Society of Radiologists in Ultrasound Consensus on Routine Pelvic US for Endometriosis.

Endometriosis is a prevalent and potentially debilitating condition that mostly affects individuals of reproductive age, and often has a substantial diagnostic delay. US is usually the first-line imaging modality used when patients report chronic pelvic pain or have issues of infertility, both common symptoms of endometriosis. Other than the visualization of an endometrioma, sonologists frequently do not appreciate endometriosis on routine transvaginal US images. Given a substantial body of literature describing techniques to depict endometriosis at US, the Society of Radiologists in Ultrasound convened a multidisciplinary panel of experts to make recommendations aimed at improving the screening process for endometriosis. The panel was composed of experts in the imaging and management of endometriosis, including radiologists, sonographers, gynecologists, reproductive endocrinologists, and minimally invasive gynecologic surgeons. A comprehensive literature review combined with a modified Delphi technique achieved a consensus. This statement defines the targeted screening population, describes techniques for augmenting pelvic US, establishes direct and indirect observations for endometriosis at US, creates an observational grading and reporting system, and makes recommendations for additional imaging and patient management. The panel recommends transvaginal US of the posterior compartment, observation of the relative positioning of the uterus and ovaries, and the uterine sliding sign maneuver to improve the detection of endometriosis. These additional techniques can be performed in 5 minutes or less and could ultimately decrease the delay of an endometriosis diagnosis in at-risk patients.

Radiology State-of-the-art Review: Endometriosis Imaging Interpretation and Reporting.

Endometriosis is a common condition impacting approximately 190 million individuals and up to 50% of women with infertility globally. The disease is characterized by endometrial-like tissue located outside of the uterine corpus, which causes cyclical hemorrhage, inflammation, and fibrosis. Based on clinical suspicion or findings at routine transvaginal pelvic US or other prior imaging, dedicated imaging for endometriosis may be warranted with MRI or advanced transvaginal US. Deep endometriosis (DE) in the pelvis includes evaluation for stromal and fibrotic components and architectural distortion resulting from fibrosis and tethering. It is a disease requiring a compartment-based, pattern-recognition approach. MRI has the benefit of global assessment of the pelvis and is effective in assessing for features of malignancy and for evaluating extrapelvic locations. Transvaginal US has the advantage of dynamic maneuvers to assess for adhesions and may achieve higher spatial resolution for assessing the depth of bowel wall invasion. T1-weighted MRI evaluation increases the specificity of diagnosis by identifying hemorrhagic components, but the presence of T1 signal hyperintensity is not essential for diagnosing DE. Endometriosis is a disease with a broad spectrum; understanding the mild through advanced manifestations, including malignancy evaluation, is within the scope and breadth of radiologists' interpretation.

Vitrification versus slow freezing of human ovarian tissue: a systematic review and meta-analysis of histological outcomes.

A systematic review and meta-analysis of pertinent literature published from 2006 to January 2022 were conducted to study and compare vitrification and slow freezing, the two prominent methods of ovarian tissue cryopreservation. The primary outcome measures for this study were (1) proportion of intact primordial follicles, (2) proportion of intact stromal cells, (3) proportion of DNA fragmentation in primordial follicles, and (4) mean primordial follicle density. This meta-analysis of 19 studies revealed a significantly greater proportion of intact stromal cells in vitrified tissue versus slow-frozen tissue. No significant differences upon pooled analyses were observed between the two cryopreservation methods with respect to the proportion of intact primordial follicles, proportion of DNA fragmentation, or mean primordial follicle density. Due to differences seen in stromal cell viability, vitrification may be a preferred option to preserve histology of tissue. However, more work should be done to compare the two freezing techniques with less heterogeneity caused by patients, samples, and protocols.

Endometriosis biomarkers of the disease: an update.

PURPOSE OF REVIEW: Endometriosis is a complex benign gynaecologic condition with heterogenous presentations and a large impact on the global healthcare system and on the quality of life for millions of women. Currently, the gold standard for diagnosis involves direct visualization of lesions during surgery confirmed by histopathological diagnosis, resulting in an average delay in its initial diagnosis of 8-10 years. Therefore, the search for noninvasive diagnostic testing options has been subject to a large body of research. RECENT FINDINGS: Multiple potential biomarkers have been explored for noninvasive testing for endometriosis, including glycoproteins, inflammatory cytokines, immunological molecules, angiogenesis markers, hormones, micro RNAs (miRNAs), proteomics, metabolomics, genomics and the microbiome. SUMMARY: Although there are challenges to consider, areas for real promise and advancement in the noninvasive diagnosis of endometriosis are currently being explored with real promise in the area of miRNAs, proteomics, metabolomics, genomics and the microbiome.

Association Between Laparoscopic Appearance of Superficial Endometriosis, Positive Histology, and Systemic Hormone Use.

STUDY OBJECTIVE: To assess the association between laparoscopic appearance of superficial endometriosis lesions, histopathology, and systemic hormone use. DESIGN: Retrospective study. SETTING: Tertiary care academic medical center. PATIENTS: We identified 266 women who underwent laparoscopic surgery at an endometriosis center with excision of lesions consistent with possible superficial endometriosis between September 2015 and November 2018. INTERVENTIONS: Appearance of the peritoneal lesions was confirmed with review of surgical videos and correlated with each pathology specimen. Lesions were dichotomized on positive or negative pathology assessment. All pathology-positive lesions were further dichotomized by hormone use within 1 month of surgery. MEASUREMENTS AND MAIN RESULTS: A total of 841 lesions were biopsied from included subjects during the study period. Of those, 251 biopsies were negative, and 590 were positive for endometriosis on pathology assessment. Lesions had significantly higher odds of positive histology when they were red (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.17-2.48), white (OR, 1.99; 95% CI, 1.47-2.70), blue/black (OR, 2.98; 95% CI, 2.00-4.44), or puckering (OR, 9.78; 95% CI, 2.46-38.91) in appearance. The following combined characteristics had significantly higher odds of positive histology: white and blue (OR, 5.98; 95% CI, 2.97-12.02), red and white (OR, 2.22; 95% CI, 1.38-3.56), red and blue (OR, 4.11; 95% CI, 1.83-9.24), and clear and white (OR, 8.77; 95% CI, 1.17-66.02). Among positive biopsies, those with hormone exposure were more likely to have clear lesions than those without hormone use (OR, 3.36; 95% CI, 1.54-7.34) and were 2.89 times more likely to have clear and white lesions (95% CI, 1.07-7.85). CONCLUSION: Although lesions suspicious for endometriosis may have differing rates of positive pathology based on appearance, no lesion characteristic was able to exclude the possibility of endometriosis. In addition, hormone use may influence lesion appearance at the time of surgery, with clear lesions more prevalent. These data have implications for appropriate identification of endometriosis at the time of laparoscopy to ensure accurate diagnosis and complete treatment of disease.

Excision of Deep Endometriosis of the Rectosigmoid: Individualizing Care to the Presenting Pathology.

STUDY OBJECTIVE: To highlight different surgical approaches for managing deep infiltrating endometriosis involving the rectosigmoid colon. DESIGN: Demonstration of specific surgical techniques with educational narrated video footage. SETTING: Bowel endometriosis is reported in 3.8% to 37% of patients with endometriosis [1]. Most commonly, the rectosigmoid colon is involved. Pelvic ultrasound and magnetic resonance imaging may be useful in diagnosis and for surgical planning [2]. Treatment options include observation, medications, or surgery. There are various surgical techniques that can be used for excision of deep infiltrating endometriosis involving the rectosigmoid colon. Serosal shaving, discoid resection, and complete resection are the possible types of surgical interventions that are demonstrated in this surgical education video at an academic medical center. Serosal shaving is used for lesions with minimal involvement of the muscularis. It can be done sharply or with electrosurgery and it is imperative to assess bowel integrity after shaving. Discoid resection is used for lesions with muscularis involvement, <3 cm in size, and encompassing less than one-third to a half of the bowel circumference. Full-thickness discoid bowel resection can be done in various ways including manual resection with primary suture closure, regular stapler transabdominally, or EEA stapler (Medtronic EEA Circular Stapler, Minneapolis, MN) transrectally. Segmental resection is used for lesions >3 cm in size, involving >50% of the bowel circumference, or for multifocal lesions. Various suture and stapler methods exist for this technique. INTERVENTIONS: Based on the imaging and intraoperative findings, a surgical technique was chosen and demonstrated. The types of surgical techniques demonstrated include laparoscopic serosal shaving, discoid resection with manual resection and primary suture closure, discoid resection with EEA stapler, and segmental resection. CONCLUSION: Knowledge of different surgical approaches to excise endometriosis is essential to appropriately address a patient's unique pathology. The choice of which surgical technique to use should include consideration of the location of the lesion, depth and circumference of involvement, and the number of nodules present.

Consult and procedure incidence outcomes following establishment of a fertility preservation program for children with cancer.

PURPOSE: Fertility is a quality of life outcome adversely affected by cancer therapy. Many childhood cancer patients, however, are not offered options to preserve their fertility. Providers acknowledge difficulty discussing impaired fertility to patients due to lack of knowledge of available options. Our objective was to review the impact of a pediatric multidisciplinary fertility preservation program on providers' fertility preservation counseling and discussion of options. METHODS: A retrospective medical chart review was conducted for pediatric cancer patients prior to and following program establishment. Fertility preservation discussions, consults, and incidence were noted. Following filtering and stratification, 198 and 237 patients were seen prior to and following program establishment, respectively. RESULTS: Following program establishment, provider-patient discussions of impaired fertility (p = 0.007), fertility preservation consults (p = 0.01), and incidence of fertility preservation procedures (p < 0.001) increased among patients. Furthermore, the number of patients who received fertility preservation consults after receiving gonadotoxic treatment decreased (p < 0.001). This trend was particularly noted in pre-pubertal and female patients, for whom fertility preservation options are limited without an established program. CONCLUSION: The establishment of a formal program greatly improved access to fertility preservation consults and procedures in children with cancer.

A novel combined transurethral and suprapubic approach for excision of mesh at the bladder neck.

INTRODUCTION AND HYPOTHESIS: Unrecognized bladder perforation of a tension-free sling is a rare situation. Removal of the intravesical sling has been done by laparotomy or transurethrally. With technique presented here we want to show a minimally invasive approach that allows complete removal of the intraluminal sling material, located at the bladder neck. METHODS: This video shows a novel combined transurethral and suprapubic approach for radical removal of the mesh. Two 3.5-mm trocars were placed suprapubically into a filled bladder. One site was used for an optic with camera and the other for a 3.5-mm grasping forceps to apply tension on the mesh to pull it out of the bladder wall while it was being excised transurethrally with a cystoscope and transurethral scissors. RESULTS: The patient's postoperative course was uneventful. At 1-month follow-up, the patient was free of dysuria and cystoscopy revealed complete healing of the mesh site. Because of recurrent stress urinary incontinence, another continence sling surgery has been performed (TVT exact). After a follow-up of 2 years, she is continent and free of dysuria. CONCLUSIONS: This novel technique provides an effective means of removing mesh perforated into the bladder, located at the bladder neck, using a combined transurethral and suprapubic approach. The technique is minimally invasive and the applied traction allows complete removal of the intraluminal part of the mesh.

Intrauterine insemination cycles: prediction of success and thresholds for poor prognosis and futile care.

PURPOSE: We aimed to define intrauterine insemination (IUI) cycle characteristics associated with viable birth, identify thresholds below which IUI treatments are consistent with very poor prognosis and futile care, and develop a nomogram for individualized application. METHODS: This retrospective cohort study evaluated couples using fresh partner ejaculate for IUI from January 2005 to September 2017. Variables included female age, semen characteristics, and ovarian stimulation type. Using cycle-level data, we evaluated the association of these characteristics with the probability of viable birth by fitting generalized regression models for a binary outcome with a logit link function, using generalized estimating equation methodology to account for the correlation between cycles involving the same patient. RESULTS: The cohort consisted of 1117 women with 2912 IUI cycles; viable birth was achieved in 275 (9.4%) cycles. Futile care (viable birth rate < 1%) was identified for women age > 43, regardless of stimulation type or inseminate motility (IM). Very poor prognosis (viable birth rate < 5%) was identified for women using oral medications or Clomid plus gonadotropins who were (1) age < 35 with IM < 49%, (2) age 35-37 with IM < 56%, or (3) age ≥ 38, and (4) women age ≥ 38 using gonadotropins only with IM < 60%. A clinical prediction model and nomogram was developed with an optimism-corrected c-statistic of 0.611. CONCLUSIONS: The present study highlights the impact of multiple clinical factors on IUI success, identifies criteria consistent with very poor prognosis and futile care, and provides a nomogram to individualize counseling regarding the probability of a viable birth.

Utilization and Outcomes of Fertility Preservation Techniques in Women Undergoing Allogeneic Hematopoietic Cell Transplant.

Iatrogenic menopause with consequent infertility is a major complication in reproductive-age women undergoing hematopoietic cell transplantation (HCT). Recent guidelines recommend a discussion of the possibility of infertility and the options for fertility preservation as part of informed consent before initiation of any cancer-directed therapy, including HCT. Women age 15 to 49 years at the time of allogeneic HCT, between the years 2001 and 2017, were identified from the Mayo Clinic Rochester institutional HCT database. One hundred seventy-seven women were eligible, of whom 49 (28%) were excluded due to documented postmenopausal state or prior hysterectomy. The median age of the cohort was 31 years (range, 15 to 49 years) with median gravidity and parity being G1P1 (range, G0 to G8, P0 to P6). Fifty-four (42%) women were nulligravid at the time of HCT. Eighty-two percent underwent myeloablative conditioning (MAC), whereas 18% underwent reduced-intensity conditioning (RIC). Only 34 women (27%) had documented fertility counseling within 72 hours of diagnosis, and a total of 61 (48%) received fertility counseling prior to HCT. Thirty-eight women (30%) were referred to a reproductive endocrinologist, of whom 13 (10%) underwent assisted reproductive technologies (ART; nine oocyte cryopreservation, four embryo cryopreservation). Of these, nine procedures yielded successful cryopreserved tissue (two completed at outside institutions). The median time to completion of the seven successful ART procedures at Mayo Clinic was 13 days (range, 9 to 15 days). The remainder of women referred to reproductive endocrinology did not undergo ART due to disease severity (68%), financial barriers (20%), and/or low antral follicle count (12%). Ninety-three women (73%) received leuprolide for ovarian suppression prior to conditioning. Three (4%) of 75 women who underwent MAC and were alive >365 days after HCT had spontaneous menstrual recovery after HCT (median time, 14 months; range, 6 to 21 months), in comparison to 10 (50%) of 20 women who underwent RIC and were alive >365 days after HCT (P < .01) (median, 21.5 months; range, 5 to 83 months). In the latter cohort, there were two spontaneous pregnancies, occurring at 71 and 72 months after HCT, respectively. Oncofertility is an emerging field due to an increasing number of young cancer survivors. Herein, we document that even at a large tertiary HCT center, the rate of documented fertility counseling and reproductive endocrinology referrals was low and the rate of ART was even lower. Spontaneous menstrual recovery was rare but more likely in the setting of nonmalignant disease and RIC HCT. A concerted multidisciplinary effort is needed to understand parenthood goals and to explore the impact of HCT on decision making about fertility preservation and parenthood. These efforts could improve oncofertility referral, ART utilization, and reproductive outcomes.

A multipurpose uterine/vaginal manipulator for laparoscopic urogynecologic procedures.

INTRODUCTION AND HYPOTHESIS: The use of an appropriate uterine manipulator is key to various laparoscopic gynecologic procedures. Adequate uterine manipulation is important for total or supracervical laparoscopic hysterectomies, laparoscopic sacrocolpopexy as well as laparoscopic repair of vaginal vault prolapse. While several uterine manipulators are available to choose from, their use may be specific to certain procedures and their cost may vary as well. METHODS: This video aims to provide an introduction to a multipurpose, reusable uterine/vaginal manipulator that can be used for laparoscopic supracervical hysterectomy, laparoscopic sacrocolpopexy, laparoscopic hysteropexy as well as laparoscopic repair of vaginal vault prolapse. RESULTS: The video highlights the user-friendly, easy-to-clean, reusable, multipurpose uterine/vaginal manipulator. CONCLUSIONS: The manipulator is designed for an efficient combination of laparoscopic urogynecologic procedures and supracervical hysterectomy.

Vaginal bromocriptine improves pain, menstrual bleeding and quality of life in women with adenomyosis: A pilot study.

INTRODUCTION: Adenomyosis is a benign uterine disease where endometrial glands and stroma are found within the myometrium surrounded by an area of hypertrophic myometrium. Symptomatology includes heavy menstrual bleeding and pelvic pain. The pathogenesis of adenomyosis is not known; however, animal models have shown increased uterine concentration of prolactin as a risk factor. Prolactin acts as a smooth muscle cell mitogen. If prolactin is central to adenomyosis pathogenesis, reducing uterine prolactin could be a possible medical treatment option. In this pilot study, we aim to evaluate the effect of bromocriptine, a prolactin inhibitor, on menstrual bleeding and pain in women with adenomyosis. MATERIAL AND METHODS: 23 women with diffuse adenomyosis were enrolled from a university hospital in Sweden and a tertiary care center in the USA. Nineteen patients completed 6 months of treatment with vaginal bromocriptine at a dose of 5 mg daily. Participants completed validated measures at baseline, 3 and 6 months of treatment, and at 9 months (3 months after cessation of bromocriptine). Validated measures utilized included Pictorial Blood Loss Assessment Chart (PBLAC), Aberdeen Menorrhagia Clinical Outcomes Questionnaire (AMCOQ), Visual Analog Scale for pain (VAS), McGill Pain Questionnaire (MPQ), Endometriosis Health Profile (EHP-30), Female Sexual Function Index (FSFI) and the Fibroid Symptom Quality of Life (UFS-QOL) symptom severity and health-related quality of life (HRQL) subscores. Scores were compared between baseline and 9 months using the Wilcoxon signed rank test. RESULTS: Mean age of participants was 44.8 years. About 77.8% reported PBLAC scores >250 and 68.4% reported moderate to severe pain at baseline. Compared with baseline, women had lower 9-month scores (median [interquartile range] for all) on PBLAC (baseline 349 [292-645] vs 9-month 233 [149-515], P = 0.003), VAS (5.0 [4-8.3] vs 2.5 [0-4.5], P < 0.001), EHP Core Pain (15.9 [9.1-50.0] vs 3.4 [2.3-34.1], P = 0.029), EHP Core Self-image (41.7 [16.7-58.3] vs 25 [0-5], P = 0.048) and Symptom Severity Score (60 [44-72] vs 44 [25-56], P < 0.001) and higher HRQL scores (57 [37-63] vs 72 [51-85], P < 0.001) following bromocriptine treatment. Other EHP core parameters and FSFI were not significantly different. CONCLUSIONS: Significant improvement in menstrual bleeding, pain and quality of life after vaginal bromocriptine treatment suggests a novel therapeutic agent for adenomyosis.

The National Physicians Cooperative: transforming fertility management in the cancer setting and beyond.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.

Hysteroscopic Management of Asherman's Syndrome.

In developed countries Asherman's syndrome is almost always the result of a prior intrauterine operative trauma. This is often asymptomatic but may result in hypo- or amenorrhea and can contribute to infertility and pregnancy complications. We review their etiology, clinical implications, and systems proposed to classify their extent. The numerous methods reported for performing lysis of intrauterine adhesions are summarized along with clinical results. Current strategies to prevent recurrence of intrauterine adhesions have not been conclusively shown to be clinically effective, but the potential for endometrial regeneration using stem cells is an exciting modality under investigation.

Options for Fertility Preservation in Children.

Fertility preservation therapies can conserve future reproductive potential for persons facing serious medical diagnoses. With cure rates for childhood cancer reaching almost 80%, quality-of-life concerns for long-term survivors, including future parenting, are becoming more pertinent. Late effects of childhood cancer can be divided into physical, social, psychological, and spiritual domains. Potential loss of fertility threatens the well-being of these children in all these domains. Providers often hesitate to discuss fertility preservation with the patients. However, parental attitudes toward discussion of fertility preservation have been found to be open to such conversations for both prepubertal and postpubertal children who have a cancer diagnosis. Multiple national and international organizations recommend discussion with all persons having gonadotoxic therapy, including children, regarding the effect of planned treatment on future fertility and their options for fertility preservation. Renal or rheumatologic disease treated with high-dose cyclophosphamide and chromosomal anomalies such as Turner or Klinefelter syndrome may be amenable to fertility preservation. This essay reviews fertility preservation options available to children, as well as the expanding list of indications for fertility preservation.

Risk Factors, Clinical Presentation, and Outcomes for Abdominal Wall Endometriosis.

STUDY OBJECTIVE: To evaluate the risk factors, presentation, and outcomes in cases of abdominal wall endometriosis. DESIGN: A case-control study (Canadian Task Force classification II-2). SETTING: An academic medical center. PATIENTS: A total of 102 (34 cases and 68 controls) were included. INTERVENTIONS: Surgical resection of abdominal wall endometriosis. MEASUREMENTS AND MAIN RESULTS: Cases underwent surgical excision for abdominal wall endometriosis at Mayo Clinic from January 1, 2000, through December 31, 2013. For each case, 2 controls were randomly selected from a list of women who had surgery in the same year with minimal (American Society for Reproductive Medicine stage I-II) endometriosis. A chart review was completed for variables of interest. Regression models were used to identify independent risk factors associated with abdominal wall endometriosis. RESULTS: In 14 years, 2539 women had surgery for endometriosis at Mayo Clinic. Of these, only 34 (1.34%) had abdominal wall endometriosis. The mean age was 35.2 ± 5.9 years, and the median parity was 2 (range, 0-5). Clinical examination diagnosed abdominal wall endometriosis in 41% of cases, with the cesarean delivery scar being the most common site (59%). There was a strong correlation between the size of the lesion on clinical examination compared with the size of the pathology specimen (r2 = 0.74, p < .001). When compared with controls, cases had significantly higher parity and body mass index, more cyclic localized abdominal pain, less dysmenorrhea, longer duration from the start of symptoms to surgery, and more gynecologic surgeries for symptoms without cure. In the final multivariable model, cyclic localized abdominal pain, absence of dysmenorrhea, and previous laparotomy were independently associated with abdominal wall endometriosis with adjusted odds ratios of 10.6 (95% CI 1.85-104.4, p < .001), 12.4 (95% CI 1.64-147.1, p < .001), and 70.1 (95% CI 14.8-597.7, p < .001), respectively, with an area under the curve for the receiver operating characteristic of 0.94 (95% CI, 0.87-0.98). After excision of the disease, repeat surgery was needed in 2 (5.9%) patients with a median time to recurrence of 50.5 (range, 36-65) months. CONCLUSIONS: Abdominal wall endometriosis is a rare but unique form of endometriosis. Careful history and clinical examination can provide accurate diagnosis and avoid unnecessary delay before surgical intervention. Localized cyclic abdominal pain with the absence of dysmenorrhea and a history of prior laparotomy are independent risk factors with very high accuracy for diagnosis.

Epigenetic Modulation of Collagen 1A1: Therapeutic Implications in Fibrosis and Endometriosis.

Progressive fibrosis is recalcitrant to conventional therapy and commonly complicates chronic diseases and surgical healing. We evaluate here a novel mechanism that regulates scar-tissue collagen (COL1A1/Col1a1) expression and characterizes its translational relevance as a targeted therapy for fibrosis in an endometriosis disease model. Endometriosis is caused by displacement and implantation of uterine endometrium onto abdominal organs and spreads with progressive scarring. Transcription factor KLF11 is specifically diminished in endometriosis lesions. Loss of KLF11-mediated repression of COL1A1/Col1a1 expression resulted in increased fibrosis. To determine the biological significance of COL1A1/Col1a1 expression on fibrosis, we modulated its expression. In human endometrial-stromal fibroblasts, KLF11 recruited SIN3A/HDAC (histone deacetylase), resulting in COL1A1-promoter deacetylation and repression. This role of KLF11 was pharmacologically replicated by a histone acetyl transferase inhibitor (garcinol). In contrast, opposite effects were obtained with a HDAC inhibitor (suberoyl anilide hydroxamic acid), confirming regulatory specificity for these reciprocally active epigenetic mechanisms. Fibrosis was concordantly reversed in Klf11(-/-)animals by histone acetyl transferase inhibitor and in wild-type animals by HDAC inhibitor treatments. Aberrant lesional COL1A1 regulation is significant because fibrosis depended on lesion rather than host genotype. This is the first report demonstrating feasibility for targeted pharmacological reversal of fibrosis, an intractable phenotype of diverse chronic diseases.

KLF10 Mediated Epigenetic Dysregulation of Epithelial CD40/CD154 Promotes Endometriosis.

Endometriosis is a highly prevalent, chronic, heterogeneous, fibro-inflammatory disease that remains recalcitrant to conventional therapy. We previously showed that loss of KLF11, a transcription factor implicated in uterine disease, results in progression of endometriosis. Despite extensive homology, co-expression, and human disease association, loss of the paralog Klf10 causes a unique inflammatory, cystic endometriosis phenotype in contrast to fibrotic progression seen with loss of Klf11. We identify here for the first time a novel role for KLF10 in endometriosis. In an animal endometriosis model, unlike wild-type controls, Klf10(-/-) animals developed cystic lesions with massive immune infiltrate and minimal peri-lesional fibrosis. The Klf10(-/-) disease progression phenotype also contrasted with prolific fibrosis and minimal immune cell infiltration seen in Klf11(-/-) animals. We further found that lesion genotype rather than that of the host determined each unique disease progression phenotype. Mechanistically, KLF10 regulated CD40/CD154-mediated immune pathways. Both inflammatory as well as fibrotic phenotypes are the commonest clinical manifestations in chronic fibro-inflammatory diseases such as endometriosis. The complementary, paralogous Klf10 and Klf11 models therefore offer novel insights into the mechanisms of inflammation and fibrosis in a disease-relevant context. Our data suggests that divergence in underlying gene dysregulation critically determines disease-phenotype predominance rather than the conventional paradigm of inflammation being precedent to fibrotic scarring. Heterogeneity in clinical progression and treatment response are thus likely from disparate gene regulation profiles. Characterization of disease phenotype-associated gene dysregulation offers novel approaches for developing targeted, individualized therapy for recurrent and recalcitrant chronic disease.

Endometrial Ablation in Women With Abnormal Uterine Bleeding Related to Ovulatory Dysfunction: A Cohort Study.

STUDY OBJECTIVE: To evaluate the efficacy and safety of endometrial ablation (EA) for the treatment of abnormal uterine bleeding (AUB) associated with ovulatory dysfunction. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An academic medical center. PATIENTS: Women with AUB who underwent EA during an 8-year period. INTERVENTIONS: EA by radiofrequency or thermal balloon ablation techniques. MEASUREMENTS AND MAIN RESULTS: Women with AUB were divided into 2 groups: irregular bleeding with ovulatory dysfunction (AUB-O) or regular heavy bleeding related to a primary endometrial disorder (AUB-E). Outcome measures included rates of amenorrhea and treatment failure (ie, need for reablation or hysterectomy). Outcomes were compared between groups using survival analyses and chi-square tests. Known confounders were adjusted for using Cox and logistic regression models. Five-year cumulative treatment failure rates were 11.7% (95% confidence interval [CI], 6.5%-16.9%) for AUB-O and 12.3% (95% CI, 8.4%-16.2%) for AUB-E (p = .62). The unadjusted hazard ratio for treatment failure was 0.87 (95% CI, 0.72-1.05, p = .16). After adjusting for known risk factors for failure, the hazard ratio was 1.48 (95% CI, 0.82-2.65, p = .19). The rates of amenorrhea were 11.8% for AUB-O and 13.8% for AUB-E with an unadjusted odds ratio of 0.84 (95% CI, 0.48-1.48, p = .55). After adjusting for factors for amenorrhea after EA, the odds ratio was 1.08 (95% CI, 0.62-1.84, p =.78). No pregnancies or endometrial cancers occurred after EA. CONCLUSION: EA is effective in women with AUB-O and can be used as an alternative to hysterectomy or in patients with contraindications to medical management of AUB-O.

Progesterone support for frozen embryo transfer: intramuscular versus vaginal suppository demonstrates no difference in a cohort.

OBJECTIVE: To evaluate pregnancy rates based on the route of progesterone replacement in frozen embryo transfer (FET) cycles. STUDY DESIGN: A randomized controlled trial and retrospective analysis. In the randomized group 76 FET cycles were randomized. In the retrospective group 508 FET cycles were reviewed. Intramuscular (IM) proges-erone in oil 100 mg daily or oral micronized progesterone prior to transfer followed by compounded vaginal proges-erone 200 mg 3 times daily (OV). The main outcome measure was the clinical pregnancy rate (CPR). RESULTS: Baseline characteristics did not vary be-ween groups in either cohort. In the randomized group there were no significant differences in CPR (31.43% vs. 21.05%) or live birth rate (LBR) (31.43% vs. 18.92%) for IM and OV progesterone replacement, respectively. In the retrospective cohort patients there wore also no significant differences in CPR (35.56% vs. 32.35%) or LBR (32.23% vs. 28.51%)f or the IM and OVp rogester-ne replacement groups, respectively. CONCLUSION: This study demonstrates that either OV or IM progesterone is effective for luteal phase support for FETs.