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Levothyroxine treatment does not alter pregnancy outcomes
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Miscarriage, intrauterine pregnancy and live-birth rates were not affected with levothyroxine treatment in women who were antithyroperoxidase-antibody positive and undergoing in vitro fertilization and embryo transfer, according to findings published in JAMA.
Jie Qiao, MD, PhD, of the Center of Reproductive Medicine, and Tianpei Hong, MD, PhD, of the department of endocrinology and metabolism, both at Peking University Third Hospital in Beijing, and colleagues evaluated 600 women (mean age, 31.6 years) who were antithyroperoxidase-antibody positive undergoing IVF and embryo transfer at Peking University Third Hospital. Participants were enrolled in the study between Sept. 6, 2012, and June 15, 2016, and follow-up was conducted until March 20, 2017.
“It is worth noting that in our trial, women with known comorbidities related to miscarriage, including recurrent miscarriage, known history of autoimmune diseases or presence of their markers (such as antinuclear antibody, anticardiolipin antibody and lupus anticoagulants), were excluded from this trial,” Qiao and Hong told Endocrine Today. “Therefore, our findings might not be applicable to women at increased risk for miscarriage.”
Participants were randomly assigned to levothyroxine treatment (n = 300; intervention group) or no levothyroxine treatment (n = 300; control group) to assess the effect of treatment on miscarriage (pregnancy loss before 28 weeks of gestation), intrauterine pregnancy rate (fetal cardiac activity seen at sonography observation on the 30th day after embryo transfer) and live-birth rate (at least one live birth after 28 weeks of gestation).
No significant differences were observed between the intervention and control groups for miscarriage rate (intervention, 10.3% vs. control, 10.6%), clinical intrauterine pregnancy rate (35.7% vs. 37.7%) or live-birth rate (31.7% vs. 32.3%).
Participants in the intervention group were more likely to have a twin pregnancy compared with the control group (36.4% vs. 28.3%). Preterm delivery rates among participants who had a live birth were 22.1% for the intervention group and 19.6% for the control group.
“We recommend against levothyroxine treatment for euthyroid women undergoing IVF and embryo transfer who test positive for thyroid autoantibodies,” Qiao and Hong said. “Levothyroxine treatment should be started after pregnancy when thyroid-stimulating hormone level exceeds the upper limit of the local normal range of pregnancy. Many infertile women with positive thyroid autoantibodies who are scheduled for IVF and embryo transfer receive levothyroxine treatment. Our findings suggest that preventive levothyroxine treatment is not necessary in this population before a pregnancy is confirmed.” – by Amber Cox
For more information:
Jie Qiao, MD, PhD, can be reached at jie.qiao@263.net and Tianpei Hong, MD, PhD, can be reached at tpho66@bjmu.edu.cn.
Disclosures: Qiao and Hong report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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In this important study, the authors aim to shed light on the long-standing question whether antithyroperoxidase-antibody positive women with a thyroid-stimulating hormone concentration in the reference range who undergo IVF would benefit from levothyroxine treatment. The idea that levothyroxine treatment in these women is beneficial comes from observational studies and expert opinion, and based on this, millions of women have probably received low-dose levothyroxine supplementation. The current study now shows that within the whole group of antithyroperoxidase-antibody positive women with a TSH within the reference range, low-dose levothyroxine supplementation does not improve miscarriage or preterm delivery rates.
Although these data are very important, this does not necessarily mean that there is no benefit of levothyroxine treatment in this specific group of women. Two small recent randomized controlled trials treating women who were antithyroperoxidase-antibody positive or those with a high-normal TSH during pregnancy have shown beneficial effects on the preterm delivery rates. However, the authors convincingly showed that this was the case for only the subset of women with higher TSH concentrations (roughly 4 mU/L) — well above the median TSH concentrations in the current study (2.94 and 2.12 mU/L; Nazarpour S, et al. J Clin Endocrinol Metab. 2017;doi:10.1210/jc.2017-01850. Nazarpour S, et al. Eur J Endocrinol. 2017;doi:10.1530/EJE-16-0548).
Moreover, recent observational studies indicate that there are very large differences in the risk for miscarriage and preterm delivery in the group of women included in the current study. For example, the combination of antithyroperoxidase-antibody concentration with TSH has a predictive value for the risk of miscarriage and premature delivery (Liu H, et al. Thyroid. 2014;doi:10.1089/thy.2014.0029) — including a study from our group that will appear online in The Journal of Clinical Endocrinology & Metabolism in December — and furthermore, women with the exact same TSH concentration can have an up to sixfold difference in premature delivery risk based on their human chorionic gonadotropin concentrations — a marker for thyroidal stimulation (Korevaar TIM, et al. J Clin Endocrinol Metab. 2017;doi:10.1210/jc.2016-2942; Korevaar TIM, et al. J Clin Endocrinol Metab. 2017;doi:10.1210/jc.2017-00846). Therefore, this study should be the start of further efforts to identify which women could benefit from treatment, rather than shutting the door to the idea of levothyroxine treatment for women with thyroid autoimmunity.
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