Maternal Endocrine Disorders Causing Early Pregnancy Loss
The primary maternal endocrine disorders that cause early pregnancy loss are hypothyroidism, hyperthyroidism, polycystic ovary syndrome (PCOS), and diabetes mellitus. 1, 2, 3
Thyroid Dysfunction
Hypothyroidism
- Hypothyroidism in the first trimester directly causes cognitive impairment in children, preterm birth, low birth weight, placental abruption, and fetal death. 1, 2
- Both clinical and subclinical hypothyroidism increase the risk of early pregnancy loss. 1
- The mechanism involves inadequate thyroid hormone for proper neurologic development of the fetus and disruption of the early implantation hormonal environment. 1, 3
- Women with hypothyroidism require levothyroxine dosage increases of 30% or more by 4-6 weeks' gestation to prevent pregnancy loss. 1
- Achieve euthyroidism before conception through levothyroxine optimization, as inadequately treated women have significantly increased pregnancy loss rates. 1, 2
Hyperthyroidism
- Uncontrolled hyperthyroidism causes preeclampsia, preterm delivery, heart failure, and miscarriage. 4, 2
- The pathophysiology involves maternal hypermetabolic state and inadequate placental perfusion. 5
- Achieve euthyroidism before pregnancy using propylthiouracil in the first trimester, then switch to methimazole in subsequent trimesters. 1, 4, 2
Thyroid Autoimmunity
- Thyroid autoimmunity independently increases early pregnancy loss risk even with normal thyroid function. 3
- Women with risk factors and symptoms should be screened, and subclinical hypothyroidism should be treated. 1
Polycystic Ovary Syndrome (PCOS)
- PCOS significantly increases the risk of early pregnancy loss through multiple mechanisms: obesity, hyperinsulinemia, elevated luteinizing hormone, and endometrial dysfunction. 6, 7
- The endometrial dysfunction in PCOS creates a hostile environment for embryo implantation and early pregnancy maintenance. 6
- Weight normalization before pregnancy and metformin treatment reduce the risk of pregnancy loss in women with PCOS. 6, 7
- PCOS also increases the risk of gestational diabetes, which further compounds pregnancy loss risk. 6
Diabetes Mellitus
- Preconception diabetes (both type 1 and type 2) causes a three-fold increase in birth defects and pregnancy loss, which is substantially reduced through proper preconception glycemic control. 1
- The mechanism involves hyperglycemia-induced embryopathy during organogenesis and early development. 1
- Transition from oral antidiabetic agents to insulin before conception, and discontinue ACE inhibitors, ARBs, and statins due to fetal renal anomalies and fetal death associations. 2
- Target A1C <6% (42 mmol/mol) if achievable without significant hypoglycemia before conception. 2
Luteal Phase Defect
- Luteal phase defect contributes to recurrent pregnancy loss through inadequate progesterone support of early pregnancy. 3, 7
- Although diagnostic criteria remain controversial, treatment with progestogen in early pregnancy appears beneficial for women with both recurrent pregnancy loss and luteal phase defect. 7
- The defect disrupts the precisely controlled hormonal milieu required for embryo attachment and implantation. 3
Clinical Approach to Screening
Screen all women with early pregnancy loss or planning conception for:
- TSH and free T4 to detect hypothyroidism and hyperthyroidism 1, 2
- Fasting glucose or A1C to identify diabetes 1, 2
- Clinical evaluation for PCOS features (irregular cycles, hyperandrogenism, obesity) 6, 7
- Thyroid antibodies in women with recurrent loss or thyroid disease risk factors 3
Common pitfall: Failing to recognize that subclinical hypothyroidism and thyroid autoimmunity without overt hypothyroidism still increase pregnancy loss risk and warrant treatment. 1, 3
Critical timing consideration: All endocrine optimization must occur before conception, as embryo attachment and early implantation occur within the first few weeks when many women don't yet know they're pregnant. 3