Pregnancy Outcomes, Placenta Histopathology and Immunohistochemistry in Patients with a History of Recurrent Pregnancy Loss or Implantation Failure Undergoing In Vitro Fertilization.

Abstract

Objective: To evaluate pregnancy outcomes, placental histopathology, and placental immune markers in pregnancies after in vitro fertilization (IVF) with a history of recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF).

Design: Retrospective cohort study.

Setting: Single academic center.

Subjects: Patients who underwent IVF with a history of RPL or RIF and age- and body mass index (BMI)-matched spontaneous pregnancies and IVF patients without a history of RPL or RIF between 2018 and 2023.

Exposure: IVF with a history of RPL or RIF.

Main outcome measures: Placental histopathology, placental immunohistochemical markers.

Results: Among 2,215 IVF cycles, 407 resulted in live births within our hospital system. We analyzed 325 IVF patients (52 with RPL, 30 with RIF and 243 without RPL/RIF) and 197 patients with spontaneous pregnancies as a reference group. Placental histopathology was available for 283 patients and immunohistochemistry (IHC) was conducted on 133 samples. After adjusting for maternal age and BMI, and correcting for multiple comparisons, pregnancies in the IVF-no RPL/RIF group had statistically increased incidence of postpartum hemorrhage, and a trend towards preeclampsia was observed in the IVF-RPL group. In placental histopathology, increased incidence of fetal vascular malperfusion, inflammatory lesions such as chronic villitis, and intervillous thrombi was noted in IVF pregnancies, especially in IVF-RPL group. IHC analysis showed significantly higher numbers of CD163+ and CD68+ placental macrophages in all IVF groups, and markedly high CD163+ cells in IVF-RIF group. IL-6 levels did not differ between groups.

Conclusion: IVF pregnancies, especially in patients with a history of RPL or RIF, are associated with adverse pregnancy outcomes and distinct placental histopathology, and elevated placental macrophages. These findings highlight the importance of individualized counseling and prenatal/postnatal surveillance although additional work is needed in larger multicenter cohorts to fully establish the pathophysiological association.