Diffuse Adenomyosis Research Articles

Adenomyosis and Adolescence: A Challenging Diagnosis and Complex Management.

Adenomyosis is a chronic, hormone-related disease characterized by the presence of the endometrial glands and stroma within the myometrium. This condition can manifest in various features, focal or diffuse adenomyosis or as an adenomyoma, and it may involve different uterine walls (posterior, anterior, and/or lateral walls). The disease can also be classified into different degrees, as mild, moderate and severe, which can be associated with more intense symptoms, although this correlation is not always directly proportional. In fact, adenomyosis can be asymptomatic in about a third of cases or it can significantly impact patients' quality of life through painful symptoms, such as dysmenorrhea and dyspareunia, abnormal uterine bleeding-particularly heavy menstrual bleeding-and potential effects on fertility. Historically, adenomyosis has been considered a disease primarily affecting premenopausal women over the age of 40, often multiparous, because the diagnosis was traditionally based on surgical reports from hysterectomies performed after the completion of reproductive desire. Data on the presence of adenomyosis in adolescent patients remain limited. However, in recent years, advancements in noninvasive diagnostic tools and increased awareness of this pathology have enabled earlier diagnoses. The disease appears to have an early onset during adolescence, with a tendency to progress in terms of extent and severity over time. Adenomyosis often coexists with endometriosis, which also has an early onset. Therefore, it is important, when diagnosing adenomyosis, to also screen for concomitant endometriosis, especially deep endometriosis in the posterior compartment. The aim of this narrative review is to investigate the prevalence of different types and degrees of adenomyosis in younger patients, assess the associated symptoms, and describe the most appropriate diagnostic procedures for effective therapeutic management and follow-up, with the goal of improving the quality of life for these young women.

Robotic-assisted excision of diffuse adenomyosis.

Adenomyosis is a chronic, debilitating condition characterised by the presence of endometrial- like glands and stroma within the myometrium. While hysterectomy remains the definitive treatment, uterus- sparing surgeries may be a possible option for patients desiring to maintain fertility. Surgical management, along with medical treatment and/or Assisted Reproductive Technology (ART), can improve outcomes. To provide a step-by-step video demonstration of robotic-assisted excision of diffuse adenomyosis affecting the posterior uterine wall. This video article describes the use of a robotic platform in conjunction with intracavitary indocyanine green (ICG) for the uterus-sparing excision of diffuse adenomyosis. Perioperative data, specifics of the surgical approach, and both objective and subjective outcomes of this surgical approach. A 38-year-old nulligravid patient with a history of chronic pelvic pain and infertility underwent surgical management of adenomyosis following two unsuccessful IVF cycles. The excisional surgery resulted in minimal blood loss (60 ml) and the patient was discharged on the same day of surgery with no complications. In select patients, robotic-assisted surgical management of diffuse adenomyosis can be advantageous. Leveraging the benefits of robotic technology, combined with appropriate surgical techniques, facilitates the performance of extensive surgeries with minimal morbidity and favourable outcomes.

Venous Thromboembolism in a Woman with Diffuse Adenomyosis and Heavy Menstrual Bleeding: Case Report

Venous Thromboembolism in a Woman with Diffuse Adenomyosis and Heavy Menstrual Bleeding: Case Report

Stress-induced phosphoprotein 1 (STIP1) gene expression in adenomyosis: An observational case-control study

Background. Endometriosis is distinguished by its high prevalence and significant impact on the quality of life and reproductive health of women; however, its etiology and essential pathogenesis of remain uncertain so far. Modern research is increasingly focusing on immune, hormonal and genetic factors that share a common structure and participate in common metabolism — so-called single nucleotide polymorphisms (SNPs), including stress-induced phosphoprotein 1 (STIP1), which participates in tissue and cellular metabolism through transcription splicing and folding of RNA. The role of this protein, known as heat shock protein (HSP)-organizing protein, is being actively studied in cancer and hyperproliferative diseases. The role of the STIP1 gene and its product in the pathogenesis of adenomyosis appears to be studied insufficiently, thereby determining the relevance of the present study.Objectives. To evaluate the expression of stress-induced phosphoprotein 1 in eutopic endometrium and myometrium in women with isolated adenomyosis, as well as in combination with other benign hyperproliferative diseases of the reproductive system.Methods. Clinical study site: Clinical and Diagnostic Department of Ott Research Institute of Obstetrics, Gynecology and Reproductology. Design: an observational case-control study of patients with verified diagnoses of diffuse adenomyosis, uterine fibroids, and external genital endometriosis (main group — n = 55). The study group (n = 43) was divided into three subgroups: patients with isolated diffuse adenomyosis (AM, n = 16), adenomyosis in combination with uterine fibroids (AM + UF, n = 16), adenomyosis in combination with external genital endometriosis (AM + EGE, n = 11)), a comparison group — patients with uterine fibroids (n = 12) and a control group (n = 17) — women of reproductive age without gynecological diseases. The study was conducted from November 1, 2022 to September 30, 2023. The target indicator of the study was the level of relative mRNA (mRNA) expression of STIP1 gene (in RQ (Relative Quantity) units) in the uterus — adenomyosis glands, surrounding myometrium and endometrium. Histological evaluation of the endometrium served as an additional indicator. Statistical analysis of the results obtained, namely the relative level of mRNA expression, was carried out by the ΔΔСt method using the Expression Suit V1.0.3 program. (https://www.thermofisher.com/ru/ru/home/technical-resources/software-downloads/expressionsuite-software.html). The data analysis was performed using the GraphPad Prizm program (Insight Partners, USA). Differences between groups were evaluated by means of single factor ANOVA analysis (followed by post-hoc pairwise comparisons (Tukey test) of the values in each group. The differences were considered statistically significant at p < 0.05.Results. A high level of STIP1 gene expression was reported in myometrium of patients with isolated adenomyosis (more than 3-fold increase in relation to the comparison group — patients with uterine fibroids). In addition, myometrium of women with adenomyosis combined with uterine fibroids demonstrated a higher expression of STIP1 gene, compared to patients with isolated uterine fibroids (p < 0.01). The evaluation of the expression of mRNA of the STIP1 gene in the eutopic endometrium of patients with adenomyosis and women in the control group revealed no significant differences; however, STIP1 in the endometrium of women with adenomyosis was significantly lower than in the endometrium of both patients with uterine fibroids and women with adenomyosis combined with external genital endometriosis.Conclusion. Increased mRNA expression of STIP1 gene in myometrium in adenomyosis confirms its role in the pathogenesis of this disease. The role of the expression of the STIP1 gene and the corresponding protein is to be further clarified in order to assess its specificity and sensitivity as a diagnostic marker and to identify new approaches to the treatment of adenomyosis.

P-277 Focal rather than diffuse nature of adenomyosis might be more detrimental to IVF outcomes after single euploid embryo transfer

Abstract Study question Is the nature of adenomyosis a factor to consider after a single euploid embryo transfer? Summary answer Focal adenomyosis was associated with lower live birth rate per transfer when compared to diffuse adenomyosis. What is known already Adenomyosis is widely described to hamper reproductive potential of women who suffer it. This uterine pathology has a detrimental impact on in vitro fertilization (IVF) clinical outcomes, as described by a series of recent metanalysis. Nevertheless, there is scarce evidence regarding clinical studies that address the impact of adenomyosis depending either on its diffuse or focal nature. Study design, size, duration A multicenter retrospective cohort study in which 229 patients undergoing IVF treatment were included. Patients with single embryo transfer (SET) in blastocyst stage after pregestational testing for aneuploidy (PGT-A) between years 2015 and May 2023 were divided into two groups: diffuse adenomyosis (n = 167) and focal adenomyosis (n = 62). Participants/materials, setting, methods Inclusion criteria consisted of patients in a PGT-A program who had a cryotransfer of a single euploid blastocyst-stage embryo. Patients were diagnosed within our facilities using transvaginal ultrasonography (TVUS) prior to their IVF cycle. Diffuse adenomyosis was diagnosed when irregular endometrial-myometrial junction, increased uterine volume, ill-defined myometrial heterogeneity, presence of anechoic round myometrial cysts, hyperechoic islands, fan-shaped shadows and/or echogenic subendometrial lines were detected. Focal adenomyosis was diagnosed when foci with adenomyotic characteristics were observed. Main results and the role of chance Clinical pregnancy rate per embryo transfer was 81/167 (48.5%) in those women diagnosed with diffuse adenomyosis versus 23/62 (37.1%) in the focal adenomyosis group (OR = 0.63 95% CI [0.33-1.18], NS). Differences found in clinical miscarriage rate were not statistically significant, being 33/81 (40.7%) for diffuse adenomyosis and 14/23 (60.1%) for the focal adenomyosis group (OR = 2.24 95% CI [0.79-6.63], NS). A lower live birth rate per euploid embryo transfer was observed in women diagnosed with focal adenomyosis, being 9/62 (14.5%) and 48/167 (28.7%) for women who presented diffuse adenomyosis (OR = 0.42 95% CI [0.17-0.95], p=0.027). There were no statistically significant differences between childbirth delivery method (vaginal versus caesarean section). Furthermore, means of gestational age at the time of delivery, newborn size and weight and incidences of low birth weight did not differ between the two groups. Limitations, reasons for caution The retrospective nature of this observational study implies that possible confounders cannot be completely excluded. Also, the accurate diagnostic of adenomyosis is not without complexity and although gynecologists were equally trained to identify direct and indirect markers, different criteria may have been used Wider implications of the findings To our knowledge this is the first study to use an euploid model to assess the impact of the focal versus diffuse nature of adenomyosis in IVF patients. This model permits to correct for numerous covariables attributed to patient’s age and embryo genetic constitution. Trial registration number Not applicable

P-311 Impact of adenomyosis on reproductive outcomes applying the revised Morphological Uterus Sonographic Assessment criteria in fresh donor oocyte recipients pretreated with GnRH agonist

Abstract Study question Could the diagnosis of adenomyosis (AD) impact reproductive outcomes when applying the revised Morphological Uterus Sonographic Assessment (MUSA) criteria in fresh donor oocyte cycles? Summary answer Adenomyosis diagnosis following the revised MUSA criteria in recipients did not have adversely affect reproductive outcomes in fresh donor oocyte recipients pretreated with GnRH agonist What is known already Prior metanalysis on IVF outcomes in patients with adenomyosis suggested lower clinical pregnancy and live birth rates, and increased miscarriage rates. Some studies suggest improved pregnancy rates with ultra-long GnRH agonist pretreatment. Most studies focused on autologous embryo transfer without euploidy confirmation, and diagnostic criteria lacked consensus, in 2021 MUSA redefined criteria distinguishing direct and indirect features with different implications. Study design, size, duration A retrospective cohort study included all fresh oocyte donation cycles from January 2014 to September 2023, evaluating adenomyosis impact on implantation rate, clinical pregnancy rate, miscarriage rate, ectopic pregnancy rate. The study analyzed 252 cycles without a formal sample size calculation due to its retrospective nature. Participants/materials, setting, methods The study included 252 first fresh oocyte reception cycle with a fresh embryo transfer. Severe male factor cases were excluded. A transvaginal ultrasound (TUS) screening for adenomyosis criteria was performed, diagnosis required at least two criteria, with one being direct. Endometrial preparation involved one dose of 3,75mg triptorelin acetate intramuscularly injected in mid luteal phase, to facilitate the synchronization with donor and estradiol patches. Main results and the role of chance Adenomyosis was diagnosed in 10,7% (AD), endometriosis (END) was present in 21,8 % and 26,6% of patients presented both diagnoses. Endometriosis patients received more pre-treatment (oral contraceptive or 2-3 long-agonist doses) than those without (40,7% AD, 43,6% END vs 17,3% non-AD/END). Comparing patients with and without adenomyosis, no statistical differences were found in embryo transfer results between groups: clinical pregnancy rate (63% vs 56,9%), miscarriage rate (23,5% vs 14,1%), ectopic pregnancy rate (11,8% vs 4,7%) and live birth rate (40,7% vs 45,8%). No differences in gestational outcomes were observed in terms of the number of adenomyosis criteria present, the number of direct criteria, the type of criteria, or when differentiating between focal and diffuse adenomyosis. Similarly, there were no differences when comparing patients with both diagnoses to those with isolated adenomyosis. The most prevalent adenomyosis features reported were hyperechogenic islands (direct criteria), followed by an irregular junctional zone and asymmetrical wall thickening (indirect criteria). Finally, no differences were found in perinatal outcomes or complications during the pregnancy follow-up between groups. Limitations, reasons for caution Although this is the largest serie evaluating adenomyosisto the low adenomyosis prevalence in our population, these results should be confirmed in larger series. In our center all adenomyosis/endometriosis symptomatic patients are under medical treatment before assisted reproduction techniques, that may modify adenomyosis criteria over time and probably pregnancy outcomes. Wider implications of the findings This is the first study to characterize adenomyosis using the revised MUSA definitions in an oocyte donation programme. Applying these criteria and preparing endometrium with GnRH analog pretreatment and treating medically symptomatic patients before ART, adenomyosis did not adversely affect reproductive outcomes. Trial registration number Not applicable

Imaging and molecular features of adenomyosis after menopause

ObjectivesTo explore the imaging features and the molecular characterization of adenomyosis after menopause. Study designAn observational cross-sectional study was performed in a group of postmenopausal patients undergoing a transvaginal ultrasound (TVUS) (n = 468). Among those presenting the US criteria for adenomyosis, also confirmed by magnetic resonance imaging (MRI), previous menstrual symptoms, gynecological and obstetric history were reviewed. In a subgroup undergoing hysterectomy, uterine specimens were analyzed by histology and expression of genes implicated in the epithelial-mesenchymal transition, inflammation and fibrosis, including the sphingosine-1-phosphate (S1P) pathway, was evaluated and compared to matched non-menopausal adenomyosis specimens. Main outcome measuresDirect and indirect US features of adenomyosis according to Morphological Uterus Sonographic Assessment at TVUS. Molecular characterization of postmenopausal versus pre-menopausal adenomyosis samples. ResultsAccording to TVUS and MRI, adenomyosis was identified in 49 patients (10.4 %). On US, diffuse adenomyosis was the most common phenotype, whereas internal adenomyosis with diffuse pattern and asymmetric type was the most prevalent on MRI. Molecular analysis showed that adenomyosis lesions express markers of epithelial-mesenchymal transition, inflammation and fibrosis also in postmenopausal women. By comparing the results with those from pre-menopausal samples, the expression of α smooth muscle actin (αSMA), a marker of fibrosis, was significantly greater after menopause, and altered S1P catabolism and signaling were observed. ConclusionsAdenomyosis may be identified in postmenopausal women by imaging, either TVUS or MRI, and fibrosis is one of the key features on molecular analysis.

Факторы риска рецидивирования внутриматочных синехий в репродуктивном возрасте

Aim. To identify risk factors for recurrent intrauterine synechiae in women of reproductive age. Design. A comparative prospective study. Materials and methods. The study enrolled 89 female patients of reproductive age with confirmed intrauterine adhesions (IUA), according to hysteroscopy and morphology. Patients were divided into two groups depending on the course of IUA: main group (n = 45) — women with recurrent IUA (at least one episode during the year), and reference group (n = 44) — patients with IUA de novo. The mean age of patients in the main and reference groups was 36 ± 6 and 30 ± 3 years old, respectively. Results. A history of emmeniopathy was statistically more common in patients with recurrent IUA (odd ratio (OR) = 4.5; 95% confidence interval (CI): 1.7–12.3) as compared to women with IUA de novo (p < 0.05), diffuse adenomyosis (OR = 5.4; 95% CI: 2.2–13.6) (p < 0.05). Patients with morphologically confirmed chronic endometritis had a high risk of recurrent IUA (OR = 4.0; 95% CI: 1.6–9.7) (p < 0.05). The risk is several times higher after surgeries: repeated curettage of uterine cavity due to abnormal uterine bleeding (OR = 17.3; 95% CI: 5.8–51.3) (p < 0.001), a history of myomectomy due to a submucous myomatous nodule (OR = 7.4; 95% CI: 2.9–18.8) (p < 0.001), hysteroresectoscopic adhesiolysis with monopolar energy (OR = 4.4; 95% CI: 1.7–11.3) (p < 0.001). Conclusion. The mentioned risk factors of recurrent IUA make it possible to timely identify women with a high risk of the disease and undertake preventive measures. Keywords: intrauterine synechiae, recurrence, risk factors, reproductive age.

The “freeze-all” strategy seems to improve the chances of birth in adenomyosis-affected women

ObjectiveTo compare assisted reproductive technologies(ART) outcomes between fresh versus freeze-all strategies in infertile women affected with adenomyosis. DesignA single-center observational study SettingsUniversity hospital-based research center PatientsAdenomyosis-affected women undergoing blastocyst embryo transfer following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between 01/01/2018 and 31/11/2021. The diagnosis of adenomyosis was based on imaging criteria (i.e., transvaginal ultrasound and/or magnetic resonance imaging). Intervention(s)Women who underwent a freeze-all strategy were compared to those who underwent a fresh embryo transfer (ET) strategy.Main outcome measure(s): cumulative live birth rate (LBR) ResultsA total of 306 women were included in the analysis: 111 in the fresh ET group and 195 in the freeze-all group. The adenomyosis phenotype (internal diffuse adenomyosis, external focal adenomyosis, and adenomyoma) was not significantly different between the two groups. The cumulative LBR [86 (44.1%) vs. 34 (30.6%), respectively; p = 0.020] and the cumulative ongoing pregnancy rate [88 (45.1%) versus 36 (32.4%), respectively; p = 0.029] were significantly higher in the freeze-all group compared to the fresh ET group. After multivariate logistic regression analysis, the freeze-all strategy in women with adenomyosis was associated with significantly higher odds of live birth compared to fresh ET (OR = 1.80; 95% CI = 1.02–3.16). ConclusionThe freeze-all strategy in women afflicted with adenomyosis undergoing ART was associated with significantly higher cumulative live birth rates. Our preliminary results suggest that the freeze-all strategy is an attractive option that increase ART success rates. Additional studies, with a randomized design, should be conducted to further test whether the freeze-all strategy enhances the pregnancy rate in adenomyosis-affected women.

Impact of adenomyosis on IVF outcomes in women undergoing donor oocyte transfers: a prospective observational study

To prospectively examine the association between adenomyosis type, location, and severity with reproductive outcomes in patients undergoing single embryo transfer (SET) with embryos derived from donor oocytes. A prospective observational cohort study. University-affiliated in-vitro fertilization center. Infertile patients with (n=114) and without (n=114) adenomyosis who received their first donor oocyte transfer between January 2019 and January 2023 were included in the study. Adenomyosis was confirmed with the presence of at least one direct feature visualized by 2D/3D transvaginal ultrasound, and classified according to type (diffuse, focal), localization (inner/outer myometrium and/or the junctional zone) and uterine extension (mild, moderate, severe). Following an artificial or natural endometrial preparation cycle, patients underwent SET in the blastocyst stage. The primary outcome was the implantation rate. The secondary outcomes were clinical pregnancy, live birth, and miscarriage rate following SET. (s): The presence of adenomyosis did not significantly affect the implantation, clinical pregnancy, or live birth rates. However, women with adenomyosis had a significantly higher miscarriage rate compared to those without adenomyosis (20.2% vs. 9.6 %, respectively; p=0.04). The multivariate analysis assessed possible risk factors for each clinical outcome considered in the study and showed that adenomyosis affected the risk of miscarriage. Specifically, TVS-detection of adenomyosis in the junctional zone was associated with over three-fold higher odds of miscarriage (RR 3.28, 95% CI 1.38-7.78; p=0.004). Conversely, adenomyosis features detected exclusively in the outer myometrium were associated with a higher ongoing pregnancy (RR 0.30, 95% CI 0.13-0.72; p=0.004). Diffuse adenomyosis in the JZ and severe adenomyosis raised the odds of miscarriage four-fold (RR 2.29, 95% CI 1.22-4.30; p=0.015; and RR 2.20, 95% CI 1.19-4.04; p=0.005). (s): This study demonstrated that while adenomyosis did not significantly reduce the odds of implantation, the direct signs of adenomyosis in the junctional zone and disease severity are significant risk factors for miscarriage in patients receiving donor oocyte transfers. This study highlights the importance of thorough ultrasound examination and detailed adenomyosis classification in the assessment and management of infertile patients.

PATHOGENETIC FEATURES OF ADENOMYOSIS DEVELOPMENT IN WOMEN OF REPRODUCTIVE AGE IN THE POST-COVID PERIOD

Purpose. To study the prevalence and forms of adenomyosis for women of reproductive age after COVID-19, to study pathomorphological changes in the uterine tissues of women of reproductive age with adenomyosis after COVID-19.
 Materials and methods. We examined 114 patients of reproductive age who underwent hysterectomy for various pathologies. Of these, 40 patients (35%) in 2019 before the COVID-19 pandemic, and during the pandemic in 2021 - 36 patients (31.6%), in 2022 - 38 (33.4%) patients.
 Results. The study found that the total number of histologically confirmed adenomyosis in patients of reproductive age increased from 55% in 2019 (before the COVID-19 pandemic) to 66.6% and 71% in 2021 and 2022, respectively; the number of diffuse adenomyosis increased significantly from 12.5% in 2019 (before the COVID-19 pandemic) to 41.6% and 47.4% in 2021 and 2022, respectively; the percentage of diffuse adenomyosis in relation to other forms of adenomyosis increased from 22.7% in 2019 (before the COVID-19 pandemic) to 62.5% and 66.6% in 2021 and 2022, respectively. Given the increase in the prevalence of adenomyosis in the post-COVID period compared to the period before the COVID-19 pandemic, we studied pathomorphological changes in the basal layer of the endometrium and the inner layer of the myometrium that correlated with the clinical features of the disease in the patients who participated in the study. The study included cases with histologically confirmed adenomyosis Pathologically detected changes in the endometrium and inner layer of the myometrium in adenomyosis after COVID-19, namely the line of separation between the endometrium and myometrium is unclear, vessels in the form of clusters, thickwalled, narrowed lumen, edema between fibers, edema between fibers and around vessels, thickening of the vessel wall and narrowing of the lumen, pronounced revascularization, the presence of myxomatous edema, foci of hemosiderosis in the interstitial tissue, thrombosis of vessels of different caliber with hemorrhages, and microcirculatory disorders.
 Conclusion. The results obtained indicate that after COVID-19 disease, the total number of histologically detected adenomyosis in women of reproductive age increased, and the number of diffuse adenomyosis increased. Characteristic changes occurred in the uterine tissue at the border of the endometrium and myometrium, which are morphologically confirmed.

Laparoscopic Eradication of Deep Endometriosis With Segmental Rectosigmoid Resection and Bilateral Posterior Parametrectomy With Nerve-sparing “Touchless” Technique According to the “Negrar Method”

ObjectiveTo demonstrate nerve-sparing laparoscopic eradication of Deep Endometriosis with rectal and parametrial resection based on the Negrar Method1 utilizing the “Touchless” Technique. Designstepwise video case demonstration with narration SettingTertiary Level Endometriosis Unit. The patient was a 28 year-old nulliparous patient referred for surgery with persistent dysmenorrhea, dyspareunia and dyschezia despite medical management (progestin containing hormonal pills). Preoperative ultrasound demonstrated bilateral endometriomas, diffuse adenomyosis and 35mm x 17mm stenosing rectal nodule. Histopathology confirmed 60% stenosis of the rectum secondary to the endometriotic nodule up to submucosal layer with margins free of endometriosis. She was discharged 7 days post-operatively with no post operative complications. InterventionsLaparoscopic nerve sparing eradication of Deep Endometriosis with Segmental Rectosigmoid Resection and bilateral posterior parametrectomy according to the “Negrar Method” with Nerve-Sparing "Touchless" Technique, sliding the nerve-bundles latero-caudally, keeping intact the visceral pelvic fascia covering them, thus without direct contact with the nerves. ConclusionIn our experience, based on more than 3000 of these procedures 3, this nerve-sparing procedure, based on identifying the nerves and their latero-caudad dissection, without a direct impact on their fibers but just on their fascial envelopes has proven successful in lowering the rates of post-operative dysfunctions and neural impairment related to neuro-apraxia and edema which occurs by directly impacting them.1 Whilst there is no robust data to demonstrate benefit of “touchless” nerve sparing dissection techniques, neuro-apraxia from compression of neural fibers which has been observed can be minimized.1,4,5

Influence of ozone therapy on emotional and pain stress in women with adenomyosis

Relevance. Adenomyosis (or endometriosis) is a common and intractable disease, which, according to various studies, affects up to 45 % of women of reproductive age worldwide and is often aggravated by the presence of chronic pelvic pain leading to the development of psycho-emotional disorders. Objective: To study the effect of complex treatment, including ozone therapy, on emotional and pain stress in women with diffuse adenomyosis stage II. Subject and methods. An open randomized controlled study was conducted in 40 women with stage II diffuse adenomyosis aged 32.5 ± 9.4 years, who were divided into two groups. Group 1 (control, n = 10) received standard drug therapy; group 2 (main group, n = 30) received additional ozone therapy. The effectiveness of the treatment was assessed using the VAS scale and the MH component of the SF-36 questionnaire, as well as statistical analysis before treatment, after treatment, and after 1, 3 and 6 months of follow-up. Results and discussion. Before the start of treatment, the patients in both groups showed significant differences in the VAS scale and the MH component compared to the norm, which confirmed a significant deterioration in their socio-psychological status, as well as the presence of severe pain. After the course of treatment and up to 6 months in the 2nd (main) group, the VAS score and MH components tended to their physiological norm. At the same time, in the patients in the 2nd (main) group, a statistically significant strong inverse correlation between VAS scores and the MH component was revealed. In the patients in the 1st (control) group, the studied parameters changed little during treatment, which was evidence of the insufficient analgesic effect of drug therapy and a high level of neuropsychic distress and emotional instability in these patients. Conclusion. The inclusion of ozone therapy in complex treatment for the patients in the 2nd (main) group contributed to a decrease in the severity of pain and symptoms of mental trauma. In addition, the trend line of the VAS indicator and the MN component tended to its normal values, which indicated a positive forecast for two more future periods. In the patients in the 1st (control) group who received only drug therapy, no significant improvement was observed.

Outcome of uterine functional structures protection by fertility preservative PUSH surgery in diffuse adenomyosis

This study reports the outcomes of an innovative fertility-preserving surgery for the treatment of diffuse adenomyosis that is known as a surgery for protection of uterine structure for healing (PUSH Surgery). Developed at Peking University Shenzhen Hospital, PUSH Surgery aims to achieve radical excision of adenomyotic lesions by reconstructing the uterus with overlapping muscle flaps to promote optimal healing of the uterine wall and reduce the risk of scar rupture in subsequent pregnancies. PUSH Surgery was performed on 146 patients with diffuse adenomyosis, with uteri measuring from 8 to 16 gestational weeks and an average volume of 230 ± 150cm³. Regular follow-up was conducted for up to 156 months, revealing a significant reduction in VAS pain scores from 9.4 ± 1.2 before the surgery to 0.3 ± 0.8 and 0.6 ± 1.0 at 1 and 2 years post-surgery, respectively, with a continuous alleviation rate of 96.4% after the operations. Notably, 100% of patients with severe menorrhagia reported normal menstruation volumes within 2 years. Additionally, 31 patients attempted to conceive, resulting in a 58% postoperative pregnancy rate and a 60.0% intrauterine live embryo rate. Operation-related complications occurred in 2.7% of patients, with a 3.6% recurrence rate after more than 2 years of follow-up. Importantly, no cases of uterine rupture or severe complications were observed in the pregnant patients. In conclusion, PUSH Surgery offers a promising approach for the radical excision of adenomyotic lesions, promoting improved tissue healing and significant symptom relief.

P-358 Impact of localization of diffuse adenomyosis on reproductive outcomes and pregnancy complications: A prospective cohort study of 585 patients after frozen embryo replacement cycle

Abstract Study question Does localization of diffuse adenomyosis impact reproductive outcomes after the frozen embryo transfer (FET)? Summary answer Diffuse adenomyotic lesions involving the junctional zone (JZ) have a greater negative impact on reproductive outcomes than diffuse adenomyosis of the outer myometrium (OM). What is known already Adenomyosis is associated with higher miscarriage rate, significantly lower live-birth (LB) rate, and increased risk for pregnancy-related complications. However, the impact of adenomyosis on IVF outcomes remains unclear. Adenomyosis is often treated as a homogenous disease and studies on the effects of different types of adenomyosis on reproductive outcomes have yielded inconsistent results, due to a lack of standardized diagnostic criteria and a lack of agreement on the phenotypic classification of the disease based on their severity or location. There is a lack of studies considering the effects of the severity or location of adenomyosis on reproductive outcomes after FET. Study design, size, duration This prospective cohort study was conducted at a tertiary-care hospital between January 2019 and December 2022. A total of 585 infertile women undergoing the first FET cycle were recruited. The study population included 368 women with diffuse adenomyosis where 201 women had diffuse adenomyosis of JZ and, 167 women had diffuse adenomyosis of OM. 217 women with male infertility were taken as controls. Participants/materials, setting, methods Adenomyosis was diagnosed with 2D-TVS using MUSA criteria where patients with two or more features and diffuse adenomyosis were included. Patients with diffuse adenomyosis were further divided based on the localization of adenomyotic lesions in OM or JZ. All the patients underwent FET-cycle. Pregnancy outcomes and complications were compared between different groups-those with diffuse adenomyosis of JZ, those with diffuse adenomyosis of OM, and controls. Adenomyosis patients as one group were also compared with controls. Main results and the role of chance The pregnancy rate was significantly lower in women with diffuse adenomyosis of JZ (26.37%) compared to diffuse adenomyosis of OM (47.9%) (OR:0.39, 95% CI 0.25-0.60; P < 0.0001). Similarly, the clinical pregnancy rate was also lower in diffuse adenomyosis with JZ involvement (23.38%) compared to women with diffuse adenomyosis of OM (42.51%) (OR:0.41, 95% CI 0.26-0.65; P = 0.0001). However, the biochemical pregnancy and miscarriage rates were comparable between the two adenomyosis groups. The LB rate was significantly lower in patients with JZ-involvement (16.42%) compared to women with OM-involvement (25.75%) (OR:0.57, 95% CI 0.34-0.94; P = 0.029). When all the adenomyosis patients were compared with the controls as one group, pregnancy rates were similar, but the miscarriage rate was significantly higher, and the LB rate was significantly lower in adenomyosis (P < 0.05). When the individual groups with adenomyosis were compared with controls, clinical pregnancy, and LB were comparable with the controls (P > 0.05) in women with OM involvement. However, when JZ was involved, the differences were significant (P < 0.05), highlighting the adverse impact of JZ involvement on IVF outcome. Pregnancy complications were comparable between the adenomyosis groups; however, there was a significantly higher incidence of gestational hypertension, IUGR, and pre-term labor for adenomyosis patients compared to the control (P < 0.05). Limitations, reasons for caution In the absence of a universally accepted diagnostic modality and classification system for adenomyosis, this study used ultrasound due to its lower cost and easy availability. The sample size of this study is limited to 368 patients from a single centre, larger multicentric studies are needed to make definitive conclusions. Wider implications of the findings Localizing adenomyotic lesions before starting IVF, may help in planning treatment strategies and provide adequate counseling on reproductive outcomes specific to each type. Pregnant women with adenomyosis should be managed carefully as high-risk pregnancies, considering the possible serious obstetric complications. Trial registration number CTRI/2019/01/016919

O-268 Presence of adenomyosis impairs clinical outcomes in women undergoing frozen embryo transfer

Abstract Study question Does the presence of adenomyosis impact the clinical outcomes of patients undergoing frozen embryo transfer (FET)? Summary answer Presence of adenomyosis is associated with higher miscarriage and lower clinical pregnancy and live birth rates. GnRH agonist pre-treatment does not increase clinical outcomes. What is known already Presence of adenomyosis among pregnant patients has been associated with a higher incidence of miscarriage and pregnancy complications. Although the role of adenomyosis in women undergoing in vitro fertilization (IVF) has been investigated in several studies demonstrating a potential detrimental effect on live birth rates following IVF, most of them were small studies in which adenomyosis diagnosis was not confirmed based on solid ultrasonographic criteria. Considering the fragmented evidence up to date, we decided to perform a large retrospective study including women with adenomyosis undergoing FET which has been confirmed based on solid ultrasonographic criteria. Study design, size, duration Retrospective cohort study of 3503 patients undergoing their first cycle of blastocyst frozen transfer in a university-affiliated fertility center between January 2017 and December 2021. Participants/materials, setting, methods Overall, 3503 patients undergoing their first blastocyst frozen transfer through a hormonal replacement (HRT) FET cycle. Patients were categorized as adenomyosis when fulfilling to the Morphological Uterus Sonographic Assessment (MUSA) criteria and as non-adenomyosis when no-adenomyosis was identified. Among them 140 women had a confirmed diagnosis of adenomyosis based on MUSA criteria. Clinical information was retrospectively collected from medical records. Main results and the role of chance Comparisons between adenomyosis and non-adenomyosis groups revealed similar baseline characteristics in terms of patients’ weight, parity, smoking status, and age. Similarly, endometrial thickness and mean serum progesterone levels the day before FET as well as the number of embryos transferred were comparable between groups. Adenomyosis patients were more likely to proceed with a deferred FET (freeze-all protocol) as compared with no-adenomyosis women (p = 0.002) and were significantly more likely to be treated with GnRH agonist pre-treatment (2 injections) (P < 0.001). Multivariable logistic regression, adjusting for age, autologous or donor oocytes, PGT-A, deferred FET, serum progesterone levels the day before FET, GnRH agonist pre-treatment, number of embryos transferred, and adenomyosis, demonstrated that the use of GnRH agonist protocol did not affect miscarriage, clinical pregnancy rate or live birth rate. However, the presence of adenomyosis significantly decreased clinical pregnancy rates (OR 0.62, 95% CI: 0.39-0.98, P = 0.040) and live birth rates (OR 0.46, 95% CI: 0.27-0.75, P = 0.003) and significantly increased miscarriage rates (OR 2.13, 95% CI 0.98-4.37, p = 0.045). PGT-A was the only factor associated with a significative reduction in miscarriage rate. Limitations, reasons for caution The main limitation of this study is the single-center retrospective approach. Furthermore, due to the limited number of cases with adenomyosis focal and diffuse adenomyosis were analyzed together although this may be clinically distinct entities. Wider implications of the findings The results of this study demonstrate that presence of adenomyosis has significant negative impact on the clinical outcomes of patients undergoing FET. Future prospective studies are needed to create a consensus on the optimal ET technique for these patients. Trial registration number Not Applicable

O-270 Does the ‘freeze all' strategy improve the chances of birth in the presence of adenomyosis?

Abstract Study question Does the freeze all strategy improve cumulative live birth rates in infertile women affected with adenomyosis? Summary answer The freeze all strategy in adenomyosis-affected women is associated with significantly higher cumulative live birth rates. What is known already Controlled ovarian stimulation enhances the efficacy of assisted reproductive technology (ART) by permitting multiple-oocyte yields, but also may alter endometrial receptivity by an earlier endometrial development which could in turn contribute to diminished pregnancy chances. Technical improvements in vitrification made deferred frozen-thawed embryo transfer (freeze –all strategy) a feasible alternative to fresh embryo transfer (ET). In adenomyosis, the eutopic endometrium is abnormal and its functional alterations are seen as likely to alter the quality of endometrial receptivity. One question in the adenomyosis ART-management is to know whether a freeze all strategy could lead to an increase in reproductive outcomes. Study design, size, duration This cohort study conducted in a tertiary care university hospital included adenomyosis-affected women undergoing blastocyst embryo transfer following in vitro fertilization / intracytoplasmic sperm injection (IVF/ICSI) between 01/01/2018 to 31/11/2021. The diagnosis of adenomyosis was based on imaging criteria (e.g. transvaginal ultrasound and/or magnetic resonance imaging). Participants/materials, setting, methods Women who underwent a freeze all strategy were compared to those who underwent a fresh ET strategy. Statistical analyses were conducted using univariate and multivariate logistic regression models. The primary outcome was the cumulative live birth rate (LBR). Main results and the role of chance A total of 306 women were included in the analysis: 111 in the fresh ET group and 195 in the freeze all group. The phenotype of adenomyosis (internal diffuse adenomyosis, external focal adenomyosis and adenomyomas) was not significantly different between the two groups. The cumulative live birth rate was significantly increased in the freeze all group compared to the fresh ET group [86 (44.1%) vs. 34 (30.6%), p = 0.020]. The cumulative OPR [89 (45.6%) versus 37 (33.3%), p = 0.035] and the cumulative CPR [122 (62.6%) vs. 53 (47.7%), p = 0.011] were significantly higher in freeze all group compared to the fresh group, whereas the early miscarriage rate was not significantly different between the two groups. After multivariate logistic regression analysis, the freeze all strategy in women with adenomyosis was associated with a significant increase in the live birth rate as compared to fresh ET (OR = 1.85; 95% CI = 1.06 – 3.24; p = 0.031). Limitations, reasons for caution This analysis consists in a retrospective cohort study. The inclusion of patients from a referral center specialized in the management of adenomyosis and endometriosis could constitute a selection bias, as these women may have had particularly severe forms of adenomyosis. Wider implications of the findings The freeze all strategy could be an attractive option to increase ART success rates, in adenomyosis-affected womenundergoing IVF/ICSI. Trial registration number NA

The role of levonorgestrel-releasing intrauterine system for recurrence prevention after conservative surgery among patients with coexistent ovarian endometrioma and diffuse adenomyosis: A retrospective case control study with long-term follow up.

When ovarian endometrioma coexist with adenomyosis, the risk of postoperative recurrence increased. How is the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) on symptomatic recurrence for those patients was unknown. This study retrospectively analyzed 119 women with coexistent endometrioma and diffuse adenomyosis who received laparoscopic excision of pelvic endometriosis from January 2009 to April 2013. Women were categorized into two groups: intervention group with LNG-IUS and control group with expectant observation after surgery. Data were compared in terms of preoperative history, laboratory and intraoperative findings, and clinical outcomes during follow-up, including pain regression, changes in uterine volume and recurrence. During a median 79 months (range, 6-107) of follow-up, patients with LNG-IUS experienced a significantly lower symptomatic recurrence of either ovarian endometrioma or dysmenorrhea (11.1% vs. 31.1%, p=0.013), compared with women under expectant observation by Kaplan-Meier survival analysis (χ2=5.448, p=0.020) and Cox univariate assessment (hazard ratio of 0.336, 95% confidence interval 0.128-0.885, p=0.027). Patients treated with LNG-IUS demonstrated a more prominent reduction in uterine volume (-14.1±20.9vs. 8.7±48.8, p=0.003) and higher percentage of complete pain remission (95.6% vs. 86.5%). For multivariate analysis, use of LNG-IUS (aHR 0.159, 95%CI 0.033-0.760, p=0.021) and severity of dysmenorrhea (aHR 4.238, 95%CI 1.191-15.082, p=0.026) were two independent factors associated with overall recurrence. Postoperative insertion of LNG-IUS may prevent recurrence in symptomatic women with comorbidity of ovarian endometrioma and diffuse adenomyosis.

Endometrial receptive status in patients of reproductive age with diffuse and focal adenomyosis

Introduction Endometriosis ranks second place in the structure of infertility. The development of endometrial dysfunction is one of the infertility factors, which affects the degree of decrease in the receptive abilities of endometrium and subsequent implantation.Purpose of the study was to reveal morpho-functional state of receptivity and nidation ability of endometrium in patients of reproductive age with diffuse and nodal forms of adenomyosis.Materials and methods The study included 104 patients, which were divided into 2 groups. The first group consisted of 30 patients with a diffuse form of adenomyosis, second group included 30 patients with a nodal form. The patients underwent aspiration biopsy of endometrium in the middle secretory phase. The level of ER and PR expression in the glandular and stromal compartments of endometrium was assessed, the percentage and degree of maturity of pinopodes were determined.Results The analysis of ER and PR number in the stromal and glandular components of endometrium in patients with diffuse adenomyosis revealed an increase in the secretion of ER in the glandular cells in contrast to patients of the comparison group. Significant differences in the expression of ER and PR in glandular cells were verified among observed with the nodal form of adenomyosis. The immunohistochemical reaction with antibodies to ER and PR in the nodal form of adenomyosis was significantly higher than in diffuse form. Both in the first and second groups, a decrease in the formation ability of pinopodes on the superficial epithelium was noted.Discussion Adenomyosis leads to damage of the morpho-functional state and receptive abilities of the endometrium. In the nodal form the degree of detected disorders was significantly higher.Conclusion The nodal form of adenomyosis is more common in patients of younger reproductive age and is associated with a higher prevalence of endometrial dysfunction. This is especially important for the selection of adequate modern therapy in order to maintain and improve reproductive function.

Short- and long-term results of organ-sparing surgery in patients with severe diffuse adenomyosis at perimenopausal transition

Aim. To study the short- and long-term results of organ-sparing surgery in patients with severe diffuse adenomyosis who are in the perimenopausal age.Materials and Methods. The study included 18 patients with severe diffuse adenomyosis who underwent fertility-sparing excision of diffuse adenomyosis by means of Osada procedure. Efficiency of surgical treatment and subsequent drug therapy was evaluated at 12 and 24 months of follow-up by pelvic ultrasound examination. The frequency of adenomyosis symptoms and quality of life were assessed using the standard SF-36 questionnaire.Results. Recovery of the menstrual cycle, freedom from pain and anemia, and improved quality of life were documented in all cases (18/18), whereas onset of menopause occurred in half of the cases (9/18). In particular, all scales of the Physical Component Summary from SF-36 questionnaire were significantly improved at both follow-up time points.Conclusion. Organ-sparing excision of diffuse adenomyosis using Osada procedure is the option of choice and might represent an alternative to hysterectomy in women with perimenopausal age, in addition to those of earlier reproductive age.