Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan, Brussels, Belgium.
Department of Gynaecology and Fertility, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan, Brussels, Belgium.
Hum Reprod. 2017 Apr 1;32(4):915-922. doi: 10.1093/humrep/dex033.
Does thyroid autoimmunity (TAI) predict live birth rate in euthyroid women after one treatment cycle in IUI patients?
TAI as such does not influence pregnancy outcome after IUI treatment.
The role of TAI on pregnancy outcome in the case of IVF/ICSI is largely debated in the literature. This is the first study to address this issue in the case of IUI.
STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study. A two-armed study design was performed: patients anti-thyroid peroxidase (TPO)+ and patients anti-TPO-. All patients who started their first IUI cycle in our fertility center between 1 January 2010 and 31 December 2014 were included. After exclusion of those patients with or being treated for thyroid dysfunction, 3143 patients were finally included in the study.
PARTICIPANTS/MATERIALS, SETTING, METHODS: After approval by the institutional review board we retrospectively included all patients who started their first IUI cycle in our center between 1 January 2010 and 31 December 2014 with follow-up of outcome until 31 December 2015. Patients with clinical thyroid dysfunction were excluded (thyroid-stimulating hormone (TSH) <0.01 mIU/l; TSH >5 mIU/l) as were patients under treatment with levothyroxine or anti-thyroid drugs. These patients were then divided into two main groups: patients anti-TPO+ and patients anti-TPO- (= control group). Live birth delivery after 25 weeks of gestation was taken as the primary endpoint of our study. As a secondary endpoint, we evaluated differences in live birth delivery after IUI according to different upper limits of preconception TSH thresholds (<2.5 and <5.0 mIU/l). Furthermore, the influence of thyroid function (TSH, free thyroxine (fT4)), anti-TPO status, age, smoking, BMI, parity, ovarian reserve (anti-mullerian hormone (AMH) and FSH), IUI indication and IUI stimulation on live birth rate was analyzed.
Between-group comparison did not show any significant difference between the anti-TPO+ and anti-TPO- group with respect to live birth delivery-, pregnancy- or miscarriage rate with odds ratio at 1.04 (95% CI: 0.63; 1.69), 0.98 (95% CI: 0.62; 1.55) and 0.74 (95% CI: 0.23; 2.39), respectively. In addition, there were no significant differences in live birth delivery-, pregnancy- or miscarriage rate when comparing subgroups according to TSH level (TSH ≥2.5 mIU/l vs. TSH <2.5 mIU/l) with an odds ratio at 1.05 (95% CI: 0.76; 1.47), 1.04 (95% CI: 0.77; 1.41) and 0.95 (95% CI: 0.47; 1.94), respectively.
LIMITATIONS, REASONS FOR CAUTION: This study was powered for the primary aim, live birth rate. The limitations of this study are the absence of region-specific reference ranges for thyroid hormones and the absence of follow-up of TSH values during ART and subsequent pregnancy. Moreover, there was a time difference of 5 months between thyroid assessment and the start of stimulation. The area where the study was conducted corresponds to a mild iodine deficient area and data should be translated with caution to areas with different iodine backgrounds.
Our findings indicate comparable pregnancy-, abortion- and delivery rates in women with and without TAI undergoing IUI. Moreover, we were unable to confirm a negative effect of TSH level above 2.5 mIU/l on live birth delivery rate. We therefore believe that advocating Levothyroxine treatment at TSH levels between 2.5 and 4 mIU/l needs to be considered with caution and requires further analysis in a prospective cohort study.
STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. No conflicts of interest are declared.
甲状腺自身免疫（TAI）是否会影响 IUI 患者治疗一个周期后的活产率？
TAI 本身并不会影响 IUI 治疗后的妊娠结局。
甲状腺自身免疫对 IVF/ICSI 情况下妊娠结局的作用在文献中存在广泛争议。这是第一项在 IUI 情况下解决这个问题的研究。
研究设计、规模、持续时间：这是一项回顾性队列研究。采用了两种研究设计：抗甲状腺过氧化物酶（TPO）+的患者和抗 TPO-的患者。纳入了 2010 年 1 月 1 日至 2014 年 12 月 31 日期间在我们生育中心开始第一次 IUI 周期的所有患者。排除了甲状腺功能障碍或正在接受治疗的患者后，最终纳入了 3143 名患者进行研究。
参与者/材料、设置、方法：在获得机构审查委员会批准后，我们回顾性地纳入了 2010 年 1 月 1 日至 2014 年 12 月 31 日期间在我们中心开始第一次 IUI 周期且随访结局至 2015 年 12 月 31 日的所有患者。排除了临床甲状腺功能障碍的患者（促甲状腺激素（TSH）<0.01 mIU/L；TSH>5 mIU/L）以及正在接受左甲状腺素或抗甲状腺药物治疗的患者。这些患者随后分为两组：抗 TPO+的患者和抗 TPO-的患者（对照组）。妊娠 25 周后活产分娩被作为我们研究的主要终点。作为次要终点，我们根据不同的妊娠前 TSH 阈值上限（<2.5 和<5.0 mIU/L）评估了 IUI 后活产分娩的差异。此外，还分析了甲状腺功能（TSH、游离甲状腺素（fT4））、抗 TPO 状态、年龄、吸烟、BMI、产次、卵巢储备（抗苗勒管激素（AMH）和 FSH）、IUI 指征和 IUI 刺激对活产率的影响。
两组之间的比较显示，在活产分娩率、妊娠率或流产率方面，抗 TPO+组与抗 TPO-组之间没有显著差异，优势比为 1.04（95%CI：0.63；1.69）、0.98（95%CI：0.62；1.55）和 0.74（95%CI：0.23；2.39）。此外，根据 TSH 水平（TSH≥2.5 mIU/L 与 TSH<2.5 mIU/L）进行亚组比较时，活产分娩率、妊娠率或流产率也没有显著差异，优势比分别为 1.05（95%CI：0.76；1.47）、1.04（95%CI：0.77；1.41）和 0.95（95%CI：0.47；1.94）。
局限性、谨慎的原因：本研究旨在评估活产率这一主要结局，因此存在一定的局限性。本研究的局限性在于缺乏甲状腺激素的特定区域参考范围，以及缺乏 ART 期间和随后妊娠期间 TSH 值的随访。此外，甲状腺评估和刺激开始之间存在 5 个月的时间差异。研究所在的区域对应于轻度碘缺乏区域，因此数据的翻译需要谨慎，并应注意到不同碘背景下的数据可能会有所不同。
我们的研究结果表明，在接受 IUI 的女性中，无论是否存在 TAI，妊娠率、流产率和分娩率相似。此外，我们无法证实 TSH 水平高于 2.5 mIU/L 对活产率的负面影响。因此，我们认为在 TSH 水平为 2.5 至 4 mIU/L 之间建议使用左甲状腺素治疗需要谨慎考虑，并需要在一项前瞻性队列研究中进一步分析。
研究资金/利益冲突：本研究无外部资金支持。无利益冲突声明。
