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A clinical practice guideline [1], based on clinical evidence and the consensus opinion of an international panel of Endocrinology experts, has recommended that in women with preexisting hypothyroidism, the TSH level should be kept below 2.5 mU/L before embarking on a pregnancy. When pregnant, levothyroxine doses should be increased by 4–6 weeks of gestation and by an increment of around 30% of the existing dose because thyroxine requirements are known to increase at the start of pregnancy in the vast majority of cases. Thyroid function should be checked 30–40 days after every dosage change. Results should be interpreted using trimester‐specific reference ranges where available, keeping the TSH within the lower half of the respective ranges. Otherwise TSH concentrations should be kept below 2.5 mU/L throughout pregnancy. (See Table 13.3)

Table 13.3 Recommendations for thyroid function monitoring in pregnancy in the absence of trimester‐specific reference ranges.

	TSH target (mU/L)	Thyroxine adjustments (average daily dose)	Thyroid function test monitoring
Preconception First trimester Second and third trimesters Postpartum	Below 2.5 Below 2.5 Below 2.5 Nonpregnant range	Adjust by 25–50 μg at a time Increase thyroxine by 30–50% when pregnancy confirmed Adjust by 12.5–25 μg at a time Reduce thyroxine back to prepregnancy dose	4–6 weeks after each dose change Every 4–6 weeks 4–6 weeks after dose changes. If stable, at least once in each trimester 6 weeks postpartum

Another set of guidelines, issued by the British Thyroid Association and Association of Clinical Biochemists [8], recommend that at the diagnosis of pregnancy, thyroxine should be increased by 25 or 50 μg. When adjusting thyroxine treatment during pregnancy TSH should be kept towards the lower end of the normal range (ideally between 0.4 and 2.0 mU/L), and free T4 at the upper end of the normal range throughout pregnancy using trimester specific reference ranges. Thyroid function should ideally be tested preconception, at the diagnosis of pregnancy, at antenatal booking and monitored at least once in each trimester of pregnancy.

Just as in pregnancy, thyroxine requirements are also increased with controlled ovarian hyperstimulation during assisted reproduction. Thus, women already on thyroxine replacement should also have a dosage increase in the region of 20–30% at the start of such infertility treatment [17].

The woman in Case History 1 should increase her thyroxine dose by 25 μg at a time with thyroid function tests performed 4–6 weeks after each dose increment until the TSH concentration is below 2.5 mU/L, before commencing IVF treatment. At the start of ovarian stimulation, she should be advised to increase her dose of thyroxine by 25 μg daily. As soon as she has a positive pregnancy test, she should be advised to increase thyroxine by a further 25 μg on 2–3 days a week (approximately 30% of her prepregnancy dose). At the same time, she should also have her TSH and free T4 concentrations tested and if results suggest inadequate thyroid hormone replacement, a further dose increase of 25 μg on the remaining days of the week may be appropriate. The aim would be to anticipate increased dose requirements and prevent abnormalities in thyroid function test results during pregnancy. As there has been no evidence that subclinical or mild hyperthyroidism is associated with any adverse outcome [18] the balance of risk is in favor of thyroxine dose increases in maternal hypothyroidism. Dose change recommendations should be made promptly, and thyroid function checks made 4–6 weeks later on every occasion.