Morphological and functional features of endometrial decidualization following long-term intrauterine levonorgestrel delivery

Abstract

Irregular bleeding remains a common reason for the discontinuation of progestin-only contraception. The levonorgestrel releasing intrauterine system (LNG-IUS) has profound morphological effects upon the endometrium. Specific features are gland atrophy and extensive decidual transformation of the stroma. Morphological changes in the endometrium may be associated with perturbation of mechanisms regulating normal endometrial function. This study describes endometrial stromal and glandular features prior to and up to 12 months following insertion of the LNG-IUS. Comparison is made with first trimester decidua. In order to elucidate further mechanisms governing endometrial function with local intrauterine delivery of LNG, we here report histological features consistent with decidualization; a significant increase in granulocyte-macrophage colony stimulating factor (GM-CSF) immunoreactivity in decidualized stromal cells; glandular and stromal prolactin receptor expression and an infiltrate of CD56 + large granular lymphocytes and CD68 + macrophages. We are unaware of previous reports which have documented longitudinally both morphological and functional observations in endometrium exposed to local intrauterine levonorgestrel delivery. These studies demonstrate that long-term administration of intrauterine levonorgestrel results in features of altered morphology and function. No correlation was apparent between the end points in the study and the bleeding patterns described by the subjects. Further evaluation of these features in the context of menstrual bleeding experience may contribute to a better understanding of this troublesome side-effect which often leads to dissatisfaction and discontinuation of the intrauterine system.

PIP: The levonorgestrel-releasing intrauterine system (LNG-IUS) has profound morphologic effects on the endometrium, including gland atrophy and extensive decidual transformation of the stroma. The present study investigated these morphologic changes in tissue samples collected from 14 UK women up to 12 months after insertion of the LNG-IUS. Observed histologic features consistent with decidualization included a significant increase in granulocyte-macrophage colony stimulating factor immunoreactivity in decidualized stromal cells, glandular and stromal prolactin receptor expression, and an infiltrate of CD56+ large granular lymphocytes and CD68+ macrophages. The features of pseudo-decidualization closely resembled the morphology of early pregnancy decidua. These findings confirm that the stromal compartment of the endometrium undergoes changes consistent with decidualization for at least up to 12 months after insertion of an LNG-IUS. There was no correlation between the study endpoints and the menstrual patterns reported by study subjects. Further study of the decidualized nature of the stromal cells in the LNG-exposed endometrium should enhance understanding of the mechanisms responsible for breakthrough bleeding in users of progestogen-only contraceptives.