Risk factors for non-previa placenta accreta spectrum in pregnancies conceived through frozen embryo transfer during a hormone replacement cycle in Japan

Abstract

Purpose: Non-previa placenta accreta spectrum (PAS) is associated with assisted reproductive technology (ART), particularly frozen embryo transfer during hormone replacement therapy (HRC-FET). We especially aimed to evaluate the prevalence and risk factors for non-previa PAS in HRC-FET pregnancies.

Methods: Overall, 279 women who conceived through ART at three ART facilities and delivered at a single center were included in this retrospective study. Data regarding endometrial thickness at embryo transfer, previous histories, and type of embryo transfer-HRC-FET, frozen embryo transfer during a natural ovulatory cycle (NC-FET), and fresh embryo transfer (Fresh-ET)-were collected. Univariable logistic regression analyses were conducted.

Results: The prevalence of non-previa PAS was 27/192 (14.1%) in the HRC-FET group and 0 (0.0%) in both the NC-FET and Fresh-ET groups. Significantly high odds ratio [95% confidence interval] of non-previa PAS was associated with a history of artificial abortion (6.45 [1.98-21.02]), endometrial thickness <8.0 mm (6.11 [1.06-35.12]), resolved low-lying placenta (5.73 [2.13-15.41]), multiparity (2.90 [1.26-6.69]), polycystic ovarian syndrome (2.62 [1.02-6.71]), and subchorionic hematoma (2.49 [1.03-6.04]).

Conclusions: A history of artificial abortion, endometrial thickness <8.0 mm, and resolved low-lying placenta may help in antenatal detection of a high-risk population of non-previa PAS in HRC-FET pregnancies.

Keywords: assisted reproductive technology; frozen embryo transfer; hormone replacement cycle; non‐previa placenta accreta spectrum; placenta accreta spectrum.

FIGURE 1

Flow diagram depicting the study design. We first analyzed 279 women who conceived via ART at three facilities and delivered after 22 weeks of gestation at Nagoya University Hospital between 2010 and 2020. Risk factor analysis was performed in HRC‐FET pregnancies after exclusion of 12 women with placenta previa/low‐lying placenta. ART, assisted reproductive technology; HRC‐FET, frozen embryo transfer during a hormone replacement cycle; NC‐FET, frozen embryo transfer during a natural ovulatory cycle; Fresh‐ET, fresh embryo transfer; PAS, placenta accreta spectrum.

FIGURE 2

Comparison of endometrial thickness on the day of embryo transfer between the non‐previa PAS (n = 12) and control (n = 102) groups. Only the thickness measured on the day of transfer was used. Student's t‐test was performed. Error bars represent mean ± standard deviation. PAS, placenta accreta spectrum; ns, not significant.

FIGURE 3

Analysis of the number of risk factors for non‐previa PAS. (A) Risk characteristics and the amount of blood loss in women with non‐previa PAS. (B) The amount of bleeding stratified by the number of risk factors. *p < 0.05, Student's t‐test. (C) Prevalence of PAS stratified by the number of risk factors. *p < 0.05, **p < 0.01, ***p < 0.001, chi‐squared test or Fisher's exact test. PAS, placenta accreta spectrum; PCOS, polycystic ovarian syndrome; na, not applicable.