Rapidly evolving pelvic lymphangioleiomyomatosis (LAM) mimicking bilateral hydrosalpinx: report of a rare case and literature review.

Lymphangioleiomyomatosis (LAM) represents a rare neoplasm affecting almost exclusively women of reproductive age. This condition mainly affects the lungs, but extrapulmonary locations such as the pelvis and the retroperitoneum are possible. Clinical evaluation and ultrasound imaging are usually non-specific, and the diagnosis is obtained through surgical excision and histopathological examination. We report a very rare case of abdominal LAM in a young female patient. A thorough literature review of this rare condition with emphasis on gynecologic implications will be presented. The patient was referred for gynecologic consultation due to pelvic pain and infertility. Unfortunately, despite prompt diagnosis and treatment, the course of the disease was severe and led to patient's exitus in a short time. We encountered an extremely rare deadly pathology mimicking a very common gynecologic condition. The gynecologist must always be alert of possible unexpected conditions that will require prompt attention.

Uterine Septum with or without Hysteroscopic Metroplasty: Impact on Fertility and Obstetrical Outcomes-A Systematic Review and Meta-Analysis of Observational Research.

Objective: we performed a systematic review/meta-analysis to evaluate the impact of septate uterus and hysteroscopic metroplasty on pregnancy rate-(PR), live birth rate-(LBR), spontaneous abortion-(SA) and preterm labor (PL) in infertile/recurrent miscarriage-(RM) patients. Data sources: a literature search of relevant papers was conducted using electronic bibliographic databases (Medline, Scopus, Embase, Science direct). Study eligibility criteria: we included in this meta-analysis all types of observational studies that evaluated the clinical impact of the uterine septum and its resection (hysteroscopic metroplasty) on reproductive and obstetrics outcomes. The population included were patients with a diagnosis of infertility or recurrent pregnancy loss. Study appraisal and synthesis methods: outcomes were evaluated according to three subgroups: (i) Women with untreated uterine septum versus women without septum (controls); (ii) Women with treated uterine septum versus women with untreated septum (controls); (iii) Women before and after septum removal. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the outcome measures. A p-value < 0.05 was considered statistically significant. Subgroup analysis was performed according to the depth of the septum. Sources of heterogeneity were explored by meta-regression analysis according to specific features: assisted reproductive technology/spontaneous conception, study design and quality of papers included Results: data from 38 studies were extracted. (i) septum versus no septum: a lower PR and LBR were associated with septate uterus vs. controls (OR 0.45, 95% CI 0.27−0.76; p < 0.0001; and OR 0.21, 95% CI 0.12−0.39; p < 0.0001); a higher proportion of SA and PL was associated with septate uterus vs. controls (OR 4.29, 95% CI 2.90−6.36; p < 0.0001; OR 2.56, 95% CI 1.52−4.31; p = 0.0004). (ii) treated versus untreated septum: PR and PL were not different in removed vs. unremoved septum(OR 1.10, 95% CI 0.49−2.49; p = 0.82 and OR 0.81, 95% CI 0.35−1.86; p = 0.62); a lower proportion of SA was associated with removed vs. unremoved septum (OR 0.47, 95% CI 0.21−1.04; p = 0.001); (iii) before-after septum removal: the proportion of LBR was higher after the removal of septum (OR 49.58, 95% CI 29.93−82.13; p < 0.0001) and the proportion of SA and PL was lower after the removal of the septum (OR 0.02, 95% CI 0.02−0.04; p < 0.000 and OR 0.05, 95% CI 0.03−0.08; p < 0.0001) Conclusions: the results show the detrimental effect of the uterine septum on PR, LBR, SA and PL. Its treatment reduces the rate of SA.

Altered Gene Expression Encoding Cytochines, Grow Factors and Cell Cycle Regulators in the Endometrium of Women with Chronic Endometritis.

To evaluate the expression of genes encoding cytokines, grow factors and cell cycle regulators in the proliferative endometrium of women with chronic endometritis (CE) compared to controls. We performed a case-control study on seven women with CE as diagnosed by hysteroscopy and histology (Cases) compared to six women without CE (Controls). All women underwent diagnostic hysteroscopy plus endometrial biopsy during the mid-proliferative phase of the menstrual cycle. Endometrial samples were divided into two different aliquots for histological and molecular analyses. The endometrial expression profile of 16 genes encoding proteins involved in the inflammatory process, proliferation and cell cycle regulation/apoptosis was assessed by using high-throughput qPCR. Study endpoints were between-group differences in the expression of VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1, BAX and IL12. RESULTS: VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1 were significantly overexpressed in women with CE compared to controls, while BAX and IL12 had similar expression between groups. In women with CE, we found an altered endometrial expression of genes involved in inflammatory, cell proliferation, and apoptosis processes. The dominance of proliferative and anti-apoptotic activity in CE may potentially promote the development of polyps and hyperplastic lesions.

Omics and Artificial Intelligence to Improve In Vitro Fertilization (IVF) Success: A Proposed Protocol.

The prediction of in vitro fertilization (IVF) outcome is an imperative achievement in assisted reproduction, substantially aiding infertile couples, health systems and communities. To date, the assessment of infertile couples depends on medical/reproductive history, biochemical indications and investigations of the reproductive tract, along with data obtained from previous IVF cycles, if any. Our project aims to develop a novel tool, integrating omics and artificial intelligence, to propose optimal treatment options and enhance treatment success rates. For this purpose, we will proceed with the following: (1) recording subfertile couples' lifestyle and demographic parameters and previous IVF cycle characteristics; (2) measurement and evaluation of metabolomics, transcriptomics and biomarkers, and deep machine learning assessment of the oocyte, sperm and embryo; (3) creation of artificial neural network models to increase objectivity and accuracy in comparison to traditional techniques for the improvement of the success rates of IVF cycles following an IVF failure. Therefore, "omics" data are a valuable parameter for embryo selection optimization and promoting personalized IVF treatment. "Omics" combined with predictive models will substantially promote health management individualization; contribute to the successful treatment of infertile couples, particularly those with unexplained infertility or repeated implantation failures; and reduce multiple gestation rates.

Comparison of endometrial polyp recurrence in fertile women after office hysteroscopic endometrial polypectomy using two widely spread techniques.

AIM: To compare the recurrence of benign endometrial polyps after office hysteroscopic polypectomy performed with a bipolar electrode (BE) or a small diameter hysteroscopic tissue removal system (HTRs). METHODS: From July 2018 to December 2019 we evaluated the charts of 114 asymptomatic fertile women who underwent office hysteroscopic polypectomy, 1 year before, for a single large benign endometrial polyp (size between 10 and 20 mm) using a 4 mm continuous flow hysteroscope with a BE or a 5 mm HTRs. Patients, divided into two groups according to surgical procedure, each performed exclusively by one expert gynecologist, were scheduled for a 12-month postoperative transvaginal sonography to evaluate the recurrence of endometrial polyps. RESULTS: Forty-eight women of the BE group and 42 of the HTRs group were considered for the 1-year transvaginal sonography follow-up. Five polyps were identified in the BE group and three in the HTRs group (5/48 vs 3/42, P = n.s.). All polyps were removed hysteroscopically (in three out of five and in two out of three cases, respectively, in the same places of the previous polypectomy) and evaluated as 'benign' by the pathologist. CONCLUSION: Office hysteroscopic endometrial polypectomy with small HTRs compared to BE revealed at a 1-year follow-up no difference in terms of complete removal and recurrence of polyps. HTRs polypectomy resulted in less pain and significantly quicker time of procedure compared to BE. This data should be kept in mind for patient comfort any time hysteroscopic polypectomy is planned in an office setting.

In-office Hysteroscopic Treatment of Herlyn-Werner-Wunderlich Syndrome: A Case Series.

Herlyn-Werner-Wunderlich syndrome (HWWs) is a rare congenital malformation of the female urogenital track characterized by a triad consisting of didelphys uterus, obstructed hemivagina, and ipsilateral renal agenesis. We report 5 consecutive cases of patients diagnosed with HWWs treated in our center. Imaging studies with 2-dimensional/3-dimensional ultrasound and abdominopelvic magnetic resonance imaging were obtained to confirm the diagnosis. The treatment consisted of a 1-step surgical in-office hysteroscopic incision of the vaginal septum using 5 Fr hysteroscopic bipolar electrodes. At the follow-up visit, between 1 and 2 months after the initial procedure, the patients underwent a diagnostic vaginoscopy with excision of exceeding vaginal tissue if needed, performed with a vaginal hysteroscopic approach. In-office hysteroscopic treatment of patients diagnosed with HWWs is a safe and effective, minimally invasive treatment modality that provides symptomatic relief and preserves fertility, avoiding the cost and risks of the use of general anesthesia in an operating room setting. We recommend shifting the management of this challenging condition to the office setting.

Long-Term Reproductive Outcomes after Hysteroscopic Treatment of Dysmorphic Uteri in Women with Reproductive Failure: An European Multicenter Study.

OBJECTIVE: To evaluate the long-term reproductive outcomes in patients with dysmorphic uterus treated by hysteroscopic metroplasty with miniaturized instruments. DESIGN: Retrospective multicenter cohort study. SETTING: Tertiary care university hospitals. PATIENTS: The study was conducted on 214 women with a dysmorphic uterus (T-shaped, infantilis, or other type of dysmorphic uterus according to the European Society of Human Reproduction and Embryology and the European Society for Gynaecological Endoscopy classification system) with history of primary unexplained infertility (group 1) or repeated (>2) early miscarriages (group 2). Dysmorphic uteri were diagnosed by office hysteroscopy and 3-dimensional transvaginal ultrasound (3D-TVS). INTERVENTIONS: All patients underwent in office hysteroscopic metroplasty using a continuous-flow hysteroscope with a 5 Fr operating channel introduced into the uterine cavity using the vaginoscopic approach. Longitudinal incisions were performed on the fibromuscular constriction rings in the isthmic area and in some cases on the other uterine walls with a 5 Fr bipolar electrode or scissors. At the end of the procedure, an antiadhesive gel was applied into the uterine cavity to minimize adhesion formation. Postsurgical assessment of the uterine cavity was carried out through office hysteroscopy and 3D-TVS. All patients were followed for at least 24 months. MEASUREMENTS AND MAIN RESULTS: The metroplasty was completed in all cases, resulting in a significant increase of uterine cavity volume (100%) and optimization of uterine morphology in 211 of 214 women (98.6%). After 60 months, the overall clinical pregnancy rate was 72.9% (n = 156/214), and the live birth rate was 80.1% (n = 125/156). Specifically, 74 of 156 women (47.4%) conceived spontaneously (with a median time to pregnancy of 5.5 months), of whom 32.4% had previously failed 1 or more attempts at in vitro fertilization/intracytoplasmic sperm injection. CONCLUSION: Our long-term follow-up data demonstrate that the hysteroscopic correction of dysmorphic uteri may result in a high live birth rate in women suffering from unexplained infertility or repeated miscarriages.

Resectoscopic Metroplasty with Uterine Septum Excision: A Histologic Analysis of the Uterine Septum.

STUDY OBJECTIVE: To evaluate the histology of the uterine septum after its complete hysteroscopic excision. DESIGN: Case series. SETTING: Second Gynecological and Obstetric Unit and Pathological Anatomy Department of the University of Bari, Italy. PATIENTS: Thirty-five patients aged between 25 and 41 years who were diagnosed with uterine septum by 3-dimensional ultrasound per the European Society for Human Reproduction and Embryology/European Society of Gastrointestinal Endoscopy 2013/Salim 2003 criteria. In addition, office hysteroscopy was performed to define the anatomy of the uterine cavity and to exclude the presence of other endometrial pathologic conditions. INTERVENTIONS: Operative hysteroscopic septum resection was performed. The septum was initially incised with an "L-shape" bipolar electrode with a 5-mm bipolar mini-resectoscope (KARL STORZ SE & Co. KG, Tuttlingen, Germany). Then, using the bipolar loop, 2 triangles of the septum were excised in parallel, obtaining uninterrupted entire septum-long strips from the fundus to the apex of the septum. These strips were immediately removed from the uterus and reassembled in vitro to reconstruct a macroscopic, 3-dimensional structure of the septum for complete morphologic and histologic evaluations. MEASUREMENTS AND MAIN RESULTS: Patients presented with an average body mass index of 24.8 kg/m2and were all nulliparous. Histologic evaluation of the uterine septa showed a different conformation of the muscle bundles along the septum. Muscle cells in the apex and edges of the septum were arranged in nodules circumscribed by a thin area of collagen fibers. Medium-sized vessels were distributed in the collagen fibers around the muscle cells. Only few capillary vessels were present in the muscle nodules. This pattern was very similar to the cell arrangement in leiomyomas. In the core of the septa, near the base, the muscle bundles showed a linear course with concurrent collagen fibers and vessels. All the aforementioned characteristics were consistently present in every patient. On high-power histologic fields (200×), the muscle portion accounted for 48.3% ± 1.8% (mean, 6%) area in the apex and borders to 48.5% ± 1.3% (mean, 6%) area in the core. Collagen fibers accounted for 27.1% ± 1.1% (mean, 4%) area in the apex and borders to 26.7% ± 1.3% (mean 5%) area in the core. CONCLUSION: By removing the septum as a whole structure, this study allowed us to redefine the concept of the septum as a complex structure according to the islands of muscle fibers irregularly arranged in vertex, in a context of collagen tissue and similar to the structure of myomas. It appears to deeply involve the anterior and posterior uterine walls, resembling a "reverse letter H."

Sonographic Differential Diagnosis in Deep Infiltrating Endometriosis: The Bowel.

Up to one-third of fertile-age women with severe endometriosis suffer from colonic involvement. Transvaginal ultrasonography has become a first-line diagnostic tool for the study of the pelvis and more specifically for the diagnosis of pelvic endometriosis. Accuracy of pelvic ultrasound for deep endometriosis increases with operator experience, but the difficulties in the differential diagnosis with diseases that can afflict the bowel tract remain a challenge. We reviewed noteworthy cases referred for secondary level diagnosis suspected of bowel endometriosis in which the subsequent ultrasound led to an alternative diagnosis. This case series aims to highlight awareness for both experts and less-experienced operators the possible differential diagnoses of bowel lesions that initially resemble endometriosis.

Pregnancy related cancer in Apulia. A population based linkage study.

OBJECTIVE: Despite a quite large number of papers in literature, the current incidence of pregnancy associated cancer still remains uncertain. Moreover, different inclusion criteria and time intervals considered after delivery make these data poorly comparable. The aim of this study was to investigate the incidence of PACs in Apulia, an Italian region, while stressing differences or similarities with other populations. STUDY DESIGN: We collected 682,173 pregnancies from national discharge forms, regarding hospitals in Apulia from January 2003 to December 2015. Our aim was not only to obtain the raw incidence of PACs but also to estimate the odds ratio (OR) for some potential risk predictors such as calendar year, age, nationality and pregnancy outcome using a logistic model. Women were sorted into different groups by age (<30, 30-34, 35-39, >=40) and by nationality (Italian or foreign nationals). Each pregnancy had two possible outcomes: delivery or abortion. RESULTS: We achieved a final cohort of 867 PACs: therefore, the raw incidence is 127.1 per 100,000 pregnancies. Breast cancer was the most common cancer (37.7 cases per 100,000 pregnancies) and as a typical feature in our population thyroid cancers followed it by incidence (22.3 per 100,000 pregnancies). Cervical cancer is, as expected, the first gynaecological cancer by incidence(3.8 per 100,000). Younger women have the lowest risk for PACs (64.5 per 100,000, OR = 1) while the highest risk for PACs was for women aged >=40 years (OR = 4.29, p < 0.05). Considering calendar years, we observed an increased OR from 2006 to 2009 (OR = 1.39 and OR = 1.41 respectively) without spotting a trend throughout the whole decade. CONCLUSIONS: The ranking of each tumour by incidence more or less reflects its demographics in reproductive age females in western countries and the incidence for any cancer is expected to grow as the rate of first deliveries in older women continues to rise. We reported noticeable differences regarding the incidence of some cancers (such as thyroid cancer) with previous literature, reflecting an epidemiologic feature of our cohort. Women older than 40 years have a more than fourfold risk for oncologic diagnosis during pregnancy, and this finding is of pivotal clinical and social importance because of the tendency of women living in developed countries to postpone childbearing.

Unified diagnostic criteria for chronic endometritis at fluid hysteroscopy: proposal and reliability evaluation through an international randomized-controlled observer study.

OBJECTIVE: To develop a consensus on the diagnostic criteria for chronic endometritis (CE) at hysteroscopy (HSC), and to evaluate these proposed criteria in a randomized-controlled observer study. DESIGN: Systematic review of studies evaluating the diagnostic accuracy of HSC in CE diagnosis; Delphi consensus on hysteroscopic diagnostic criteria for CE; randomized-controlled observer study to evaluate the reproducibility of the proposed diagnostic criteria. SETTING: Not applicable. PARTICIPANT(S): Experts from different countries were involved in the systematic review and contributed to the Delphi consensus. Physicians from different countries were involved in the observer study. INTERVENTION(S): After reaching consensus on the diagnostic criteria, the Delphi poll created a questionnaire including 100 hysteroscopic pictures (50 from women with CE [domain 1] and 50 from women without CE [domain 2]), with a single question per picture (Answer_A: suggestive of CE; answer B: not suggestive of CE). A total of 200 physicians were invited to take part in the observer study. Before completing the questionnaire, physicians were randomized to receive a description of the diagnostic criteria (group A) or no such information (group B). MAIN OUTCOME MEASURE(S): The primary outcome was to compare the questionnaire scores for the two groups of observers. The secondary outcome was to assess the interobserver agreement in the diagnosis of CE in each group. RESULT(S): A total of 126 physicians completed the questionnaire (62 in group A and 64 in group B). Observers in group A obtained higher total scores compared with those in group B (P<.001). Specifically, group A showed higher mean score in domain 1 (P<.001), but not in domain 2 (P=.975). A substantial agreement was found among observers in group A (intraclass correlation coefficient [ICC] 0.78), whereas a fair agreement was found among observers in group B (ICC 0.40). CONCLUSION(S): This randomized-controlled observer study found a positive impact of our criteria on physicians' ability to recognize CE.

Chronic Endometritis, a Common Disease Hidden Behind Endometrial Polyps in Premenopausal Women: First Evidence From a Case-Control Study.

STUDY OBJECTIVE: To investigate the correlation between endometrial polyps (EPs) and chronic endometritis (CE). DESIGN: Single-center retrospective case-control study. SETTING: Academic center. PATIENTS: A total of 480 premenopausal women with abnormal uterine bleeding (AUB) were enrolled. Group A included 240 women suffering from EPs (diagnosed by hysteroscopy and histology), and group B included 240 patients without EPs at hysteroscopy. INTERVENTIONS: In group A, 2 separate samples were obtained from the EPs (group A polyps) and endometrium (group A endometrium). In group B, a single sample of endometrial tissue was evaluated (group B endometrium). All tissue samples were subjected to immunohistochemistry for CD-138 for plasma cell identification. MEASUREMENTS AND MAIN RESULTS: The primary study endpoint was to compare the rates of CE in group A endometrium versus group B endometrium. The secondary endpoint was to evaluate the consistency in CD-138 immunoreactivity between group A polyps and compared with group A endometrium. A higher prevalence of CE was observed in group A endometrium compared with group B endometrium (p < .0001). The total percentage of EPs showing CD-138 positivity was 76.7% (184 of 240). CE was more frequent in women with CD-138+ EPs compared to those with CD-138- EPs (p < .0001). CONCLUSIONS: EPs were commonly associated with CE in the premenopausal women suffering from AUB. Moreover, the majority of EPs were positive for CD-138 staining, suggesting a possible hidden association between chronic inflammation and EPs.

Age at menarche and clinical outcomes following medically assisted reproduction (MAR): a cohort study.

Medically assisted reproduction (MAR) technologies have advanced rapidly, but in contrast to the specificity of modern approaches, they provide limited effectiveness in the management of the infertile couple. The purpose of this study was to assess the possible relationship between age at menarche and MAR outcomes of clinical pregnancy, live birth and the adverse incident of miscarriage, and to determine the offspring sex ratio according to age at menarche. In a cohort of 254 infertile couples who underwent 426 IVF/ICSI cycles, statistical analysis was performed by applying Student's t-test, chi-square test, and logistic regression models, adequately in the respective parameters and outcomes. The results indicated a strong association of age at menarche with the outcomes of clinical pregnancy (p = .0007) and live birth (p < .0001), especially by applying a threshold of 12 years in the first occurrence of menstruation (p = .0019 for clinical pregnancy, p < .0001 for live birth), also demonstrating a negative effect for earlier menarche that acts in parallel with the increasing age of the woman. Calculation of sex ratio demonstrated a tendency towards female offspring close to the age at menarche of 12 years. Age at menarche could serve as a surrogate parameter for reproductive potential towards personalized management of infertility.

Office treatment of large endometrial polyps using truclear 5C: Feasibility and acceptability.

AIM: This retrospective multicenter study was carried out to evaluate feasibility, effectiveness and patient acceptability of a small diameter hysteroscopic tissue removal system in the treatment of large endometrial polyps (≥20 mm), usually not removed in an office setting. METHODS: Hundred and forty-six women with a single greater than 10-mm diameter polyp considered for polypectomy between April 2016 and August 2017. Sixty-five of these patients had a polyp size greater than 20 mm. All hysteroscopic polypectomy, using Hysteroscopic Tissue Removal system (TruClear 5C System Medtronic), were performed in an office setting with vaginoscopic approach. RESULTS: Procedural success, time to complete the polypectomy and patient pain scores were evaluated. Polyps less than 20 mm were completely removed in 79/81 cases (97.53%). The completeness of greater than or equal to 20-mm polyp removal was achieved in 63/65 cases (96.92%). The median time for polypectomy was 4.19 ± 1.03 min for polyps less than 20 mm and 4.97 ± 1.30 min for polyps greater than or equal to 20 mm, respectively. Pain was minimal and brief, and the mean pain score measured on a 10-point visual analog scale at the end of polypectomy showed no significant difference between the two groups. In 4/79 (5.06%) cases with polyps less than 20 mm and in 4/63 (6.35%) cases with polyps greater than or equal to 20 mm women reported moderate pain. All specimens were adequate for pathologic measurements. CONCLUSION: Hysteroscopic treatment of polyps greater than or equal to 20 mm in size with TruClear 5C is feasible and well tolerated in an office setting with no significant difference regarding completeness compared to polyps less than 20 mm, but with a minimal increase in procedure times.