Different strategies for medical management before frozen embryo transfer in patients with adenomyosis

Adenomyosis is associated with reduced implantation and live birth rates after in vitro fertilization, and medical pretreatment is widely used before frozen embryo transfer (FET), although its benefit remains debated. This narrative review, informed by a systematic literature search, appraises the evidence on gonadotropin-releasing hormone agonist (GnRHa) pretreatment, alternative medical strategies and FET management, grading each strategy by study design and certainty of evidence and separating crude from confounder-adjusted estimates. Meta-analyses restricted to FET and the only randomized trial comparing GnRHa pretreatment with no pretreatment did not show improved live birth, and adjusted cohort studies yielded inconsistent results; the overall certainty of evidence is low. However, adenomyosis is a heterogeneous disease: junctional-zone involvement, particularly when combined with outer-myometrial disease, carries the poorest prognosis, and pooling different phenotypes may conceal a benefit in selected women. Because GnRHa does not suppress estrogen production within adenomyotic lesions, combined suppression with an aromatase inhibitor is biologically plausible, but clinical data are limited to case series and one retrospective cohort and remain hypothesis-generating. Letrozole monotherapy was comparable with GnRHa in one randomized trial, whereas progestin-based strategies and oral GnRH antagonists lack robust reproductive data. Randomized trials stratified by standardized phenotype are needed to identify the women who benefit from pretreatment. Different strategies for medical management prior to frozen embryo transfer in patients with adenomyosis.