Clinical features and reproductive outcomes after first frozen embryo transfer in patients with different ultrasound-diagnosed adenomyosis subtypes following ultralong gonadotropin-releasing hormone agonist pretreatment: a retrospective cohort study

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This study compared adenomyosis subtypes, finding differences in clinical features and that adenomyosis was linked to lower implantation rates but not live birth rates after frozen embryo transfer.

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This retrospective cohort study compared clinical features and reproductive outcomes after the first frozen embryo transfer in infertility patients with various ultrasound-diagnosed adenomyosis subtypes against those without the condition. The results indicated that while live birth rates were similar between groups, patients with adenomyosis experienced significantly lower implantation rates, and greater reduction in junctional zone thickness was associated with improved live birth odds within the adenomyosis group. The authors caution that these findings require careful interpretation due to the study's retrospective design and limited statistical power in subgroup analyses. This paper is centrally about adenomyosis — specifically examining how different anatomical subtypes and pretreatment responses influence assisted reproduction outcomes.

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Abstract

BACKGROUND: The differences between adenomyosis subtypes in clinical features and reproductive outcomes remain largely unexplored. This study aimed to compare clinical features and reproductive outcomes after the first frozen embryo transfer (FET) among patients with different ultrasound-diagnosed adenomyosis subtypes following ultralong gonadotropin-releasing hormone agonist (GnRHa) pretreatment. METHODS: A retrospective cohort study was conducted and included infertility patients with (n = 179) and without (n = 179) adenomyosis undergoing first FET. Patients with adenomyosis underwent the ultralong GnRHa pretreatment before their first FET cycle. Adenomyosis was diagnosed by two-dimensional (2D) and three-dimensional (3D) transvaginal sonography (TVS) and classified into subtypes according to types (diffuse/focal/mixed) and locations (inner/outer myometrium) of lesions. Baseline characteristics, sonographic features and pregnancy outcomes after the first FET cycle were collected. The primary outcome was live birth rate after the first FET cycle. Secondary outcomes included implantation rate, clinical pregnancy rate, and miscarriage rate. RESULTS: For different subtypes of adenomyosis, patients with internal adenomyosis had a significantly higher incidence of secondary infertility than those with external adenomyosis (70.0% vs. 47.0%, P = 0.006). Patients with external adenomyosis had higher incidence of coexisting ovarian endometriosis than internal adenomyosis (27.3% vs. 13.6%, P = 0.029). Patients with diffuse and internal adenomyosis exhibited significantly larger uterine sizes and thicker anterior walls compared to those with focal (180.57 ± 33.90 mm vs. 164.32 ± 25.12 mm, P = 0.026; 21.86 ± 8.35 mm vs. 18.54 ± 7.25 mm, P = 0.042) and external adenomyosis (183.73 ± 33.56 mm vs. 165.95 ± 28.44 mm, P < 0.001; 22.92 ± 8.47 mm vs. 18.13 ± 6.81 mm, P < 0.001), respectively. No statistically significant differences were found between infertility patients with adenomyosis and without adenomyosis in baseline characteristics. Patients with adenomyosis had a lower implantation rate than those without adenomyosis (50.7% vs. 62.8%, P = 0.010), whereas live birth rate after the first FET cycle did not differ significantly between groups (49.2% vs. 47.5%, P = 0.833). In adenomyosis patients, multivariable logistic regression showed that greater reduction in junctional zone thickness after treatment was associated with a lower risk of failure to achieve live birth after the first FET cycle (OR = 0.694; 95% CI: 0.502-0.961; P = 0.028). Endometrial thickness was independently associated with failure to achieve implantation after the first FET cycle (OR = 1.257; 95% CI: 1.039-1.521; P = 0.018). CONCLUSIONS: Ultrasound-based adenomyosis subtyping revealed distinct clinical profiles. Although live birth rate after the first FET cycle did not differ significantly between groups, adenomyosis was associated with reduced implantation rate. Exploratory regression analyses suggested that greater JZ thickness reduction indicated a favorable effect on live birth, and increased endometrial thickness may be associated with implantation failure. These findings should be interpreted cautiously because of the retrospective design and limited power of subgroup analyses.
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Abstract

Background The differences between adenomyosis subtypes in clinical features and reproductive outcomes remain largely unexplored. This study aimed to compare clinical features and reproductive outcomes after the first frozen embryo transfer (FET) among patients with different ultrasound-diagnosed adenomyosis subtypes following ultralong gonadotropin-releasing hormone agonist (GnRHa) pretreatment.

Methods

A retrospective cohort study was conducted and included infertility patients with (n = 179) and without (n = 179) adenomyosis undergoing first FET. Patients with adenomyosis underwent the ultralong GnRHa pretreatment before their first FET cycle. Adenomyosis was diagnosed by two-dimensional (2D) and three-dimensional (3D) transvaginal sonography (TVS) and classified into subtypes according to types (diffuse/focal/mixed) and locations (inner/outer myometrium) of lesions. Baseline characteristics, sonographic features and pregnancy outcomes after the first FET cycle were collected. The primary outcome was live birth rate after the first FET cycle. Secondary outcomes included implantation rate, clinical pregnancy rate, and miscarriage rate.

Results

For different subtypes of adenomyosis, patients with internal adenomyosis had a significantly higher incidence of secondary infertility than those with external adenomyosis (70.0% vs. 47.0%, P = 0.006). Patients with external adenomyosis had higher incidence of coexisting ovarian endometriosis than internal adenomyosis (27.3% vs. 13.6%, P = 0.029). Patients with diffuse and internal adenomyosis exhibited significantly larger uterine sizes and thicker anterior walls compared to those with focal (180.57 ± 33.90 mm vs. 164.32 ± 25.12 mm, P = 0.026; 21.86 ± 8.35 mm vs. 18.54 ± 7.25 mm, P = 0.042) and external adenomyosis (183.73 ± 33.56 mm vs. 165.95 ± 28.44 mm, P < 0.001; 22.92 ± 8.47 mm vs. 18.13 ± 6.81 mm, P < 0.001), respectively. No statistically significant differences were found between infertility patients with adenomyosis and without adenomyosis in baseline characteristics. Patients with adenomyosis had a lower implantation rate than those without adenomyosis (50.7% vs. 62.8%, P = 0.010), whereas live birth rate after the first FET cycle did not differ significantly between groups (49.2% vs. 47.5%, P = 0.833). In adenomyosis patients, multivariable logistic regression showed that greater reduction in junctional zone thickness after treatment was associated with a lower risk of failure to achieve live birth after the first FET cycle (OR = 0.694; 95% CI: 0.502–0.961; P = 0.028). Endometrial thickness was independently associated with failure to achieve implantation after the first FET cycle (OR = 1.257; 95% CI: 1.039–1.521; P = 0.018).

Conclusions

Ultrasound-based adenomyosis subtyping revealed distinct clinical profiles. Although live birth rate after the first FET cycle did not differ significantly between groups, adenomyosis was associated with reduced implantation rate. Exploratory regression analyses suggested that greater JZ thickness reduction indicated a favorable effect on live birth, and increased endometrial thickness may be associated with implantation failure. These findings should be interpreted cautiously because of the retrospective design and limited power of subgroup analyses. Similar content being viewed by others Abbreviations - ART: - Assisted reproductive technology - FET: - Frozen embryo transfer - MUSA: - The international Morphological Uterus Sonographic Assessment - FAOM: - Focal adenomyosis of the outer myometrium - GnRHa: - Gonadotropin-releasing hormone agonist - JZ: - Junctional zone - PGT: - Preimplantation genetic testing - 2D: - Two-dimensional - 3D: - Three-dimensional - BMI: - Body mass index - SD: - Standard deviation - AFC: - Antral follicle count - CYP-19: - Cytochrome P450 Family 19 - CLBR: - cumulative live birth rate

Acknowledgements

Not applicable. Funding This work was supported by the National Natural Science Foundation of China (No. 82071646, 82371678), Scientific research project of Jiangsu Province Association of Maternal and Child Health (No. FYX202203), Open project of the Affiliated Jiangning Hospital of Nanjing Medical University Immune Cell Transformation Research Center (JNYYZXKY202213), Nanjing Drum Tower Hospital Medical Center Project (2022-YXZX-FC-03), Fertility Research Program of Young and Middle-aged Physicians-Clinical Research In 2022 (Beijing Health Promotion Association, BJHPA-2022-SHZHYXZHQNYJ-LCH-002). There are no conflicts of interest. Author information Authors and Affiliations Corresponding authors Ethics declarations Ethics approval and consent to participate This retrospective study received ethical approval from the ethics committee of Nanjing Drum Tower Hospital. All methods followed the relevant guidelines and regulations, strictly adhering to the Declaration of Helsinki. The informed consent was waived by the same ethics committee that approved the study (the ethics committee of Nanjing Drum Tower Hospital). Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Jiang, J., Li, L., Hou, X. et al. Clinical features and reproductive outcomes after first frozen embryo transfer in patients with different ultrasound-diagnosed adenomyosis subtypes following ultralong gonadotropin-releasing hormone agonist pretreatment: a retrospective cohort study. BMC Pregnancy Childbirth (2026). https://doi.org/10.1186/s12884-026-09624-x Received: Accepted: Published: DOI: https://doi.org/10.1186/s12884-026-09624-x

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