Adenomyosis and Second-Trimester Pregnancy Loss After IVF: What a 2025 Study Shows

By Emanuela Lazzaroni Tealdi, MSc Senior Embryologist & Reproductive Biologist Endometriosis Surgical Specialists International (ESSI)

Second-trimester pregnancy loss is uncommon, but when it occurs, it has a significant emotional and clinical impact. Understanding which factors are associated with these rare losses is essential—not to create fear, but to support informed care and proactive monitoring.

A major 2025 study published in F&S Reports by Rubin, Nussbaum, Keltz, and colleagues examined the risk factors for second-trimester pregnancy loss in the modern era of elective single-embryo transfer (eSET). One of the uterine factors most clearly associated with these losses was adenomyosis.

Study Overview

The authors conducted a rigorous single-institution retrospective cohort study to analyze modern IVF outcomes.

• Cohort Size: 971 clinical IVF pregnancies

• Study Period: 2015–2023

• Patient Age: 18–42 years old

• Definition: Second-trimester loss was defined as pregnancy loss between 13 and 27 weeks gestation.

• Exclusions: Therapeutic terminations for fetal anomalies were excluded to focus on spontaneous loss.

How Common Was Second-Trimester Loss?

In this modern cohort, second-trimester loss was relatively rare:

• 14 out of 971 pregnancies resulted in loss.

• Overall Rate: 1.6%

This represents a marked reduction compared with the authors’ earlier IVF cohort data from 1999–2002, when the rate was 7.7%. The researchers attribute this decline to major advancements in IVF practice, particularly the widespread adoption of elective single-embryo transfer, which reduces high-risk multiple gestations.

Causes of Loss

Among the 14 confirmed losses:

• 13 cases were attributed to preterm premature rupture of membranes (PPROM) and/or cervical insufficiency.

• 1 case was attributed to fetal demise.

Notably, these losses were not primarily attributed to embryo aneuploidy (chromosomal abnormalities), suggesting that uterine and maternal factors played the dominant role.

Uterine Factors: Key Findings

The study compared patients who experienced second-trimester loss against a control group of patients who achieved live births. The data revealed a stark difference in uterine pathology.

Factors NOT Associated with Increased Risk:

• Uterine Fibroids

• Congenital Uterine Anomalies (e.g., septate uterus)

Factors STRONGLY Associated with Increased Risk:

1. Adenomyosis

• Loss Group: Present in 35.7% of patients.

• Control Group: Present in only 6.4% of patients.

• Conclusion: The presence of adenomyosis was statistically significant in the loss group.

2. Intrauterine Scarring (Asherman’s Syndrome)

• Loss Group: Present in 35.7% of patients.

• Control Group: Present in 12.6% of patients.

3. Tubal Factor Infertility

• Loss Group: 42.9% prevalence.

• Control Group: 13.6% prevalence.

• This finding aligns with earlier data suggesting that hydrosalpinx or tubal disease may create an inflammatory environment hostile to pregnancy maintenance.

Demographic Disparities

The study also analyzed self-reported race and ethnicity, uncovering persistent disparities in outcomes despite the overall reduction in loss rates.

Reported Rates of Second-Trimester Loss:

• Black Patients: 8.7%

• Hispanic Patients: 4.3%

• White Patients: 0.4%

• Asian Patients: 2.3%

In both univariate and multivariate analyses, the associations with Black race and Hispanic ethnicity remained statistically significant. While the study does not identify the specific mechanisms (e.g., systemic health factors, access to care, or environmental stressors) and does not attribute these to genetic causes, it highlights a critical area for ongoing clinical awareness and support.

Key Takeaway

Second-trimester pregnancy loss after IVF is now uncommon, thanks to modern transfer protocols. However, this 2025 data confirms that uterine health matters.

Adenomyosis was identified as a primary uterine risk factor for these rare losses, alongside intrauterine scarring and tubal factor infertility. For patients with a diagnosis of adenomyosis, this underscores the importance of:

1. Pre-conception Optimization: Addressing the inflammatory uterine environment before transfer.

2. High-Risk Monitoring: Vigilance for cervical shortening or signs of preterm labor during the second trimester.

 

 

Rubin et al., “Second-trimester pregnancy loss after in vitro fertilization: risk factors and risk reduction,” published in F&S Reports (2025).