Organoid co-culture model of the human endometrium in a fully synthetic extracellular matrix enables the study of epithelial-stromal crosstalk.

BACKGROUND: The human endometrium undergoes recurring cycles of growth, differentiation, and breakdown in response to sex hormones. Dysregulation of epithelial-stromal communication during hormone-mediated signaling may be linked to myriad gynecological disorders for which treatments remain inadequate. Here, we describe a completely defined, synthetic extracellular matrix that enables co-culture of human endometrial epithelial and stromal cells in a manner that captures healthy and disease states across a simulated menstrual cycle. METHODS: We parsed cycle-dependent endometrial integrin expression and matrix composition to define candidate cell-matrix interaction cues for inclusion in a polyethylene glycol (PEG)-based hydrogel crosslinked with matrix metalloproteinase-labile peptides. We semi-empirically screened a parameter space of biophysical and molecular features representative of the endometrium to define compositions suitable for hormone-driven expansion and differentiation of epithelial organoids, stromal cells, and co-cultures of the two cell types. FINDINGS: Each cell type exhibited characteristic morphological and molecular responses to hormone changes when co-encapsulated in hydrogels tuned to a stiffness regime similar to the native tissue and functionalized with a collagen-derived adhesion peptide (GFOGER) and a fibronectin-derived peptide (PHSRN-K-RGD). Analysis of cell-cell crosstalk during interleukin 1B (IL1B)-induced inflammation revealed dysregulation of epithelial proliferation mediated by stromal cells. CONCLUSIONS: Altogether, we demonstrate the development of a fully synthetic matrix to sustain the dynamic changes of the endometrial microenvironment and support its applications to understand menstrual health and endometriotic diseases. FUNDING: This work was supported by The John and Karine Begg Foundation, the Manton Foundation, and NIH U01 (EB029132).

Infertility services integrated within the maternal health department of a public hospital in a low-income country, Rwanda.

Objective: To describe the initiation, integration, and costs of reduced-cost infertility services within the maternal health department of a public hospital in a low-income country. Design: Retrospective review of the clinical and laboratory components of patients undergoing in vitro fertilization (IVF) treatment in Rwanda from 2018 to 2020. Setting: Academic tertiary referral hospital in Rwanda. Patients: Patients seeking infertility services beyond the primary gynecological options. Interventions: The national government furnished facilities and personnel, and the Rwanda Infertility Initiative, an international nongovernmental organization, provided training, equipment, and materials. The incidence of retrieval, fertilization, embryo cleavage, transfer, and conception (observed until ultrasound verification of intrauterine pregnancy with fetal heartbeat) were analyzed. Cost calculations used the government-issued tariff specifying insurers' payments and patients' copayments with projected delivery rates using early literature. Main Outcome Measures: Assessment of functional clinical and laboratory infertility services and costs. Results: A total of 207 IVF cycles were initiated, 60 of which led to transfer of ≥1 high-grade embryo and 5 to ongoing pregnancies. The projected average cost per cycle was 1,521 USD. Using optimistic and conservative assumptions, the estimated costs per delivery for women <35 years were 4,540 and 5,156 USD, respectively. Conclusions: Reduced-cost infertility services were initiated and integrated within a maternal health department of a public hospital in a low-income country. This integration required commitment, collaboration, leadership, and a universal health financing system. Low-income countries, such as Rwanda, might consider infertility treatment and IVF for younger patients as part of an equitable and affordable health care benefit.

Take it or leave it: oophorectomy at the time of benign hysterectomy.

PURPOSE OF REVIEW: Previous modeling data suggest ovarian conservation up to age 65 for women without adnexal disease and at average risk of ovarian cancer because of an increase in mortality associated with ovarian removal. Recent modeling data challenges this practice. This review of recent literature will update providers regarding consideration for oophorectomy at time of benign hysterectomy. RECENT FINDINGS: Oophorectomy at time of hysterectomy for women less than 50 years with estrogen supplementation and greater than 50 years without estrogen supplementation is not associated with increased mortality. SUMMARY: Although not associated with increased mortality, the decision to remove the ovaries at time of hysterectomy in women older than 50 years is nuanced and requires careful shared decision-making, considering unique patient factors.

Incidence of Intrauterine Adhesions After Hysteroscopic Myomectomy in Patients Seeking Fertility.

STUDY OBJECTIVE: To study the incidence of intrauterine adhesions (IUAs) after hysteroscopic myomectomy. Previous studies report a range of incidence for IUAs after hysteroscopic myomectomy. DESIGN: A retrospective review study. SETTING: An academic community hospital in the Boston metropolitan area. PATIENTS: Patients undergoing hysteroscopic myomectomy at our institution from January 2019 to February 2022. Patients were excluded if they did not have plans for future fertility or had a new diagnosis of cancer. INTERVENTIONS: All patients underwent hysteroscopic myomectomy using bipolar resectoscope without postoperative medical or barrier treatment. All procedures were performed by 1 of 4 fellowship-trained high-volume gynecologic surgeons with resident and fellow assistance. Incidence of postoperative IUAs was assessed and treated using second-look office hysteroscopy. MEASUREMENTS AND MAIN RESULTS: A total of 44 patients without preoperative IUAs underwent hysteroscopic myomectomy during our study period, and 4 patients (9.1%) developed new IUAs. Among 9 patients who were found to have preoperative IUAs and underwent concurrent hysteroscopic myomectomy and lysis of adhesions, we found a recurrence of IUAs in 5 patients (55.6%). We found the number, size, and deepest type of myoma removed were not correlated to an increased risk of new IUA formation. In addition, removing myomas on opposing walls during the same operation did not increase the incidence of new IUAs. CONCLUSION: Formation of IUAs after hysteroscopic myomectomy is a well-documented consequence. Our reported incidence of 9.1% of new IUAs that are not affected by the number, size, deepest type of myoma resected, and resection of myomas on opposing uterine walls contributes to the current literature. In addition, our finding of 55.6% of recurrent IUAs in patients undergoing both hysteroscopic myomectomy and lysis of adhesions highlights a high-risk population requiring additional study.

Restoring Fertility of Patients with Severe Asherman's Syndrome in the Office Setting: A Step-by-Step Recipe for Success.

OBJECTIVE: To describe an effective in-office hysteroscopic strategy to restore fertility of patients with severe Asherman's syndrome. DESIGN: A step-by-step video demonstration of the technique with an emphasis on the key portions of the procedure. A detailed narrated description of the steps is provided. SETTING: Tertiary care University Hospital. INTERVENTIONS: Three patients were managed by hysteroscopy performed in the office setting without anesthesia. Case 1 is a 34-year-old woman with obstetrical history of first-trimester incomplete abortion treated with Dilation and Curettage (D&C), followed by a tubal ectopic pregnancy treated with laparoscopic partial salpingectomy and a subsequent pregnancy on the tubal stump treated with uterine artery embolization. Case 2 is a 40-year-old woman with history of tubal ectopic pregnancy treated with salpingectomy, a surgical first-trimester voluntary termination of pregnancy with D&C and a full term vaginal delivery complicated with retained products of conception that were removed with D&C. Case 3 is a 35-year-old woman with two previous first-trimester spontaneous miscarriages both treated with D&C. Case 1 and 3 were treated using miniaturized mechanical instruments only; in case 2, miniaturized mechanical instruments and the 15 Fr bipolar mini-resectoscope were used. Preoperative 2D and 3D ultrasound were used to predict the complexity of the cases and to guide the surgeon during the procedure. Intrauterine lysis of adhesions was concluded when both tubal ostia were visualized, and the uterine cavity was determined to have adequate shape and volume. At the end of the procedures, hyaluronic acid-based gel was applied to prevent new intrauterine adhesion formation. Two weeks after the initial procedure, a second look diagnostic hysteroscopy was performed. Only one patient (#1) needed additional lysis of adhesions; in this case, at the end of the procedure, a Word catheter was inserted as a barrier method for the prevention of adhesion formation. Eight weeks later, the word catheter was removed, and additional lysis of adhesions was performed. All the surgical procedures were performed without complication, and a healthy endometrium was observed at the second look hysteroscopy, in all the three patients. All 3 patients conceived after the procedure. Pregnancy was achieved after one IVF cycle with the transfer of one frozen embryo in case 1 and spontaneously in cases 2 and 3. Patient 1 was delivered by elective caesarean section due to placenta previa, while the other two patients had normal vaginal deliveries. Patient 1 had Retained Products of Conception requiring hysteroscopic removal using a 27 Fr Resectoscope. CONCLUSION: When using innovative miniaturized instruments and adequate surgical technique, hysteroscopic lysis of adhesions is a feasible and effective in-office strategy to restore fertility in patients with severe Asherman's syndrome. The use of 2D and 3D ultrasound played an important role in the preoperative workup of the patient with Asherman's syndrome.

Incidence and Clinical Implications of Placenta Accreta Spectrum after Treatment for Asherman Syndrome.

STUDY OBJECTIVE: To investigate the incidence, predictors, and clinical implications of placenta accreta spectrum (PAS) in pregnancies after hysteroscopic treatment for Asherman syndrome (AS). DESIGN: This is a retrospective cohort study, conducted through a telephone survey and chart review. SETTING: Minimally invasive gynecologic surgery center in an academic community hospital. PATIENTS: Database of 355 patients hysteroscopically treated for AS over 4 years. We identified patients who achieved pregnancy past the first trimester and evaluated the incidence and predictors for PAS as well as associated clinical implications. INTERVENTIONS: Telephone survey. MEASUREMENTS AND MAIN RESULTS: We identified 97 patients meeting the inclusion criteria. Among these patients, 23 (23.7%) patients had PAS. History of cesarean delivery was the only variable statistically significantly associated with having PAS (adjusted odds ratio 4.03, 95% confidence interval 1.31-12.39). PAS was diagnosed antenatally in 3 patients (14.3%), with patients having placenta previa more likely to be diagnosed (p <.01). Nine patients (39.13%) with PAS required cesarean hysterectomy, which is 9.3% of those with a pregnancy that progressed past the first trimester. Factors associated with cesarean hysterectomy were the etiology of AS (dilation and evacuation after the second trimester pregnancy or postpartum instrumentation, p <.01), invasive placenta (increta or percreta, p <.05), and history of morbidly adherent placenta in previous pregnancies (p <.05). Two patients with PAS (9.5%) had uterine rupture, and another 2 (9.5%) experienced uterine inversion. CONCLUSION: There is a high incidence of PAS and associated morbidity in pregnancies after hysteroscopic treatment for AS. There is a low rate of antenatal diagnosis as well as a lack of reliable clinical predictors, which both stress the importance of clinical awareness, careful counseling, and delivery planning.

Adenomyosis and fertility: does adenomyosis impact fertility and does treatment improve outcomes.

PURPOSE OF REVIEW: Adenomyosis has recently been associated with infertility. Relief of bleeding and pain has been demonstrated with medical and surgical therapy. Less is known about reproductive outcomes after treatment. RECENT FINDINGS: Imaging findings during infertility evaluation can be suggestive of adenomyosis without pathologic evaluation. Among women with infertility undergoing assisted reproductive technologies (ART), adenomyosis is associated with lower live birth rates and clinical pregnancy rates. Treatment with gonadotropin releasing hormone (GnRH) modulators prior to frozen embryo transfer may increase the live birth rate and clinical pregnancy rate among women with adenomyosis. Pregnancy has been documented following image-guided adenomyosis ablation; however, the reproductive impact is not well established. Pregnancy following excisional procedures appears to be well tolerated, although may carry a higher risk of uterine rupture compared with pregnancy following myomectomy. It is not clear if ablative therapy or resection increases pregnancy rates. SUMMARY: Adenomyosis is associated with lower embryo implantation rates and ongoing pregnancy rates. Adenomyotic changes in the uterus can be seen by ultrasound and MRI. GnRH modulators may be useful for women with adenomyosis undergoing ART. Additional prospective data is warranted to determine the optimal medical or surgical therapy for women with adenomyosis desiring conception.Video abstract Supplementary digital content, http://links.lww.com/COOG/A78.

Endometrial cytokines in patients with and without endometriosis evaluated for infertility.

OBJECTIVE: To evaluate whether endometrial molecular profiles distinguish subsets of patients according to clinical characteristics, and to infer dysregulated immune networks, by measuring cytokines, chemokines, and growth factors in endometrial biopsy specimens from a cohort of infertile women with a high incidence of endometriosis. DESIGN: Prospective cohort study. SETTING: Department of Gynecology at a university hospital. PATIENT(S): Patients undergoing laparoscopy for infertility assessment (n = 103). INTERVENTION(S): Endometrial biopsies were performed during surgery. Fertility outcome and clinical parameters were registered preoperatively and after 6 months. MAIN OUTCOME MEASURE(S): The concentrations of 48 factors in endometrial biopsy specimens were analyzed with respect to clinical status in univariate and multivariate frameworks. RESULT(S): The concentrations of 44 factors from endometrial tissues of 74 patients were suitable for analysis. Although the tissue concentrations of interleukin (IL)15, IL-7, and interferon γ-induced protein (IP)-10 were individually lower in patients with endometriosis than in those without endometriosis, the differences were not significant after multiple comparison. However, multivariate modeling incorporating covariation showed separation between subsets of endometriotic and nonendometriotic patients, based predominantly on IP-10, monocyte chemoattractant protein-1, IL-16, and IL-18; this result was independent of cycle and fertility status. Analysis restricted to endometrial tissues from the secretory phase separated endometriotic and nonendometriotic patients by a combination of IL-15, IP-10, monocyte chemoattractant protein-1, IL-16, and IL-18. This combination suggests a uterine natural killer cell defect. We found no significant correlations between endometrial cytokines and fertility outcome. CONCLUSION(S): A molecular signature in endometrial tissue was able to distinguish endometriotic from nonendometriotic patients, implicating uterine natural killer cells in endometriosis.

International Consensus Statement for Recommended Terminology Describing Hysteroscopic Procedures.

OBJECTIVE: To develop a consensus statement of recommended terminology to use for describing different aspects of hysteroscopic procedures that can be uniformly used in clinical practice and research. DESIGN: Open forum discussion followed by online video meetings. SETTING: International community of hysteroscopy experts PATIENTS: Not applicable. INTERVENTIONS: Series of online video meetings to complete a previously established agenda until a final agreement for standardized nomenclature was obtained. MEASUREMENT AND MAIN RESULTS: The adoption and implementation of a common terminology to standardize reporting of hysteroscopic procedures was proposed to cover five domains: pain management, healthcare setting, model of care, type of hysteroscopic procedure and the hysteroscopic approach to the uterine cavity. A final agreement was obtained after 3 online video meetings. CONCLUSION: Hysteroscopy is the gold standard technique for the evaluation and management of uterine disorders. A clear definition and understanding of the terminology used to describe hysteroscopic procedures is lacking. The production of this international consensus statement for terminology to describe hysteroscopic procedures, covering pain management, setting, model of care, type of procedure and hysteroscopic approach, has the potential to enable more effective communication for both clinical and research purposes with the ultimate aim of improving patient care and clinical outcomes.

Patient-reported menstrual and obstetric outcomes following hysteroscopic adhesiolysis for Asherman syndrome.

OBJECTIVE: Review the menstrual and obstetric outcomes among Asherman syndrome patients when stratified by disease severity. DESIGN: Retrospective cohort study. SETTING: A community teaching hospital affiliated with a large academic medical center. PATIENTS: A total of 355 Asherman syndrome patients stratified by March classification who underwent hysteroscopic adhesiolysis. INTERVENTIONS: Telephone survey, analyzed with multivariable analysis. MAIN OUTCOME MEASURES: Return of menstruation. Pregnancy, miscarriage, and live birth rate. RESULTS: A total of 355 patients underwent hysteroscopic adhesiolysis. Of these, 150 (42.3%) patients completed the telephone survey with a mean follow-up of 2.21 years. Additionally, 40.7% had mild, 52.7% had moderate, and 6.6% had severe disease. Furthermore, 25.3% of patients reported amenorrhea at presentation, with mild disease patients having the highest rate of returning menstruation (93.8%) following treatment. The cumulative pregnancy rate was 81.9%, and the cumulative live birth rate was 51.2%, with no statistical differences identified by the classification group. CONCLUSION: Asherman syndrome disease severity predicted returning menstruation but not pregnancy or live birth rate.

Effects of Asherman Syndrome on Maternal and Neonatal Morbidity with Evaluation by Conception Method.

STUDY OBJECTIVE: Create a comprehensive summary of maternal and neonatal morbidities from patients previously treated for Asherman syndrome and evaluate for differences in perinatal outcomes based on conception method. DESIGN: Retrospective cohort. SETTING: Community teaching hospital affiliated with a large academic medical center. PATIENTS: Total of 43 singleton births identified from 40 patients previously treated at our institution for Asherman syndrome. INTERVENTIONS: Review of fertility and obstetric data to summarize the maternal and neonatal outcomes in singleton births from patients with Asherman syndrome who had been treated with hysteroscopic adhesiolysis. MEASUREMENTS AND MAIN RESULTS: Primary outcomes of maternal morbidity (i.e., hypertensive disease, gestational diabetes, ruptured membranes, postpartum hemorrhage, morbidly adherent placenta [MAP]) and secondary outcomes of neonatal morbidity (i.e., gestational age at birth, method of delivery, weight, length, 1- and 5-minute Apgar score oxygen requirement, anatomic malformations, length of neonatal admission) were evaluated. We identified 40 patients who completed successful treatment of Asherman syndrome and went on to carry a singleton gestation within our institution: 20 (50%) with mild disease, 18 (45%) with moderate disease, and 2 (5%) with severe disease under the March classification system. In total, 43 singleton births were examined, with 27 of 43 (62.8%) conceived without in vitro fertilization (IVF) (group A: non-IVF conception) and 16 of 43 (37.2%) conceived through IVF (group B: IVF conception). The overall rate of preterm birth in Asherman pregnancies was 11.6%, with no difference between the 2 conception groups. We documented 9.3% cases with intrauterine growth restriction, with no difference based on conception groups. The rate of MAP in patients with Asherman syndrome was 14.0%, and the rate of postpartum hemorrhage was 32.6%, with no differences between the conception groups. Newborn anatomic malformations of any cause were documented in 18.6% of all singleton births, with no difference between the conception groups. CONCLUSION: Our series indicates a higher incidence of intrauterine growth restriction, MAP, postpartum hemorrhage, and newborn anatomic malformations in Asherman syndrome pregnancies than that reported in pregnancies within the general population. However, we found no significant differences in the maternal and neonatal outcomes of patients with Asherman syndrome who conceived with or without IVF after being treated with hysteroscopic adhesiolysis.

Novel Technology to Capture Objective Data from Patients' Recovery from Laparoscopic Endometriosis Surgery.

STUDY OBJECTIVE: To assess the feasibility of a noncontact radio sensor as an objective measurement tool to study postoperative recovery from endometriosis surgery. DESIGN: Prospective cohort pilot study. SETTING: Center for minimally invasive gynecologic surgery at an academically affiliated community hospital in conjunction with in-home monitoring. PATIENTS: Patients aged above 18 years who sleep independently and were scheduled to have laparoscopy for the diagnosis and treatment of suspected endometriosis. INTERVENTIONS: A wireless, noncontact sensor, Emerald, was installed in the subjects' home and used to capture physiologic signals without body contact. The device captured objective data about the patients' movement and sleep in their home for 5 weeks before surgery and approximately 5 weeks postoperatively. The subjects were concurrently asked to complete a daily pain assessment using a numeric rating scale and a free text survey about their daily symptoms. MEASUREMENTS AND MAIN RESULTS: Three women aged 23 years to 39 years and with mild to moderate endometriosis participated in the study. Emerald-derived sleep and wake times were contextualized and corroborated by select participant comments from retrospective surveys. In addition, self-reported pain levels and 1 sleep variable, sleep onset to deep sleep time, showed a significant (p <.01), positive correlation with next-day-pain scores in all 3 subjects: r = 0.45, 0.50, and 0.55. In other words, the longer it took the subject to go from sleep onset to deep sleep, the higher their pain score the following day. CONCLUSION: A patient's experience with pain is challenging to meaningfully quantify. This study highlights Emerald's unique ability to capture objective data in both preoperative functioning and postoperative recovery in an endometriosis population. The utility of this uniquely objective data for the clinician-patient relationship is just beginning to be explored.

Concomitant Adenomyosis among Patients with Asherman Syndrome.

STUDY OBJECTIVE: To characterize obstetric outcomes for concomitant Asherman syndrome and adenomyosis. DESIGN: A retrospective cohort study. SETTING: A community teaching hospital affiliated with a large academic medical center. PATIENTS: A total of 227 patients with Asherman syndrome with available hysteroscopy and pelvic ultrasound reports. INTERVENTIONS: Telephone survey to assess and compare the obstetric outcomes of patients with Asherman syndrome with concomitant adenomyosis (Group A) vs patients with Asherman syndrome without concomitant adenomyosis (Group B). MEASUREMENTS AND MAIN RESULTS: A telephone survey and confirmatory chart review were conducted to obtain information on patients' demographics, gynecologic and obstetric history, past medical and surgical history, and Asherman syndrome management. Adenomyosis was a common sonographic finding, detected in 39 patients with Asherman syndrome (17.2%). In this cohort, 77 patients attempted pregnancy and produced 87 pregnancies. Age (odds ratio [OR] 0.67; 95% confidence intervals [CI], 0.52-0.86) was negatively associated with a pregnancy outcome. Age (OR 0.83; 95% CI, 0.73-0.95) and severe Asherman disease (OR 0.06; 95% CI, <0.01-0.99) were negatively associated with a live birth outcome. Adenomyosis was not an independent predictor of pregnancy rate, miscarriage rate, or live birth rate among patients with Asherman syndrome. CONCLUSION: Adenomyosis is relatively common in patients with Asherman syndrome. Adenomyosis does not seem to add any distinct detriment to fertility among patients with Asherman syndrome.

Comparison of cytokines in the peritoneal fluid and conditioned medium of adolescents and adults with and without endometriosis.

PROBLEM: To compare inflammatory- and immune-associated peritoneal cytokines of adolescents and adults with and without endometriosis. METHODS OF STUDY: In a nested case-control study in multiple university-affiliated scientific centers, ten adolescents and thirteen adults with visually and histologically confirmed endometriosis (cases), thirteen adolescents with visually suspected endometriosis but indeterminate (seven patients) or negative (six patients) histology, and fifteen adults undergoing surgery for non-malignant gynecologic disease without endometriosis (controls) underwent laparoscopic aspiration of peritoneal fluid (PF), from which PF and conditioned medium (CM) cytokine levels were assayed. RESULTS: Compared to adults with endometriosis, MCP-3, IL-12p40, MIP-1ß, and IL-15 were significantly higher among adolescents with endometriosis, while TNF-ß and CTACK were lower among adolescents. These differences were similar comparing adolescents with endometriosis to adult controls except for MIP-1ß, which was not statistically different. MIP-1ß was, however, the only cytokine observed to differ between adult cases and controls. There were no significant differences in CM cytokines among the three groups. Results were similar when analyses were restricted to samples collected (a) during menstrual cycle days 1-10, (b) from patients unexposed to exogenous hormones, or (c) from all adolescents despite presence or absence of histologic endometriosis. CONCLUSION: Biologically relevant and statistically significant differences in six PF cytokines were observed and suggest a more pro-invasion cytokine profile among adolescents with endometriosis. Adolescents with endometriosis have unique peritoneal cytokine profiles and molecular behavior when compared to adults with and without endometriosis.

A Systematic Review of Adenomyosis: It Is Time to Reassess What We Thought We Knew about the Disease.

OBJECTIVE: To summarize and update our current knowledge regarding adenomyosis diagnosis, prevalence, and symptoms. DATA SOURCES: Systematic review of PubMed between January 1972 and April 2020. Search strategy included: "adenomyosis [MeSH Terms] AND (endometriosis[MeSH Term OR prevalence study [MeSH Terms] OR dysmenorrhea[text word] OR prevalence[Text Word] OR young adults [Text Word] OR adolesce* [Text Word] OR symptoms[Text Word] OR imaging diagnosis [Text Word] OR pathology[Text Word]. METHODS OF STUDY SELECTION: Articles published in English that addressed adenomyosis and discussed prevalence, diagnosis, and symptoms were included. The included articles described pathology diagnosis, imaging, biopsy diagnosis, prevalence and age of onset, symptoms, and concomitant endometriosis. TABULATION, INTEGRATION, AND RESULTS: Sixteen articles were included in the qualitative analysis. The studies are heterogeneous when diagnosing adenomyosis with differing criteria, protocols, and patient populations. The prevalence estimates range from 20% to 88.8% in women who are symptomatic (average 30%-35%), with most diagnosed between the ages of 32 years and 38 years. The correlation between imaging and pathology continues to evolve. As imaging advances, newer studies report that younger women who are symptomatic are being diagnosed with adenomyosis on the basis of both magnetic resonance imaging and/or transvaginal ultrasound. High rates of concomitant endometriosis create challenges when discerning the etiology of pelvic pain. Symptoms that are historically attributed to endometriosis may actually be caused by adenomyosis. CONCLUSION: Adenomyosis remains a challenge to identify, assess, and research because of the lack of standardized diagnostic criteria, especially in women who wish to retain their uterus. As noninvasive diagnostics such as imaging and myometrial biopsies continue to improve, younger women with variable symptoms will likely create criteria for diagnosis with adenomyosis. The priority should be to create standardized histopathologic and imaging diagnoses to gain a deeper understanding of adenomyosis.

Symptoms of Adenomyosis and Overlapping Diseases.

To summarize and update our current knowledge regarding adenomyosis diagnosis, prevalence, and symptoms. Systematic review of PubMed between January 1972 and April 2020. Search strategy included: "adenomyosis [MeSH Terms] AND (endometriosis[MeSH Term OR prevalence study [MeSH Terms] OR dysmenorrhea[Text Word] OR prevalence[Text Word] OR young adults [Text Word] OR adolesce* [Text Word] OR symptoms[Text Word] OR imaging diagnosis [Text Word] OR pathology[Text Word]. Articles published in English that addressed adenomyosis and discussed prevalence, diagnosis, and symptoms were included. Included articles described: pathology diagnosis, imaging, biopsy diagnosis, prevalence and age of onset, symptoms, and concomitant endometriosis. Sixteen articles were included in the qualitative analysis. The studies are heterogeneous when diagnosing adenomyosis with differing criteria, protocols, and patient populations. Prevalence estimates range from 20% to 88.8% in symptomatic women (average 30-35%) with most diagnosed between 32-38 years old. The correlation between imaging and pathology continues to evolve. As imaging advances, newer studies report younger symptomatic women are being diagnosed with adenomyosis based on both magnetic resonance imaging (MRI) and/or transvaginal ultrasound (TVUS). High rates of concomitant endometriosis create challenges when discerning the etiology of pelvic pain. Symptoms that are historically attributed to endometriosis may actually be caused by adenomyosis. Adenomyosis remains a challenge to identify, assess and research because of the lack of standardized diagnostic criteria, especially in women who wish to retain their uterus. As noninvasive diagnostics such as imaging and myometrial biopsies continue to improve, younger women with variable symptoms will likely create criteria for diagnosis with adenomyosis. The priority should be to create standardized histopathological and imaging diagnoses to gain deeper understandings of adenomyosis.

Endometrial thickness measurements among Asherman syndrome patients prior to embryo transfer.

STUDY QUESTION: Is there an association between endometrial thickness (EMT) measurement and clinical pregnancy rate among Asherman syndrome (AS) patients utilizing IVF and embryo transfer (ET)? SUMMARY ANSWER: EMT measurements may not be associated with successful clinical pregnancy among AS patients undergoing IVF. WHAT IS KNOWN ALREADY: Clinical pregnancy rate after IVF is significantly lower in patients with a thin endometrium, defined as a maximum EMT of <7 mm. However, AS patients often have a thin EMT measurement due to intrauterine scarring, with a paucity of data and no guidance on what EMT cutoff is appropriate when planning an ET among these patients. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study of 45 AS patients treated at a specialized advanced hysteroscopic clinic from 1 January 2015, to 1 March 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Review of EMT measurements prior to a total of 90 ETs, among 45 AS patients. The impact of the maximum EMT measurement prior to ET on clinical pregnancy rate was analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 25/45 (55.6%) AS patients ultimately went on to have ≥1 clinical pregnancy following a mean ± SD of 2.00 ± 1.26 ET attempts. There was a total of 90 ETs among the 45 AS patients, with 29/90 (32.2%) ETs resulting in a clinical pregnancy. Younger patient age (P = 0.05) and oocyte donation (P = 0.01) were the only variables identified to be significant predictors for a positive clinical pregnancy outcome on bivariate analysis. The mean EMT measurement prior to all ETs among AS patients was 7.5 ± 1.6 mm. EMT measurement prior to ET did not predict a positive clinical pregnancy on either bivariate (P = 0.84) or multivariable analysis (odds ratio 0.91, P = 0.60). 31.8% of EMT measurements measured <7.0 mm. In this small cohort, no difference in the clinical pregnancy rate was detected when comparing ETs with EMT measurements of <7.0 mm versus ≥7.0 mm (P = 0.83). The mean EMT measurement decreased with increasing AS disease severity; 8.0 ± 1.6 mm for mild disease, 7.0 ± 1.4 mm for moderate disease and 5.4 ± 0.1 mm for severe disease. LIMITATIONS, REASONS FOR CAUTION: Our small sample size limits our ability to draw any definitive conclusions. In addition, patients utilized various infertility clinics. This limits our ability to evaluate the consistency of EMT measurements and the IVF care that was received. WIDER IMPLICATIONS OF THE FINDINGS: EMT measurement cutoff values should be used with caution if canceling a scheduled ET in AS patients. STUDY FUNDING/COMPETING INTEREST(S): This study was not funded. K.I. reports personal fees from Karl Stroz and personal fees from Medtronics outside the submitted work. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.