Subclinical Hypothyroidism and Intracytoplasmic Sperm Injection Outcomes

Whether preconception elevated concentrations of thyroid-stimulating hormone (TSH) compromises reproductive outcomes in patients undergoing assisted reproduction techniques (ARTs) remains unclear. This study therefore compared the reproductive outcomes in patients with TSH concentrations of < 2.5 mIU/L, 2.5-4.0 mIU/L, and 4.0-10.0mIU/L undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).

Methods

This retrospective cohort study evaluated the medical records of all women with measured TSH concentrations who underwent IVF/ICSI between January 2011 and December 2012. The patients were divided into three groups: TSH < 2.5mIU/L (group 1); THS ≥2.5 and < 4.0 mIU/L (group 2); and THS ≥4 mIU/L and < 10.0 mIU/L (group 3). Patients who were administered levothyroxine for treating hypothyroidism were excluded from the analysis. The primary endpoints were clinical pregnancy,miscarriage, live birth and multiple pregnancy rates.

Results

During the study period, 787 women underwent IVF/ICSI. Sixty were excluded because their TSH concentrations were unavailable, and 77 were excluded due to their use of levothyroxine. The prevalence of patients presenting elevated concentrations of TSHwas of 5.07% (using a TSH threshold of 4.0 mIU/L) and of 29.99% (using a TSH threshold of 2.5 mIU/L). Patient characteristics, type of COS, and response to COS did not differ among the three groups, and there were no differences in clinical pregnancy (24.4% versus 25.9% versus 24.2%, p = 0.93); miscarriage (17.1% versus 14.3% versus 12.5%, p = 0.93); live birth (20.2% versus 22.2% versus 21.2%, p = 0.86); and multiple pregnancy rates (27.0% versus 21.4% versus 25.0%, p = 0.90) respectively.

Conclusion

Response to COS, live birth, and miscarriage rates were not altered in women with elevated concentrations of TSH undergoing IVF/ICSI, regardless of using a TSH threshold of 2.5mIU/L or 4.0mIU/L. These findings reinforce the uncertainties related to the impact of subclinical hypothyroidism on reproductive outcomes in women undergoing COS for ARTs.

Keywords
thyrotropin (TSH); subclinical hypothyroidism; intracytoplasmic sperm injection (ICSI); live birth; miscarriage

	Group 1TSH < 2.5 mIU/L	Group 2TSH 2.5–4.0 mIU/L	Group 3TSH 4.0–10 mIU/L
	(n= 455)	(n= 162)	(n= 33)	p
TSH (mIU/L)	1.5 (1.1–1.9)	2.9 (2.7–3.4)	4.4 (4.1–4.6)	< 0.001
Interval between TSH dosage and cycle (months)	8 (4–18)	8 (3–13)	6 (1–12)	0.23
Age (years)	35 (31–38)	35 (32–38)	35 (31–39)	0.36
Duration of subfertility (months)	60 (38–92)	54 (30.3–86)	60.5 (36.3–91.8)	0.26
Weight (kg)	64 (57–73)	64 (57.9–72.3)	64.7 (53.3–74.1)	0.86
Height (m)	1.63 (1.58–1.67)	1.64 (1.59–1.68)	1.62 (1.6–1.65)	0.46
BMI (kg/m²)	24.2 (21.6–27.4)	24 (21.9–27.3)	24.2 (21.2–27.3)	0.94
AFC	10 (6–18)	10 (6 -17)	12 (6–18)	0.62
Causes of subfertility	n (%)	n (%)	n (%)	0.90
Ovulatory factor	15 (3.3)	3 (1.9)	1 (3)
Endometriosis	71 (15.6)	28 (17.3)	3 (9.1)
Male Factor	136 (29.9)	46 (28.4)	11 (33.3)
Tubal factor	42 (9.2)	20 (12.3)	4 (12.1)
Combined factors	136 (29.9)	43 (26.5)	10 (30.3)
Unexplained	55 (12.1)	22 (13.6)	4 (12.1)

	Group 1TSH < 2.5 mIU/L	Group 2TSH 2.5–4.0 mIU/L	Group 3TSH 4.0–10 mIU/L
	(n= 455)	(n= 162)	(n= 33)	p
COS protocol				0.77
Antagonist, n (%)	292 (64.2)	108 (66.7)	21 (63.6)
Agonist, n (%)	100 (22)	32 (19.8)	9 (27.3)
CC + Antagonist, n (%)	63 (13.8)	22 (13.6)	3 (9.1)
Total dose of FSH (IU)	1650 (1,200–2,325)	1,600 (1,213–2,225)	1,427 (1,206–1,856)	0.08
Length of COS (days)	9 (8–11)	9 (8–11)	9 (8–10.8)	0.83
Number of retrieved oocytes	5 (3–10)	6 (2–10)	5 (3–9)	0.88
Number of mature oocytes (MII)	4 (2–7)	4 (2–7.5)	3.5 (2–6)	0.67
Suspension due to poor response, n (%)	19 (4.2)	5 (3.1)	2 (6.1)	0.69

	Group 1TSH < 2.5 mIU/L	Group 2TSH 2.5–4.0 mIU/L	Group 3TSH 4.0–10 mIU/L
	(n= 455)	(n= 162)	(n= 33)	p
Cycles with fresh embryo transfer, n (%)	369 (81.1)	136 (84)	24 (72.7)	0.31
Cycles with fresh top quality embryo transfer, n (%)	214 (47)	75 (46.3)	14 (42.4)	0.87
Cycles with oocyte cryopreservation, n (%)	20 (4.4)	4 (2.5)	2 (6.1)	0.46
Cycles with embryo cryopreservation, n (%)	183 (40.2)	63 (38.9)	12 (36.4)	0.88
Positive pregnancy test, n (%)	133 (29.2)	52 (32.1)	9 (27.3)	0.75
Clinical pregnancy rate, n (%)	111 (24.4)	42 (25.9)	8 (24.2)	0.93
Live birth rate, n (%)	92 (20.2)	36 (22.2)	7 (21.2)	0.86
Miscarriage rate, n (%)	19 (17.1)	6 (14.3)	1 (12.5)	0.93
Multiple pregnancy rate, n (%)	30 (27)	9 (21.4)	2 (25)	0.90

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[1] Address for correspondence Marcela A. Coelho Neto, MD, Universidade de São Paulo, Av. Bandeirantes 3900, 8 andar, HCRP, Campus Universitário, 14049-900, Ribeirão Preto, SP, Brazil (e-mail: marcelalencar@hotmail.com).