DOI: https://doi.org/10.18370/2309-4117.2019.50.56-64

Reproductive health and pregnancy problems of systemic lupus erythematosus

И. Ю. Головач, Е. Д. Егудина

Abstract


Nowadays, the majority of young women with systemic lupus erythematosus (SLE) can successfully become pregnant, carry pregnancy to term and give birth to a healthy child due to improved therapeutic approaches and consequently reduction in morbidity and mortality. Pregnancy outcomes in these women have also improved significantly over the past decades. Correct timing of conception (taking into account disease activity and target organ damage), careful monitoring of patients for three trimesters and the postpartum period (to timely identify and treat possible obstetric complications or maternal disease flares), as well as the concept of multidisciplinary management, are currently the main points of SLE patients of reproductive age. Growing knowledge about the compatibility of drugs with pregnancy has improved treatment approaches for these patients, which allows controlling maternal disease without harming the fetus.

Particular attention and strict monitoring should be dedicated to SLE pregnant women in particular clinical settings: patients with lupus nephritis, patients with a positive titer of antiphospholipid antibodies, antiphospholipid syndrome, and patients with Ro/SSA and/or La/SSB antibodies. Family planning discussions and contraceptive counseling should be part of everyday practice for doctors who observe women with SLE at reproductive age. Another problem is the possible decrease in fertility in these women, which may be due to different reasons. As a result, in recent years, the demand for assisted reproduction methods has increased, so rheumatologists and gynecologists should be ready to advise patients with SLE in this situation. This literature review is based on the evidence-based recommendations on family planning management and women's health issues in SLE and/or antiphospholipid syndrome developed by a multidisciplinary group of experts of the European League Against Rheumatism in 2017.


Keywords


systemic lupus erythematosus; pregnancy; contraception; lupus nephritis; antiphospholipid antibodies

References


Lazzaroni, M.G., Dall’Ara, F., Fredi, M., et al. “A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus.” J Autoimmun 74 (2016): 106–17. DOI: 10.1016/j.jaut.2016.06.016

Andreoli, L., Bertsias, G.K., Agmon-Levin, N., et al. “EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.” Ann Rheum Dis 76 (2017): 476–85. DOI: 10.1136/annrheumdis-2016-209770

Gotestam Skorpen, C., Hoeltzenbein, M., Tincani, A., et al. “The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation.” Ann Rheum Dis 75 (2016): 795–810. DOI: 10.1136/annrheumdis-2015-208840

Knight, C.L., Nelson-Piercy, C. “Management of systemic lupus erythematosus during pregnancy: challenges and solutions.” Open Access Rheumatol 9 (2017): 37–53. DOI: 10.2147/OARRR.S87828

Bundhun, P.K., Soogund, M.Z., Huang, F. “Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: a meta-analysis of studies published between years 2001–2016.” J Autoimmun 79 (2017): 17–27. DOI: 10.1016/j.jaut.2017.02.009

Arkema, E.V., Palmsten, K., Sjowall, C., et al. “What to expect when expecting with systemic lupus erythematosus (SLE): a population-based study of maternal and fetal outcomes in SLE and pre-SLE.” Arthritis Care Res (Hoboken) 68 (2016): 988–94. DOI: 10.1002/acr.22791

Bellver, J., Pellicer, A. “Ovarian stimulation for ovulation induction and in vitro fertilization in patients with systemic lupus erythematosus and antiphospholipid syndrome.” Fertil Steril 92.6 (2009): 1803–10. DOI: 10.1016/j.fertnstert.2009.06.033

Clowse, M.E., Chakravarty, E., Costenbader, K.H., et al. “Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus.” Arthritis Care Res (Hoboken) 64 (2012): 668–74. DOI: 10.1002/acr.21593

Gasparin, A.A., Souza, L., Siebert, M., et al. “Assessment of anti-M€ullerian hormone levels in premenopausal patients with systemic lupus erythematosus.” Lupus 25 (2016): 227–32. DOI: 10.1177/0961203315598246

Ateka-Barrutia, O., Nelson-Piercy, C. “Management of rheumatologic diseases in pregnancy.” International Journal of Clinical Rheumatology 7.5 (2012): 541–58.

Ateka-Barrutia, O., Nelson-Piercy, C. “Connective tissue disease in pregnancy.” Clin Med 13.6 (2013): 580–84.

Buyon, J.P., Kim, M.Y., Salmon, J.E. “Predictors of pregnancy outcomes in patients with lupus.” Ann Intern Med 164 (2016): 131. DOI: 10.7326/M14-2235

Zuppa, A.A., Riccardi, R., Frezza, S., et al. “Neonatal lupus: follow-up in infants with anti-SSA/

Ro antibodies and review of the literature.” Autoimmun Rev 16 (2017): 427–32.

Khanyukov, A.A., Yehudina, E.D., Kalashnikova, O.S., Sapozhnichenko, L.V. “Maintaining patients with systemic lupus erythematosus during the pregestational and antenatal periods: problems and their solutions.” Georgian Medical Journal 7.8 (280.281) (2018): 54–61.

Smiyan, S.I., Kuzmina, A.P. “Pregnancy: short-term effects and long-term aftermaths in rheumatic diseases – general issues (first report).” Ukrainian Rheumatologist Journal 54.4 (2013): 25–33.

Ostensen, M., Cetin, I. “Autoimmune connective tissue diseases.” Best Pract Res Clin Obstet Gynaecol 29.5 (2015): 658–70. DOI: 10.1016/j. bpobgyn.2015.03.003

Bortkevych, O.P., Biliavska, Y.Y., Korendovych, V.V. “Updated approaches to treatment of rheumatic diseases in women during pregnancy and lactation.” Ukrainian Rheumatologist Journal 64.2 (2016): 25–33.

Clark, C.A., Spitzer, K.A., Laskin, C.A. “Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period.” J Rheumatol 32 (2005): 1709–12.

Vinet, E., Genest, G., Scott, S., et al. “Brief report: causes of stillbirths in women with systemic lupus erythematosus.” Arthritis Rheumatol 68 (2016): 2487–91. DOI: 10.1002/art.39742

Bundhun, P.K., Soogund, M.Z., Huang, F. “Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: a meta-analysis of studies published between years 2001–2016.” J Autoimmun 79 (2017): 17–27. DOI: 10.1016/j.jaut.2017.02.009

Simard, J.F., Arkema, E.V., Nguyen, C., et al. “Early-onset preeclampsia in lupus pregnancy.” Paediatr Perinat Epidemiol 31 (2017): 29–36. DOI: 10.1111/ppe.12332

Moroni, G., Doria, A., Giglio, E., et al. “Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study.” J Autoimmun 74 (2016): 6–12. DOI: 10.1016/j.jaut.2016.07.010

Bramham, K., Soh, M.C., Nelson-Piercy, C. “Pregnancy and renal outcomes in lupus nephritis: an update and guide to management.” Lupus 21 (2012): 1271–128. DOI: 10.1177/0961203312456893

Tedeschi, S.K., Guan, H., Fine, A., et al. “Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.” Clin Rheumatol 35 (2016): 1725–32. DOI: 10.1007/s10067-016-3270-5

Ruiz-Irastorza, G., Khamashta, M. “Lupus and pregnancy: integrating clues from the bench and bedside.” Eur J Clin Invest 41.6 (2011): 672–8. DOI: 10.1111/j.1365-2362.2010.02443.x

Tingstrom, J., Hjelmstedt, A., Welin Henriksson, E., et al. “Anti-Ro/SSA autoantibody-positive women’s experience of information given on the risk of congenital heart block.” Lupus 25 (2016): 536–42. DOI: 10.1177%2F0961203315620760

Koh, J.H., Ko, H.S., Kwok, S.K., et al. “Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus.” Lupus 24 (2015): 210–17. DOI: 10.1177/0961203314555352

Sciascia, S., Branch, D.W., Levy, R.A., et al. “The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies. Evidence and clinical judgment.” Thromb Haemost 115 (2016): 285–90. DOI: 10.1160/TH15-06-0491

Schramm, A.M., Clowse, M.E. “Aspirin for prevention of preeclampsia in lupus pregnancy.” Autoimmune Dis 2014 (2014): 920467. DOI: 10.1155/2014/920467

Mak, A., Cheung, M.W., Cheak, A.A., Ho, R.C. “Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive antiphospholipid antibodies: a meta- analysis of randomized controlled trials and meta-regression.” Rheumatology (Oxford) 49 (2010): 281–8. DOI: 10.1093/rheumatology/kep373

Hofmeyr, G., Lawrie, T., Atallah, A., et al. “Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.” Cochrane Database Syst Rev 6 (2014): CD001059.

DOI: 10.1002/14651858

Nelson-Piercy, C. Handbook of Obstetric Medicine. 5th ed. Florida, USA: CRC Press (2015).

Yazdany, J., Trupin, L., Kaiser, R., et al.

“Contraceptive counseling and use among women with systemic lupus erythematosus: a gap in healthcare quality?” Arthritis Care Res (Hoboken) 63 (2011): 358–65. DOI: 10.1002/acr.20402

Gensous, N., Doassans-Comby, L., Lazaro, E., Duffau, P. “Systemic lupus erythematosus and contraception: a systematic literature review.” Rev Med Interne 38.6 (2017): 358–67. DOI: 10.1016/j.revmed.2016.12.009

Faculty of Sexual and Reproductive Healthcare. UK Medical Eligibility Criteria (UKMEC) for contraceptive use. London: FSRH (2016).

Sammaritano, L.R. “Contraception in patients with systemic lupus erythematosus and antiphospholipid syndrome.” Lupus 23 (2014): 1242–5. DOI: 10.1177/0961203314528062

Levine, A.B., Lockshin, M.D. “Assisted reproductive technology in SLE and APS.” Lupus 23 (2014): 1239–41. DOI: 10.1177/0961203314527370

Henriksson, P., Westerlund, E., Wallen, H., et al. “Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilisation: cross sectional study.” BMJ 346 (2013): e8632. DOI: 10.1136/bmj.e8632

Bellver, J., Pellicer, A. “Ovarian stimulation for ovulation induction and in vitro fertilization in patients with systemic lupus erythematosus and antiphospholipid syndrome.” Fertil Steril 92.6 (2009): 1803–10. DOI: 10.1016/j.fertnstert.2009.06.033

Orquevaux, P., Masseau, A., Le Guern, V., et al. “In vitro fertilization in 37 women with systemic lupus erythematosus or antiphospholipid syndrome: a series of 97 procedures.” J Rheumatol 44.5 (2017): 613–8. DOI: 10.3899/jrheum.160462

Guballa, N., Sammaritano, L., Schwartzman, S., et al. “Ovulation induction and in vitro fertilization in systemic lupus erythematosus and antiphospholipid syndrome.” Arthritis Rheum 43 (2000): 550–6. DOI: 10.1002/1529-0131(200003)43:3<550::AID-ANR10>3.0.CO;2-Y

Huong, D.L., Wechsler, B., Vauthier-Brouzes, D., et al. “Importance of planning ovulation induction therapy in systemic lupus erythematosus and antiphospholipid syndrome: a single center retrospective study of 21 cases and 114 cycles.” Semin Arthritis Rheum 32 (2002): 174–88. DOI: 10.1053/sarh.2002.37212


GOST Style Citations


1.         Lazzaroni, M.G., Dall’Ara, F., Fredi, M., et al. “A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus.” J Autoimmun 74 (2016): 106–17. DOI: 10.1016/j.jaut.2016.06.016

2.         Andreoli, L., Bertsias, G.K., Agmon-Levin, N., et al. “EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.” Ann Rheum Dis 76 (2017): 476–85. DOI: 10.1136/annrheumdis-2016-209770

3.         Gotestam Skorpen, C., Hoeltzenbein, M., Tincani, A., et al. “The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation.” Ann Rheum Dis 75 (2016): 795–810. DOI: 10.1136/annrheumdis-2015-208840

4.         Knight, C.L., Nelson-Piercy, C. “Management of systemic lupus erythematosus during pregnancy: challenges and solutions.” Open Access Rheumatol 9 (2017): 37–53. DOI: 10.2147/OARRR.S87828

5.         Bundhun, P.K., Soogund, M.Z., Huang, F. “Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: a meta-analysis of studies published between years 2001–2016.” J Autoimmun 79 (2017): 17–27. DOI: 10.1016/j.jaut.2017.02.009

6.         Arkema, E.V., Palmsten, K., Sjowall, C., et al. “What to expect when expecting with systemic lupus erythematosus (SLE): a population-based study of maternal and fetal outcomes in SLE and pre-SLE.” Arthritis Care Res (Hoboken) 68 (2016): 988–94. DOI: 10.1002/acr.22791

7.         Bellver, J., Pellicer, A. “Ovarian stimulation for ovulation induction and in vitro fertilization in patients with systemic lupus erythematosus and antiphospholipid syndrome.” Fertil Steril 92.6 (2009): 1803–10. DOI: 10.1016/j.fertnstert.2009.06.033

8.         Clowse, M.E., Chakravarty, E., Costenbader, K.H., et al. “Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus.” Arthritis Care Res (Hoboken) 64 (2012): 668–74. DOI: 10.1002/acr.21593

9.         Gasparin, A.A., Souza, L., Siebert, M., et al. “Assessment of anti-M€ullerian hormone levels in premenopausal patients with systemic lupus erythematosus.” Lupus 25 (2016): 227–32. DOI: 10.1177/0961203315598246

10.       Ateka-Barrutia, O., Nelson-Piercy, C. “Management of rheumatologic diseases in pregnancy.” International Journal of Clinical Rheumatology 7.5 (2012): 541–58.

11.       Ateka-Barrutia, O., Nelson-Piercy, C. “Connective tissue disease in pregnancy.” Clin Med 13.6 (2013): 580–84.

12.       Buyon, J.P., Kim, M.Y., Salmon, J.E. “Predictors of pregnancy outcomes in patients with lupus.” Ann Intern Med 164 (2016): 131. DOI: 10.7326/M14-2235

13.       Zuppa, A.A., Riccardi, R., Frezza, S., et al. “Neonatal lupus: follow-up in infants with anti-SSA/

Ro antibodies and review of the literature.” Autoimmun Rev 16 (2017): 427–32.

14.       Ханюков, А.А. Ведение пациенток с системной красной волчанкой в прегестационный и антенатальный периоды: проблемы и их решения / А.А. Ханюков, Е.Д. Егудина,

О.С. Калашникова, Л.В. Сапожниченко // Грузинский медицинский журнал. – 2018. – № 7–8 (280–281). – С. 54–61.

15.       Сміян, С.І. Вагітність: короткострокові ефекти і довгострокові наслідки при ревматичних захворюваннях – загальні питання (перше повідомлення) / С.І. Сміян, А.П. Кузьміна // Український ревматологічний журнал. – 2013. – №54 (4). – C. 25–33.

16.       Ostensen, M., Cetin, I. “Autoimmune connective tissue diseases.” Best Pract Res Clin Obstet Gynaecol 29.5 (2015): 658–70. DOI: 10.1016/j. bpobgyn.2015.03.003

17.       Борткевич, О.П. Оновлені підходи до лікування ревматичних хвороб у жінок в період вагітності та лактації / О.П. Борткевич, Ю.В. Білявська, В.В. Корендович // Український ревматологічний журнал. – 2016. – №64 (2). – С. 25–33.

18.       Clark, C.A., Spitzer, K.A., Laskin, C.A. “Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period.” J Rheumatol 32 (2005): 1709–12.

19.       Vinet, E., Genest, G., Scott, S., et al. “Brief report: causes of stillbirths in women with systemic lupus erythematosus.” Arthritis Rheumatol 68 (2016): 2487–91. DOI: 10.1002/art.39742

20.       Bundhun, P.K., Soogund, M.Z., Huang, F. “Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: a meta-analysis of studies published between years 2001–2016.” J Autoimmun 79 (2017): 17–27. DOI: 10.1016/j.jaut.2017.02.009

21.       Simard, J.F., Arkema, E.V., Nguyen, C., et al. “Early-onset preeclampsia in lupus pregnancy.” Paediatr Perinat Epidemiol 31 (2017): 29–36. DOI: 10.1111/ppe.12332

22.       Moroni, G., Doria, A., Giglio, E., et al. “Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study.” J Autoimmun 74 (2016): 6–12. DOI: 10.1016/j.jaut.2016.07.010

23.       Bramham, K., Soh, M.C., Nelson-Piercy, C. “Pregnancy and renal outcomes in lupus nephritis: an update and guide to management.” Lupus 21 (2012): 1271–128. DOI: 10.1177/0961203312456893

24.       Tedeschi, S.K., Guan, H., Fine, A., et al. “Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.” Clin Rheumatol 35 (2016): 1725–32. DOI: 10.1007/s10067-016-3270-5

25.       Ruiz-Irastorza, G., Khamashta, M. “Lupus and pregnancy: integrating clues from the bench and bedside.” Eur J Clin Invest 41.6 (2011): 672–8. DOI: 10.1111/j.1365-2362.2010.02443.x

26.       Tingstrom, J., Hjelmstedt, A., Welin Henriksson, E., et al. “Anti-Ro/SSA autoantibody-positive women’s experience of information given on the risk of congenital heart block.” Lupus 25 (2016): 536–42. DOI: 10.1177%2F0961203315620760

27.       Koh, J.H., Ko, H.S., Kwok, S.K., et al. “Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus.” Lupus 24 (2015): 210–17. DOI: 10.1177/0961203314555352

28.       Sciascia, S., Branch, D.W., Levy, R.A., et al. “The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies. Evidence and clinical judgment.” Thromb Haemost 115 (2016): 285–90. DOI: 10.1160/TH15-06-0491

29.       Schramm, A.M., Clowse, M.E. “Aspirin for prevention of preeclampsia in lupus pregnancy.” Autoimmune Dis 2014 (2014): 920467. DOI: 10.1155/2014/920467

30.       Mak, A., Cheung, M.W., Cheak, A.A., Ho, R.C. “Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive antiphospholipid antibodies: a meta- analysis of randomized controlled trials and meta-regression.” Rheumatology (Oxford) 49 (2010): 281–8. DOI: 10.1093/rheumatology/kep373

31.       Hofmeyr, G., Lawrie, T., Atallah, A., et al. “Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.” Cochrane Database Syst Rev 6 (2014): CD001059.

DOI: 10.1002/14651858

32.       Nelson-Piercy, C. Handbook of Obstetric Medicine. 5th ed. Florida, USA: CRC Press (2015).

33.       Yazdany, J., Trupin, L., Kaiser, R., et al.

“Contraceptive counseling and use among women with systemic lupus erythematosus: a gap in healthcare quality?” Arthritis Care Res (Hoboken) 63 (2011): 358–65. DOI: 10.1002/acr.20402

34.       Gensous, N., Doassans-Comby, L., Lazaro, E., Duffau, P. “Systemic lupus erythematosus and contraception: a systematic literature review.” Rev Med Interne 38.6 (2017): 358–67. DOI: 10.1016/j.revmed.2016.12.009

35.       Faculty of Sexual and Reproductive Healthcare. UK Medical Eligibility Criteria (UKMEC) for contraceptive use. London: FSRH (2016).

36.       Sammaritano, L.R. “Contraception in patients with systemic lupus erythematosus and antiphospholipid syndrome.” Lupus 23 (2014): 1242–5. DOI: 10.1177/0961203314528062

37.       Levine, A.B., Lockshin, M.D. “Assisted reproductive technology in SLE and APS.” Lupus 23 (2014): 1239–41. DOI: 10.1177/0961203314527370

38.       Henriksson, P., Westerlund, E., Wallen, H., et al. “Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilisation: cross sectional study.” BMJ 346 (2013): e8632. DOI: 10.1136/bmj.e8632

39.       Bellver, J., Pellicer, A. “Ovarian stimulation for ovulation induction and in vitro fertilization in patients with systemic lupus erythematosus and antiphospholipid syndrome.” Fertil Steril 92.6 (2009): 1803–10. DOI: 10.1016/j.fertnstert.2009.06.033

40.       Orquevaux, P., Masseau, A., Le Guern, V., et al. “In vitro fertilization in 37 women with systemic lupus erythematosus or antiphospholipid syndrome: a series of 97 procedures.” J Rheumatol 44.5 (2017): 613–8. DOI: 10.3899/jrheum.160462

41.       Guballa, N., Sammaritano, L., Schwartzman, S., et al. “Ovulation induction and in vitro fertilization in systemic lupus erythematosus and antiphospholipid syndrome.” Arthritis Rheum 43 (2000): 550–6. DOI: 10.1002/1529-0131(200003)43:3<550::AID-ANR10>3.0.CO;2-Y

42.       Huong, D.L., Wechsler, B., Vauthier-Brouzes, D., et al. “Importance of planning ovulation induction therapy in systemic lupus erythematosus and antiphospholipid syndrome: a single center retrospective study of 21 cases and 114 cycles.” Semin Arthritis Rheum 32 (2002): 174–88. DOI: 10.1053/sarh.2002.37212





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