurol Prax 2010; 11(5): 293– 295.

7. Confavreux C, Hutchinson M, Hours 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(5): 285– 291.

8. Runmarker B, Andersen O. Pregnancy is as­sociated with a lower risk of onset and a better prognosis in multiple sclerosis. Brain 1995; 118(1): 253– 261.

9. Crha I. Farmakoterapie v reprodukční medicíně. Prakt Lekaren 2010; 6(4): 173– 176.

10. Řežábek K. Asistovaná reprodukce. Praha: Maxdorf 2008.

11. Mosher WD, Pratt WF. Fecundity and infertility in the United States: incidence and trends. Fertil Steril 1991; 56(2): 192– 193.

12. Caval­la P, Rovei V, Masera S, Vercel­lino M, Mas­sobrio M, Mutani R et al. Fertility in patients with multiple sclerosis: cur­rent knowledge and future perspectives. Neurol Sci 2006; 27(4): 231– 239.

13. 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(8): 950– 955. doi: 10.1177/ 1352458510372629.

14. 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(4): 241– 244.

15. 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(4): 1138– 1146. doi: 10.1111/ j.1743‑ 6109.2010.02161.x.

16. Sloka JS, Phil­lips PW, Stefanel­li M, Joyce C. Co‑ occur­rence of autoim­mune thyroid disease in a multiple sclerosis cohort. J Autoim­mune Dis 2005; 2: 9.

17. Demirkiran M, Sarica Y, Uguz S, Yerdelen D, Aslan K. Multiple sclerosis patients with and without sexual dysfunction: are there any dif­ferences? Mult Scler 2006; 12(2): 209– 214.

18. Gnoth C, Godehardt E, Frank‑ Her­rmann P, Friol K, Tig­ges J, Freundl G. Definition and prevalence of subfertility and infertility. Hum Reprod 2005; 20(5): 1144– 1147.

19. Zorzon M, Zivadinov R, Bosco A, Bragadin LM, Moret­­ti R, Bonfigli L et al. Sexual dysfunction in multiple sclerosis: a case‑ control study. I. Frequency and comparison of groups. Mult Scler 1999; 5(6): 418– 427.

20. Foley FW, Zemon V, Campagnolo D, Mar­rie RA, Cutter G, Tyry T et al. The Multiple Sclerosis Intimacy and Sexuality Question­naire –  re‑validation and development of a 15- item version with a large US sample. Mult Scler 2013; 19(9): 1197– 1203. doi: 10.1177/ 1352458512471876.

21. Borel­lo‑ France D, Leng W, O‘Leary M, Xavier M, Erickson J, Chancel­lor MB et al. Bladder and sexual function among women with multiple sclerosis. Mult Scler 2004; 10(4): 455– 461.

22. Barnhart K, Osheroff J. Fol­licle stimulat­ing hormone as a predictor of fertility. Curr Opin Obstet Gynecol 1998; 10(3): 227– 232.

23. Sil­ls ES, Alper M­M, Walsh AP. Ovarian reserve screen­ing in infertility: practical applications and theoretical directions for research. Eur J Obstet Gynecol Reprod Biol 2009; 146(1): 30– 36. doi: 10.1016/ j.ejogrb.2009.05.008.

24. Cil AP, Leventoğlu A, Sönmezer M, Soylukoç R, Oktay K. As­ses­sment of ovarian reserve and Doppler characteristics in patients with multiple sclerosis us­ing im­munomodulat­ing drugs. J Turk Ger Gynecol As­soc 2009; 10(4): 213– 219.

25. Thöne J, Kol­lar S, Nousome D, El­lrichmann G, Kleiter I, Gold R et al. Serum anti‑Mül­lerian hormone levels in reproductive‑ age women with relapsing‑ remitt­ing multiple sclerosis. Mult Scler 2015; 21(1): 41– 47. doi: 10.1177/ 1352458514540843.

26. Kučera R, Topolčan O, Rumpíková T, Rumpík D, Dostál J. Stanovení anti‑Mül­lerova hormonu u žen. Čes Gynek 2013; 78(3): 282– 288.

27. Sicotte NL, Liva SM, Klutch R, Pfeif­fer P, Bouvier S, Odesa S et al. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 2002; 52(4): 421– 428.

28. Soldan SS, Alvarez Retuerto AI, Sicotte NL, Voskuhl RR. Im­mune modulation in multiple sclerosis patients treat­ed with the pregnancy hormone estriol. J Im­munol 2003; 171(11): 6267– 6274.

29. Falaschi P, Martocchia A, Proietti A, D‘Urso R, Antonini G. High incidence of hyperandrogenism‑related clinical signs in patients with multiple sclerosis. Neuro Endocrinol Lett 2001; 22(4): 248– 250.

30. Safarinejad MR. Evaluation of endocrine profile, hypothalamic‑ pituitary‑ testis axis and semen quality in multiple sclerosis. J Neuroendocrinol 2008; 20(12): 1368– 1375.

31. Goldstein DP, deCholnoky C, Emans SJ, Leventhal JM. Laparoscopy in the dia­gnosis and management of pelvic pain in adolescents. J Reprod Med 1980; 24(6): 251– 256.

32. Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am 1997; 24(2): 235– 258.

33. Sinaii N, Cleary SD, Bal­lweg ML, Nieman LK, Stratton P. High rates of autoim­mune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod 2002; 17(10): 2715– 2724.

34. Berkkanoglu M, Arici A. Im­munology and endometriosis. Am J Reprod Im­munol 2003; 50(1): 48– 59.

35. Karásek D, Oborná I, Fryšák Z. Autoimunitní tyreoiditida a neplodnost. Interní Med 2007; 9(9): 394– 397.

36. Havrdova E, Horakova D, Kovarova I. Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use. Ther Adv Neurol Disord 2015; 8(1): 31– 45.

37. Magyari M, Koch‑ Henriksen N, Pfleger CC, Sørensen PS. Gender and autoim­mune comorbidity in multiple sclerosis. Mult Scler 2014; 20(9): 1244– 1251.

38. Lu E, Zhu F, Zhao Y, van der Kop M, Sadovnick A, Syn­nes A et al. Birth outcomes of pregnancies fathered by men with multiple sclerosis. Mult Scler 2014; 20(9): 1260– 1264.

39. Khademi A, Al­leyas­sin A, Aghhos­seini M, Ramezanzadeh F, Abhari AA. Pretreatment beck depres­sion inventory score is an important predictor for post‑treatment score in infertile patients; a before‑after study. BMC Psychiatry 2005; 5(1): 25

40. El Kis­si Y, Romdhane AB, Hidar S, Ban­nour S, Ayoubi Idris­si K, Khairi H et al. General psychopathology, anxiety, depres­sion and self‑ esteem in couples undergo­ing infertility treatment: a comparative study between men and women. Eur J Obstet Gynecol Reprod Biol 2013; 167(2): 185– 189. doi: 10.1016/ j.ejogrb.2012.12.014.

41. Siegert RJ, Abernethy DA. Depres­sion in multiple sclerosis: a review. J Neurol Neurosurg Psychiatry 2005; 76(4): 469– 475.

42. Feinstein A, O‘Con­nor P, Feinstein K. Multiple sclerosis, interferon beta‑1b and depres­sion: a prospective investigation. J Neurol 2002; 249(7): 815– 820.

43. Masopust J, Vališ M, Taláb R. Psychické příznaky roztroušené mozkomíšní sklerózy. Čes Slov Psychiat 2007; 103(1): 47– 54.

44. Jans­sens AC, van Doorn PA, de Boer JB, van der Meché FG, Pas­schier J, Hintzen RQ. Impact of recently dia­gnosed multiple sclerosis on quality of life, anxiety, depres­sion and distress of patients and partners. Acta Neurol Scand 2003; 108(6): 389– 395.

45. Csemiczky G, Landgren BM, Col­lins A. The influence of stress and state anxiety on the outcome of IVF‑ treatment: psychological and endocrinological as­ses­sment of Swedish women enter­ing IVF‑ treatment. Acta Obstet Gynecol Scand 2000; 79(2): 113– 118.

46. Smeenk JM, Verhaak CM, Eugster A, van Min­nen A, Zielhuis GA, Braat DD. The ef­fect of anxiety and depres­sion on the outcome of in vitro fertilization. Hum Reprod 2001; 16(7): 1420– 1423.

47. Amato MP, Portaccio E. Fertility, pregnancy and child­birth in patients with multiple sclerosis: impact of dis­ease‑ modify­ing drugs. CNS Drugs 2015; 29(3): 207– 220. doi: 10.1007/ s40263‑ 015‑ 0238‑ y.

48. Štourač P. Imunomodulační léčba roztroušené sklerózy mozkomíšní v klinických a zobrazovacích parametrech. Cesk Slov Neurol N 2012; 108(4): 404– 410.

49. Meistrich ML, Wilson G, Mathur K, Ful­ler LM, Rodriguez MA, McLaughlin P et al. Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin‘s disease. J Clin Oncol 1997; 15(12): 3488– 3495.

50. Cocco E, Sardu C, Gal­lo P, Capra R, Amato MP, Trojano M. Frequency and risk factors of mitoxantrone‑induced amenor­rhea in multiple sclerosis: the FEMIMS study. Mult Scler 2008; 14(9): 1225– 1233.

51. 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– 1281.

52. Michel L, Foucher Y, Vukusic S, Confavreux C, de Sèze J, Bras­sat D et al. Increased risk of multiple sclerosis relapse after in vitro fertilisation. J Neurol Neurosurg Psychiatry 2012; 83(8): 796– 802.

53. Hel­lwig K, Beste C, Brune N, Haghikia A, Mül­ler T, Schimrigk S et al. Increased MS relapse rate dur­ing as­sisted reproduction technique. J Neurol 2008; 255(4): 592– 593. doi: 10.1007/ s00415‑ 008‑ 0607‑ 2.

54. 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– 68. doi: 10.1159/ 000177937.

55. Cor­reale J, Farez MF, Ysr­raelit MC. Increase in multiple sclerosis activity after as­sisted reproduction technology. Ann Neurol 2012; 72(5): 682– 694. doi: 10.1002/ ana.23745.

56. 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– 618.

57. Vaknin‑Dembinsky A, Bdolah Y, Karus­sis D, Rosenthal G, Petrou P, Fel­lig Y et al. Tumefactive demyelination fol­low­ing in vitro fertilization (IVF). J Neurol Sci 2015; 348(2): 256– 258.

58. Okáčová I, Benešová Y, Štourač P, Pikulová H, Praksová P, Mitášová A et al. Neurologické komplikace spojené s asistovanou reprodukcí –  kazuistika. Cesk Slov Neurol N 2012; 75/ 108(5): 637– 640.

59. Dafopoulos K, Griesinger G, Schultze‑ Mosgau A, Orief Y, Schöpper B, Nikolettos N et al. Cumulative pregnancy rate after ICSI with cryopreserved testicular tis­sue in non‑obstructive azoospermia. Reprod Biomed Online 2005; 10(4): 461– 466.

60. Huser M, Zakova J, Smardova L, Crha I, Janku P, Hudecek R et al. Combination of fertility preservation strategies in young women with recently dia­gnosed cancer. Eur J Gynaecol Oncol 2012; 33(1): 42– 50.

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