Optimizing evaluation of endometrial receptivity in recurrent pregnancy loss: a preliminary investigation integrating radiomics from multimodal ultrasound via machine learning.

Background: Recurrent pregnancy loss (RPL) frequently links to a prolonged endometrial receptivity (ER) window, leading to the implantation of non-viable embryos. Existing ER assessment methods face challenges in reliability and invasiveness. Radiomics in medical imaging offers a non-invasive solution for ER analysis, but complex, non-linear radiomic-ER relationships in RPL require advanced analysis. Machine learning (ML) provides precision for interpreting these datasets, although research in integrating radiomics with ML for ER evaluation in RPL is limited. Objective: To develop and validate an ML model that employs radiomic features derived from multimodal transvaginal ultrasound images, focusing on improving ER evaluation in RPL. Methods: This retrospective, controlled study analyzed data from 346 unexplained RPL patients and 369 controls. The participants were divided into training and testing cohorts for model development and accuracy validation, respectively. Radiomic features derived from grayscale (GS) and shear wave elastography (SWE) images, obtained during the window of implantation, underwent a comprehensive five-step selection process. Five ML classifiers, each trained on either radiomic, clinical, or combined datasets, were trained for RPL risk stratification. The model demonstrating the highest performance in identifying RPL patients was selected for further validation using the testing cohort. The interpretability of this optimal model was augmented by applying Shapley additive explanations (SHAP) analysis. Results: Analysis of the training cohort (242 RPL, 258 controls) identified nine key radiomic features associated with RPL risk. The extreme gradient boosting (XGBoost) model, combining radiomic and clinical data, demonstrated superior discriminatory ability. This was evidenced by its area under the curve (AUC) score of 0.871, outperforming other ML classifiers. Validation in the testing cohort of 215 subjects (104 RPL, 111 controls) confirmed its accuracy (AUC: 0.844) and consistency. SHAP analysis identified four endometrial SWE features and two GS features, along with clinical variables like age, SAPI, and VI, as key determinants in RPL risk stratification. Conclusion: Integrating ML with radiomics from multimodal endometrial ultrasound during the WOI effectively identifies RPL patients. The XGBoost model, merging radiomic and clinical data, offers a non-invasive, accurate method for RPL management, significantly enhancing diagnosis and treatment.

The predictive value of ultrasound markers for pregnancy outcomes in recurrent pregnancy loss: a retrospective study.

Establishing prediction models of pregnancy outcomes for recurrent pregnancy loss women at specific gestational weeks will provide patients and physicians with more precise information, ultimately leading to time and cost savings associated with unnecessary revisits. Therefore, our aim was to develop a prediction model for first trimester pregnancy loss in RPL patients. We used ultrasound indices during the first trimester of pregnancy in combination with demographic characteristics and commonly used serum markers. The independent risk factors for each week were as follows: age and P in the fifth week; age, mGSD and CRL in the sixth week; age, hCG and CRL in the seventh week; CRL in the eighth week; mGSD and CRL in ninth week. The corresponding AUC was 0.671, 0.796, 0.872, 0.871, 0.813, respectively. There is a linear relationship between age and first trimester pregnancy loss. hCG < 69,636.6 mIU/ml was associated with a higher risk of pregnancy loss in the seventh gestation week. An mGSD < 18.3 mm, adjusted for age, BMI, and previous pregnancy loss in the sixth week, was linked to an increased risk of first trimester pregnancy loss. A small CRL measurement (less than 2.4 mm, 9.9 mm, 16.9 mm, and 18.6 mm) in the sixth, seventh, eighth and ninth week was closely correlated with higher risk of first trimester pregnancy loss. Furthermore, an mGSD < 33.3 mm and > 48.3 mm in ninth gestational week was associated with a higher risk of pregnancy loss. These models and thresholds may help physicians and patients make more informed decisions together. Further studies are needed to confirm the results.

The importance of the 'uterine factor' in recurrent pregnancy loss: a retrospective cohort study on women screened through 3D transvaginal ultrasound.

STUDY QUESTION: What is the prevalence of congenital and acquired anomalies of the uterus in women with recurrent pregnancy loss (RPL) of unknown etiology examined using 3D transvaginal ultrasound (US)? SUMMARY ANSWER: Depending on the adopted diagnostic criteria, the prevalence of partial septate uterus varies between 7% and 14% and a T-shaped uterus is 3% or 4%, while adenomyosis is 23%, at least one of type 0, type 1 or type 2 myoma is 4%, and at least one endometrial polyp is 4%. WHAT IS KNOWN ALREADY: ESHRE and the Royal College of Obstetricians and Gynaecologists guidelines on RPL recommend the adoption of the 3D transvaginal US to evaluate the 'uterine factor'. Nevertheless, there are no published studies reporting the prevalence of both congenital and acquired uterine anomalies as assessed by 3D transvaginal US and diagnosed according to the criteria proposed by the most authoritative panels of experts in a cohort of women with RPL. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study including 442 women with at least two previous first-trimester spontaneous pregnancy losses (i.e. non-viable intrauterine pregnancies), who referred to the obstetrics and gynecology unit of two university hospitals between July 2020 and July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Records of eligible women were reviewed. Women could be included in the study if: they were between 25 and 42 years old; they had no relevant comorbidities; they were not affected by infertility, and they had never undergone ART; they and their partner tested negative to a comprehensive RPL diagnostic work-up; and they had never undergone metroplasty, myomectomy, minimally invasive treatments for uterine fibroids or adenomyomectomy. Expert sonographers independently re-analyzed the stored 2- and 3D transvaginal US images of all included patients. Congenital uterine anomalies (CUAs) were reported according to the American Society for Reproductive Medicine (ASRM) 2021, the ESHRE/European Society for Gynaecological Endoscopy (ESGE) and the Congenital Uterine Malformation by Experts (CUME) criteria. Acquired uterine anomalies were reported according to the International Federation of Gynecology and Obstetrics (FIGO) and the Morphological Uterus Sonographic Assessment (MUSA) criteria. MAIN RESULTS AND THE ROLE OF CHANCE: The partial septate uterus was diagnosed in 60 (14%; 95% CI: 11-17%), 29 (7%; 95% CI: 5-9%), and 47 (11%; 95% CI: 8-14%) subjects, according to the ESHRE/ESGE, the ASRM 2021, and the CUME criteria, respectively. The T-shaped uterus was diagnosed in 19 women (4%; 95% CI: 3-7%) according to the ESHRE/ESGE criteria and in 13 women (3%; 95% CI: 2-5%) according to the CUME criteria. The borderline T-shaped uterus (diagnosed when two out of three CUME criteria for T-shaped uterus were met) was observed in 16 women (4%; 95% CI: 2-6%). At least one of FIGO type 0, type 1, or type 2 myoma was detected in 4% of included subjects (95% CI: 3-6%). Adenomyosis was detected in 100 women (23%; 95% CI: 19-27%) and was significantly more prevalent in women with primary RPL and in those with three or more pregnancy losses. At least one endometrial polyp was detected in 4% of enrolled women (95% CI: 3-7%). LIMITATIONS, REASONS FOR CAUTION: The absence of a control group prevented us from investigating the presence of an association between both congenital and acquired uterine anomalies and RPL. Second, the presence as well as the absence of both congenital and acquired uterine anomalies detected by 3D US was not confirmed by hysteroscopy. Finally, the results of the present study inevitably suffer from the intrinsic limitations of the adopted classification systems. WIDER IMPLICATIONS OF THE FINDINGS: The prevalence of CUAs in women with RPL varies depending on the classification system used. For reasons of clarity, the US reports should always state the name of the uterine anomaly as well as the adopted classification and diagnostic criteria. Adenomyosis seems to be associated with more severe forms of RPL. The prevalence rates estimated by our study as well as the replicability of the adopted diagnostic criteria provide a basis for the design and sample size calculation of prospective studies. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Optical coherence tomography angiography evaluation of retinal and choroidal microvascular changes in pregnant women with a history of unexplained recurrent spontaneous abortions.

PURPOSE: To study retinal and choroidal microcirculation by optical coherence tomography angiography (OCTA) in pregnant women with unexplained recurrent spontaneous abortion (RSA) and to compare them with healthy pregnant and nonpregnant subjects. METHODS: Pregnant women with an unexplained history of RSA (group 1), healthy pregnant (group 2), and healthy non-pregnant women (group 3) were included in the study. After a thorough ophthalmologic examination:best-corrected visual acuity, intraocular pressure,slit-lamp biomicroscopy, fundus examination,autorefractometer, biometry, and axial length measurement; OCT and OCTA measurements were performed with Swept Source OCT-Angiography (Topcon Co, Japan). RESULTS: The nonpregnant group had higher values for central foveal superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD) and lower values for superior, inferior, and mean VD compared with pregnant groups (p < 0.001). Choriocapillaris values (CC) VD were higher in groups 1 and 2 than in group 3 (p < 0.001). The group with unexplained RSA had a relatively smaller FAZ (foveal avascular zone) area than the group of healthy pregnant women (p:0.047). There were no statistically significant differences between groups in the retina, retinal nerve fiber layer, ganglion cell layer, and choroidal thickness (p > 0.05). CONCLUSION: Although our study did not identify any etiology in pregnant women with RSA, we observed detectable differences in FAZ area and vessel density values using OCTA, when comparing them with healthy pregnant women and healthy nonpregnant controls. We believe that OCTA, as used in many pathologies such as diabetic and hypertensive retinopathy and retinal vascular occlusion, can also be extended to unexplained RSA both to detect etiology and to monitor treatment in studies with a larger number of patients.

Type and Location of Adenomyosis in Women with Recurrent Pregnancy Loss: A Transvaginal Ultrasonographic Assessment.

The current knowledge on adenomyosis as a risk factor for RPL is very scant. Overall 120 women were included in this retrospective observational study. They were divided in three groups each of which consisted of 40 subjects: Group 1: women with RPL who were diagnosed to have adenomyosis on transvaginal ultrasound (TVS); Group 2: patients with RPL without ultrasonographic findings of adenomyosis; Group 3: patients with ultrasound diagnosis of adenomyosis without RPL and at least one live birth pregnancy. The copresence of endometriosis was also investigated. Among women with RPL, patients with adenomyosis (Group 1) had higher number of pregnancy losses (p = 0.03) and lower age at first pregnancy loss (p = 0.03) than women without adenomyosis (Group 2). Moreover, they had more frequently primary RPL (p = 0.008). Adenomyosis of the inner myometrium was found more frequently (p = 0.04) in patients of Group 1 than in patients of Group 3 in which adenomyosis was mainly in the outer myometrium (p= 0.02). No differences were found in the severity of adenomyosis between these two groups of women. TVS findings for endometriosis were observed more frequently in women with adenomyosis without RPL (Group 3) than in the other two groups of patients. Adenomyosis can be a factor involved in RPL. Differences in adenomyosis localization are associated with different risks for RPL. Patients with RPL should be investigated for the presence of adenomyosis and also for the type and localization of the disease in the different myometrial layers.

Uterine factors in recurrent pregnancy losses.

Congenital and acquired uterine anomalies are associated with recurrent pregnancy loss (RPL). Relevant congenital Müllerian tract anomalies include unicornuate, bicornuate septate, and arcuate uterus. Recurrent pregnancy loss has also been associated with acquired uterine abnormalities that distort the uterine cavity such as, notably, intrauterine adhesions, polyps, and submucosal myomas. Initial evaluation of women with RPLs should include an assessment of the uterine anatomy. Even if proof of efficacy of surgical management of certain uterine anomalies is often lacking for managing RPLs, surgery should be encouraged in certain circumstances for improving subsequent pregnancy outcome. Uterine anomalies such as uterine septa, endometrial polyps, intrauterine adhesions, and submucosal myomas are the primary surgical indications for managing RPLs.

Atualidades em perda gestacional de repetição: definição, diagnóstico e propedêutica / Current guidelines for recurrent pregnancy loss: definition, diagnostic tests and investigation

Classicamente, a perda gestacional de repetição (PGR) é a ocorrência de três ou mais perdas consecutivas antes de 20 semanas de gestação. Entretanto, as diretrizes para definição, propedêutica e tratamento são controversas. As causas de PGR podem ser multifatoriais e incluem alterações anatômicas do útero, distúrbios endócrinos, alterações imunológicas, infecções, alterações genéticas, obesidade materna, entre outras. Entretanto, na maioria dos casos, a causa de PGR é desconhecida. Os protocolos para o diagnóstico de PGR variam muito e são direcionados à pesquisa de possíveis fatores causais. Neste artigo foi realizada uma revisão e comparação das últimas diretrizes para diagnóstico e propedêutica das causas de PGR da Sociedade Europeia de Reprodução Humana e Embriologia (ESHRE), da Sociedade Americana de Medicina Reprodutiva (ASRM) e do Royal College of Obstetricians and Gynaecologists (RCOG).(AU)

Recurrent pregnancy loss (RPL) is traditionally defined by the occurrence of three or more consecutive losses before 20 weeks of gestation. The guidelines for definition, investigations and treatments are controversial. The causes of RPL can be multifactorial and includes structural uterine anomalies, endocrine alterations, immunological dysfunction, infections, genetic anomalies, maternal obesity, among others. However, in most cases the cause of RPL is unknown. The diagnosis protocols of RPL vary widely and causal factors are the major goal. In this article, we review and compare the latest RPL diagnosis and investigations guidelines, including the European Society for Human Reproduction and Embryology (ESHRE), American Society for Reproductive Medicine (ASRM) and the UK Royal College of Obstetricians and Gynaecologists (RCOG).(AU)

Uterine and placental blood flow indexes and antinuclear autoantibodies in unexplained recurrent pregnancy loss: should they be investigated in pregnancy as correlated potential factors? A retrospective study.

BACKGROUND: The potential role of antinuclear antibodies (ANA) in recurrent pregnancy loss (RPL) pathogenesis is still debated, although some evidences suggest that they could affect pregnancy outcome, leading to a higher miscarriage rate in these patients. A hypothesized mechanism is through changes in uterine flow in pre-conceptional stage, by modifying endometrial receptivity in RPL. However, scant data are available, in pregnancy, about their role in RPL placental perfusion, also in relation to its potential treatments, such as low molecular weight heparin (LMWH). The aim of this study is to retrospectively further investigate the correlation between two-dimensional (2D) and three-dimensional (3D) uterine and placental flow indexes and the presence or the absence of ANA in women with unexplained RPL (uRPL), treated or not treated with LMWH. METHODS: 2D Doppler measurement of pulsatility index (PI) of the uterine arteries and 3D ultrasonography determination of vascularization index (VI), flow index (FI) and vascularization flow index (VFI) was carried out with the aid of the virtual organ computer-aided analysis (VOCAL) technique in LMWH treated (n 24) and not treated-uRPL patients (n 20) and in the relative control group (n 27), each group divided in ANA+ and ANA- subgroups. Serum assay for the presence of ANA was performed in all women. RESULTS: No differences were found in PI, VFI and VI values, by comparing the different groups. A difference in VI values was found for ANA- patients between RPL women not treated with LMWH and the treated ones (p = 0,01), which have lower VI values and similar to controls. By considering only ANA- treated and not treated RPL patients, the ROC curve shows an area of 0,80 and at the VI cut-off of 11,08 a sensitivity of 85% and a specificity of 67%. CONCLUSIONS: LMWH could exert a potential beneficial effect in restoring the physiological blood flow supply in terms of VI in uRPL ANA- status, suggesting to include ANA and VI investigations in the RPL diagnostic algorithm in a research context, since further studies are needed to clarify this challenging hypothesis in order to try to ameliorate ANA and abnormal placental vascularization negative influence on RPL pregnancy outcome .

Uterine artery flow velocity waveform (FVW) type and subednometrial vascularity in recurrent pregnancy loss.

Purpose: To assess the subendometrial and uterine artery blood flow and pattern of the waveform of the uterine artery in cases of recurrent pregnancy loss compared with normal controls.Subjects and methods: Fifty women with a history of two or more successive pregnancy losses were investigated by Doppler transvaginal ultrasound to assess the subendometrial blood flow resistance index (RI), type of Doppler waveform of the uterine artery, and uterine artery pulsatility index (PI) in the mid-luteal phase. Fifty normal women acted as controls.Results: Subendometrial blood flow RI and uterine artery PI were higher in cases than controls. The majority of cases of recurrent pregnancy loss had a waveform pattern of A, or loss of diastolic flow, whereas the controls were mainly C wave.Conclusions: Some sort of endometrial and subendometrial ischemia can be suggested in cases of recurrent pregnancy loss, waveform pattern of uterine artery changes may be used to monitor changes in vascularity of endometrium if vascular enhancers are given in such cases.

Uterine Radial Artery Resistance Index Predicts Reproductive Outcome in Women with Recurrent Pregnancy Losses and Thrombophilia.

Uterine radial artery resistance index (URa-RI) by Doppler ultrasound may reflect the changes in the uteroplacental circulation and be associated with adverse events in early pregnancy. Recurrent pregnancy losses (RPL) are associated with thrombophilia, and anticoagulation treatment with low molecular weight heparin improves pregnancy outcome in women with RPL and thrombophilia. A retrospective cohort study was conducted in 139 pregnant women with 3 or more RPL and thrombophilia. The relationship between pregnancy outcome and dynamic changes of URa-RI was analyzed in 116 women who delivered a liveborn infant and 23 who miscarried the index pregnancy. Patients were on preconception low molecular weight heparin, low-dose aspirin (81mg per day), and prednisone treatment. URa-RI was measured during periovulation time, at the time of positive pregnancy test, and then repeated every two weeks until 32-week gestation or the time of miscarriage. The URa-RI at 8-week gestation was significantly higher in women who miscarried the index pregnancy than those who delivered alive born infant (0.51±0.08 vs. 0.42±0.03, P<0.001). Receiver operating characteristic curve analysis demonstrated that URa-RI of 8 wk gestation effectively distinguished women who miscarried from those who had a live birth with an area under the curve of 82.6% (95% CI 69.01-97.17). After adjusting for covariates including age, BMI, and number of miscarriages, multiple logistic regression models showed that each 0.1 unit increase of URa-RI of 8 wk gestation was associated with 18.70-point increase in the risk of miscarriage (OR19.70, 95%CI 4.26-91.1, P<0.001), and women with an URa-RI≥0.45 had an OR of 49.48 (95% CI 8.01-307.95; P<0.001) for miscarriage compared to those who had URa-RI<0.45. In women with RPL and inherited thrombophilia, increased URa-RI at 8-week gestation was associated with spontaneous abortion independent of other risk factors while they were on anticoagulation treatment.

Uterine factor in recurrent pregnancy loss.

OBJECTIVE: To review the current understanding of the role the uterus plays in recurrent pregnancy loss. FINDINGS: Congenital and acquired uterine abnormalities are associated with recurrent pregnancy loss in the first and second trimester. Relevant congenital Mullerian tract anomalies include unicornuate, didelphys, bicornuate and septate uteri. Pregnancy loss has also been associated with acquired uterine abnormalities that distort the uterine cavity such as intrauterine adhesions and submucosal myomas. Initial evaluation of women with recurrent pregnancy loss should include a uterine assessment such as a pelvic ultrasound or sonohysterography. Uterine abnormalities such as uterine septum, intrauterine adhesions and submucosal myomas may be managed surgically with operative hysteroscopy. CONCLUSION: Uterine abnormalities, both congenital and acquired, can be responsible for recurrent pregnancy loss.

Antiphospholipid syndrome in obstetrics.

Antiphospholipid syndrome (APS) covers a spectrum of clinical manifestations ranging from recurrent pregnancy loss and obstetric complications from placental dysfunction through to thrombotic disease. This article will focus on the common manifestations of the pregnancy-related complications of APS. This includes clinical manifestations, diagnosis and management, as general practitioners will need to be able to recognize the disorder and will also have patients under their care receiving treatment for APS.

Comparison of the prevalence of chronic endometritis as determined by means of different diagnostic methods in women with and without reproductive failure.

OBJECTIVE: To compare the prevalence of chronic endometritis (CE) when different diagnostic methods are used. DESIGN: Prospective observational study. SETTING: University-affiliated hospital. PATIENT(S): Four groups of women were studied, including women with proven fertility (Fertile; n = 40), unexplained recurrent miscarriage (RM; n = 93), recurrent implantation failure (RIF; n = 39), and infertile subjects undergoing endometrial scratch in a natural cycle preceding frozen-thawed embryo transfer (Infertility; n = 48). INTERVENTION(S): Endometrial biopsy was performed precisely 7 days after LH surge (LH+7). Plasma cells were identified by means of traditional hematoxylin and eosin (HE) staining and by means of immunohistochemistry (IHC) for Syndecan-1 (CD138). MAIN OUTCOME MEASURE(S): Prevalence of CE. RESULT(S): The use of CD138 epitope was more sensitive than HE staining in identifying plasma cells. The use of plasma cell count per unit area had the lowest observer variability compared with cell count per ten randomly chosen high-power fields and cell count per section. Using this method, the prevalence of CE in women with RM, RIF, and Infertility were 10.8%, 7.7%, and 10.4%, respectively, not significantly higher than that of Fertile subjects (5.0%). CONCLUSION(S): Using what may be a new method of plasma cell assessment, it appears that the prevalence rates of CE reported in many earlier studies may have been overestimated. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IOC-16007882.

Recurrent Abortion and Tethered Cord Syndrome Caused by Anterior Sacral Meningocele: A Report of a Rare Case with a Review of the Literature.

BACKGROUND: Anterior sacral meningocele is a rare congenital anomaly. CASE DESCRIPTION: This rare anomaly is described in a young woman who presented with recurrent abortion and later with a huge palpable mass of pelvic origin, measuring 14 × 12 cm. CONCLUSIONS: The various radiologic features, associations such as presacral dermoid as a part of incomplete Currarino syndrome, and the management options available are also discussed.

Histological Structure and Vascularity of Hysteroscopically Removed Uterine Septa in Patients With Primary Infertility and Patients With Recurrent Pregnancy Loss.

OBJECTIVE: To examine the histological structure and vascularity of uterine septa in patients with unexplained primary infertility and patients with recurrent pregnancy loss (RPL). DESIGN: Case-control study (Canadian Task Force classification II-2). SETTING: Kasr Al Aini Hospital, Cairo University, Egypt. PATIENTS AND INTERVENTIONS: A total of 41 patients with uterine septa presenting with either unexplained primary infertility or RPL underwent 3-dimensional (3D) and power Doppler (PD) ultrasound to calculate the septum volume, septal vascularization index (VI), and myometrial VI. Hysteroscopically removed septa were examined histologically for myometrial and fibrous tissue content. MEASUREMENTS AND MAIN RESULTS: Septal characteristics differed between the primary infertility group (24 patients) and the RPL group (17 patients). Mean septal VI was significantly higher in the RPL group compared with the infertility group (18.39% ± 7.57% vs 11.67% ± 4.56%; p = .003), as was septal myometrial area (20.74% ± 5.97% vs 13.57% ± 5.55%; p < .001). In both groups, septal VI was strongly correlated with myometrial VI and myometrial content, but not with fibrous tissue content. CONCLUSION: Uterine septa of patients with RPL are more vascularized and contain more muscular tissue compared with those of patients with primary unexplained infertility.

Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group.

Pregnancy loss prior to viability is common and research in the field is extensive. Unfortunately, terminology in the literature is inconsistent. The lack of consensus regarding nomenclature and classification of pregnancy loss prior to viability makes it difficult to compare study results from different centres. In our opinion, terminology and definitions should be based on clinical findings, and when possible, transvaginal ultrasound. With this Early Pregnancy Consensus Statement, it is our goal to provide clear and consistent terminology for pregnancy loss prior to viability.

Uterine junctional zone at three-dimensional transvaginal ultrasonography in patients with recurrent miscarriage: a new diagnostic tool?

OBJECTIVE: To evaluate the characteristics of the uterine junctional zone (JZ) by three-dimensional (3D) transvaginal sonography (TVS) in women with recurrent miscarriage (RM) as compared to normal fertile controls. STUDY DESIGN: The thickness and the morphology of the JZ were evaluated in 75 women with a history of RM due to different causes and in 20 fertile women without a history of miscarriages or pelvic disease. All patients included in the study were selected among those who attended the outpatient clinic of "Tor Vergata" University. The JZ characteristics were evaluated in the midluteal phase of the cycle on the uterine coronal section obtained by 3D TVS. RESULTS: Patients with RM showed a JZ maximum thickness significantly increased when compared to that observed in control group (5.8±0.7 vs. 5.0±1.1mm). When grouped according to the different causes of RM, all groups of patients with RM showed an increased JZ thickness when compared to fertile women, with the exception of those with anti-phospholipid antibody syndrome, probably due to the small number of cases with this pathology. CONCLUSIONS: A thickened JZ could be an independent indicator of the risk of miscarriage and may represent an important contributing factor to some causes of RM. These observations may offer new perspectives for the screening and treatment of patients with RM. Although further studies are needed to ascertain if the reduction of the JZ thickness can determine a better pregnancy outcome, 3D TVS evaluation of the JZ could provide the opportunity to identify women in which appropriate therapeutic protocols can improve the possibility of successful pregnancy.

Identification of key contributory factors responsible for vascular dysfunction in idiopathic recurrent spontaneous miscarriage.

Poor endometrial perfusion during implantation window is reported to be one of the possible causes of idiopathic recurrent spontaneous miscarriage (IRSM). We have tested the hypothesis that certain angiogenic and vasoactive factors are associated with vascular dysfunction during implantation window in IRSM and, therefore, could play a contributory role in making the endometrium unreceptive in these women. This is a prospective case-controlled study carried out on 66 women with IRSM and age and BMI matched 50 fertile women serving as controls. Endometrial expression of pro-inflammatory (IL-1ß, TNF-α, IFN-γ, TGF-ß1), anti-inflammatory (IL-4, -10), angiogenesis-associated cytokines (IL-2, -6, -8), angiogenic and vasoactive factors including prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), nitric oxide (NO) and adrenomedullin (ADM) were measured during implantation window by ELISA. Subendometrial blood flow (SEBF) was assessed by color Doppler ultrasonography. Multivariate analysis was used to identify the significant factor(s) responsible for vascular dysfunction in IRSM women during window of implantation and further correlated with vascular dysfunction. Endometrial expression of pro-inflammatory cytokines and PGE2 were up-regulated and anti-inflammatory and angiogenesis-associated cytokines down-regulated in IRSM women as compared with controls. Further, the angiogenic and vasoactive factors including VEGF, eNOS, NO and ADM were found to be down-regulated and SEBF grossly affected in these women. Multivariate analysis identified IL-10, followed by VEGF and eNOS as the major factors contributing towards vascular dysfunction in IRSM women. Moreover, these factors strongly correlated with blood flow impairment. This study provides an understanding that IL-10, VEGF and eNOS are the principal key components having a contributory role in endometrial vascular dysfunction in women with IRSM. Down-regulation of these factors is also associated with impaired endometrial perfusion which possibly makes the endometrium unreceptive that may eventually cause early pregnancy loss.

Combined hysteroscopic findings and 3-dimensional reconstructed coronal view of the uterus to avoid laparoscopic assessment for inpatient hysteroscopic metroplasty: pilot study.

STUDY OBJECTIVE: To assess the use of 3-dimensional (3D) reconstructed coronal view of the uterus and intraoperative hysteroscopic findings to avoid diagnostic laparoscopy during inpatient hysteroscopic metroplasty. DESIGN: Pilot study (Canadian Task Force classification II). SETTING: University hospital infertility clinic. PATIENTS: Fifty-nine patients with recurrent abortion and double uterine cavity with 3D sonographic diagnosis of septate uterus undergoing inpatient hysteroscopic metroplasty. INTERVENTIONS: Inpatient hysteroscopic treatment of septate uterus without laparoscopic diagnosis. In addition to sonographic observations, 2 intraoperative hysteroscopic criteria were used to confirm the diagnosis: visualization of muscular fibers and myometrial blood vessels. MEASUREMENTS AND MAIN RESULTS: Operative parameters (operative time and fluid absorption), complications (incomplete resection and uterine perforation), requirement for a second intervention, and shape of the uterine cavity at hysteroscopic follow-up. In 56 of 59 patients (94.9%), intervention was performed without complications, and in 3 cases, intervention was suspended because of intraoperative suspicion of bicornate uterus. These 3 patients underwent laparoscopy, which confirmed the diagnosis of septate uterus. In all cases, incision was considered sufficient. Postoperative diagnostic hysteroscopy in all patients showed a normal cavity (fundal notch <1 cm). CONCLUSIONS: Combined use of hysteroscopic confirming criteria and 3D sonography seems to be a reliable and simple strategy for characterizing the presence of septate uterus and to perform inpatient metroplasty usually without laparoscopic visualization of the uterine fundus.

A comparison of endometrial and subendometrial vascularity assessed by three-dimensional ultrasonography and power Doppler angiography between healthy fertile women and women with unexplained primary recurrent miscarriage.

We compared the characteristics of endometrial-subendometrial vascularity 7 days after ovulation of a natural cycle by transvaginal three-dimensional ultrasonography and power Doppler angiography between 88 patients with unexplained recurrent miscarriage and 46 healthy fertile women. Endometrial vascularization index, flow index, and vascularization flow index, as well as subendometrial vascularization index and vascularization flow index, were reduced significantly in the group with unexplained recurrent miscarriage.