Assisted reproductive technologies in multiple sclerosis

Literature review

Authors

DOI:

https://doi.org/10.18370/2309-4117.2024.72.60-70

Keywords:

assisted reproductive technologies, multiple sclerosis, fertility, pregnancy, disease-modifying therapy, in vitro fertilization, oocyte cryopreservation

Abstract

Objective of the review: to study the topic of fertility, pregnancy and assisted reproductive technologies (ART) in patients with multiple sclerosis (MS). The analysis of scientific literature in international medical databases was performed.
Analysis of literary data. MS is a chronic inflammatory demyelinating disease of the central nervous system that most often affects young people of reproductive age. Research in this area is important given that the average age of MS diagnosis in Ukraine is approximately 31–34 years. As a result, patients are in the process of making important decisions about their future lifestyle and family planning.
According to the data of modern research, MS does not affect the course of pregnancy and is not associated with obstetric pathologies. However, patients are often forced to postpone their desire to become pregnant due to the risks of taking drugs for disease-modifying therapy (DMT), the need to stabilize the disease along with reducing its radiological activity. It is also important to consider the presence of sexual dysfunction in patients with MS, particularly in men, which often negatively affects male fertility and requires timely diagnosis and treatment. For example, in case of ejaculation disorders, a testicular biopsy or electroejaculation can be used to collect seminal fluid.
The algorithm of proper counseling before conception for both partners was analyzed. It is important to use a multidisciplinary approach for joint decision-making of the patient with both a neurologist and a gynecologist, which allows for the formation of the most reasonable conclusions regarding pregnancy planning. In particular, the elimination periods of the main DMT drugs are discussed and drugs that can be used during pregnancy are specified.
Conclusions. Women with MS are more likely to need AR than the general population. This is associated with a later age of pregnancy planning and infertility. In this regard, the method of in vitro fertilization and cryopreservation of oocytes as the most effective types of ART for patients with MS was considered in detail.

Author Biographies

O.D. Shulga, Volyn National Lesya Ukrainka Universit; CE “Volyn Regional Clinical Hospital”, Lutsk, Ukraine

MD, associate professor of the Department Internal and Family Medicine;
head of the Neurology Department

M.I. Hrytsko, Danylo Halytsky Lviv National Medical University; Medical Center “Mother and Child”, Lviv

PhD, associate professor, Department of Obstetrics, Gynecology and Perinatology, FPGE;
head of the IVF Department

A.S. Romaniuk, CE “Volyn Regional Clinical Hospital”, Lutsk

intern, Neurology Department

O.G. Kotsiuba, CE “Volyn Regional Clinical Hospital”, Lutsk

intern, Neurology Department

References

  1. The Multiple Sclerosis International Federation, Atlas of MS, 3rd Edition [Internet]. 2020 Sept. Available from: https://www.msif.org/wp-content/uploads/2020/12/Atlas-3rd-Edition-Epidemiology-report-EN-updated-30-9-20.pdf
  2. Zeydan B, Atkinson EJ, Weis DM, et al. Reproductive history and progressive multiple sclerosis risk in women. Brain Commun. 2020 Nov 17;2(2):fcaa185. DOI:10.1093/braincomms/fcaa185
  3. Voskuhl RR, Sawalha AH, Itoh Y. Sex chromosome contributions to sex differences in multiple sclerosis susceptibility and progression. Mult Scler. 2018 Jan;24(1):22–31. DOI:10.1177/1352458517737394
  4. Roux T, Courtillot C, Debs R, et al. Fecundity in women with multiple sclerosis: an observational mono-centric study. J Neurol. 2015;262(4):957–960. DOI:10.1007/s00415-015-7663-1
  5. Sepúlveda M, Ros C, Martínez-Lapiscina EH, et al. Pituitary-ovary axis and ovarian reserve in fertile women with multiple sclerosis: A pilot study. Mult Scler. 2016 Apr;22(4):564–568. DOI:10.1177/1352458515602339
  6. Smith AL, Cohen JA, Ontaneda D, Rensel M. Pregnancy and multiple sclerosis: Risk of unplanned pregnancy and drug exposure in utero. Mult Scler J Exp Transl Clin. 2019;5(4):2055217319891744. DOI:10.1177/2055217319891744
  7. Sadeghpour N, Mirmosayyeb O, Bjørklund G, Shaygannejad V. Is Fertility Affected in Women of Childbearing Age with Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder?. J Mol Neurosci. 2020;70(11):1829–1835. DOI:10.1007/s12031-020-01576-x
  8. Delaney KE, Donovan J. Multiple sclerosis and sexual dysfunction: A need for further education and interdisciplinary care. NeuroRehabilitation. 2017;41(2):317–329. DOI:10.3233/NRE-172200
  9. Drulovic J, Kisic-Tepavcevic D, Pekmezovic T. Epidemiology, diagnosis and management of sexual dysfunction in multiple sclerosis. Acta Neurol Belg 2020; 120(4):791–797. DOI:10.1007/s13760-020-01323-4
  10. Pintér A, Cseh D, Sárközi A, et al. Autonomic Dysregulation in Multiple Sclerosis. Int J Mol Sci. 2015;16(8):16920–16952. DOI:10.3390/ijms160816920
  11. Balsamo R, Arcaniolo D, Stizzo M, et al. Increased risk of erectile dysfunction in men with multiple sclerosis: an Italian cross-sectional study. Cent European J Urol. 2017;70(3):289–295. DOI:10.5173/ceju.2017.1380
  12. Mikkelsen AP, Egerup P, Kolte AM, et al. Pregnancy loss and risk of multiple sclerosis and autoimmune neurological disorder: A nationwide cohort study. PLoS One. 2022;17(3):e0266203. DOI:10.1371/journal.pone.0266203
  13. Pozzilli C, Pugliatti M. An overview of pregnancy-related issues in patients with multiple sclerosis. Eur J Neurol. 2015;22(S2):34–9. DOI:10.1111/ene.12797
  14. Coyle PK. Management of women with multiple sclerosis through pregnancy and after childbirth. Ther Adv Neurol Disord. 2016;9(3):198–210. DOI:10.1177/1756285616631897
  15. Andersen ML, Jølving LR, Stenager E, et al. Maternal Multiple Sclerosis and Health Outcomes Among the Children: A Systematic Review. Clin Epidemiol. 2023 Mar 19;15:375–389. DOI:10.2147/CLEP.S392273
  16. Yeh WZ, Widyastuti PA, Van der Walt A, et al. Natalizumab, fingolimod and dimethyl fumarate use and pregnancy-related relapse and disability in women with multiple sclerosis. Neurology 2021 Jun 15;96(24):e2989–e3002. DOI:10.1212/WNL.0000000000012084
  17. Ghafoori F, Dehghan-Nayeri N, Khakbazan Z, et al. Pregnancy and Motherhood Concerns Surrounding Women with Multiple Sclerosis: A Qualitative Content Analysis. Int J Community Based Nurs Midwifery. 2020 Jan;8(1):2–11. DOI:10.30476/IJCBNM.2019.73900.0
  18. Moberg JY, Laursen B, Thygesen LC, Magyari M. Reproductive history of the Danish multiple sclerosis population: A register-based study. Mult Scler. 2020 Jul;26(8):902–911. DOI:10.1177/1352458519851245
  19. Hellwig K, Correale J. Artificial reproductive techniques in multiple sclerosis. Clin Immunol. 2013 Nov;149(2):219–224. DOI:10.1016/j.clim.2013.02.001
  20. Topcu G, Griffiths H, Bale C, et al. Psychosocial adjustment to multiple sclerosis diagnosis: A meta-review of systematic reviews. Clin Psychol Rev. 2020 Dec;82:101923. DOI:10.1016/j.cpr.2020.101923
  21. Wilski M, Gabryelski J, Brola W, Tomasz T. Health-related quality of life in multiple sclerosis: Links to acceptance, coping strategies and disease severity. Disabil Health J. 2019 Oct;12(4):608–614. DOI:10.1016/j.dhjo.2019.06.003
  22. Oreja-Guevara C, Rabanal A, Rodríguez CH, et al. Assisted Reproductive Techniques in Multiple Sclerosis: Recommendations from an Expert Panel. Neurol Ther. 2023 Apr;12(2):427-439. DOI:10.1007/s40120-023-00439-y
  23. Yureneva S, Averkova V, Silachev D, et al. Searching for female reproductive aging and longevity biomarkers. Aging (Albany NY). 2021 Jun 22;13(12):16873–16894. DOI:10.18632/aging.203206
  24. Doosti R, Togha M, Naser Moghadasi A, et al. Evaluation of the risk of cervical cancer in patients with multiple sclerosis treated with cytotoxic agents: a cohort study. Curr J Neurol. 2018;17(2):64–70.
  25. Rauma I, Mustonen T, Seppä JM, et al. Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients. J Neurol. 2022;269(2):824–835. DOI:10.1007/s00415-021-10664-w
  26. Carlson AK, Ontaneda D, Rensel MR, et al. Reproductive issues and multiple sclerosis: 20 questions. Cleve Clin J Med. 2023;90(4):235–243. DOI:10.3949/ccjm.90a.22066
  27. Cleveland Clinic Mellen Center for Multiple Sclerosis. Mellen Center approach: management of multiple sclerosis during pregnancy. [Internet].October 14, 2021. [Accessed March 24, 2024]. Available from: https://my.clevelandclinic.org/-/scassets/files/org/neurological/mellen-center/management-of-multiple-sclerosis-during-pregnancy.pdf?la=en.
  28. Krysko KM, Bove R, Dobson R, et al. Treatment of Women with Multiple Sclerosis Planning Pregnancy. Curr Treat Options Neurol. 2021;23(4):11. DOI:10.1007/s11940-021-00666-4
  29. Biogen, Inc. Avonex (interferon beta-1a) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. avonex.com/content/dam/commercial/avonex/pat/en_us/pdf/Avonex_US_Prescribing_Information.pdf.
  30. Novartis Pharmaceuticals Corp. Extavia (interferon-1b) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. novartis.com/us-en/sites/novartis_us/files/extavia.pdf.
  31. Teva Neuroscience, Inc. Copaxone (glatiramer acetate) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. copaxone.com/globalassets/copaxone/prescribing-information.pdf.
  32. Biogen, Inc. Tecfidera (dimethyl fumarate) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. tecfidera.com/content/dam/commercial/tecfidera/pat/en_us/pdf/full-prescribing-info.pdf.
  33. Biogen, Inc. Vumerity (diroximel fumarate) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. vumerity.com/content/dam/commercial/vumerity/pat/en_us/pdf/vumerity-prescribing-information.pdf.
  34. Banner Life Sciences, LLC. Bafiertam (monomethyl fumarate) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. bafiertam.com/pdf/bafiertam-prescribing-information.pdf.
  35. Novartis Pharmaceuticals Corp. Gilenya (fingolimod) package insert [Internet]. [Accessed March 24, 2024]. Available from: https://www.novartis.com/us-en/sites/novartis_us/files/gilenya.pdf.
  36. Novartis Pharmaceuticals Corp. Mayzent (siponimod) package insert. [Internet]. [Accessed March 24, 2024]. Available from:https://www.novartis.com/us-en/sites/novartis_us/files/mayzent.pdf.
  37. Bristol Meyers Squibb. Zeposia (ozanimod) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. accessdata.fda.gov/drugsatfda_docs/label/2020/209899s000lbl.pdf
  38. Janssen Pharmaceuticals, Inc. Ponvory (ponesimod) package insert. [Internet]. Available from: https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/PONVORY-pi.pdf. [Accessed March 24, 2024].
  39. EMD Serono, Inc. Mavenclad (Cladribine) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. emdserono.com/us-en/pi/mavenclad-pi.pdf.
  40. Genzyme Corp. Aubagio (teriflunomide) package insert.[Internet]. [Accessed March 24, 2024]. Available from: https://products. sanofi.us/aubagio/aubagio.pdf.
  41. Biogen, Inc. Tysabri (natalizumab) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www.tysabri.com/content/dam/commercial/tysabri/pat/en_us/pdf/tysabri_prescribing_information.pdf.
  42. F. Hoffmann-La Roche AG, Local ocrelizumab instruction. [Internet]. [Applicable since Jan 2023]. Available from: http://www. drlz.com.ua/ibp/lz_www.nsf/id/1ECFC42042D462E3422589DD003C2 A19/$file/UA162780101_00B5.mht.
  43. Novartis Pharmaceuticals Corp. Kesimpta (ofatumumab) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. novartis.com/us-en/sites/novartis_us/files/kesimpta.pdf.
  44. Genentech, Inc. Rituxan (rituximab) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. gene.com/download/pdf/rituxan_prescribing.pdf.
  45. TG Therapeutics. Briumvi (ublituximab-xiiy) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://www. tgtherapeutics.com/label-prescribing-info/uspi-briumvi.pdf.
  46. Genzyme Corp. Lemtrada (alemtuzumab) package insert. [Internet]. [Accessed March 24, 2024]. Available from: https://products. sanofi.us/lemtrada/lemtrada.pdf.
  47. Galati A, McElrath T, Bove R. Use of B-Cell-Depleting Therapy in Women of Childbearing Potential With Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder. Neurol Clin Pract. 2022;12(2):154–163. DOI:10.1212/CPJ.0000000000001147.
  48. García-Merino A. Bruton’s Tyrosine Kinase Inhibitors: A New Generation of Promising Agents for Multiple Sclerosis Therapy. Cells. 2021 Sep 27;10(10):2560. DOI:10.3390/cells10102560.
  49. SWP/NcWP recommendations on the duration of contraception following the end of treatment with a genotoxic drug (Document ID: CHMP/SWP/74077/2020 rev. 1). [Internet]. European Medicines Agency. 2020. Available from: https://www.ema.europa.eu/en/documents/other/safety-working-party-swp-non-clinical-working-party-ncwp-recommendations-duration-contraception-following-end-treatment-genotoxic-drug_en.pdf
  50. Infertility prevalence estimates, 1990–2021. [Internet]. World Health Organization. 2023. [Accessed March 24, 2024. Available from: https://www.who.int/publications-detail-redirect/978920068315.
  51. Houtchens MK, Edwards NC, Hayward B, et al. Live birth rates, infertility diagnosis, and infertility treatment in women with and without multiple sclerosis: Data from an administrative claims database. Mult Scler Relat Disord. 2020;46:102541. DOI:10.1016/j.msard.2020.102541
  52. Szeliga A, Calik-Ksepka A, Maciejewska-Jeske M, et al. Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge. Int J Mol Sci. 2021;22(5):2594. DOI:10.3390/ijms22052594.
  53. Pinborg A. Short- and long-term outcomes in children born after assisted reproductive technology. BJOG. 2019;126(2):145-148. DOI:10.1111/1471-0528.15437.
  54. Jain M. Assisted Reproductive Technology (ART) techniques. StatPearls [Internet]. June 7, 2023. [Accessed March 24, 2024]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK576409/.
  55. Yeh WZ, Widyastuti PA, Van der Walt A, et al. Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis. Neurology. 2021 Jun 15;96(24):e2989-e3002. DOI:10.1212/WNL.0000000000012084.
  56. Bove R, Rankin K, Lin C, et al. Effect of assisted reproductive technology on multiple sclerosis relapses: Case series and meta-analysis. Mult Scler. 2020;26(11):1410–1419. DOI:10.1177/1352458519865118
  57. Mainguy M, Tillaut H, Degremont A, et al. Assessing the Risk of Relapse Requiring Corticosteroids After In Vitro Fertilization in Women With Multiple Sclerosis. Neurology. 2022 Oct 24;99(17):e1916-e1925. DOI:10.1212/WNL.0000000000201027.
  58. Kopp TI, Pinborg A, Glazer CH, Magyari M. Assisted reproductive technology treatment and risk of multiple sclerosis – a Danish cohort study. Fertil Steril. 2023;119(2):291-299. DOI:10.1016/j.fertnstert.2022.10.027.
  59. Gorgui J, Bérard A. Medically assisted reproduction and the risk of adverse perinatal outcomes. [Internet]. IntechOpen. November 5, 2018. [Accessed March 24, 2024]. Available from: https://www.intechopen.com/chapters/63784.
  60. Bahadur G, Homburg R, Bosmans JE, et al. Observational retrospective study of UK national success, risks and costs for 319,105 IVF/ICSI and 30,669 IUI treatment cycles. BMJ Open. 2020 Mar 16;10(3):e034566. doi:10.1136/bmjopen-2019-034566.
  61. Wu Y, Liu H, Liu J. The Livebirth Rate Per In Vitro Fertilization Cycle Is Higher Than The Cumulative Live Birth Rates of Intrauterine Insemination for Patients of Poseidon Group 3 With Unexplained Infertility. Front Endocrinol (Lausanne). 2021 Dec 1;12:768975. DOI:10.3389/fendo.2021.768975.
  62. ESHRE Clinic PI Working Group, Vlaisavljevic V, Apter S, et al. The Maribor consensus: report of an expert meeting on the development of performance indicators for clinical practice in ART. Hum Reprod Open. 2021 Jul 3;2021(3):hoab022. DOI:10.1093/hropen/hoab022
  63. Reimundo P, Romero JM G, Pérez TR, Veiga E. Single-embryo transfer: a key strategy to reduce the risk for multiple pregnancy in assisted human reproduction. Adv Lab Med. 2021 Apr;2(2):179-198. DOI:10.1515/almed-2021-0013
  64. Dodd JM, Grivell RM, OBrien CM, et al. Prenatal administration of progestogens for preventing spontaneous preterm birth in women with a multiple pregnancy. Cochrane Database Syst Rev. 2019;2019(11):CD012024. DOI:10.1002/14651858.CD012024.pub3
  65. Oseguera-López I, Ruiz-Díaz S, Ramos-Ibeas P, Pérez-Cerezales S. Novel Techniques of Sperm Selection for Improving IVF and ICSI Outcomes. Front Cell Dev Biol. 2019 Nov 29;7:298. OI:10.3389/fcell.2019.00298
  66. De Geyter C, Calhaz-Jorge C, Kupka MS, et al. ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod. 2018 Sep 1;33(9):1586–1601. DOI:10.1093/humrep/dey242
  67. Kamath MS, Mascarenhas M, Kirubakaran R, Bhattacharya S. Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection. Cochrane Database Syst Rev. 2020 Aug 21;8(8):CD003416. DOI:10.1002/14651858.CD003416.pub5.
  68. Jungheim ES, Meyer MF, Broughton DE. Best practices for controlled ovarian stimulation in in vitro fertilization. Semin Reprod Med. 2015;33(2):77-82. DOI:10.1055/s-0035-1546424
  69. Wang R, Lin S, Wang Y, Qian W, Zhou L. Comparisons of GnRH antagonist protocol versus GnRH agonist long protocol in patients with normal ovarian reserve: A systematic review and meta-analysis. PLoS One. 2017;12(4):e0175985. DOI:10.1371/journal.pone.0175985
  70. Jahromi BN, Parsanezhad ME, Shomali Z, et al. Ovarian Hyperstimulation Syndrome: A Narrative Review of Its Pathophysiology, Risk Factors, Prevention, Classification, and Management. Iran J Med Sci. 2018 May;43(3):248–260.
  71. National Institute for Health and Care Excellence (NICE). [Internet]. Fertility problems: assessment and treatment. 2017. [Accessed March 24, 2024]. Available from: https://www.nice.org.uk/guidance/cg156.
  72. Esteves SC, Roque M, Bedoschi GM, et al. Defining Low Prognosis Patients Undergoing Assisted Reproductive Technology: POSEIDON Criteria-The Why. Front Endocrinol (Lausanne). 2018;9:461. DOI:10.3389/fendo.2018.00461
  73. Wong KM, Mastenbroek S, Repping S. Cryopreservation of human embryos and its contribution to in vitro fertilization success rates. Fertil Steril. 2014;102(1):19–26. DOI:10.1016/j.fertnstert.2014.05.027
  74. Thöne J, Thiel S, Gold R, Hellwig K. Treatment of multiple sclerosis during pregnancy – safety considerations. Expert Opin Drug Saf. 2017;16(5):523–534. DOI:10.1080/14740338.2017.131132175.
  75. Meng X, Fan L, Wang T, et al. Electroejaculation combined with assisted reproductive technology in psychogenic anejaculation patients refractory to penile vibratory stimulation. Transl Androl Urol. 2018;7(Suppl 1):S17–S22. DOI:10.21037/tau.2018.01.15
  76. Electroejaculation: Purpose, procedure & results. [Internet]. Cleveland Clinic. Accessed March 24, 2024. Available from: https://my.clevelandclinic.org/health/treatments/23997-electroejaculation.
  77. Mesen TB, Mersereau JE, Kane JB, Steiner AZ. Optimal timing for elective egg freezing. Fertil Steril. 2015;103(6):1551–6.e64. DOI:10.1016/j.fertnstert.2015.03.002
  78. Doyle JO, Richter KS, Lim J, et al. Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval. Fertil Steril. 2016 Feb;105(2):459–66.e2.DOI:10.1016/j.fertnstert.2015.10.026

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2024-06-30

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Shulga, O., Hrytsko, M., Romaniuk, A., & Kotsiuba, O. (2024). Assisted reproductive technologies in multiple sclerosis: Literature review. REPRODUCTIVE ENDOCRINOLOGY, (72), 60–70. https://doi.org/10.18370/2309-4117.2024.72.60-70

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No. 72 (2024)

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Interdisciplinary problems

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