Combined treatment of prednisone and hydroxychloroquine may improve outcomes of frozen embryo transfer in antinuclear antibody-positive patients undergoing IVF/ICSI treatment

Abstract

Background

The influence of anti-nuclear antibody (ANA) on induced ovulation was controversial, and the effect of prednisone plus hydroxychloroquine (HCQ) treatment on frozen embryo transfer outcomes of in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for ANA-positive women was unclear.

Methods

Fifty ANA-positive women and one-hundred ANA-negative women matched for age and anti-Mullerian hormone (AMH) were included from a Reproductive Medical Central of a University Hospital. Sixty-one oocytes pick-up (OPU) cycles in ANA+ group and one-hundred OPU cycles in ANA− group were compared; 30 frozen embryo transfer cycles without treatment and 66 with prednisone plus HCQ treatment among ANA-positive women were compared.

Results

There was no statistical difference in number of retrieved oocytes (13.66 ± 7.71 vs 13.72 ± 7.23, p = .445), available embryos (5.23 ± 3.37 vs 5.47 ± 3.26, p = .347), high-quality embryos (3.64 ± 3.25 vs 3.70 ± 3.52, p = .832), and proportion of high-quality embryos (26.5% vs. 26.7%, p = .940). Biochemical pregnancy rate (33.3% vs. 68.2%, p < .05), clinical pregnancy rate (20.0% vs. 50.1%, p < .05), and implantation rate (5.6% vs. 31.8%, p < .05) were lower, and pregnancy loss rate (83.3% vs. 23.1%, p < .05) was higher in patients with treatment than no treatment.

Conclusion

The influence of ANA on number of retrieved oocytes, available embryos, high-quality embryos, and proration of high-quality embryos was not found. The treatment of prednisone plus HCQ may improve implantation rate, biochemical pregnancy rate, and clinical pregnancy rate, and reduce pregnancy loss rate in frozen embryo transfer outcomes for ANA-positive women.

Keywords

anti-nuclear antibody induced ovulation in-vitro fertilization intracytoplasmic sperm injection treatment

Get full access to this article

View all access options for this article.

References

Pisetsky

. Antinuclear antibody testing - misunderstood or misbegotten? Nat Rev Rheumatol 2017; 13: 495–502. DOI: 10.1038/nrrheum.2017.74.

Bossuyt

De Langhe

Borghi

, et al. Understanding and interpreting antinuclear antibody tests in systemic rheumatic diseases. Nat Rev Rheumatol 2020; 16: 715–726. DOI: 10.1038/s41584-020-00522-w.

Chen

Yang

, et al. Antinuclear antibodies positivity is a risk factor of recurrent pregnancy loss: a meta-analysis. Semin Arthritis Rheum 2020; 50: 534–543. DOI: 10.1016/j.semarthrit.2020.03.016.

Cavalcante

CTdMB

Sarno

, et al. Antinuclear antibodies and recurrent miscarriage: systematic review and meta‐analysis. Am J Reprod Immunol 2020; 83: e13215. DOI: 10.1111/aji.13215.

Journal EM . Review of the 34th European Society of Human Reproduction and Embryology congress, Barcelona, Spain, 1–4 Jul 2018. 2018.

Zeng

Wen

Duan

. Association of antinuclear antibody with clinical outcome of patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment: a meta-analysis. Am J Reprod Immunol 2019; 82: e13158. DOI: 10.1111/aji.13158.

Ying

Zhong

Y-p

Zhou

C-q

, et al. Antinuclear antibodies predicts a poor IVF-ET outcome: impaired egg and embryo development and reduced pregnancy rate. Immunol Invest 2012; 41: 458–468. DOI: 10.3109/08820139.2012.660266.

Ying

Zhong

Y-P

Zhou

C-Q

, et al. A further exploration of the impact of antinuclear antibodies on in vitrofertilization-embryo transfer outcome. Am J Reprod Immunol 2013; 70: 221–229. DOI: 10.1111/aji.12111.

Chen

M-L

Huang

C-Y

, et al. Association of serum autoantibodies with pregnancy outcome of patients undergoing first IVF/ICSI treatment: A prospective cohort study. J Reprod Immunol 2017; 122: 14–20. DOI: 10.1016/j.jri.2017.08.002.

10.

Fan

Zhong

Chen

. Impacts of anti-dsDNA antibody on in vitro fertilization-embryo transfer and frozen-thawed embryo transfer. J Immunol Res 2017; 2017: 8596181. DOI: 10.1155/2017/8596181.

11.

Fan

Zhong

Chen

. Combined treatment of prednisone and aspirin, starting before ovulation induction, may improve reproductive outcomes in ANA-positive patients. Am J Reprod Immunol 2016; 76: 391–395. DOI: 10.1111/aji.12559.

12.

Stern

Chamley

Norris

, et al. A randomized, double-blind, placebo-controlled trial of heparin and aspirin for women with in vitro fertilization implantation failure and antiphospholipid or antinuclear antibodies. Fertil Steril 2003; 80: 376–383. DOI: 10.1016/s0015-0282(03)00610-1.

13.

Taniguchi

. Results of prednisolone given to improve the outcome of in vitro fertilization-embryo transfer in women with antinuclear antibodies. J Reprod Med 2005; 50: 383–388.

14.

Zhu

, et al. A retrospective study on IVF/ICSI outcome in patients with anti-nuclear antibodies: the effects of prednisone plus low-dose aspirin adjuvant treatment. Reprod Bio Endocrinol 2013; 11: 98. DOI: 10.1186/1477-7827-11-98.

15.

Nyborg

Kolte

Larsen

, et al. Immunomodulatory treatment with intravenous immunoglobulin and prednisone in patients with recurrent miscarriage and implantation failure after in vitro fertilization/intracytoplasmic sperm injection. Fertil Sterility 2014; 102: 1650–1655. DOI: 10.1016/j.fertnstert.2014.08.029.

16.

Lédée

Prat-Ellenberg

Petitbarat

, et al.

Impact of prednisone in patients with repeated embryo implantation failures: beneficial or deleterious?

J Reprod Immunol 2018; 127: 11–15. DOI: 10.1016/j.jri.2018.03.003.

17.

Andreoli

Bertsias

Agmon-Levin

, 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: 476–485. DOI: 10.1136/annrheumdis-2016-209770.

18.

Tektonidou

Andreoli

Limper

, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis 2019; 78: 1296–1304. DOI: 10.1136/annrheumdis-2019-215213.

19.

Denton

Khanna

. Systemic sclerosis. Lancet 2017; 390: 1685–1699. DOI: 10.1016/s0140-6736(17)30933-9.

20.

Petri

. Pregnancy and systemic lupus erythematosus. Best Pract Res Clin Obstet Gynaecol 2020; 64: 24–30. DOI: 10.1016/j.bpobgyn.2019.09.002.

21.

Radin

Schreiber

Cecchi

, et al. A multicentre study of 244 pregnancies in undifferentiated connective tissue disease: maternal/fetal outcomes and disease evolution. Rheumatology 2020; 59: 2412–2418. DOI: 10.1093/rheumatology/kez620.

22.

Zucchi

Tani

Monacci

, et al. Pregnancy and undifferentiated connective tissue disease: outcome and risk of flare in 100 pregnancies. Rheumatology 2020; 59: 1335–1339. DOI: 10.1093/rheumatology/kez440.

23.

Deroux

Dumestre-Perard

Dunand-Faure

, et al. Female infertility and serum auto-antibodies: a systematic review. Clin Rev Allergy Immunol 2017; 53: 78–86. DOI: 10.1007/s12016-016-8586-z.

24.

Carp

HJA

Selmi

Shoenfeld

. The autoimmune bases of infertility and pregnancy loss. J Autoimmun 2012; 38: J266–J274. DOI: 10.1016/j.jaut.2011.11.016.

25.

Malinowski

Szpakowski

Wilczyński

, et al. [Occurrence of antinuclear antibodies in women with endometriosis and unexplained infertility]. Ginekologia Polska 1995; 66: 420–424.

26.

Wang

Lan

, et al. Antinuclear antibodies in follicular fluid may reduce efficacy of in vitro fertilization and embryo transfer by invading endometrium and granular cells. Am J Reprod Immunol 2020; 84: e13289. DOI: 10.1111/aji.13289.

27.

Veglia

D’Ippolito

Marana

, et al. Human IgG antinuclear antibodies induce pregnancy loss in mice by increasing immune complex deposition in placental tissue:in vivostudy. Am J Reprod Immunol 2015; 74: 542–552. DOI: 10.1111/aji.12429.

28.

Bruno

Ticconi

Martelli

, et al. Uterine and placental blood flow indexes and antinuclear autoantibodies in unexplained recurrent pregnancy loss: should they be investigated in pregnancy as correlated potential factors? A retrospective study. BMC Pregnancy and Childbirth 2020; 20: 44. DOI: 10.1186/s12884-020-2724-6.

29.

Cheloufi

Wackenheim

Dumestre-Pérard

, et al. Utilisation de l'hydroxychloroquine et de la prednisone en présence d'une auto-immunité sérique dans l'infertilité féminine. Gynécologie Obstétrique Fertilité & Sénologie 2018; 46: 112–117. DOI: 10.1016/j.gofs.2017.12.008.