The impact of adenomyosis localization in myometrium on fertility and pregnancy outcomes: a narrative systematic review of the literature

Background: Adenomyosis can be categorized using various systems based on its extent, location, and severity. Depending on its location within the endometrium adenomyosis can be classified as intrinsic (inner myometrium) or extrinsic (outer myometrium). This narrative systematic review aims to comprehensively analyze existing literature to determine whether a significant correlation exists between the localization of adenomyosis within the uterus and infertility. Additionally, it evaluates the impact of intrinsic and extrinsic adenomyosis on outcomes of medically assisted reproduction, with a particular focus on clinical pregnancy and live birth rates. Methods: We conducted a narrative systematic literature search in PubMed, Scopus, ScienceDirect, Cochrane and Embase Databases from inception to June 2024. The search was based on the key words Keywords such "infertility", "assisted reproductive technologies (ART)", "adenomyosis," and "adenomyosis uteri". All English full-text prospective and retrospective observational and interventional studies with at least ten patients that described reproductive outcomes of women diagnosed with intrinsic or extrinsic adenomyosis; either through sonographic or through MRI modalities, were included. This protocol has been registered with PROSPERO (CRD42023479565). Results: A total of 5608 articles were initially identified from the search strategy with only 9 of them included in the review. Among them our review incorporated data from six retrospective studies and three prospective observational studies. Our findings revealed noteworthy difference among the different patient groups. Extrinsic adenomyosis was consistently associated with a higher prevalence of endometriosis, particularly deep infiltrating endometriosis (DIE) and ovarian endometriomas, with reported association rates reaching up to 89%. Additionally, extrinsic adenomyosis correlated with a higher prevalence of primary infertility (41.3%), compared to intrinsic adenomyosis (20.7%). In contrast, intrinsic adenomyosis exhibited a stronger association with recurrent pregnancy loss (RPL) and secondary infertility. Regarding assisted reproductive technology (ART) outcomes, available data remain limited and safe conclusions cannot be made. Conclusions: Despite the limited number of available studies and the heterogeneity in definitions of mixed, diffuse, and advanced adenomyosis, the existing evidence suggests that adenomyosis subtypes differ in clinical presentation according to their localization within the myometrium and may exert distinct effects on fertility, pregnancy, and ART outcomes. With the continuous development of our diagnostic tools and minimal invasive therapeutic methods this insight could empower clinicians to provide accurate information to their patients with adenomyosis according to the classification and potentially modify therapeutic plans based on clinical suspicions. Systematic Review Registration: PROSPERO CRD42023479565.