Evaluation of the Ovarian Reserve in Women With Systemic Lupus Erythematosus
-
Felipe Arturo Morales-Martínez
,
Celina Salas-Castro
,
Manuel Rolando García-Garza
,
Otto Valdés-Martínez
,
Selene Marysol García-Luna
,
Mario Garza-Elizondo
,
Oscar Vidal-Gutiérrez
,
Donato Saldívar-Rodríguez
,
Luis Humberto Sordia-Hernández
Abstract
Objective: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder where the disease activity itself and the medications used for its treatment, may have adverse effects on ovarian function. This study aimed to assess the ovarian reserve (OR) in SLE patients.
Materials and methods: The anti-müllerian hormone (AMH) and the antral follicle count (AFC), two markers to evaluate the OR was assessed in 64 SLE patients and compared to normal individuals. Additionally, we assessed whether the disease per se or the pharmacological treatments affect the OR.
Results: Patients with SLE displayed alterations in the OR regardless of the presence of alterations of the menstrual cycle. The AFC and AMH were significantly lower in SLE patients with and without menstrual alterations when compared to control individuals (p<0.0001). However, the AFC and AMH levels were significantly correlated (p=0.006) in the SLE patients with menstrual alterations. Except for hydroxychloroquine that was statistically higher in SLE patients with menstrual alterations (p=0.04), the cumulative dose for cyclophosphamide, corticosteroid, and methotrexate was similar in SLE patients regardless of the occurrence of menstrual alterations.
Conclusion: The monitoring of AMH and AFC in SLE patients should be used to detect the rapid and irreversible decline of the OR to provide a possibility of pregnancy to the SLE patients.
1. Justiz Vaillant AA, Goyal A, Bansal P, Varacallo M. Systemic Lupus Erythematosus. 2020. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.
2. Ugarte-Gil MF, González LA, Alarcón GS. Lupus: the new epidemic. Lupus. 2019; 28: 1031–50.
3. Weckerle CE, Niewold TB. The unexplained female predominance of systemic lupus erythematosus: Clues from genetic and cytokine studies. Clin Rev Allergy Immunol. 2011; 40: 42–9.
4. Fischer-Betz R, Specker C. Pregnancy in systemic lupus erythematosus and antiphospholipid syndrome. Best Pract Res Clin Rheumatol 2017; 31: 397-414.
5. Kartoz CR. Reproductive Health Concerns in Women with Systemic Lupus Erythematosus. MCN Am
J Matern Child Nurs 2015; 40: 220–6.
6. Chambers C, Michaud K. Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res (Hoboken) 2012; 64: 668–74.
7. Ekblom-Kullberg S, Kautiainen H, Alha P, Helve T, Leirisalo-Repo M, Julkunen H. Reproductive Health in Women With Systemic Lupus Erythematosus Compared to Population Controls. Scand J Rheumatol 2009; 38: 375–80.
8. Baird DT, Collins J, Egozcue J, Evers LH, Gianaroli L, Leridon H, et al. Fertility and ageing. Hum Reprod Update 2005; 11: 261–76.
9. Crawford NM, Steiner AZ. Age-related infertility. Obstet Gynecol Clin North Am 2015; 42: 15–25.
10. Jirge PR. Poor ovarian reserve. J Hum Reprod Sci 2016; 9: 63–9.
11. Gonzalez-Crespo MR, Gomez-Reino JJ, Merino R, Ciruelo E, Gomez-Reino FJ, Muley R, et al. Menstrual Disorders in Girls With Systemic Lupus Erythematosus Treated With Cyclophosphamide. Br J Rheumatol 1995; 34: 737–41.
12. Mandal D, Sircar G, Pandey A, Mandal S, Banerjee D, Ghosh A, et al. Menstrual and gonadal function alterations in women with systemic lupus erythematosus. J Assoc Physicians India 2015; 63: 38–42.
13. Appenzeller S, Blatyta PF, Costallat LT. Ovarian Failure in SLE Patients Using Pulse Cyclophosphamide: Comparison of Different Regimes. Rheumatol Int 2008; 28: 567–71.
14. Ulug P, Oner G, Kasap B, Akbas EM, Ozcicek F. Evaluation of Ovarian Reserve Tests in Women with Systemic Lupus Erythematosus. Am J Reprod Immunol 2014; 72: 85–8.
15. Hickman RA, Gordon C. Causes and management of infertility in systemic lupus erythematosus. Rheumatology (Oxford) 2011; 50: 1551–8.
16. Wetzels JF. Cyclophosphamide-induced gonadal toxicity: A treatment dilemma in patients with lupus nephritis? Neth J Med 2004; 62: 347–52.
17. Bermas BL, Sammaritano LR. Fertility and pregnancy in rheumatoid arthritis and systemic lupus erythematosus. Fertil Res Pract 2015; 1: 13.
18. Oktem O, Guzel Y, Aksoy S, Aydin E, Urman B. Ovarian function and reproductive outcomes of female patients with systemic lupus erythematosus and the strategies to preserve their fertility. Obstet Gynecol Surv 2015; 70: 196–210.
19. Petri M. Pregnancy and Systemic Lupus Erythematosus. Best Pract Res Clin Obstet Gynaecol 2020; 64: 24–30.
20. Boumpas DT, Austin HA, Vaughan EM, Yarboro CH, Klippel JH, Balow JE. Risk for Sustained Amenorrhea in Patients With Systemic Lupus Erythematosus Receiving Intermittent Pulse Cyclophosphamide Therapy. Ann Intern Med 1993; 119: 366–9.
21. Felten R, Sagez F, Gavand PE, Martin T, Korganow AS, Sordet C, et al. 10 most important contemporary challenges in the management of SLE. Lupus Sci Med 2019; 6: e000303.
22. Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau 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 2017; 76: 476–85.
23. Orquevaux P, Masseau A, Le Guern V, Gayet V, Vauthier D, Guettrot-Imbert G, et al. In vitro fertilization in 37 women with systemic lupus erythematosus or antiphospholipid syndrome: A series of 97 procedures. J Rheumatol 2017; 44: 613–8.
24. Reggia R, Andreoli L, Sebbar H, Canti V, Ceccarelli F, Favaro M, et al. An observational multicentre study on the efficacy and safety of assisted reproductive technologies in women with rheumatic diseases. Rheumatol Adv Pract 2019; 3: rkz005.
25. Hoek A, Schoemaker J, Drexhage HA. Premature Ovarian Failure and Ovarian Autoimmunity. Endocr Rev 1997; 18: 107–34.
26. Goswami R, Marwaha RK, Goswami D, Gupta N, Ray D, Tomar N, et al. Prevalence of Thyroid Autoimmunity in Sporadic Idiopathic Hypoparathyroidism in Comparison to Type 1 Diabetes and Premature Ovarian Failure. J Clin Endocrinol Metab 2006; 91: 4256–9.
27. Singh G, Misra R, Aggarwal A. Ovarian insufficiency is major short-term toxicity in systemic lupus erythematosus patients treated with cyclophosphamide. J Assoc Physicians India 2016; 64: 28–31.
28. Medeiros MM, Silveira VA, Menezes AP, Carvalho RC. Risk factors for ovarian failure in patients with systemic lupus erythematosus. Braz J Med Biol Res 2001; 34: 1561–8.
29. Ekblom-Kullberg S, Kautiainen H, Alha P, Helve T, Leirisalo-Repo M, Julkunen H. Reproductive health in women with systemic lupus erythematosus compared to population controls. Scand J Rheumatol 2009; 38: 375-80.
30. Tal R, Seifer DB. Ovarian reserve testing: a user’s guide. Am J Obstet Gynecol 2017; 217: 129–40.
31. Weenen C, Laven JS, von Bergh AR, Cranfield M, Groome NP, Visser JA, et al. Anti-Müllerian hormone expression pattern in the human ovary: Potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004; 10: 77–83.
32. Ulug P, Oner G, Kasap B, Akbas EM, Ozcicek F. Evaluation of Ovarian Reserve Tests in Women with Systemic Lupus Erythematosus. Am J Reprod Immunol 2014; 72: 85–8.
33. De Araujo DB, Yamakami LY, Aikawa NE, Bonfá E, Viana VS, Pasoto SG, et al. Ovarian reserve in adult patients with childhood-onset lupus: A possible deleterious effect of methotrexate? Scand J Rheumatol 2014; 43: 503–11.
34. Lawrenz B, Henes J, Henes M, Neunhoeffer E, Schmalzing M, Fehm T, et al. Impact of systemic lupus erythematosus on ovarian reserve in premenopausal women: Evaluation by using anti-Muellerian hormone. Lupus 2011; 20: 1193–7.
35. Gao H, Ma J, Wang X, Lv T, Liu J, Ren Y, et al. Preliminary study on the changes of ovarian reserve, menstruation, and lymphocyte subpopulation in systemic lupus erythematosus (SLE) patients of childbearing age. Lupus 2018; 27: 445–53.
36. Luo W, Mao P, Zhang L, Chen X, Yang Z. Assessment of ovarian reserve by serum anti-Müllerian hormone in patients with systemic lupus erythematosus: A
meta-analysis. Ann Palliat Med 2020; 9: 207–15.
37. Malheiro OB, Rezende CP, Rocha AL, Del Puerto HL, Ferreira GA, Reis FM. Regular menstrual cycles do not rule out ovarian damage in adult women with systemic lupus erythematosus. Gynecol Endocrinol 2014; 30: 701–4.
38. Angley M, Lim SS, Spencer JB, Howards PP. Infertility Among African American Women With Systemic Lupus Erythematosus Compared to Healthy Women: A Pilot Study. Arthritis Care Res (Hoboken) 2020; 72: 1275–81.
39. LI Yan-Mei; ZHAO Yi; CI Chun-zeng; LI Zhan.
Anti-Müllerian hormone:its significance in female lupus patients and relatin with anti-ovarian antibody. Chinese J Rheumatol 2010; 14: 5: 305–7.
40. Di Mario C, Petricca L, Gigante MR, Barini A, Barini A, Varriano V, et al. Anti-Müllerian hormone serum levels in systemic lupus erythematosus patients: Influence of the disease severity and therapy on the ovarian reserve. Endocrine 2019; 63: 369–75.
41. Gasparin AA, Souza L, Siebert M, Xavier RM, Chakr RM, Palominos PE, et al. Assessment of anti-Müllerian Hormone Levels in Premenopausal Patients With Systemic Lupus Erythematosus. Lupus 2016; 25: 227–32.
42. Pasoto SG, Mendonça BB, BonfáE. E. Menstrual disturbances in patients with systemic lupus erythematosus without alkylating therapy: Clinical, hormonal and therapeutic associations. Lupus 2002; 11: 175–80.
43. Bedenk J, Vrtačnik-Bokal E, Virant-Klun I. The role of anti-Müllerian hormone (AMH) in ovarian disease and infertility. J Assist Reprod Genet 2020; 37: 89–100.
44. Amanvermez R, Tosun M. An update on ovarian aging and ovarian reserve tests. Int J Fertil Steril 2015; 9 : 411–5.
45. Ghaleb RM, Fahmy KA. Anti-Müllerian hormone: A marker for ovarian function in systemic lupus erythematosus patients treated with cyclophosphamide. Joint Bone Spine 2013; 80: 434–5.
46. Gonzalez-Crespo MR, Gomez-Reino JJ, Merino R, Ciruelo E, Gomez-Reino FJ, Muley R, et al. Menstrual disorders in girls with systemic lupus erythematosus treated with cyclophosphamide. Br J Rheumatol 1995; 34 : 737–41.
47. Ataya K, Rao LV, Lawrence E, Kimmel R. Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide-induced ovarian follicular depletion in rhesus monkeys. Biol Reprod 1995; 52: 365–72.
48. Morel N, Bachelot A, Chakhtoura Z, Ghillani-Dalbin P, Amoura Z, Galicier L, et al. Study of anti-müllerian hormone and its relation to the subsequent probability of pregnancy in 112 patients with systemic lupus erythematosus, exposed or not to cyclophosphamide.
J Clin Endocrinol Metab 2013; 98: 3785–92.
49. Mok CC, Chan PT, To CH. Anti-müllerian hormone and ovarian reserve in systemic lupus erythematosus. Arthritis Rheum 2013; 65: 206–10.
2. Ugarte-Gil MF, González LA, Alarcón GS. Lupus: the new epidemic. Lupus. 2019; 28: 1031–50.
3. Weckerle CE, Niewold TB. The unexplained female predominance of systemic lupus erythematosus: Clues from genetic and cytokine studies. Clin Rev Allergy Immunol. 2011; 40: 42–9.
4. Fischer-Betz R, Specker C. Pregnancy in systemic lupus erythematosus and antiphospholipid syndrome. Best Pract Res Clin Rheumatol 2017; 31: 397-414.
5. Kartoz CR. Reproductive Health Concerns in Women with Systemic Lupus Erythematosus. MCN Am
J Matern Child Nurs 2015; 40: 220–6.
6. Chambers C, Michaud K. Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res (Hoboken) 2012; 64: 668–74.
7. Ekblom-Kullberg S, Kautiainen H, Alha P, Helve T, Leirisalo-Repo M, Julkunen H. Reproductive Health in Women With Systemic Lupus Erythematosus Compared to Population Controls. Scand J Rheumatol 2009; 38: 375–80.
8. Baird DT, Collins J, Egozcue J, Evers LH, Gianaroli L, Leridon H, et al. Fertility and ageing. Hum Reprod Update 2005; 11: 261–76.
9. Crawford NM, Steiner AZ. Age-related infertility. Obstet Gynecol Clin North Am 2015; 42: 15–25.
10. Jirge PR. Poor ovarian reserve. J Hum Reprod Sci 2016; 9: 63–9.
11. Gonzalez-Crespo MR, Gomez-Reino JJ, Merino R, Ciruelo E, Gomez-Reino FJ, Muley R, et al. Menstrual Disorders in Girls With Systemic Lupus Erythematosus Treated With Cyclophosphamide. Br J Rheumatol 1995; 34: 737–41.
12. Mandal D, Sircar G, Pandey A, Mandal S, Banerjee D, Ghosh A, et al. Menstrual and gonadal function alterations in women with systemic lupus erythematosus. J Assoc Physicians India 2015; 63: 38–42.
13. Appenzeller S, Blatyta PF, Costallat LT. Ovarian Failure in SLE Patients Using Pulse Cyclophosphamide: Comparison of Different Regimes. Rheumatol Int 2008; 28: 567–71.
14. Ulug P, Oner G, Kasap B, Akbas EM, Ozcicek F. Evaluation of Ovarian Reserve Tests in Women with Systemic Lupus Erythematosus. Am J Reprod Immunol 2014; 72: 85–8.
15. Hickman RA, Gordon C. Causes and management of infertility in systemic lupus erythematosus. Rheumatology (Oxford) 2011; 50: 1551–8.
16. Wetzels JF. Cyclophosphamide-induced gonadal toxicity: A treatment dilemma in patients with lupus nephritis? Neth J Med 2004; 62: 347–52.
17. Bermas BL, Sammaritano LR. Fertility and pregnancy in rheumatoid arthritis and systemic lupus erythematosus. Fertil Res Pract 2015; 1: 13.
18. Oktem O, Guzel Y, Aksoy S, Aydin E, Urman B. Ovarian function and reproductive outcomes of female patients with systemic lupus erythematosus and the strategies to preserve their fertility. Obstet Gynecol Surv 2015; 70: 196–210.
19. Petri M. Pregnancy and Systemic Lupus Erythematosus. Best Pract Res Clin Obstet Gynaecol 2020; 64: 24–30.
20. Boumpas DT, Austin HA, Vaughan EM, Yarboro CH, Klippel JH, Balow JE. Risk for Sustained Amenorrhea in Patients With Systemic Lupus Erythematosus Receiving Intermittent Pulse Cyclophosphamide Therapy. Ann Intern Med 1993; 119: 366–9.
21. Felten R, Sagez F, Gavand PE, Martin T, Korganow AS, Sordet C, et al. 10 most important contemporary challenges in the management of SLE. Lupus Sci Med 2019; 6: e000303.
22. Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau 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 2017; 76: 476–85.
23. Orquevaux P, Masseau A, Le Guern V, Gayet V, Vauthier D, Guettrot-Imbert G, et al. In vitro fertilization in 37 women with systemic lupus erythematosus or antiphospholipid syndrome: A series of 97 procedures. J Rheumatol 2017; 44: 613–8.
24. Reggia R, Andreoli L, Sebbar H, Canti V, Ceccarelli F, Favaro M, et al. An observational multicentre study on the efficacy and safety of assisted reproductive technologies in women with rheumatic diseases. Rheumatol Adv Pract 2019; 3: rkz005.
25. Hoek A, Schoemaker J, Drexhage HA. Premature Ovarian Failure and Ovarian Autoimmunity. Endocr Rev 1997; 18: 107–34.
26. Goswami R, Marwaha RK, Goswami D, Gupta N, Ray D, Tomar N, et al. Prevalence of Thyroid Autoimmunity in Sporadic Idiopathic Hypoparathyroidism in Comparison to Type 1 Diabetes and Premature Ovarian Failure. J Clin Endocrinol Metab 2006; 91: 4256–9.
27. Singh G, Misra R, Aggarwal A. Ovarian insufficiency is major short-term toxicity in systemic lupus erythematosus patients treated with cyclophosphamide. J Assoc Physicians India 2016; 64: 28–31.
28. Medeiros MM, Silveira VA, Menezes AP, Carvalho RC. Risk factors for ovarian failure in patients with systemic lupus erythematosus. Braz J Med Biol Res 2001; 34: 1561–8.
29. Ekblom-Kullberg S, Kautiainen H, Alha P, Helve T, Leirisalo-Repo M, Julkunen H. Reproductive health in women with systemic lupus erythematosus compared to population controls. Scand J Rheumatol 2009; 38: 375-80.
30. Tal R, Seifer DB. Ovarian reserve testing: a user’s guide. Am J Obstet Gynecol 2017; 217: 129–40.
31. Weenen C, Laven JS, von Bergh AR, Cranfield M, Groome NP, Visser JA, et al. Anti-Müllerian hormone expression pattern in the human ovary: Potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004; 10: 77–83.
32. Ulug P, Oner G, Kasap B, Akbas EM, Ozcicek F. Evaluation of Ovarian Reserve Tests in Women with Systemic Lupus Erythematosus. Am J Reprod Immunol 2014; 72: 85–8.
33. De Araujo DB, Yamakami LY, Aikawa NE, Bonfá E, Viana VS, Pasoto SG, et al. Ovarian reserve in adult patients with childhood-onset lupus: A possible deleterious effect of methotrexate? Scand J Rheumatol 2014; 43: 503–11.
34. Lawrenz B, Henes J, Henes M, Neunhoeffer E, Schmalzing M, Fehm T, et al. Impact of systemic lupus erythematosus on ovarian reserve in premenopausal women: Evaluation by using anti-Muellerian hormone. Lupus 2011; 20: 1193–7.
35. Gao H, Ma J, Wang X, Lv T, Liu J, Ren Y, et al. Preliminary study on the changes of ovarian reserve, menstruation, and lymphocyte subpopulation in systemic lupus erythematosus (SLE) patients of childbearing age. Lupus 2018; 27: 445–53.
36. Luo W, Mao P, Zhang L, Chen X, Yang Z. Assessment of ovarian reserve by serum anti-Müllerian hormone in patients with systemic lupus erythematosus: A
meta-analysis. Ann Palliat Med 2020; 9: 207–15.
37. Malheiro OB, Rezende CP, Rocha AL, Del Puerto HL, Ferreira GA, Reis FM. Regular menstrual cycles do not rule out ovarian damage in adult women with systemic lupus erythematosus. Gynecol Endocrinol 2014; 30: 701–4.
38. Angley M, Lim SS, Spencer JB, Howards PP. Infertility Among African American Women With Systemic Lupus Erythematosus Compared to Healthy Women: A Pilot Study. Arthritis Care Res (Hoboken) 2020; 72: 1275–81.
39. LI Yan-Mei; ZHAO Yi; CI Chun-zeng; LI Zhan.
Anti-Müllerian hormone:its significance in female lupus patients and relatin with anti-ovarian antibody. Chinese J Rheumatol 2010; 14: 5: 305–7.
40. Di Mario C, Petricca L, Gigante MR, Barini A, Barini A, Varriano V, et al. Anti-Müllerian hormone serum levels in systemic lupus erythematosus patients: Influence of the disease severity and therapy on the ovarian reserve. Endocrine 2019; 63: 369–75.
41. Gasparin AA, Souza L, Siebert M, Xavier RM, Chakr RM, Palominos PE, et al. Assessment of anti-Müllerian Hormone Levels in Premenopausal Patients With Systemic Lupus Erythematosus. Lupus 2016; 25: 227–32.
42. Pasoto SG, Mendonça BB, BonfáE. E. Menstrual disturbances in patients with systemic lupus erythematosus without alkylating therapy: Clinical, hormonal and therapeutic associations. Lupus 2002; 11: 175–80.
43. Bedenk J, Vrtačnik-Bokal E, Virant-Klun I. The role of anti-Müllerian hormone (AMH) in ovarian disease and infertility. J Assist Reprod Genet 2020; 37: 89–100.
44. Amanvermez R, Tosun M. An update on ovarian aging and ovarian reserve tests. Int J Fertil Steril 2015; 9 : 411–5.
45. Ghaleb RM, Fahmy KA. Anti-Müllerian hormone: A marker for ovarian function in systemic lupus erythematosus patients treated with cyclophosphamide. Joint Bone Spine 2013; 80: 434–5.
46. Gonzalez-Crespo MR, Gomez-Reino JJ, Merino R, Ciruelo E, Gomez-Reino FJ, Muley R, et al. Menstrual disorders in girls with systemic lupus erythematosus treated with cyclophosphamide. Br J Rheumatol 1995; 34 : 737–41.
47. Ataya K, Rao LV, Lawrence E, Kimmel R. Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide-induced ovarian follicular depletion in rhesus monkeys. Biol Reprod 1995; 52: 365–72.
48. Morel N, Bachelot A, Chakhtoura Z, Ghillani-Dalbin P, Amoura Z, Galicier L, et al. Study of anti-müllerian hormone and its relation to the subsequent probability of pregnancy in 112 patients with systemic lupus erythematosus, exposed or not to cyclophosphamide.
J Clin Endocrinol Metab 2013; 98: 3785–92.
49. Mok CC, Chan PT, To CH. Anti-müllerian hormone and ovarian reserve in systemic lupus erythematosus. Arthritis Rheum 2013; 65: 206–10.
| Files | ||
| Issue | Vol 15, No 1 (March 2021) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/jfrh.v15i1.6076 | |
| Keywords | ||
| Ovarian Reserve Anti-Mullerian Hormone Ovarian Follicle Systemic Lupus Erythematosus | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Morales-Martínez F, Salas-Castro C, García-Garza M, Valdés-Martínez O, García-Luna S, Garza-Elizondo M, Vidal-Gutiérrez O, Saldívar-Rodríguez D, Sordia-Hernández L. Evaluation of the Ovarian Reserve in Women With Systemic Lupus Erythematosus. J Family Reprod Health. 2021;15(1):38-44.
