Abstract
Objective
Antiovarian autoantibodies (AOA) have been associated with reproductive failure, especially in in vitro fertilization (IVF) patients. Thus, the success rate of IVF might be improved by the use of corticosteroids. However, therapeutic trials with these drugs have yielded conflicting results, particularly because of heterogeneous inclusion criteria. Among women with previous IVF failure, we selected those who presented with a positive serum AOA assay, and analysed the efficacy of corticosteroids in improving the IVF outcome in these patients.
Methods
One hundred patients with serum AOA detected by ELISA and at least two previously failed IVF attempts were selected. These patients underwent a further IVF cycle with 0.5 mg/kg prednisolone, started on the first day of the treatment cycle. In patients who became pregnant, corticosteroids were administered until the end of the first trimester of pregnancy and then progressively discontinued. AOA were assessed before and after oocyte retrieval. Clinical data of the corticosteroid-treated cycle were compared with data from the preceding IVF cycle for each patient.
Results
No adverse effects resulting from corticosteroids were observed. Post oocyte retrieval antiovarian IgG were significantly lower in corticosteroid-treated attempts when compared with the preceding cycles. Twenty-six pregnancies resulted in the birth of 30 healthy children. The pregnancy rate, implantation rate, and live birth rate were 38.8%, 17.8%, and 26.5% respectively in prednisolone-treated cycles.
Conclusion
This study confirms the usefulness of corticosteroids in improving the success rate in a subset of patients with previous IVF failure and significant serum AOA levels.
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References
Nyboe Andersen A, Gianaroli L, Nygren KG (2004) Assisted reproductive technology in Europe, 2000. Results generated from European registers by ESHRE. Hum Reprod 19:490–503
Ahonen P, Miettinen A, Perheentupa J (1987) Adrenal and steroidal cell antibodies in patients with autoimmune polyglandular disease type I and risk of adrenocortical and ovarian failure. J Clin Endocrinol Metab 64:494–500
Anasti JN (1998) Premature ovarian failure: an update. Fertil Steril 70:1–15
Fenichel P, Sosset C, Barbarino-Monnier P, Gobert B, Hieronimus S, Bene MC, Harter M (1997) Prevalence, specificity and significance of ovarian antibodies during spontaneous premature ovarian failure. Hum Reprod 12:2623–2628
Betterle C, Rossi A, Dalla Pria S, Artifoni A, Pedini B, Gavasso S, Caretto A (1993) Premature ovarian failure: autoimmunity and natural history. Clin Endocrinol (Oxf) 39:35–43
Gobert B, Barbarino-Monnier P, Guillet-Rosso F, Béné MC, Faure GC (1990) Ovary antibodies after IVF. Lancet i:723
Gobert B, Barbarino-Monnier P, Guillet-May F, Bene MC, Faure GC (1992) Anti-ovary antibodies after attempts at human in vitro fertilization induced by follicular puncture rather than hormonal stimulation. J Reprod Fertil 96:213–218
Luborsky J, Pong R (2000) Pregnancy outcome and ovarian antibodies in infertility patients undergoing controlled ovarian hyperstimulation. Am J Reprod Immunol 44:261–265
Barbarino-Monnier P, Gobert B, Guillet-Rosso F, Bene MC, Landes P, Faure G (1991) Antiovary antibodies, repeated attempts, and outcome of in vitro fertilization. Fertil Steril 56:928–932
Narayanan M, Murthy PS, Munaf SA, Shah LC, Kini MD (1995) Antiovarian antibodies and their effect on the outcome of assisted reproduction. J Assist Reprod Genet 12:599–605
Geva E, Vardinon N, Lessing JB, Lerner-Geva L, Azem F, Yovel I, Burke M, Yust I, Grunfeld R, Amit A (1996) Organ-specific autoantibodies are possible markers for reproductive failure: a prospective study in an in-vitro fertilization-embryo transfer programme. Hum Reprod 11:1627–1631
Moustafa M, Ozornek MH, Krussel JS, Cupisti S, Bodden-Heidrich R, Koldovsky U, Bielfeld P (1997) The effect of antigamete antibodies on the success of assisted reproduction. Clin Exp Obstet Gynecol 24:67–69
Kemeter P, Feichtinger W (1986) Prednisolone supplementation to Clomid and/or gonadotrophin stimulation for in-vitro fertilization-a prospective randomized trial. Hum Reprod 1:441–444
Cohen J, Malter H, Elsner C, Kort H, Massey J, Mayer MP (1990) Immunosuppression supports implantation of zona pellucida dissected human embryos. Fertil Steril 53:662–665
Polak de Fried E, Blanco L, Lancuba S, Asch RH (1993) Improvement of clinical pregnancy rate and implantation rate of in-vitro fertilization-embryo transfer patients by using methylprednisone. Hum Reprod 8:393–395
Dmowski WP, Rana N, Michalowska J, Friberg J, Papierniak C, el-Roeiy A (1995) The effect of endometriosis, its stage and activity, and of autoantibodies on in vitro fertilization and embryo transfer success rates. Fertil Steril 63:555–562
Ando T, Suganuma N, Furuhashi M, Asada Y, Kondo I, Tomoda Y (1996) Successful glucocorticoid treatment for patients with abnormal autoimmunity on in vitro fertilization and embryo transfer. J Assist Reprod Genet 13:776–781
Kim CH, Chae HD, Kang BM, Chang YS, Mok JE (1997) The immunotherapy during in vitro fertilization and embryo transfer cycles in infertile patients with endometriosis. J Obstet Gynaecol Res 23:463–470
Hasegawa I, Yamanoto Y, Suzuki M, Murakawa H, Kurabayashi T, Takakuwa K, Tanaka K (1998) Prednisolone plus low-dose aspirin improves the implantation rate in women with autoimmune conditions who are undergoing in vitro fertilization. Fertil Steril 70:1044–1048
Geva E, Fait G, Lerner-Geva L, Lessing JB, Swartz T, Wolman I, Daniel Y, Amit A (1999) The possible role of antiovary antibodies in repeated in vitro fertilization failures. Am J Reprod Immunol 42:292–296
Ishihara O, Saitoh M, Hayashi N, Kinoshita K, Takeuchi T (2001) Successful treatment of embryo implantation failure in patients with the Sjogren syndrome with low-dose prednisolone. Fertil Steril 75:640–641
Keay SD, Lenton EA, Cooke ID, Hull MG, Jenkins JM (2001) Low-dose dexamethasone augments the ovarian response to exogenous gonadotrophins leading to a reduction in cycle cancellation rate in a standard IVF programme. Hum Reprod 16:1861–1865
Taniguchi F (2005) Results of prednisolone given to improve the outcome of in vitro fertilization-embryo transfer in women with antinuclear antibodies. J Reprod Med 50:383–388
Mottla GL, Smotrich DB, Gindoff PR, Stillman RJ (1996) Increasing clinical pregnancy rates after IVF/ET. Can immunosuppression help? J Reprod Med 41:889–891
Lee KA, Koo JJ, Yoon TK, Do BR, Ko JJ, Cha KY (1994) Immunosuppression by corticosteroid has no effect on the pregnancy rate in routine in-vitro fertilization/embryo transfer patients. Hum Reprod 9:1832–1835
Bider D, Hourvitz A, Tur Kaspa I, Dirnfeld M, Dor J (1999) Dexamethasone supplementation to gonadotropin stimulation for in vitro fertilization in polycystic ovarian disease. J Assist Reprod Genet 16:233–235
Ubaldi F, Rienzi L, Ferrero S, Anniballo R, Iacobelli M, Cobellis L, Greco E (2002) Low dose prednisolone administration in routine ICSI patients does not improve pregnancy and implantation rates. Hum Reprod 17:1544–1547
Rein MS, Jackson KV, Sable DB, Thomas PP, Hornstein MD (1996) Dexamethasone during ovulation induction for in-vitro fertilization: a pilot study. Hum Reprod 11:253–255
Moffitt D, Queenan JT Jr, Veeck LL, Schoolcraft W, Miller CE, Muasher SJ (1995) Low-dose glucocorticoids after in vitro fertilization and embryo transfer have no significant effect on pregnancy rate. Fertil Steril 63:571–577
Bider D, Amoday I, Tur-Kaspa I, Livshits A, Dor J (1996) The addition of a glucocorticoid to the protocol of programmed oocyte retrieval for in-vitro fertilization-a randomized study. Hum Reprod 11:1606–1608
Barbarino-Monnier P, Gobert B, Guillet-May F, Bene MC, Barbarino A, Foliguet B, Faure GC (1995) Ovarian autoimmunity and corticotherapy in an in-vitro fertilization attempt. Hum Reprod 10:2006–2007
Gobert B, Jolivet-Reynaud C, Dalbon P, Barbarino-Monnier P, Faure GC, Jolivet M, Bene MC (2001) An immunoreactive peptide of the FSH involved in autoimmune infertility. Biochem Biophys Res Commun 289:819–824
Luborsky JL, Visintin I, Boyers S, Asari T, Caldwell B, DeCherney A (1990) Ovarian antibodies detected by immobilized antigen immunoassay in patients with premature ovarian failure. J Clin Endocrinol Metab 70:69–75
Horejsi J, Martinek J, Novakova D, Madar J, Brandejska M (2000) Autoimmune antiovarian antibodies and their impact on the success of an IVF/ET program. Ann N Y Acad Sci 900:351–356
Meyer WR, Lavy G, DeCherney AH, Visintin I, Economy K, Luborsky JL (1990) Evidence of gonadal and gonadotropin antibodies in women with a suboptimal ovarian response to exogenous gonadotropin. Obstet Gynecol 75:795–799
Luborsky JL, Thiruppathi P, Rivnay B, Roussev R, Coulam C, Radwanska E (2002) Evidence for different aetiologies of low estradiol response to FSH: age-related accelerated luteinization of follicles or presence of ovarian autoantibodies. Hum Reprod 17:2641–2649
Forges T, Monnier-Barbarino P, Faure GC, Bene MC (2004) Autoimmunity and antigenic targets in ovarian pathology. Hum Reprod Update 10:163–175
Luborsky J, Llanes B, Roussev R, Coulam C (2000) Ovarian antibodies, FSH and inhibin B: independent markers associated with unexplained infertility. Hum Reprod 15:1046–1051
Nothnick WB (2001) Treating endometriosis as an autoimmune disease. Fertil Steril 76:223–231
Fenichel P, Gobert B, Carre Y, Barbarino-Monnier P, Hieronimus S (1999) Polycystic ovary syndrome in autoimmune disease. Lancet 353:2210
Luborsky J, Llanes B, Davies S, Binor Z, Radwanska E, Pong R (1999) Ovarian autoimmunity: greater frequency of autoantibodies in premature menopause and unexplained infertility than in the general population. Clin Immunol 90:368–374
Cowchock S (1996) Prevention of fetal death in the antiphospholipid antibody syndrome. Lupus 5:467–472
Acknowledgements
This work was supported by a grant from the French Ministry of Health (PHRC n°1707). The authors are grateful to Prof. B. Foliguet and Prof. H. Gérard for fruitful collaboration in IVF protocols.
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Forges, T., Monnier-Barbarino, P., Guillet-May, F. et al. Corticosteroids in patients with antiovarian antibodies undergoing in vitro fertilization: a prospective pilot study. Eur J Clin Pharmacol 62, 699–705 (2006). https://doi.org/10.1007/s00228-006-0169-0
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DOI: https://doi.org/10.1007/s00228-006-0169-0