Thyroid ultrasonic changes relate to implantation failure in euthyroid women with thyroid autoimmunity undergoing in vitro fertilization/intracytoplasmic sperm injection

Figures & data

Figure 1. Flow chart of study population selection.

Abbreviations: IVF = in vitro fertilization; ICSI = intracytoplasmic sperm injection; TSH = thyroid stimulating hormone; FT3 = free triiodothyroinine; FT4 = free thyroxine; TPOAb = antithyroperoxidase antibody; TGAb = antithyroglobulin antibody; TAI = thyroid autoimmunity.

Table 1. Baseline characteristics of patients.

Characteristics	Control group	Thyroid autoimmunity group	p-value
No. of patients	375	214
Age (years)	31.3 ± 4.0	32.0 ± 4.4	0.07
BMI (kg/m^2)	23.6 ± 3.6	23.8 ± 3.7	0.55
Duration of infertility (years)	3.0 (1.5, 5.0)	3.0 (2.0, 4.6)	0.57
FSH (IU/L) ^*	6.4 (5.7, 8.0)	6.5 (5.7, 8.0)	0.74
LH (IU/L) ^*	4.9 (3.7, 6.6)	4.9 (3.6, 6.7)	0.93
Estradiol (pg/mL) ^*	36.6 (27.6, 51.2)	37.5 (28.0, 49.0)	0.64
Prolactin (ng/mL) ^*	14.9 (11.2, 20.0)	15.0 (10.8, 20.7)	0.99
Total testosterone (ng/dL) ^*	25.0 (15.3, 36.3)	23.9 (14.4, 33.2)	0.18
AMH (ng/mL)	2.5 (1.3, 4.8)	2.8 (1.3, 5.1)	0.65
No. of antral follicle counts	13 (9, 20)	14 (9, 20)	0.95
TSH (μIU/mL)	2.2 (1.6, 3.0)	2.3 (1.6, 3.1)	0.51
FT3 (pmol/L)	4.8 (4.3, 5.2)	4.8 (4.3, 5.2)	0.89
FT4 (pmol/L)	14.9 (11.3, 17.0)	16.1 (14.2, 17.9)	<0.001
TPOAb (IU/mL)	9.0 (0.9, 15.5)	61.8 (24.4, 205.5)	<0.001
TgAb (IU/mL)	10.1 (0.5, 14.1)	221.9 (57.8, 438.2)	<0.001

Notes: Values are presented as means ± standard deviation or median (interquartile range). t test (normal distributed variables, such as age and BMI) or Mann-Whitney U test (non-normally distributed continuous variables) was used to compare the difference between the two groups.

Abbreviations: BMI = body mass index; FSH = follicle-stimulating hormone; LH = luteinizing hormone; AMH = anti-Müllerian hormone; TSH = thyroid stimulating hormone; FT3 = free triiodothyroinine; FT4 = free thyroxine; TPOAb = antithyroperoxidase antibody; TGAb = antithyroglobulin antibody.

*The baseline hormones were measured at the early follicular phase, mostly on days 1–3 of the menstrual cycle.

Table 2. Baseline characteristics of patients with Hashimoto’s thyroiditis or with normal structure under ultrasonography.

Characteristics	Normal	Hashimoto’s thyroiditis	p-value
N	39	146
Age (years)	32.6 ± 4.1	31.5 ± 4.3	0.17
BMI (kg/m^2)	23.7 ± 4.8	23.8 ± 3.4	0.82
Duration of infertility (years)	3.0 (1.5, 5.0)	3.0 (2.0, 4.0)	0.68
FSH (IU/L) ^*	6.6 (5.3, 8.0)	6.6 (5.7, 8.0)	0.38
LH (IU/L) ^*	5.3 (3.5, 6.6)	4.8 (3.7, 6.7)	0.93
Estradiol (pg/mL) ^*	39.7 (30.1, 64.3)	35.7 (27.5, 46.0)	0.08
Prolactin (ng/mL) ^*	15.4 (9.8, 18.9)	15.4 (11.5, 22.6)	0.16
Total testosterone (ng/dL) ^*	26.7 (17.6, 36.4)	23.9 (13.4, 32.7)	0.25
AMH (ng/mL)	2.2 (1.3, 4.5)	3.1 (1.5, 5.3)	0.22
No. of antral follicle counts	12 (9.5, 19)	14 (9, 20)	0.62
TSH (μIU/mL)	2.4 (1.5, 3.3)	2.3 (1.7, 3.1)	0.75
FT3 (pmol/L)	4.9 (4.4, 5.4)	4.8 (4.3, 5.1)	0.43
FT4 (pmol/L)	16.0 (14.1, 17.6)	16.1 (14.1, 17.9)	0.97
TPOAb (IU/mL)	47.7 (20.0, 100.0)	118.9 (24.9, 251.9)	0.05
TgAb (IU/mL)	171.1 (45.6, 340.3)	249.5 (74.4, 461.6)	0.14

Notes: Values are presented as means ± standard deviation or median (interquartile range). t test (normal distributed variables, such as age and BMI) or Mann-Whitney U test (non-normally distributed continuous variables) was used to compare the difference between the two groups. 3 women with nodular goiter, 1 woman with follicular cyst, 4 women with cystic nodule, 21 women with solid nodule were excluded from the further analysis.

Abbreviations: BMI = body mass index; FSH = follicle-stimulating hormone; LH = luteinizing hormone; AMH = anti-Müllerian hormone; TSH = thyroid stimulating hormone; FT3 = free triiodothyroinine; FT4 = free thyroxine; TPOAb = antithyroperoxidase antibody; TGAb = antithyroglobulin antibody.

*The baseline hormones were measured at the early follicular phase, mostly on days 1–3 of the menstrual cycle.

Table 3. Outcomes of embryo development and pregnancy in TAI and control group.

Characteristics	Control group	Thyroid autoimmunity group	p-value
No. of retrieved oocytes	10 (5,15)	10 (5,15)	0.98
Normal fertilization rate, % (n/N)
IVF	58.7% (1850/3151)	58.3% (1102/1889)	0.79
ICSI	76.4% (507/664)	80.1% (253/316)	0.19
No. of good-quality embryos	3 (1,6)	2 (1,5)	0.11
Transplantation type, % (n/N)
Fresh embryos	60.8% (194/319)	65.6% (126/192)	0.28
Frozen embryos	39.2% (125/319)	34.4% (66/192)
Implantation rate, % (n/N)	73.0% (233/319)	65.5% (125/191)	0.07
Adjusted OR (95% CI)	Reference	0.65 (0.44,0.97)
Adjusted p-value		0.04
Clinical pregnancy rate, % (n/N)	61.4% (194/316)	56.3% (107/190)	0.26
Adjusted OR (95% CI)	Reference	0.79 (0.54,1.15)
Adjusted p-value		0.22
Miscarriage rate, % (n/N)	14.4% (28/194)	21.5% (23/107)	0.12
Adjusted OR (95% CI)	Reference	1.60 (0.85,3.00)
Adjusted p-value		0.12
Live birth rate, % (n/N)	52.0% (166/319)	44.2% (84/190)	0.09
Adjusted OR (95% CI)	Reference	0.63 (0.33,1.17)
Adjusted p-value		0.78

Notes: Values are presented as median (interquartile range) or percentage. Adjusted p-value after correcting for FT4. Adjusted OR (95% CI) was analyzed by binary logistic regression and corrected for FT4.

Abbreviations: IVF = in vitro fertilization; ICSI = intracytoplasmic sperm injection; OR = odds ratio; CI = confidence interval.

Table 4. Outcomes of embryo development and pregnancy based on ultrasonography.

Characteristics	Control group	Thyroid autoimmunity group		p-value
Thyroid ultrasonography		Normal	Hashimoto’s thyroiditis
No. of retrieved oocytes	10 (5,15)	10 (4,15)	10(5,15)	0.74
Normal fertilization rate, % (n/N)
IVF	58.7% (1850/3151)	55.8% (196/351)	59.2% (783/1322)	0.51
ICSI	76.4% (507/664)	78.4% (40/51)	81.3% (165/203)	0.33
No. of good-quality embryos	3 (1,6)	2 (1,5)	3 (1,5)	0.79
Transplantation type, % (n/N)
Fresh embryos	60.8% (194/319)	57.1% (20/35)	68.9% (91/132)	0.21
Frozen embryos	39.2% (125/319)	42.9% (15/35)	31.1% (41/132)
Implantation	233 (73.0)	25 (73.5)	84 (64.1)	0.16
Adjusted OR (95% CI)	Reference	0.85 (0.37,1.93)	0.63 (0.41,0.99)
Adjusted p-value	Reference	0.70	0.04
Clinical pregnancy	194 (60.8)	21 (61.8)	75 (57.3)	0.76
Adjusted OR (95% CI)	Reference	1.09 (0.50,2.37)	0.82 (0.54,1.25)
Adjusted p-value	Reference	0.83	0.36
Miscarriage	28 (14.4)	6 (28.6)	14 (18.7)	0.22
Adjusted OR (95%CI)	Reference	2.08 (0.72,6.03)	1.21 (0.60,2.46)
Adjusted p-value	Reference	0.18	0.59
Live birth	166 (52.04)	15 (44.1)	61 (46.6)	0.45
Adjusted OR (95% CI)	Reference	0.76 (0.36,1.61)	0.80 (0.53,1.21)
Adjusted p-value	Reference	0.48	0.29

Notes: Values are presented as median (interquartile range) or percentage. Adjusted p-value after correcting for FT4. Adjusted OR (95% CI) was analyzed by binary logistic regression and corrected for FT4.

Abbreviations: IVF = in vitro fertilization; ICSI = intracytoplasmic sperm injection; OR = odds ratio; CI = confidence interval.

Data availability statement

The data of this study is available from the corresponding author upon reasonable request.