Familial endocrine diseases may increase risk of pregnancy losses

Having close family members with endocrine diseases, including type 2 diabetes (T2D), thyroid diseases, and polycystic ovary syndrome (PCOS), appears to increase the risk of pregnancy losses in a first-of-a-kind study presented at ESHRE 2024.

Researchers examined the link between endocrine diseases and pregnancy losses among 366,539 women in Denmark from 1973 to 2022.

Interestingly, women with parents diagnosed with endocrine diseases had a 6 percent higher risk of pregnancy losses than those without a family history of endocrine diseases. Similarly, women with sisters who had an endocrine disease had a 7 percent higher risk of experiencing pregnancy losses. These patterns persisted even for individual cases.

“Having a family history of endocrine disease is an important, yet previously underexplored, factor in assessing the risk of pregnancy loss,” said lead study author Dr Pia Egerup from Copenhagen University Hospital Hvidovre in Hvidovre, Denmark. “This study is the first to link familial endocrine disease with pregnancy loss, providing evidence that these familial conditions contribute to the risk.”

Mechanism behind the link

The mechanism linking familial endocrine disease and pregnancy loss could be a “shared genetic background,” according to Egerup. “High-risk human leukocyte antigens (HLAs), which define the ability of the immune system to distinguish ‘good from bad’, could be involved. Specific HLA types are known to be associated with several endocrine and autoimmune diseases and could be associated with pregnancy loss.”

Apart from the link between familial endocrine disease and pregnancy loss, there was also a significant association between pregnancy loss and endocrine disease. The association increased with the number of losses.

Women with endocrine disease had a 15 percent higher risk of having one pregnancy loss (odds ratio [OR], 1.15) vs women without an endocrine disease, and a 30 percent higher risk of two losses (OR, 1.30). Additionally, the risk was higher at 81 percent, for women experiencing three or more losses (OR, 1.81).

Recurrent pregnancy loss affects 2 to 5 percent of women trying to conceive. Almost half of cases remain unexplained. [Int J Womens Health 2017; 9:331-345] It can have a significant psychological and emotional toll, with symptoms of moderate or severe depression present in approximately 10 percent of affected couples, along with feelings of anxiety, grief, guilt, and anger. [Front Glob Womens Health 2023;3:1032212]

Take a detailed family history

“Understanding the shared mechanisms between pregnancy loss and endocrine diseases could pave the way for novel preventive and therapeutic approaches to help avert pregnancy loss,” said Egerup. “Additionally, we encourage healthcare providers to consider family history when diagnosing and managing women with recurrent pregnancy losses.”

Commenting on the study, Dr Carlos Calhaz-Jorge from Hospital de Santa Maria, Lisbon, Portugal and the immediate past chair of ESHRE agreed with Egerup. “The findings underscore the importance of taking a detailed family history for all pregnant women to inform potential preventive measures.”