Du Yuan-Jie, Xin Xin, Cui Na, Jiang Lei, Yang Ai-Min, Hao Gui-Min, Gao Bu-Lang
Department of Reproductive Medicine, The Second Hospital, Hebei Medical University, China.
Department of Reproductive Medicine, The Second Hospital, Hebei Medical University, China.
Eur J Obstet Gynecol Reprod Biol. 2019 Mar;234:207-212. doi: 10.1016/j.ejogrb.2019.01.025. Epub 2019 Jan 30.
To study the effects of long-acting gonadotropin-releasing hormone agonist (GnRH-a) on thyroid function in euthyroid patients of in vitro fertilization (IVF)/ intracytoplasmic sperm injection of embryo transfer (ICSI-ET) and to investigate the timing and alteration of thyroid stimulating hormone (TSH) during controlled ovarian stimulation(COS).
Euthyroid patients scheduled for IVF/ICSI were enrolled. Euthyroidism was defined as having no history of hypothyroidism with normal TSH before IVF. Long GnRH-a protocol was chosen as COS protocol. 207 patients were divided into two groups based on basal serum TSH level: group A with 0.35mIU/L<TSH<2.5mIU/L (n = 137) and group B with 2.5mIU/L ≤ TSH<4.5mIU/L (n = 70). Serum TSH was tested on 6 time points: before COS (2-5days in menstrual cycle, before GnRH-a injection), Gn injection day 1, Gn injection day 5, human chorionic gonadotropin (HCG) day, 14 and 28 days after transplantation. The serum TSH, clinical pregnancy and abortion rate were investigated.
The serum TSH value was significantly (P < 0.05) increased after injection of long-acting GnRH-a in all patients. Both groups had significant (P < 0.05) increases in serum TSH level after long-acting GnRH-a injection. The TSH level was increased in 131(63.3%) patients after GnRH-a injection, of which twenty (9.7%) had subclinical hypothyroidism with TSH level over 4.5 mIU/L. The other 76 (36.7%) patients had decreased TSH. In group A, 79 (57.7%) patients showed an increase of TSH, including three patients (2.2%) with simultaneous rise of TPOAb and four (2.9%) diagnosed of subclinical hypothyroidism with TSH level over 4.5 mIU/L, and the rest fifty-eight (42.3%) patients had decreased TSH with one patient with elevated TPOAb who was diagnosed with subclinical hyperthyroidism. In group B, fifty-two (74.3%) patients showed an increase of TSH, including thirteen (18.6%) patients with elevated TPOAb and sixteen (22.9%) patients diagnosed of subclinical hypothyroidism with TSH level over 4.5 mIU/L, and the rest eighteen (25.7%) patients had decreased TSH with one patient diagnosed with subclinical hyperthyroidism. Group B had a significant higher proportion of patients with elevated serum TSH than group A (P < 0.05). Compared to the baseline level, serum TSH ascended distinctly and reached peak level on HCG day in all patients. Group A and B had similar trends of alteration. Patients in group A had significantly (P<0.05) higher clinical pregnancy rate than in group B. No significant (P>0.05) difference in abortion rate were observed between the two groups.
GnRH-a can significantly increase serum TSH levels with possible development of subclinical thyroid dysfunction. Infertile patients with serum TSH > 2.5 mIU/L are more susceptible to GnRH-a while patients with basal TSH less than 2.5 mIU/L may get a higher clinical pregnancy rate when receiving IVF/ICSI.
研究长效促性腺激素释放激素激动剂(GnRH-a)对体外受精(IVF)/卵胞浆内单精子注射胚胎移植(ICSI-ET)甲状腺功能正常患者甲状腺功能的影响,并探讨在控制性卵巢刺激(COS)期间促甲状腺激素(TSH)的变化时间及改变情况。
纳入计划进行IVF/ICSI的甲状腺功能正常患者。甲状腺功能正常定义为无甲状腺功能减退病史且IVF前TSH正常。选择长效GnRH-a方案作为COS方案。根据基础血清TSH水平将207例患者分为两组:A组0.35mIU/L<TSH<2.5mIU/L(n = 137),B组2.5mIU/L≤TSH<4.5mIU/L(n = 70)。在6个时间点检测血清TSH:COS前(月经周期第2 - 5天,GnRH-a注射前)、Gn注射第1天、Gn注射第5天、人绒毛膜促性腺激素(HCG)日、移植后14天和28天。观察血清TSH、临床妊娠率及流产率。
所有患者注射长效GnRH-a后血清TSH值显著升高(P<0.05)。两组患者注射长效GnRH-a后血清TSH水平均显著升高(P<0.05)。GnRH-a注射后131例(63.3%)患者TSH水平升高,其中20例(9.7%)出现亚临床甲状腺功能减退,TSH水平超过4.5 mIU/L。另外76例(36.7%)患者TSH降低。A组79例(57.7%)患者TSH升高(其中伴有TPOAb升高3例(2.2%),诊断为亚临床甲状腺功能减退且TSH水平超过4.5 mIU/L 4例(2.9%)),其余58例(42.3%)患者TSH降低,其中1例TPOAb升高患者诊断为亚临床甲状腺功能亢进。B组52例(74.3%)患者TSH升高(其中伴有TPOAb升高13例(18.6%),诊断为亚临床甲状腺功能减退且TSH水平超过4.5 mIU/L 16例(22.9%)),其余18例(25.7%)患者TSH降低,其中1例诊断为亚临床甲状腺功能亢进。B组血清TSH升高患者比例显著高于A组(P<0.05)。与基线水平相比,所有患者血清TSH均明显上升,并在HCG日达到峰值水平。A组和B组变化趋势相似。A组患者临床妊娠率显著高于B组(P<0.05)。两组流产率差异无统计学意义(P>0.05)。
GnRH-a可显著升高血清TSH水平,可能导致亚临床甲状腺功能障碍。血清TSH>2.5 mIU/L的不孕患者对GnRH-a更敏感,而基础TSH低于2.5 mIU/L的患者接受IVF/ICSI时可能获得更高的临床妊娠率。