Association between adenomyosis and placenta accreta and mediation effect of assisted reproductive technology on the association: A nationwide observational study

Yoshimitsu Wada, Hironori Takahashi, Manabu Ogoyama, Kenji Horie, Hirotada Suzuki, Rie Usui, Seung Chik Jwa, Akihide Ohkuchi, Hiroyuki Fujiwara
International Journal of Gynecology & Obstetrics · 2024 · vol. 167(1) , pp. 360–367 · doi:10.1002/ijgo.15565 · PMID:38676352
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Adenomyosis was found to be significantly associated with placenta accreta spectrum, with assisted reproductive technology mediating 26.5% of this relationship in a nationwide study of Japanese women.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

This nationwide observational study used Japanese perinatal registry data (2013–2019) to examine whether adenomyosis is associated with placenta accreta spectrum (PAS) and whether assisted reproductive technology (ART) mediates that association, analyzing singleton pregnancies while excluding women with prior adenomyomectomy. Using multivariable logistic regression with multiple imputation for missing data and causal mediation analysis, the authors found that adenomyosis was significantly associated with PAS (OR 1.95, 95% CI 1.26–3.00), and that ART explained 26.5% of the association (natural indirect effect OR 1.15, 95% CI 1.01–1.41; natural direct effect OR 1.72, 95% CI 0.86–2.82). The paper’s major caveat is that it is observational and relies on mediation assumptions inherent to the causal mediation counterfactual approach. This paper is centrally about adenomyosis — specifically, its association with placenta accreta spectrum and the mediating role of assisted reproductive technology.

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Abstract

OBJECTIVES: To investigate the association between adenomyosis and placenta accreta spectrum (PAS) and to evaluate the effect of assisted reproductive technology (ART) in mediating this association. METHODS: We retrieved data for singleton women from the Japanese nationwide perinatal registry between 2013 and 2019, excluding women with a history of adenomyomectomy. To investigate the association between adenomyosis and PAS among women, we used a multivariable logistic regression model with multiple imputation for missing data. We evaluated mediation effect of ART including in vitro fertilization and intracytoplasmic sperm injection on the association between adenomyosis and PAS using causal mediation analysis based on the counterfactual approach. RESULTS: Of 1 500 173 pregnant women, 1539 (0.10%) had adenomyosis. The number receiving ART was 489/1539 (31.8%) and 117 482/1 498 634 (7.8%) in women with and without adenomyosis, respectively. The proportion of women who developed PAS was 21/1539 (1.4%) in women with adenomyosis and 7530/1 498 634 (0.5%) in women without adenomyosis. Adenomyosis was significantly associated with PAS (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.26-3.00; P = 0.002). Mediation analysis showed that OR of the total effect of adenomyosis on PAS was 1.98 (95% CI 1.13-3.04), OR of natural indirect effect (effect explained by ART) was 1.15 (95% CI 1.01-1.41), and OR of natural direct effect (effect unexplained by ART) was 1.72 (95% CI 0.86-2.82). The proportion mediated (natural indirect effect/total effect) was 26.5%. Adenomyosis was also significantly associated with PAS without previa (OR 1.96; 95% CI 1.23-3.13, P = 0.005). CONCLUSION: Adenomyosis was significantly associated with PAS. ART mediated 26.5% of the association between adenomyosis and PAS.
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Abstract

Objectives To investigate the association between adenomyosis and placenta accreta spectrum (PAS) and to evaluate the effect of assisted reproductive technology (ART) in mediating this association.

Methods

We retrieved data for singleton women from the Japanese nationwide perinatal registry between 2013 and 2019, excluding women with a history of adenomyomectomy. To investigate the association between adenomyosis and PAS among women, we used a multivariable logistic regression model with multiple imputation for missing data. We evaluated mediation effect of ART including in vitro fertilization and intracytoplasmic sperm injection on the association between adenomyosis and PAS using causal mediation analysis based on the counterfactual approach.

Results

Of 1 500 173 pregnant women, 1539 (0.10%) had adenomyosis. The number receiving ART was 489/1539 (31.8%) and 117 482/1 498 634 (7.8%) in women with and without adenomyosis, respectively. The proportion of women who developed PAS was 21/1539 (1.4%) in women with adenomyosis and 7530/1 498 634 (0.5%) in women without adenomyosis. Adenomyosis was significantly associated with PAS (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.26–3.00; P = 0.002). Mediation analysis showed that OR of the total effect of adenomyosis on PAS was 1.98 (95% CI 1.13–3.04), OR of natural indirect effect (effect explained by ART) was 1.15 (95% CI 1.01–1.41), and OR of natural direct effect (effect unexplained by ART) was 1.72 (95% CI 0.86–2.82). The proportion mediated (natural indirect effect/total effect) was 26.5%. Adenomyosis was also significantly associated with PAS without previa (OR 1.96; 95% CI 1.23–3.13, P = 0.005).

Conclusion

Adenomyosis was significantly associated with PAS. ART mediated 26.5% of the association between adenomyosis and PAS. CONFLICT OF INTEREST STATEMENT The authors have no conflicts of interest. DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the Japan Society of Obstetrics and Gynecology. Restrictions apply to the availability of these data, which were used under license for this study. Data are available at https://www.jsog.or.jp/modules/en/index.php?content_id=1 with the permission of the Japan Society of Obstetrics and Gynecology.

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Condition tags

adenomyosis

MeSH descriptors

Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Placenta Accreta Placenta Accreta

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