Short-term dexamethasone plus acetylsalicylic acid treatment during in vitro fertilization procedure
Abstract
Objectives: Embryo implantation represents the major limiting step during in vitro fertilization (IVF) procedure. Immu- nological and coagulation abnormalities were shown to have a substantial part in multifactorial etiology of IVF failure. We aimed to investigate the effect of short-term low-dose dexamethasone plus acetylsalicylic acid (ASA) treatment, starting at the time of embryo transfer, on the implantation and clinical pregnancy rates in general IVF population.
Material and methods: Out of 233 consecutive patients undergoing fresh IVF/intracytoplasmic sperm injection (ICSI) cycles 64 received an adjuvant treatment consisting of dexamethasone (0.5 mg/day) plus ASA (100 mg/day) (DA group), starting on the day of embryo transfer. Patients not receiving these medications comprised a control group.
Results: Significantly more patients in DA group had positive ß-hCG values than controls (59.38% vs. 37.67%, p = 0.004) (OR = 2.42, 95% CI: 1.33–4.41). Implantation rate was 26.53% in DA group and 15.92% in controls (p = 0.0294). Clinical preg- nancy rate per started cycle was higher in DA group (43.59%) than controls (28.92%), but the difference was not significant (p = 0.0879; OR = 1.99, 95% CI: 0.89–4.41).
Conclusions: Our study shows a potential benefit of dexamethasone plus ASA adjuvant treatment in females undergoing IVF/ICSI procedure. As these results show improvement of IVF outcome, a greater number of patients undergoing this type and regime of adjuvant treatment should be investigated.
Keywords: embryo implantationpregnancy rateassisted reproductive techniquesspontaneous abortioncoagulation disordersglucocorticoid effects
References
- Larsen EC, Christiansen OB, Kolte AM, et al. New insights into mechanisms behind miscarriage. BMC Med. 2013; 11: 154.
- Khairy M, Banerjee K, El-Toukhy T, et al. Aspirin in women undergoing in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2007; 88(4): 822–831.
- Siristatidis CS, Basios G, Pergialiotis V, et al. Aspirin for in vitro fertilisation. Cochrane Database Syst Rev. 2016; 11: CD004832.
- Hasegawa I, Yamanoto Y, Suzuki M, et al. Prednisolone plus low-dose aspirin improves the implantation rate in women with autoimmune conditions who are undergoing in vitro fertilization. Fertility and Sterility. 1998; 70(6): 1044–1048.
- Duvan CI, Ozmen B, Satiroglu H, et al. Does addition of low-dose aspirin and/or steroid as a standard treatment in nonselected intracytoplasmic sperm injection cycles improve in vitro fertilization success? A randomized, prospective, placebo-controlled study. J Assist Reprod Genet. 2006; 23(1): 15–21.
- Ruiz-Irastorza G, Crowther M, Branch W, et al. Antiphospholipid syndrome. The Lancet. 2010; 376(9751): 1498–1509.
- Boomsma CM, Eijkemans M, Keay SD, et al. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev. . 2012(6): CD005996.
- Pelaia G, Vatrella A, Cuda G, et al. Molecular mechanisms of corticosteroid actions in chronic inflammatory airway diseases. Life Sciences. 2003; 72(14): 1549–1561.
- Schimmer BP, Funder JW. ACTH. Adrenal Steroids, and Pharmacology of the Adrenal Cortex. In: Brunton LL, Chabner BA, Knollmann BC. ed. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. 12th ed. McGraw-Hill Companies Inc, New York 2011: 1209–1235.
- Parrillo JE, Fauci AS. Mechanisms of corticosteroid action on lymphocyte subpopulations. III. Differential effects of dexamethasone administration on subpopulations of effector cells mediating cellular cytotoxicity in man. Clin Exp Immunol. 1978; 31(1): 116–125.
- Perez SA, Mahaira LG, Demirtzoglou FJ, et al. A potential role for hydrocortisone in the positive regulation of IL-15-activated NK-cell proliferation and survival. Blood. 2005; 106(1): 158–166.
- Akhanoba F, MacDougall J, Mathur R, et al. Severe systemic candidiasis following immunomodulation therapy in in vitro fertilisation-embryo transfer (IVF-ET). BMJ Case Rep. 2014; 2014.
- Zhu Q, Wu Li, Xu Bo, 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 Biol Endocrinol. 2013; 11: 98.
- American College of Obstetricians and Gynecologists Women's Health Care Physicians. ACOG Practice Bulletin No. 138: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2013; 122(3): 706–717.
- Rendi M, Muehlenbachs A, Garcia R, et al. Female Reproductive System. Comparative Anatomy and Histology. 2012: 253–284.
- Dentali F, Ageno W, Rezoagli E, et al. Low-dose aspirin for in vitro fertilization or intracytoplasmic sperm injection: a systematic review and a meta-analysis of the literature. J Thromb Haemost. 2012; 10(10): 2075–2085.
- Rubinstein M. Low-dose aspirin treatment improves ovarian responsiveness, uterine and ovarian blood flow velocity, implantation, and pregnancy rates in patients undergoing in vitro fertilization: a prospective, randomized, double-blind placebo-controlled assay. Fertility and Sterility. 1999; 71(5): 825–829.
- Clarke RJ, Mayo G, Price P, et al. Suppression of thromboxane A2 but not of systemic prostacyclin by controlled-release aspirin. N Engl J Med. 1991; 325(16): 1137–1141.
- Boomsma CM, Macklon NS. Does glucocorticoid therapy in the peri-implantation period have an impact on IVF outcomes? Curr Opin Obstet Gynecol. 2008; 20(3): 249–256.
- Keay SD, Lenton EA, Cooke ID, et al. Low-dose dexamethasone augments the ovarian response to exogenous gonadotrophins leading to a reduction in cycle cancellation rate in a standard IVF programme. Human Reproduction. 2001; 16(9): 1861–1865.
- Kalampokas T, Pandian Z, Keay SD, et al. Glucocorticoid supplementation during ovarian stimulation for IVF or ICSI. Cochrane Database Syst Rev. 2017; 3: CD004752.
- Liu S, Shi L, Wang T, et al. Effect of low-dose dexamethasone on patients with elevated early follicular phase progesterone level and pregnancy outcomes in IVF-ET treatment: A randomized controlled clinical trial. Clin Endocrinol (Oxf). 2018; 89(6): 771–778.
- Quenby S, Kalumbi C, Bates M, et al. Prednisolone reduces preconceptual endometrial natural killer cells in women with recurrent miscarriage. Fertil Steril. 2005; 84(4): 980–984.
- Lédée-Bataille N, Bonnet-Chea K, Hosny G, et al. Role of the endometrial tripod interleukin-18, -15, and -12 in inadequate uterine receptivity in patients with a history of repeated in vitro fertilization-embryo transfer failure. Fertil Steril. 2005; 83(3): 598–605.
- Zhang T, Huang C, Du Y, et al. Successful treatment with intrauterine delivery of dexamethasone for repeated implantation failure. Am J Reprod Immunol. 2017; 78(6).
- Kalkunte SS, Mselle TF, Norris WE, et al. VEGF C facilitates immune tolerance and endovascular activity of human uterine NK cells at the maternal-fetal interface. J Immunol. 2009; 182(7): 4085–4092.
- Morgan DJ, Davis DM. Distinct Effects of Dexamethasone on Human Natural Killer Cell Responses Dependent on Cytokines. Front Immunol. 2017; 8: 432.
- Revelli A, Casano S, Piane LD, et al. A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments. Reprod Biol Endocrinol. 2009; 7: 137.
- Taniguchi F. Results of prednisolone given to improve the outcome of in vitro fertilization-embryo transfer in women with antinuclear antibodies. J Reprod Med. 2005; 50(6): 383–388.
- Poppe K, Velkeniers B, Glinoer D. Thyroid disease and female reproduction. Clin Endocrinol (Oxf). 2007; 66(3): 309–321.
- Weghofer A, Himaya E, Kushnir VA, et al. The impact of thyroid function and thyroid autoimmunity on embryo quality in women with low functional ovarian reserve: a case-control study. Reprod Biol Endocrinol. 2015; 13: 43.
- Teklenburg G, Salker M, Molokhia M, et al. Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation. PLoS One. 2010; 5(4): e10258.
