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In Case History 2, TSH is very low suggesting the presence of TSH stimulating antibodies in the circulation even though carbimazole has successfully brought the free T4 and free T3 levels into the normal range. It is, therefore, unwise to stop treatment abruptly at this stage.

Given the risks of active Graves’ disease and antithyroid medication in pregnancy, the woman should be given the option of deferring ICSI treatment until the disease becomes quiescent again off‐treatment or is definitively treated. Carbimazole dosage could be gradually reduced then stopped under the careful monitoring of an endocrinologist. If the disease cannot be controlled with such conservative measures, a more definitive therapeutic approach with radioiodine thyroid ablation or a subtotal thyroidectomy could be considered.

If the woman chooses to proceed with ICSI while on antithyroid medication, her treatment should be converted from carbimazole to PTU (see Table 13.4 for conversion) in consultation with her endocrinologist.

Thyroid function tests should be performed 4–6 weeks after each dosage change. The aim preconceptually and during pregnancy is to maintain the free T4 level in the upper third of the normal range on as low a dose of antithyroid medication as possible to protect the fetus from hypothyroidism [11]. It is common to find that TSH concentrations remain low or fully suppressed and is thus not a good indicator of disease control.

Once thyroid function test results are stable on PTU, ICSI treatment may be commenced. During ovulation stimulation, PTU dosage may need to be reduced because of increased thyroxine requirements. Thyroid function should be checked during controlled ovarian stimulation (COS). Thyroid function should be checked again as soon as pregnancy is confirmed and at 2– to 4–weekly intervals thereafter [1,19]. Keeping the free T4 in the upper end of the normal range is particularly critical in the first trimester of pregnancy when even mild hypothyroidism should be avoided given the risks to the pregnancy and the fetus outlined in the previous section. It is not unusual for Graves’ disease to go into remission in the second half of pregnancy and PTU can often be tailed off or stopped altogether.

Table 13.4 The conversion of carbimazole to propylthiouracil (PTU) treatment in hyperthyroidism.

Carbimazole (administered once a day)	Propylthiouracil (PTU; administered twice a day)
10 mg o.d.	Total 100mg/day given 50mg b.d.
30 mg o.d.	Total 300mg/day given 150mg b.d.
60 mg o.d.	Total 600mg/day given 300mg b.d.

In addition to regular assessments of maternal blood pressure and urine as screening tests for preeclampsia, fetal growth should be monitored with regular ultrasound scans during the third trimester.

The levels of TSH receptor antibodies should be quantified during pregnancy to help predict the risk of fetal thyrotoxicosis. Levels that are greater than 3 times the upper limit of normal confer a higher risk of fetal and neonatal thyrotoxicosis [20]. Regular fetal heart auscultation for persistent fetal tachycardia can be used to screen for fetal thyrotoxicosis at each antenatal visit from 16 weeks’ gestation onwards, around the time when the fetal thyroid gland is believed to begin releasing thyroid hormones into the circulation. Left untreated, fetal thyrotoxicosis is associated with intrauterine growth restriction, fetal goiter, fetal hydrops, preterm delivery and fetal death. Thus, any suspicion of this diagnosis warrants urgent ultrasound scanning of the fetus and treatment in a specialist fetal medicine center.

The size of the maternal goiter should be monitored clinically during pregnancy. Investigations such as ultrasound scanning of the thyroid gland and a flow‐volume loop should be considered if there is significant enlargement of the gland or development of symptoms suggestive of tracheal or esophageal compression.

There is greater than 50% chance that Graves’ disease will flare postpartum and thyroid function tests should be performed over the course of the following 6 to 9 months. Breast feeding is considered safe with the lower doses of carbimazole and PTU (up to 30 mg or 300 mg daily, respectively) administered postfeeds. Monthly thyroid function tests in the baby should be considered on higher dose regimens.