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.
Hyperthyroidism
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.
Key points
Challenge: ART in women with thyroid disease.
Background:
Abnormal thyroid function, particularly during the first trimester of pregnancy, is associated with increased pregnancy risks and can impact on the neurodevelopment of the child.
Controlled ovarian stimulation and pregnancy are associated with increased thyroxine requirements.
Carbimazole, methimazole and propylthiouracil are associated with teratogenicity, but the risk is least with propylthiouracil.
Reference ranges for thyroid function tests vary according to the laboratory assay, ethnicity of the population and stage of pregnancy. Thyroid treatments should ideally be optimized.
Management options:
In hypothyroid women already on thyroxine treatment:Thyroxine dosage should be increased at the start of ovarian stimulation and as soon as pregnancy is confirmed to prevent the development of hypothyroidism.Thyroid function test should be performed every 4–6 weeks during pregnancy.Thyroxine requirements should be adjusted to maintain TSH within the lower half of the trimester specific reference ranges.
In hyperthyroid women on anti‐thyroidal treatment:If on carbimazole or methimazole, convert to propylthiouracil prior to conception.Thyroid function test should be performed during COS and every 2–4 weeks during pregnancy.Antithyroid treatment should be kept to the minimum dosage required to maintain free T4 concentrations in the upper third of the normal range.
Answers to questions patients ask
1 Q1 Is levothyroxine safe to be taken in pregnancy? A1. Yes. Levothyroxine is identical to the natural thyroid hormone you produce and replaces the deficiency you have. Inadequate replacement will increase your risk of pregnancy loss and complications. Thyroxine requirements go up during ovarian stimulation and in pregnancy, so we recommend increasing your dose of levothyroxine at the start to prevent your thyroid function becoming abnormal.
2 Q2 Will taking too much levothyroxine harm my baby? A2. little too much levothyroxine taken over a short period of time does not harm your pregnancy, but too little levothyroxine is more likely to lead to complications. So, we would aim to keep your thyroid function at the more favorable end of the normal range. This means that we have to monitor your thyroid function regularly during pregnancy and adjust the dose accordingly.
3 Q3