Second-trimester pregnancy loss after in vitro fertilization: risk factors and risk reduction

To study changes in the rate and potential causes of second-trimester loss (STL) after in vitro fertilization (IVF) after 2 decades marked by the gradual adoption of elective single embryo transfer.

Retrospective cohort study.

All patients who conceived via IVF between 2015 and 2023 at an academic fertility center. Patients who underwent therapeutic termination were excluded.

In vitro fertilization.

The primary outcome was the rate of STL after IVF. Secondary associated factors assessed included multiple pregnancy, race, uterine defects and tubal factor infertility. Secondary factors were compared with all live births (n = 853), uterine factors were compared with a subset with equivalent uterine structural evaluation. (n = 595). Outcomes were compared with our prior data from 1999-2002.

A total of 971 patients with clinical pregnancies were included; 10.2% resulted in a first-trimester loss and a total of 14 patients in our group had a STL. These patients were compared with a control group of 853 patients. Adenomyosis was found to be associated with an increased risk of STL, 35.7% (5/14), compared with 6.4% (38/595) of patients in our control group. Additionally, intrauterine scarring was associated with a higher rate of STL at 35.7% (5/14) vs. 12.6% (75/595). Tuboperitoneal disease was positively associated with STL with 42.9% (6/14), compared with 13.6% (116/853) among the control group. Additionally, patients who identified as Black were associated with an 8.0% (6/75) risk of STL and patients who identified as Hispanic were associated with increased risk of STL at 4.1% (5/122). In univariate analysis, a significant association was found between patients who identified as Black and STL, with 20 times higher odds of STL than patients who identified as White. A significant association was also found between patients who identified as Hispanic or Latino and STL, with 7.90 times higher odds of STL than patients who identified as White. When adjusting for race and ethnicity, parity, and preimplantation genetic testing for aneuploidy (PGT-A) usage in the multivariate model, uterine factor was found to have a significant association with STL, with 32.95 times higher odds of STL in patients with uterine factor.

Factors associated with STL include Black race, Hispanic ethnicity, adenomyosis, tubal factor infertility, and intrauterine scarring, with the racial and ethnic disparities in STL largely unchanged over 2 decades. Further study is needed to tailor risk prevention for reducing STL after IVF in at-risk groups.