Ultrasound-defined adenomyosis subtypes and their impact on outcomes following frozen embryo transfer: a propensity score-matched cohort study

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This study found that adenomyosis, especially internal and mixed types defined by ultrasound, is linked to lower live birth rates and higher early pregnancy loss after frozen embryo transfer.

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This retrospective single-center study evaluated whether ultrasound-defined adenomyosis subtypes using revised MUSA criteria are associated with reproductive and obstetric outcomes after a first frozen embryo transfer (FET) cycle with high-quality embryos, comparing 879 women with adenomyosis to 879 propensity score-matched controls without ultrasound evidence of adenomyosis. The primary outcome was live birth (≥28 weeks), and live birth was significantly lower in women with adenomyosis overall (35.38% vs 45.16%; OR 0.67, P < 0.001). External adenomyosis had live-birth rates comparable to controls, whereas internal and mixed subtypes had progressively lower live-birth rates (internal OR 0.52; mixed OR 0.28) and adenomyosis was associated with higher early pregnancy loss among clinical pregnancies (22.25% vs 15.65%; OR 1.54, P = 0.011), with no broad differences in most other outcomes among those achieving live birth. The authors note limitations inherent to a retrospective, single-center design, and prospective validation is needed, and data are not publicly available due to privacy/ethics. This paper is centrally about adenomyosis — it uses ultrasound-defined MUSA subtypes to assess their impact on live birth and early pregnancy loss after FET.

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Abstract

OBJECTIVE: To evaluate the association of adenomyosis subtypes defined by ultrasound using the revised Morphological Uterus Sonographic Assessment (MUSA) criteria, with reproductive and obstetric outcomes following frozen embryo transfer (FET). METHODS: This retrospective, single-center cohort study included women who underwent their first FET cycle, as well as transvaginal ultrasound evaluation for the diagnosis of adenomyosis using the revised MUSA criteria, between August 2022 and June 2024. We included only FET cycles in which transferred embryos were of high quality. Adenomyosis subtypes were defined as follows: external (confined to the outer myometrium), internal (involving the inner myometrium, corresponding to the endometrial-myometrial junction, and/or the middle myometrium) and mixed (affecting both inner and outer myometrium). Controls were selected from women without ultrasound evidence of adenomyosis who underwent FET during the same period. Propensity score matching (1:1) was performed using patient age, body mass index, anti-Müllerian hormone level, infertility type, embryo stage, cause of infertility, FET protocol and number of embryos transferred. Comparative analyses were conducted to assess differences in reproductive and obstetric outcomes in women with adenomyosis, both overall and its subtypes, vs matched controls. The primary outcome was live birth, defined as delivery of at least one live infant at ≥ 28 weeks' gestation. Secondary outcomes were: implantation, clinical pregnancy, ectopic pregnancy, early pregnancy loss (< 12 weeks), late pregnancy loss (12-28 weeks), multiple pregnancy, preterm birth (< 37 weeks), low birth weight (< 2500 g), fetal growth restriction, hypertensive disorders of pregnancy, gestational diabetes mellitus, placenta previa, placenta accreta, placental abruption, premature rupture of membranes and delivery by Cesarean section. RESULTS: Of 4146 eligible women, 879 with adenomyosis and 879 matched controls without adenomyosis were included in the analysis. Their age ranged from 20 to 42 years. The rate of live birth was significantly lower in the group with adenomyosis compared to controls (35.38% vs 45.16%, P < 0.001; odds ratio (OR), 0.67 (95% CI, 0.55-0.81)). Women with external adenomyosis, accounting for over 50% of cases, had a live-birth rate comparable with that of their matched controls (45.80% vs 46.85%, P = 0.795; OR, 0.96 (95% CI 0.74-1.24)), whereas the live-birth rate was significantly lower for women with internal adenomyosis (27.44% vs 42.33%, P = 0.002; OR, 0.52 (95% CI, 0.34-0.77)) and even lower for those with mixed-type adenomyosis (18.09% vs 44.15%, P < 0.001; OR, 0.28 (95% CI, 0.17-0.45)) compared with controls. The rate of early pregnancy loss was higher in adenomyosis patients compared with controls (22.25% vs 15.65% of clinical pregnancies, P = 0.011; OR, 1.54 (95% CI, 1.10-2.15)). There were no significant differences in most of the other secondary outcomes in women with a live birth, between those with adenomyosis and controls. However, subgroup analysis revealed several significant associations between adenomyosis phenotypes, mainly internal and mixed-type adenomyosis, and specific obstetric outcomes. CONCLUSIONS: Adenomyosis, particularly internal and mixed-type, is associated with a reduced live-birth rate and an increased risk of early pregnancy loss in those achieving clinical pregnancy following FET. Ultrasound-based phenotyping of adenomyosis prior to FET may support individualized assisted reproductive technology management. Further prospective studies are needed to validate these results. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.
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Abstract

Objective To evaluate the association of adenomyosis subtypes defined by ultrasound using the revised Morphological Uterus Sonographic Assessment (MUSA) criteria, with reproductive and obstetric outcomes following frozen embryo transfer (FET).

Methods

This retrospective, single-center cohort study included women who underwent their first FET cycle, as well as transvaginal ultrasound evaluation for the diagnosis of adenomyosis using the revised MUSA criteria, between August 2022 and June 2024. We included only FET cycles in which transferred embryos were of high quality. Adenomyosis subtypes were defined as follows: external (confined to the outer myometrium), internal (involving the inner myometrium, corresponding to the endometrial–myometrial junction, and/or the middle myometrium) and mixed (affecting both inner and outer myometrium). Controls were selected from women without ultrasound evidence of adenomyosis who underwent FET during the same period. Propensity score matching (1:1) was performed using patient age, body mass index, anti-Müllerian hormone level, infertility type, embryo stage, cause of infertility, FET protocol and number of embryos transferred. Comparative analyses were conducted to assess differences in reproductive and obstetric outcomes in women with adenomyosis, both overall and its subtypes, vs matched controls. The primary outcome was live birth, defined as delivery of at least one live infant at ≥ 28 weeks' gestation. Secondary outcomes were: implantation, clinical pregnancy, ectopic pregnancy, early pregnancy loss (< 12 weeks), late pregnancy loss (12–28 weeks), multiple pregnancy, preterm birth (< 37 weeks), low birth weight (< 2500 g), fetal growth restriction, hypertensive disorders of pregnancy, gestational diabetes mellitus, placenta previa, placenta accreta, placental abruption, premature rupture of membranes and delivery by Cesarean section.

Results

Of 4146 eligible women, 879 with adenomyosis and 879 matched controls without adenomyosis were included in the analysis. Their age ranged from 20 to 42 years. The rate of live birth was significantly lower in the group with adenomyosis compared to controls (35.38% vs 45.16%, P < 0.001; odds ratio (OR), 0.67 (95% CI, 0.55–0.81)). Women with external adenomyosis, accounting for over 50% of cases, had a live-birth rate comparable with that of their matched controls (45.80% vs 46.85%, P = 0.795; OR, 0.96 (95% CI 0.74–1.24)), whereas the live-birth rate was significantly lower for women with internal adenomyosis (27.44% vs 42.33%, P = 0.002; OR, 0.52 (95% CI, 0.34–0.77)) and even lower for those with mixed-type adenomyosis (18.09% vs 44.15%, P < 0.001; OR, 0.28 (95% CI, 0.17–0.45)) compared with controls. The rate of early pregnancy loss was higher in adenomyosis patients compared with controls (22.25% vs 15.65% of clinical pregnancies, P = 0.011; OR, 1.54 (95% CI, 1.10–2.15)). There were no significant differences in most of the other secondary outcomes in women with a live birth, between those with adenomyosis and controls. However, subgroup analysis revealed several significant associations between adenomyosis phenotypes, mainly internal and mixed-type adenomyosis, and specific obstetric outcomes.

Conclusions

Adenomyosis, particularly internal and mixed-type, is associated with a reduced live-birth rate and an increased risk of early pregnancy loss in those achieving clinical pregnancy following FET. Ultrasound-based phenotyping of adenomyosis prior to FET may support individualized assisted reproductive technology management. Further prospective studies are needed to validate these results. © 2025 International Society of Ultrasound in Obstetrics and Gynecology. DATA AVAILABILITY STATEMENT The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Outcome instruments

MUSA

Condition tags

adenomyosisinfertility

MeSH descriptors

Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis

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