Previous studies have provided substantial evidence to directly correlate thyroid auto-immunity (TAI) with the etiology of diverse reproductive disorders, including recurrent miscarriage and unexplained infertility. Also, the presence of antithyroid antibodies (ATA), particularly anti-thyroid peroxidase and anti-thyroglobulin antibodies, is significant in causing adverse IVF outcome even in euthyroid patients. Now, a retrospective analysis published in Reproductive Biology and Endocrinology reports that the outcome of IVF treatment in ATA+ euthyroid patients could be improved with levothyroxine (LT), acetyl-salicylic acid (ASA), and prednisolone (P) adjuvant treatment.
Alberto Revelli from the Reproductive Medicine and IVF Unit, Department of Obstetrical and Gynecological Sciences, University of Torino, Italy, and coworkers, analyzed the following:
• ATA prevalence in euthyroid infertile subjects
• IVF outcome in ATA+ euthyroid women
• IVF outcome following adjuvant treatment (LT monotherapy, or in conjunction with ASA and P) in ATA+ patients
The prevalence of ATA positivity in infertile euthyroid women was observed to be 10.5% and this was comparable to other large population-based studies conducted in euthyroid fertile women between 18 and 45 years of age. Comparison of 129 euthyroid ATA+ patients receiving IVF treatment without any adjuvant therapy, against 200 ATA- controls showed that the ovarian responsiveness to stimulation and the IVF outcomes were substantially poor in the former group. Additionally, 38 study participants who received LT+ASA+P demonstrated significantly higher rates of implantation and pregnancy when compared to 38 ATA+ subjects who did not receive any adjuvant treatment. The overall IVF outcome was found to be similar to that noted in ATA- patients. The study also reported the following results:
| Study Group | Pregnancy Rate/Embryo Transfer (%) | Implantation Rate (%) |
| ATA+ patients undergoing LT+ASA+P treatment | 25.6 | 17.7 |
| Untreated ATA+ patients | 7.5 | 4.7 |
| ATA- patients | 32.8 | 19 |
Several former studies support the use of ASA in combination with P to improve IVF treatment outcome in women suffering from autoimmune disorders or recurrent abortion. The following are some of the probable mechanisms by which the adjuvant therapy enhances the IVF treatment outcome in euthyroid ATA+ women:
• Immunomodulatory activity exerted by LT and P, along with the enhanced ovarian and endometrial blood perfusion produced by ASA
• Prednisolone administration may aid in alleviating the local inflammatory response to the embryo transfer catheter, thereby facilitating implantation through enhanced immune tolerance towards transferred embryos
The administration of intravenous immunoglobulin (IVIg) was earlier reported to positively influence the IVF outcome in ATA+ patients. However, there is no specific treatment for such patients suffering from recurrent abortion unless associated with other abnormalities.
The recent study, suggesting the clinical applications of the adjuvant therapy in the specific group of patients undergoing IVF, should be validated through further prospective randomized studies to better understand the treatment effectiveness and related side effects.
References
1. Revelli A ,Casano S, Delle Piane L, 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 Nov 27;7:137.
