Adenomyosis

The impact of endometriosis and adenomyosis on reproduction and pregnancy is significant, with both conditions linked to increased rates of infertility, poor ovarian function in women with endometriosis, and elevated pregnancy complications in those with adenomyosis. However, the underlying mechanisms remain largely unclear. Both conditions share a similar pathophysiological process characterized by the growth of ectopic endometrium, which may originate from the eutopic endometrium. Notably, surgical removal of ectopic lesions does not appear to significantly improve reproductive and pregnancy outcomes, further underscoring the importance of eutopic endometrium in these adverse effects. Emerging evidence indicates substantial differences in endometrial NK cells, macrophages, and T cells, leading to inflammatory responses in women with endometriosis and adenomyosis. These alterations may contribute not only to disease progression but also to defective endometrial receptivity, insufficient angiogenesis remodeling, impaired maternal-fetal immune tolerance, and poor placentation, thereby influencing embryo implantation and pregnancy maintenance. This provides an immunological perspective to explain the higher rates of infertility and pregnancy complications observed in affected women. Therefore, we systematically review the alterations in endometrial immune cells in women with endometriosis and adenomyosis compared to healthy controls, exploring the potential impacts of these changes on reproduction and pregnancy. This review aims to lay the groundwork for future studies on the immunopathogenesis associated with endometriosis and adenomyosis-related reproductive failure and pregnancy complications, shedding lights on the development of immunotherapeutic strategies to mitigate these adverse impacts in affected women.

The potential for repeated ovulation and menstruation is thought to have provided a Darwinian advantage during the Palaeolithic. Reproductive conditions remained relatively stable until the pre-industrial era, characterized by late menarche, very young age at first birth, multiple pregnancies, and prolonged periods of lactational amenorrhoea. For hundreds of thousands of years, menstruators experienced few ovulatory cycles, even though they were genetically adapted to ovulate and menstruate every month. In the post-industrial era, the age at menarche gradually declined, the age at first birth progressively increased, and breastfeeding became optional and often of short duration. This created a mismatch between genetic adaptation and socio-environmental evolution, so that what was initially a probable reproductive advantage subsequently contributed to increased susceptibility to diseases associated with lifetime oestrogen exposure, such as ovarian, endometrial and breast cancer and, hypothetically, also those associated with the number of ovulatory menstruations, such as endometriosis and adenomyosis. The incidence of endometriosis shows a steep and progressive increase around the age of 25 years, but given the consistently reported delay in diagnosis, the actual incidence curve should be shifted to the left, supporting the possibility that the disease has its roots in adolescence. This raises the question of whether, from an evolutionary point of view, anovulation and amenorrhoea should not still be considered the physiological state, especially in the postmenarchal period. However, an increase in the frequency of endometriosis in recent decades has not been demonstrated, although this deserves further epidemiological investigation. In addition, as endometriosis occurs in a minority of individuals exposed to retrograde menstruation, other important pathogenic factors should be scrutinised. Research should be resumed to explore in more detail the transtubal reflux of not only blood, but also endometrial cells, and whether they are systematically present in the peritoneal fluid after menstruation. If repetitive ovulatory menstruation during the early reproductive years is shown to increase the risk of endometriosis and adenomyosis development and progression in susceptible individuals, hormonal interventions could be used as secondary prevention in symptomatic adolescents.

Background and Objectives: Adenomyosis (the presence of ectopic endometrial glands and stroma below the endometrial-myometrial junction) is a benign condition which is increasingly diagnosed in younger women suffering from infertility. The aim of this narrative review was to study the pathophysiology and prevalence of adenomyosis, the mechanisms causing infertility, treatment options, and reproductive outcomes in infertile women suffering from adenomyosis. Materials and Methods: A literature search for suitable articles published in the English language was performed using PubMed from January 1970 to July 2022. Results: The literature search retrieved 50 articles that met the purpose of this review and summarized the most recent findings regarding the accuracy of diagnostic methods, pathophysiology, and the prevalence of adenomyosis and optimal strategies for the treatment of infertile women with adenomyosis. Conclusions: Adenomyosis is a common gynecological disorder, affecting women of reproductive age. It negatively affects in vitro fertilization, pregnancy and the live birth rate, as well as increases the risk of miscarriage. With the advent of non-invasive diagnoses with MRI and TVUS, the role of adenomyosis in infertility has been better recognized. Overall, more randomized controlled trials (RCTs) are needed to provide strong data on the accuracy of diagnostic methods, the pathophysiology and the prevalence of adenomyosis, the fertility outcomes of patients and the optimal strategy for the treatment.

Uterine adenomyosis (AM), a common gynecological disorder, is characterized by the invasion of endometrial glands and stroma into the myometrium, resulting in chronic pelvic inflammation and severe pain. This condition not only adversely affects patients' quality of life but also correlates with diminished fertility. Recent findings underscore the critical role of natural killer (NK) cells in the pathophysiology of AM. As a vital component of innate immunity, NK cells are responsible for identifying and eliminating abnormal cells, and functional alterations of NK cells may contribute to the progression of this disease. Although existing research has suggested preliminary associations between NK-cell dysfunction and AM, the exact mechanistic pathways and their clinical implications are still not fully elucidated. This review comprehensively explores the involvement of NK cells in AM, emphasizing their functional adaptability within the immune microenvironment, interactions with cytokine networks, and potential for therapeutic targeting. Furthermore, we critically assess the translational hurdles and propose a strategic framework for implementing NK cell-based immunomodulatory approaches in clinical practice.