Impact of Multiple Sclerosis on Infertility and Impact of Infertility Treatments on Multiple Sclerosis Relapses in Slovenia: Medical Outline, Legal and Ethical Outcomes

  • Eda Vrtačnik Bokal University Medical Centre Ljubljana, Department of Reproductive Medicine
  • Urban Vrtačnik Law Firm Vrtačnik, Ltd.
Keywords: multiple sclerosis, infertility and in vitro fertilization, MAR, ZZNPOB and ZPacP, medical ethics


Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system. It is common in the reproductive period and can lead to infertility and significant disability. The treatment on multiple sclerosis is recently more successful and enables better quality of life, therefore rising hope and desire for the future parents, also in terms of successful infertility treatments. In this context the couples should be managed concerning the detrimental effect of the disease itself on fertility, detrimental effect of the drugs used for treatment on gonads and in terms of the implementation of drugs used for ovarian stimulation and their impact on the basic disease (MS). Article finds solutions on the legal outcomes in situations where infertility treatments may negatively impact the progress of MS, as well as the solutions on how to (successfully) provide infertility treatments to the patients with MS. It proposes interdisciplinary approach between gynecologists and neurologists to perform required weighting of benefits and risks (burdens), deriving from specific action or treatment, whereas for the patients who shall not undergo infertility treatments due to their medical status, related to MS, it proposes storage of gametes under conditions, set by the law.


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Author Biographies

Eda Vrtačnik Bokal, University Medical Centre Ljubljana, Department of Reproductive Medicine

Ljubljana, Slovenia. E-mail:

Urban Vrtačnik, Law Firm Vrtačnik, Ltd.

Ljubljana, Slovenia. E-mail:


Al-Inany, H. G., Youssef, M., Aboulghar, T., et al. (2011) Gonadotrophin-releasing hormone antagonists for assisted reproductive technology, Cochrane Database of Systematic Reviews, 5, CD001750, doi: 10.1002/14651858.CD001750.pub3.

Alwan, S., & Sadovnick, A. D. (2012) Multiple sclerosis and pregnancy: maternal considerations, Women’s Health, 8, pp. 399-414, doi: 10.2217/WHE.12.33.

Beauchamp, T. L. & Childress, J. F. (2013) Principles of Biomedical Ethics, 7th ed. (New York: Oxford University Press).

Bruck, W., & Stadelmann, C. (2005) The spectrum of multiple sclerosis: new lessons from pathology, Current Opinion in Neurology, 18(3), pp. 221-224, doi: 10.1097/01.wco.0000169736.60922.20.

Cavalla, P., Rovei, V., Masera, S., et al. (2006) Fertility in patients with multiple sclerosis: current knowledge and future perspectives, Neurological Sciences, 27(4), pp. 231-239, doi: 10.1007/s10072-006-0676-x.

Chen, H. F., Jeung, E. B., Stephenson, M., et al. (1999) Human peripheral blood mononuclear cells express gonadotropin-releasing hormone (GnRH), GnRH receptor, and interleukin-2 receptor gamma-chain messenger ribonucleic acids that are regulated by GnRH in vitro, Journal of Clinical Endocrinology and Metabolism, 84(2), pp. 743-750, doi: 10.1210/jcem.84.2.5440.

Cil, A.P., Leventoglu, A., Sonmezer, M., et. al. (2010) Ovarian reserve assessment in patients with multiple sclerosis, Fertility and Sterility, 94(4), supplement, pp. S98, doi: 10.1016/j.fertnstert.2010.07.410.

Cocco, E., Sardu, C., Gallo, P., et al. (2008) Frequency and risk factors of mitoxantrone-induced amenorrhea in multiple sclerosis: the FEMIMS study, Multiple Sclerosis, 14(9), pp. 1225-1233, doi: 10.1177/1352458508094882.

Confavreux, C., Hutchinson, M., Hours, M. M., et al. (1998) Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group, New England Journal of Medicine, 339(5), pp. 285-291, doi: 10.1056/NEJM199807303390501.

Correale, J., Farez, M.F., Ysrraelit, M. C., et al. (2012) Increase in multiple sclerosis activity after assisted reproduction technology, Annals of Neurology, 72(5), pp. 682-694, doi: 10.1002/ana.23745.

Dewailly, D., Andersen, C. Y., Balen, A., et al. (2014) The physiology and clinical utility of antiMullerian hormone in women, Human Reproduction Update, 20(3), pp. 370-385, doi: 10.1093/humupd/dmt062.

Ditkoff, E. C., Cassidenti, D. L., Paulson, R. J., et al. (1991) The gonadotropin-releasing hormone antagonist (Nal-Glu) acutely blocks the luteinizing hormone surge but allows for resumption of folliculogenesis in normal women, America Journal of Obstetrics and Gynecology, 165, pp. 1811‒1817, doi: 10.1016/0002-9378(91)90037-r.

Ferrero, S., Pretta, S., Ragni, N., et al. (2004) Multiple sclerosis: management issues during pregnancy, European Journal of Obstetrics, Gynecology, and Reproductive Biology, 115(1), pp. 3-9, doi: 10.1016/j.ejogrb.2003.10.020.

Fleming, R., Haxton, M. J., Hamilton, M. P., et al. (1988) Combined gonadotropin-releasing hormone analog and exogenous gonadotropins for ovulation induction in infertile women: efficacy related to ovarian function assessment, American Journal of Obstetrics and Gynecology, 159(2), pp. 376‒481, doi: 10.1016/s0002-9378(88)80088-7.

Gonzales, D. A., Diaz, B. B., Rodrigues Perez, M. D. C., et al. (2010) Sex hormones and autoimmunity, Immunology Letters, 133(1), pp. 6-13, doi: 10.1016/j.imlet.2010.07.001.

Grinsted, L., Heltberg, A., Hagen, C., et al. (1989) Serum sex hormone and gonadotropin concentrations in premenopausal women with multiple sclerosis, Journal of Internal Medicine, 226(4), pp. 241-244, doi: 10.1111/j.1365-2796.1989.tb01387.x.

Haensch, C. A, & Jörg, J. (2006) Autonomic dysfunction in multiple sclerosis, Journal of Neurology, 253(Suppl. 1), pp. S3-S9, doi: 10.1007/s00415-006-1102-2.

Hellwig, K., & Correale, J. (2013) Artificial reproductive techniques in multiple sclerosis, Clinical Immunology, 149(2), pp. 219-224, doi: 10.1016/j.clim.2013.02.001.

Jacobson, J. D., Nisula, B.C., Steinberg, A. D., et al. (1994) Modulation of the expression of murine lupus by gonadotropin-releasing hormone analogs, Endocrinology, 134, pp. 2516-2523, doi: 10.1210/endo.134.6.8194477.

Kelsey, T. W., Wright, P., Nelson, S. M., et al. (2011) A validated model of serum anti-Müllerian hormone from conception to menopause, PLoS One, 6(7), e22024, doi: 10.1371/journal.pone.0022024.

Kister, I., E. Chamot, A. R., Salter, G. R., et al. (2013) Disability in multiple sclerosis: a reference for patients and clinicians, Neurology, 80(11), pp. 1018-1024, doi: 10.1212/WNL.0b013e3182872855.

Kolibianakis, E. M., Collins, J., Tarlatzis, B. C., et al. (2006) Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis, Human Reproduction Update, 12(6), pp. 651‒71, doi: 10.1093/humupd/dml038.

Lawrenz, B., Henes, J., Henes, M., et al. (2011) Impact of systemic lupus erythematosus on ovarian reserve in premenopausal women: Evaluation by using anti-Muellerian hormone, Lupus, 20(11), pp. 1193-1197, doi: 10.1177/0961203311409272.

Lee, J. Y., Jee, B. C., Lee, J. R., et al. (2012) Age-related distributions of anti-Müllerian hormone level and anti-Müllerian hormone models, Acta Obstetricia et Gynecologica Scandinavica, 91(8), pp. 970-975, doi: 10.1111/j.1600-0412.2012.01448.x.

Lublin, F. D., & Reingold, S. C. (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis, Neurology, 46(4), pp. 907-911, doi: 10.1212/wnl.46.4.907.

Martinelli, V., Radaelli, M., Straffi, L., et. al. (2009) Mitoxantrone: benefits and risks in multiple sclerosis patients, Neurological Sciences, 30(Suppl. 2), pp. S167–S170, doi: 10.1007/s10072-009-0142-7.

Miller, D. F., Barkhof, X. Montalban, A. et al. (2005) Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis, Lancet. Neurology, 4(5), pp. 281-288, doi: 10.1016/S1474-4422(05)70071-5.

Mitsonis, C. I., Potagas, C., Zervas, I., et al. (2009) The effects of stressful life events on the course of multiple sclerosis: a review, International Journal of Neuroscience, 119(3), pp. 315-335, doi: 10.1080/00207450802480192.

Mohr, D. C., Hart, S. L., Julian, L., et al. (2004) Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis, BMJ, 328(7442), pp. 1-5, doi: 10.1136/bmj.38041.724421.55.

Nielsen, N. M., Jorgensen, K. T., Stenager, E., et al. (2011) Reproductive history and risk of multiple sclerosis, Epidemiology, 22, pp. 546–552, doi: 10.1097/EDE.0b013e31821c7adc.

Orton, S. M., Herrera, B. M., Yee, I. M., et al. (2006) Sex ratio of multiple sclerosis in Canada: a longitudinal study, Lancet. Neurology, 5(11), pp. 932-936, doi: 10.1016/S1474-4422(06)70581-6.

Prestipino, E., Squitieri, M., Razzolini, L., et al. (2018) A case of Takotsubo syndrome during a multiple sclerosis brainstem relapse, Multiple sclerosis and related disorders, 24, pp. 1-2, doi: 10.1016/j.msard.2018.05.005.

Prévinaire, J. G., Lecourt, G., Soler, J. M., et al. (2014) Sexual disorders in men with multiple sclerosis: evaluation and management, Annals of Physical and Rehabilitation Medicine, 57(5), pp. 329-336, doi: 10.1016/

Safarinejad, M. R. (2008) Evaluation of endocrine profile, hypothalamic-pituitary-testis axis and semen quality in multiple sclerosis, Journal of. Neuroendocrinology, 20(12), pp. 1368-1375, doi: 10.1111/j.1365-2826.2008.01791.x.

Şenateş, E., Çolak, Y., Erdem, E. D., et al. (2013) Serum anti-Müllerian hormone levels are lower in reproductive-age women with Crohn’s disease compared to healthy control women, Journal of Crohn’s & Colitis, 7(2), pp. e29-e34, doi: 10.1016/j.crohns.2012.03.003.

Sepulvela, M., Ros, C., Martinez-Lapiscina, H., et al. (2016) Pituitary-ovary axis and ovarian reserve in fertile women with multiple sclerosis: A pilot study, Multiple Sclerosis, 22(4), pp. 564-568, doi: 10.1177/1352458515602339.

The Ethics Committee of the American Society for Reproductive Medicine (ASRM) (2012) Fertility treatment when the prognosis is very poor or futile: a committee opinion, Fertility and Sterility, 98(1), pp. e6-e9, doi: 10.1016/j.fertnstert.2012.03.045.

Thone, J., Kollar, S., Nousome, D., et al. (2015) Serum anti-Mullerian hormone levels in reproductiveage women with relapsing remitting multiple sclerosis, Multiple Sclerosis, 21(1), pp. 41-45, doi: 10.1177/1352458514540843.

Vrtačnik, U. (2018) Pravni vidiki biomedicinske pomoči pri spočetju, doktorska disertacija [PhD thesis] (Ljubljana: Pravna fakulteta).

Vrtačnik, U. (2019) Rules on Assisted Reproduction on Slovenia – Collision Between Legislation on Biomedically Assisted Procreation and Regulation Relating to Safety and Quality of Tissues and Cells, Medicine Law & Society, 12(2), pp. 109-126, doi: 10.18690/mls.12.2.109-126.2019.

Weinshenker, B. G., Bass, B., Rice, G. P. et al. (1989) The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability, Brain, 112(Pt 1), pp.133-146, doi: 10.1093/brain/112.1.133.

Zegers-Hochschild, F., Adamson, G.D., de Mouzon, J., et al. (2009) International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World HealthOrganization (WHO) revised glossary of ART terminology, 2009, Fertility and Sterility, 92(5), pp. 1520‒1524, doi: 10.1016/j.fertnstert.2009.09.009.

Acts, Regulations and Court Decisions

Act on Quality and Safety of Human Tissues and Cells, for the Purposes of Medical Treatment/ Zakon o kakovosti in varnosti človeških tkiv in celic, namenjenih za zdravljenje – ZKVČTC, Official Gazette of RS, No. 61/07 w/amendments.

Act Regulating the Obtaining and Transplantation of Human Body Parts for the Purposes of Medical Treatment / Zakon o pridobivanju in presaditvi delov človeškega telesa zaradi zdravljenja – ZPPDČT, Official Gazette of RS, No. 56/15.

Administrative Dispute Act/Zakon o upravnem sporu – ZUS-1, Official Gazette of RS, št. 105/06 w/amendments.

Code of Medical Ethics/Kodeks zdravniške etike, 2016,, last accessed, September 21st, 2020.

Code of Obligations/Obligacijski zakonik - OZ, Official Gazette of RS, No. 83/01 w/amendments.

Criminal Code/Kazenski zakonik RS - KZ-1, Official Gazette of RS, No. 55/08 w/amendments.

General Administrative Procedure Act/Zakon o splošnem upravnem postopku - ZUP, Official Gazette of RS, No. 80/99 w/amendments.

Health Care and Health Insurance Act/Zakon o zdravstvenem varstvu in zdravstvenem zavarovanju – ZZVZZ, Official Gazette of RS, No. 9/92 w/amendments.

Health Measures in Exercising Freedom of Choice in Childbearing Act / Zakon o zdravstvenih ukrepih pri uresničevanju pravice do svobodnega odločanja o rojstvu otrok – ZZUUP, Official Gazette of SRS, No. 11/77, 42/86 w/amendments.

Health Services Act/Zakon o zdravstveni dejavnosti - ZZDej, Official Gazette of RS, No. 23/05 w/amendments.

Infertility Treatment and Procedures of Biomedically-Assisted Procreation Act/Zakon o zdravljenju neplodnosti in postopkih oploditve z biomedicinsko pomočjo – ZZNPOB, Official Gazette of RS, No. 70/00 w/amendments.

Judgment of Administrative Court of RS, Reg. No. I U 1669/2013 of April 15th, 2014,, last accessed, September 21st, 2020.

Judgment of Administrative Court of RS, Reg. No. I U 877/2015 of September 29th, 2015,, last accessed, September 21st, 2020.

Medical Practitioners Act/Zakon o zdravniški službi – ZZdrS, Official Gazette of RS, No. 72/06 w/amendments.

Patients’ Rights Act/Zakon o pacientovih pravicah - ZPacP, Official Gazette of RS, No. 15/08 w/amendments.

Rules of the Slovenian Medical Chamber Tribunal/Pravilnik o organizaciji in delu razsodišča Zdravniške zbornice Slovenije,, last accessed, September 21st, 2020.

Slovenian Code of Medical Deontology/Kodeks medicinske deontologije Slovenije, 12.12.1992, w/amendments,, last accessed September 21st, 2020.

The Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (ETS No. 164),, last accessed September 21st, 2020.

How to Cite
Vrtačnik Bokal E., & Vrtačnik U. (2020). Impact of Multiple Sclerosis on Infertility and Impact of Infertility Treatments on Multiple Sclerosis Relapses in Slovenia: Medical Outline, Legal and Ethical Outcomes. Medicine, Law & Society, 13(2), 153-172.