ESHRE 2023: Management of Adenomyosis: Current Strategies and Future Perspectives

Increased CD8 T-cell exhaustion due to high NKG2A/HLA-E engagement and IL-15 induction in adenomyosis - Xue Jiao

Adenomyosis is a benign gynecological disorder by the presence of endometrial glands and stroma within the myometrium.  Around 20% of the reproductive-aged women suffer from adenomyosis. There are multiple hypotheses regarding the pathogenesis of adenomyosis, but it needs to be yet fully understood. One process involved in the development of adenomyosis is the increased capacity of some endometrial cells to infiltrate the myometrium. Moreover, the local and systemic immune systems are associated with the onset of the disease and with maintaining it. Numerous observations have highlighted the activation of immune cells and the release of immune soluble factors in adenomyosis. The contribution of immunity occurs in conjunction with hormonal aberrations and activation of the epithelial to mesenchymal transition (EMT) pathway, which promotes migration of endometrial cells. The pathogenic immune subsets and functional disturbance in uterine environments in adenomyosis remains unknown. Increased NKG2A*CD8* T cell exhaustion is seen due to high NKG2A/HLA-E engagement and IL-5 induction which causes severity in adenomyosis. Neonatal tamoxifen treatment induces adenomyosis in adulthood. Targeting exhausted T cells by NKG2A blockade holds a therapeutic potential for adenomyosis.

Anti-angiogenic therapy as treatment for adenomyosis in mice - Marissa Harmsen

Adenomyosis leads to clinical symptoms like dysmenorrhea, abnormal uterine bleeding and infertility, thus reducing the quality of life in women. The treatment of adenomyosis is important not only to reduce the symptoms but also to possibly restore fertility. It is important to understand the pathogenesis of adenomyosis and treatment should be based accordingly rather than focusing on treating symptoms only. This study was done in mice to test the effect of angiogenesis inhibition. The results showed reduction in the severity of adenomyosis with axitinib treatment. There was a promising effect of low dose angiogenesis inhibition seen. Further studies are required to provide safety and side-effect profile tolerability in human population and if angiogenesis inhibition can be a treatment option for fertility sparing in adenomyosis.

Uterine contractility in women with adenomyosis differs significantly from healthy control women: the WAVES study - Sophie Thomas

Uterine contractility has a wave-like rhythm which differs during menstrual phases and is different in abnormal uteri. The WAVES study was done to measure uterine dynamics using speckle tracking during 2D transvaginal ultrasound (TVUS), describe uterine contractility characteristics in adenomyosis patients compared to healthy women and correlated with the degree of dysmenorrhea. This is an ongoing multicenter prospective observational cohort study with a study population of 31 women with adenomyosis and 106 women with healthy uteri. A 3-4 minute TVUS was performed in different phases  like menstrual, mid-follicular, periovulatory, early luteal and late luteal and dysmenorrhea was scored according to Visual analogue score (VAS). The results show that the uterine contractility differs significantly between patients with adenomyosis versus healthy women throughout the menstrual cycle and more dysmenorrhea in adenomyosis patients was associated with a different contractility pattern. This can be a potential marker for therapeutic intervention. Further study is ongoing to evaluate extent of adenomyosis, track performance of treatment over time, evaluate extent of adenomyosis on subfertility and research of uterine contractility in other abnormal uteri.

Presence of adenomyosis impairs clinical outcomes in women undergoing frozen embryo transfer - N.Sachs-Guedi

This retrospective cohort study was done to assess the clinical outcomes in women undergoing frozen embryo transfer with the presence of adenomyosis. The study population included 3363 control patients and 140 adenomyosis patients and a multivariable logistic regression was performed. The results showed that the presence of adenomyosis is associated with lower clinical pregnancy rate, higher miscarriage rate, lower live birth rate when practicing artificial cycle frozen blastocyst transfer. It was also found that GnRH antagonist pretreatment does not increase the clinical outcomes. Future prospective studies are needed to reach a consensus on the optimal ET technique for these patients.

Reproductive and neonatal outcomes in women with adenomyosis : a population based study - M Bazorah

Uterine adenomyosis is a disorder in which endometrial glands and stroma are present within the myometrium, resulting in hypertrophy of the surrounding myometrium. Patients with adenomyosis experience greater  adverse obstetrical and gynecological events which include but are not limited to, infertility, preterm delivery and endometriosis. Currently, the literature provides limited evidence regarding obstetrical risk in patients diagnosed with adenomyosis. This study was done to provide an in-depth analysis of a population database to expand and provide evidence-based insight on pregnancy and neonatal outcomes in women with adenomyosis. A retrospective population-based study was conducted utilizing data from the Health care cost and utilization project nationwide inpatient sample database (HCUP-NIS) over 11 years from 2004 to 2014. A cohort of all deliveries was created by using international classification of diseases. Within this group, all women with adenomyosis were identified using ICD-9 diagnostic code and the remaining deliveries were categorized as non-adenomyosis births and comprised the reference group. An initial analysis was performed to identify the prevalence of pregnant women with adenomyosis over the entire duration of the study. Subsequently, logistic regression analysis were conducted to explore association between adenomyosis and pregnancy, delivery and neonatal outcomes. The results showed that there were 9096788 births between 2004 and 2014. Of these pregnancies, 2467 women were diagnosed with adenomyosis. It was concluded that patients with adenomyosis are at greater risk for adverse obstetrical and neonatal outcomes and may benefit from increased surveillance to reduce and/or prevent the risk of associated maternal and neonatal morbidities. The mechanism behind adverse pregnancy, and neonatal outcomes observed in relation to adenomyosis remain unknown. A number of dysregulated mechanisms are suggested to contribute to the development of adenomyosis and may contribute to pregnancy complications, including endometrial proliferation and invasiveness, aberrant immune responses and abnormal sex steroid signaling.

Does the ‘freeze all’ strategy improve live birth rates in the presence of adenomyosis? - Mathilde Bourdon

This observational cohort study was done to compare ART outcomes between a fresh versus a freeze all strategy in infertile women affected with adenomyosis. The study population included 111 in the fresh group and 195 in the freeze all group. The results showed that the freeze-all strategy in women afflicted with adenomyosis undergoing ART was associated with significantly higher cumulative live birth rates. The preliminary results suggest that the freeze-all strategy is an attractive option that can increase ART success rate. Additional studies, with a randomized design, should be conducted to further confirm that the freeze-all strategy enhances the pregnancy rate in adenomyosis-affected women.

Application of HyFoSy in the assessment of fallopian tube patency compared to HyCoSy and HSG, results of a systematic review and meta-analysis- Elias Tsakos

Tubal factor infertility contributes to around 25-35% of infertility in women. An accurate diagnosis significantly impacts the management and there is a clinical need for non-invasive diagnostic alternatives to current gold standard diagnostic intervention of  laparoscopic chrome-pertubation HyFoSy was introduced in 2007 which is a hydrocellular and glycerol gel which when mixed with water produces foam and is infused via a small catheter in the uterus and salpinges The foam is hyperechoic during the ultrasound, thus denoting tubal shape and patency. This research was done with evaluation of 527 studies according to the PRISMA 2020 guidelines to compare the application of HyFoSy in assessment of fallopian tube patency vs HyCoSy and HSG. The results showed that HyFoSy is diagnostically superior to HyCoSy and may be used for first-line tubal patency assessment. X-ray HSG remains superior diagnostically, however, due to its disadvantages it may be reserved as a second-line test for challenging or inconclusive cases.  HyFoSy  offers a plethora of advantages in clinical practice and may serve as a useful tool in all clinical settings (primary, secondary and tertiary).

39th annual meeting of European society of human reproduction and embryology (ESHRE), Copenhagen, 25-28 June, 2023