# Effect of extended hormonal suppression in patients with adenomyosis undergoing embryo transfer

**Authors:** Andrea Etrusco, Antonio Maiorana, Ilaria Roncarati, Mauro Cozzolino

PMC · DOI: 10.3389/frph.2026.1760832 · Frontiers in Reproductive Health · 2026-02-05

## TL;DR

This paper reviews how extended hormonal suppression before embryo transfer may improve outcomes for women with adenomyosis, a uterine condition linked to infertility.

## Contribution

The paper systematically evaluates various hormonal suppression protocols and their effectiveness in improving reproductive outcomes for adenomyosis patients undergoing embryo transfer.

## Key findings

- Extended GnRHa pretreatment, especially in frozen embryo transfers, may improve implantation and reduce miscarriage.
- Deeper suppression with aromatase inhibitors or progestins may offer additional benefits in severe adenomyosis cases.
- Current evidence is limited by study heterogeneity and methodological weaknesses, requiring further well-designed trials.

## Abstract

Adenomyosis is an estrogen-dependent uterine disorder increasingly recognized as a major cause of infertility and adverse obstetric outcomes, yet optimal medical preparation before embryo transfer (ET) remains uncertain. Adenomyotic lesions create a hyperestrogenic, inflammatory, and architecturally distorted uterine environment that may impair endometrial receptivity and increase miscarriage risk, compromising assisted reproductive technology (ART) success. This review summarizes current evidence on extended hormonal suppression in patients with adenomyosis undergoing in vitro fertilization and ET. We examine the rationale, protocols, and reproductive outcomes of ultra-long gonadotropin-releasing hormone agonist (GnRHa) regimens, intensified suppression with GnRHa plus aromatase inhibitors, levonorgestrel-releasing intrauterine systems, oral dienogest, and continuous combined oral contraceptives. Available data suggest that prolonged GnRHa pretreatment, particularly in freeze-all strategies with frozen ET, may improve implantation and reduce miscarriage, with additional benefit from deeper suppression in selected severe cases. Progestin-based approaches appear promising but remain less well studied, while combined oral contraceptives mainly provide symptom control. The review highlights the heterogeneity and methodological limitations of existing studies and underscores the need for well-designed trials to define the optimal regimen, duration, and patient selection criteria for extended hormonal suppression before ET in women with adenomyosis.

## Linked entities

- **Chemicals:** dienogest (PubChem CID 68861), levonorgestrel (PubChem CID 13109)
- **Diseases:** adenomyosis (MONDO:0010888)

## Full-text entities

- **Genes:** LIF (LIF interleukin 6 family cytokine) [NCBI Gene 3976] {aka CDF, DIA, HILDA, MLPLI}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588] {aka ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX}, MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, HSD17B13 (hydroxysteroid 17-beta dehydrogenase 13) [NCBI Gene 345275] {aka FLDP, HMFN0376, NIIL497, SCDR9, SDR16C3}, HOXA10 (homeobox A10) [NCBI Gene 3206] {aka HOX1, HOX1.8, HOX1H, PL}
- **Diseases:** adenomyotic uterus (MESH:D014594), progesterone (MESH:C564871), IVF failures (MESH:D051437), atrophy (MESH:D001284), inflammation (MESH:D007249), headache (MESH:D006261), ovarian cysts (MESH:D010048), endometriosis (MESH:D004715), pain (MESH:D010146), COCs (MESH:D053632), bleeding (MESH:D006470), nausea (MESH:D009325), Adenomyotic lesions (MESH:D009059), weight gain (MESH:D015430), Adenomyosis (MESH:D062788), bone density loss (MESH:D001851), fatigue (MESH:D005221), infertility (MESH:D007246), infection (MESH:D007239), heavy (MESH:D008595), arthralgia (MESH:D018771), hot flushes (MESH:D005483), ET (MESH:D020964), pelvic pain (MESH:D017699), dysmenorrhea (MESH:D004412), venous thromboembolism (MESH:D054556), breast tenderness (MESH:D061325), ovarian over-suppression (MESH:D010049), acne (MESH:D000152), cysts (MESH:D003560), IVF (MESH:C566179), miscarriage (MESH:D000022), dryness (MESH:D014987), fibroids (MESH:D007889), estrogen (MESH:D056828), uterine disorder (MESH:D014591), vaginal dryness (MESH:D014627), thromboembolism (MESH:D013923)
- **Chemicals:** prostaglandins (MESH:D011453), estradiol (MESH:D004958), LNG (MESH:D016912), Dienogest (MESH:C023635), progesterone (MESH:D011374), aspirin (MESH:D001241), GnRHa (-), Letrozole (MESH:D000077289)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12916556/full.md

## References

59 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916556/full.md

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Source: https://tomesphere.com/paper/PMC12916556