Live birth rate after intrauterine insemination is not different between women with lower quartile versus higher quartile normal range thyroid stimulating hormone levels

Abstract

STUDY QUESTION Does lower quartile normal range thyroid stimulating hormone (TSH) compared to higher quartile normal range in women without thyroid hormone substitution affect live birth rate after a complete IUI treatment series? SUMMARY ANSWER Lower quartile normal range TSH, in women without thyroid hormone substitution, does not affect live birth rate after a complete intrauterine insemination treatment series compared to higher quartile normal range TSH. WHAT IS KNOWN ALREADY TSH is historically seen as the most sensitive test for thyroid function. Its distribution is right-skewed. Whether the preconceptional upper reference TSH values in subfertile women should be 2.5 or 4.5 mIU/L is under debate. Studies have shown that IUI patients treated with levothyroxine for TSH levels above 2.5 mIU/L show higher pregnancy rates. However, no adverse outcome is associated with untreated high normal TSH levels studied in first IUI cycles. Thyroid peroxidase antibodies have also impaired outcomes in some studies whereas others have shown an effect only in combination with high normal TSH levels. As a subgroup, patients with unexplained infertility showed increased levels of TSH. This article adds to the value of TSH evaluation and fertility outcome in four quartiles and in the context of a completed IUI treatment modus of a maximum of six inseminations. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort study in 909 women undergoing 3588 IUI cycles starting treatment between the first of January 2008 and the first of March 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS Women aged 22–45 years with TSH 0.3–4.5 mIU/L without thyroid hormone substitution were included at Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands, an Iodine-sufficient area. The primary endpoint was live birth. Clinical pregnancy, pregnancy loss and ongoing pregnancy were secondary endpoints. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Chi-square tests and logistic regression were used to compare groups of patients based on TSH values in four quartile TSH groups (0.3–1.21 mIU/L; 1.22–1.75 mIU/L; 1.76–2.34 mIU/L; 2.35–4.5 mIU/L) on basic characteristics and on the endpoints while adjusting for confounders. MAIN RESULTS AND THE ROLE OF CHANCE Analysis with the natural logarithm of TSH as a continuous variable showed no association with live birth, pregnancy chance or pregnancy loss. There were no differences in any of the outcomes across the quartile TSH level ranges after regression analysis before and after adjusting for age, BMI, use of alcohol, tobacco, use or gonadotrophins, sperm count, diminished ovarian reserve, unexplained infertility and primary or secondary subfertility. The distribution of primary and secondary subfertility and smoking characteristics were remarkably different across th...

Effect of thyroxine treatment on pregnancy outcomes in infertile Japanese women with TSH levels between 2.5 μIU/mL and the upper reference limit: a retrospective study

“…In addition, the rates of pregnancy, miscarriage, and live births in infertile women with TSH ≥2.5 μIU/mL were similar to those with TSH <2.5 μIU/mL [9,10,13,15]. Although a few studies have reported that infertile women with TSH ≥2.5 μIU/mL have a lower pregnancy rate [16] and lower ovarian reserve [17] than those with TSH <2.5 μIU/mL, the present study was not able to show the difference mentioned before, similar to most previous studies [9,10,13,15].…”

“…Previous studies have reported the obstetric characteristics and outcomes of infertile women with 2.5 ≤ TSH < 4.5 μIU/mL compared with those with TSH <2.5 μIU/mL [9,10,[13][14][15]. Infertile women with TSH ≥2.5 μIU/mL had similar embryo quality as those with TSH <2.5 μIU/mL [14].…”

“…Two RCTs showed that LT4 treatment to maintain TSH <2.5 μIU/mL known as the TSH upper-reference during the first trimester in pregnant women [6], is beneficial for pregnancy outcomes such as pregnancy rate and miscarriage rate among TA-positive infertile women with subclinical hypothyroidism [7,8]. However, some observational studies showed that pregnancy and miscarriage rates in infertile women with 2.5 μIU/mL ≤ TSH < URL who underwent artificial insemination were similar to those with TSH <2.5 μIU/mL [9,10]. Furthermore, RCTs did not find the benefits of LT4 treatment for TApositive euthyroid infertile women [11,12].…”

Impact of preconceptional serum thyroid stimulating hormone values ranging between 2.5 and 4.5 mIU/L on live birth rates following ovulation induction and intrauterine insemination treatment for unexplained infertility

“…Similarly, Karmon et al reported that preconception TSH levels in the high normal range (2.5-4.99 mIU/ml) had no significant effect on clinical pregnancy rates in infertile patients undergoing IUI treatment for various indications, including male factor infertility, diminished ovarian reserve, anovulation and unexplained infertility [15]. Repelaer van Driel-Delprat et al studied the effects of TSH levels in a heterogenous group of euthyroid women who underwent up to a maximum of six cycles of IUI and found no difference in the rate of live birth, clinical and ongoing pregnancy, or pregnancy loss in patients with TSH levels between 2.35 and 4.5 mIU/L compared to women with TSH levels below 2.5 mIU/L [16].…”

Impact of Preconceptional Serum Thyroid Stimulating Hormone Values Ranging Between 2.5 and 4.5 mIU/L on Intrauterine Insemination Outcomes in Euthyroid Women with Unexplained Infertility

“…Similarly, Karmon et al reported that preconception TSH levels in the high normal range (2.5-4.99mIU/ml) had no signi cant effect on clinical pregnancy rates in infertile patients undergoing IUI treatment for various indications, including male factor infertility, diminished ovarian reserve, anovulation and unexplained infertility (15). Repelaer van Driel-Delprat et al studied the effects of TSH levels in a heterogenous group of euthyroid women who underwent up to a maximum of six cycles of IUI and found no difference in the rate of live birth, clinical and ongoing pregnancy, or pregnancy loss in patients with TSH levels between 2.35 and 4.5mIU/L compared to women with TSH levels below 2.5mIU/L (16). Independent from thyroid hormone status, thyroid autoimmunity has been linked with an increased risk of pregnancy loss due to miscarriage or premature delivery (17).…”