Title: Investigating the fertility and pregnancy outcomes in women screened preconception for thyroid disease: an observational cohort study
Funder: The Academy of Medical Sciences

Abstract: The aims of this study are: 1) To explore the fertility, pregnancy, maternal and neonatal outcomes of women with a history of subfertility or miscarriage, screened preconception for thyroid stimulating hormone (TSH) and free thyroxine (fT4). 2) To identify a cut-off value for TSH at which adverse outcomes are highly prevalent. 3) To identify if initiation of levothyroxine, at any time point, has an effect on the outcomes. Normal functioning of the thyroid gland is essential for successful conception and pregnancy. Subclinical hypothyroidism (SCH) has been linked to adverse outcomes such as subfertility, miscarriage, pre-term birth, pre-eclampsia, gestational hypertension, and perinatal mortality. Internationally, there is variation in the diagnosis and management of SCH. There is also disagreement in the definition of SCH. International societies recommend lowering the preconception limit of TSH to 2.5mIU/L, particularly in women who are considered â€œhigh riskâ€ such as those with history of subfertility or miscarriage. This management strategy is controversial, since data showing evidence of benefit are conflicting and often do not consider thyroid antibody status. Furthermore, there is insufficient evidence suggesting reduced fertility outcomes or higher miscarriage rates exist in women with mild thyroid dysfunction (TSH 2.5-4.0mIU/L). It is now known that up-to 20% of women with history of subfertility or miscarriage will have TSH levels >2.5mIU/L. This will be the first large-scale observational study linking preconception thyroid function data to fertility and obstetric outcomes in women considered â€œhigh-riskâ€ and will form the foundation for a clinical trial of preconception levothyroxine in subclinical hypothyroidism.

Lay abstract: Normal functioning of the thyroid gland is essential for successful conception and pregnancy. Subclinical hypothyroidism (SCH) is a form of mild thyroid dysfunction and is a diagnosis given to those who have normal levels of thyroid hormone (thyroxine) and higher than normal levels of another hormone (thyroid stimulating hormone; TSH). SCH has been shown to be a risk factor for adverse pregnancy outcomes such as miscarriage and pre-term birth, however there is disagreement over what is defined as SCH. It remains unknown whether mildly raised levels of TSH (2.5-4.0mIUL) are linked to adverse fertility and pregnancy outcomes. Despite this, international societies recommend that for women who are considered â€œhigh riskâ€ such as those with a history of subfertility or miscarriage, a lower level of TSH should be achieved before getting pregnant (TSH <â€‹2.5mIU/L) and this is through initiating a treatment called levothyroxine. It is unknown whether this management strategy is beneficial. In addition, data from a large study has shown that up-to 20% of women will have mildly raised TSH levels (>2.5mIU/L). The aim of this study is to explore the fertility and pregnancy outcomes for women who had their thyroid function tested preconception. I wish to define SCH using an accurate cut-off which clinicians can apply when diagnosing women pre-pregnancy. Finally, I want to investigate whether levothyroxine treatment had any effect on outcomes. This will be the first study to use pre-pregnancy thyroid data and will form the foundation for a clinical trial on the subject.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: METABOLIC AND ENDOCRINE;REPRODUCTIVE HEALTH AND CHILDBIRTH