Pregnancy loss risk heightened by family history of endocrine diseases

Women who have close family members with endocrine diseases, including type 2 diabetes, thyroid diseases and polycystic ovary syndrome (PCOS), are at higher risk of pregnancy loss, a new study has found.

The research, presented today at the ESHRE 40^th Annual Meeting in Amsterdam, examined the association between various endocrine diseases and the incidence of pregnancy loss. The study investigated 366,539 women in Denmark between 1973 and 2022.

The study found that women with parents diagnosed with endocrine diseases faced a 6% higher risk of pregnancy loss compared to those without a family history of endocrine diseases. Similarly, if a woman's sister had an endocrine disease, her risk of experiencing pregnancy loss increased by 7%. These patterns persisted even when individual cases of the diseases were considered.

The results highlight having a family history of endocrine disease as an important, yet previously underexplored, factor in assessing the risk of pregnancy loss.

This study is the first of its kind to link familial endocrine disease with pregnancy loss, providing evidence that these familial conditions contribute to the risk.

We believe that the mechanism linking familial endocrine disease and pregnancy loss could be a shared genetic background, predisposing individuals to both endocrine disease and pregnancy loss. One potential mechanism could involve high risk human leukocyte antigens (HLAs), which define the immune system's ability to distinguish 'good from bad'. Specific HLA types are known to be associated with several endocrine and autoimmune diseases and could also be associated with pregnancy loss."

Dr. Pia Egerup, from Copenhagen University Hospital Hvidovre and lead author of the study

The endocrine system is a complex collection of glands and organs that use hormones to regulate various bodily processes, including metabolism, growth and mood. Dysfunction in one or more parts of the system can lead to hormone imbalances, or improper responses from the body to the hormones produced. Endocrine diseases have different causes dependent on the condition, which include type 1 and 2 diabetes, PCOS and hyperthyroidism or hypothyroidism.

In addition to uncovering the link between familial endocrine disease and pregnancy loss, the research also demonstrated a significant association between pregnancy loss and endocrine disease, showing that the association increases with the number of losses. Women with endocrine disease had a 15% higher risk of experiencing one pregnancy loss (OR 1.15, 95% CI 1.12-1.17) compared to women without an endocrine disease, and a 30% higher risk of experiencing two losses (OR 1.30, 95% CI 1.24-1.37). Additionally, the risk was notably higher, at 81%, for women experiencing three or more losses (OR 1.81, 95% CI 1.70-1.93).

Recurrent pregnancy loss affects between 2-5% of women trying to conceive and almost half of cases remain unexplained. It can have a significant psychological and emotional toll, with symptoms of moderate or severe depression present in approximately 10% of affected couples, along with feelings of anxiety, grief, guilt and anger.

Dr Egerup furthers, "Understanding the shared mechanisms between pregnancy loss and endocrine diseases could pave the way for novel preventive and therapeutic approaches to help prevent pregnancy loss. Additionally, we encourage healthcare providers to consider family history when diagnosing and managing women with recurrent pregnancy loss as a result of these findings."

Professor Dr Carlos Calhaz-Jorge, Immediate Past Chair of ESHRE, comments, "This study provides evidence of an increased risk of pregnancy loss if certain endocrine diseases are present in a woman's family. This information underscores the importance of taking a detailed family history for all pregnant women to inform potential preventive measures."

The study abstract will be published today in Human Reproduction, one of the world's leading reproductive medicine journals.