The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial.

BACKGROUND: Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) trial, which compares the use of angiogenic factors and Doppler to manage small fetuses at term. OBJECTIVE: The primary objective is to demonstrate that classification based on angiogenic factors is not inferior to estimated fetal weight and Doppler at detecting fetuses at risk of adverse perinatal outcomes. METHODS: This is a multicenter, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1030 singleton pregnancies with an estimated fetal weight ≤10th percentile at 36+0 to 37+6 weeks+days will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio ≥38 will be classified as having fetal growth restriction; otherwise, they will be classified as being small for gestational age. In both arms, the fetal growth restriction group will be delivered at ≥37 weeks and the small for gestational age group at ≥40 weeks. We will assess differences between the groups by calculating the relative risk, the absolute difference between incidences, and their 95% CIs. RESULTS: Recruitment for this study started on September 28, 2020. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences in early 2023. CONCLUSIONS: The angiogenic factor-based protocol may reduce the number of pregnancies classified as having fetal growth restriction without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities. TRIAL REGISTRATION: ClinicalTrials.gov NCT04502823; https://clinicaltrials.gov/ct2/show/NCT04502823. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37452.

Evaluation of Pre-malignant Lesions of the Uterine Cervix by Shear Wave Elastography: A New Diagnostic Tool.

The objective of the study was to evaluate the difference in the stiffness between a healthy cervix (no pre-invasive lesions [NPILs]) and a cervix with a pre-invasive lesion (PIL). In the PIL group, we determined whether there was a difference in stiffness between the cervix with persistent low-grade lesions (>2 y, LSIL-persistent) and that with high-grade lesions (HSILs). Evaluation was performed using 2-D shear-wave elastography (SWE) in the midsagittal-plane of the uterine cervix (UC) at 0.5 cm (cervical canal, anterior and posterior cervical lips). In this prospective observational study (consecutive series), we evaluated 96 non-pregnant women: a group with PIL (LSIL-persistent, 22 cases; HSIL, 26 cases) with indications for cervical conization (48 cases) and a group without UC pathology (NPIL, 48 cases). Although we did not observe statistically significant differences (SSDs) in epidemiological characteristics, we did find an SSD in the speed and stiffness between the PIL versus NPIL groups at all evaluated depths (speed: 4.1 m/s vs 3.0 m/s, stiffness: 58.6 and 34.5kPa in the PIL and NPIL groups, respectively, p < 0.001). An SSD in speed and stiffness (speed: 4.9 m/s vs. 3.2 m/s, and stiffness: 76.1 and 38.0 kPa) between the HSIL (26 cases) and LSIL-persistent (22 cases) groups, respectively, was also detected (p < 0.001). The area under the curve of speed differentiation between a cervix with HSILs and without lesions was 73.4% (95% confidence interval [CI]: 63.1-83.7), and the best cutoff of speed was 3.25 m/s (sensitivity = 62.5%, 95% CI: 47.3-76.0), with a specificity of 75.5% (95% CI: 60.4-87.1).

Evaluation of Placental Micro-vascularization by Superb Micro-vascular Imaging Doppler in Cases of Intra-uterine Growth Restriction: A First Step.

Superb micro-vascular imaging (SMI) Doppler has proven to be a valid method to assess normal placental micro-vascularization. In this study, we present the application of SMI Doppler to assess placental micro-vascularization in cases of placental insufficiency. We observed fewer secondary and tertiary villi in cases of intra-uterine growth restriction, as well as a lower pulsatile index of secondary villi. The observations made in our study stress the diagnostic potential of SMI Doppler in placental insufficiency.

Differential diagnosis of middle compartment pelvic organ prolapse with transperineal ultrasound.

INTRODUCTION AND HYPOTHESIS: The objective was to identify the best parameter (pubis-cervix measurement, pubis-uterine fundus measurement or pubis-pouch of Douglas measurement) on transperineal ultrasound, based on the difference between measurements taken at rest and with the Valsalva maneuver, for presurgical differential diagnosis between uterine prolapse (UP) and cervical elongation (CE) without UP. METHODS: A prospective observational study of 60 consecutively recruited patients who underwent corrective surgery of the middle compartment (UP or CE without UP). A transperineal ultrasound was performed, and the descent of the pelvic organ was measured in relation to the posteroinferior margin of the pubis in the midsagittal plane, referencing the uterine fundus, pouch of Douglas and the cervix at rest and with the Valsalva test. RESULTS: Receiver operating characteristic (ROC) curves were constructed for the three evaluated measures, based on the difference between rest and Valsalva, for the diagnosis of UP. For the pubis-cervix distance, an area under the curve (AUC) of 0.59 was obtained; for the pubis-uterine fundus distance, the AUC was 0.81; and for the pubis-pouch of Douglas distance, the AUC was 0.69. Based on the best AUC (the difference in the pubis-uterine fundus distance at rest and with the Valsalva maneuver), a cut-off point of 15 mm was established for the diagnosis of UP (sensitivity: 75%; specificity: 95%; positive predictive value: 86%; and negative predictive value: 89%). CONCLUSION: A difference of ≥15 mm in the pubis-uterine fundus distance at rest and with the Valsalva maneuver is useful for differentiating UP from CE without UP by ultrasound.

Study of the Development of Placental Microvascularity by Doppler SMI (Superb Microvascular Imaging): A Reality Today.

Our objective was to evaluate the development of placental vascularization in normal gestation by using Doppler superb microvascular imaging (SMI). The fetal and maternal parameters of 20 pregnant women without pathology were evaluated at weeks 12, 16, 20-22, 24-26, 28-30, 32-34, 36-38 and 40-42. Doppler SMI was used to evaluate the placental vascularization (pulsatile index and peak systolic velocity) of the primary, secondary and tertiary (third) villi, and qualitative placental descriptions and anatomic-pathologic studies of these placentas were performed. The number of cotyledons identified by Doppler SMI increased from two between weeks 16 and 18 to 24 between weeks 28 and 38. The secondary and tertiary villi began developing at 20 wk of gestation. The pulsatile index of the primary villi remained constant (0.8-0.9 in all pregnancies). The pulsatile index of the secondary and tertiary villi increased from 1.1 to 1.53 and from 1.4 to 1.68, respectively. The peak systolic velocity underwent a significant increase throughout gestation in the secondary and tertiary villi (9.2 to 34.9 cm/s and 7.5 to 52.9 cm/s, respectively). We evaluated the development of placental microvascularization using Doppler SMI in pregnancies without pathology and describe normal placental Doppler SMI findings.

Type of levator ani muscle avulsion as predictor for the disappearance of avulsion.

OBJECTIVES: The objective of our study was to establish whether the type of levator ani muscle (LAM) avulsion diagnosed 6 months after delivery influences the integrity of the LAM at 1 year after delivery and determine its influence on the levator hiatus area. STUDY DESIGN: This observational prospective cohort study included 192 primiparous women with vaginal delivery. Transperineal ultrasound examinations were performed at 6 months and 1 year postpartum. Levator hiatus measurements (anteroposterior diameter, transverse diameter, and area) were performed in the plane of minimal dimensions. Complete avulsion was defined based on maximum contraction in multislice mode. Type I LAM avulsion was present when most lateral fibers of the pubovisceral muscle were observed at its insertion at the pubic level (the arch of the elevator remained intact). Type II LAM avulsion was defined as a complete detachment of the pubovisceral muscle from its insertion at the pubic level. RESULTS: In total, 192 patients were recruited after delivery; 48 patients were diagnosed with complete LAM avulsion, and 13 patients with avulsion did not attend the second ultrasound follow-up at 1 year after delivery. Thirty-five patients with complete LAM avulsion were included in the study. At 6 months after delivery, 51 LAM avulsions were observed in 35 patients (including bilateral LAM avulsion in 16 cases), of which 54.9% were right avulsions and 45.1% left avulsions. Furthermore, 11 (five right and six left) were type I LAM avulsions at the 6-month assessment, and all of these had disappeared 1 year after delivery. However, none of the type II LAM avulsions (23 right and 17 left) observed at 6 months had disappeared at the second ultrasound examination. There were no differences between the LAM areas detected at the first and second ultrasound examinations (10.2 ± 3.3 vs 9.3 ± 1.8; P = .404). CONCLUSIONS: The type of LAM avulsion observed at 6 months after childbirth predicts LAM persistence at 1 year postpartum.

Influence of epidemiological characteristics (age, parity and other factors) in the assessment of healthy uterine cervical stiffness evaluated through shear wave elastography as a prior step to its use in uterine cervical pathology.

PURPOSE: The purpose of this study was to evaluate stiffness changes occurring in the healthy uterine cervix according to age, parity, phase of the menstrual cycle and other factors by shear wave elastography (SWE). METHODS: Evaluations of cervical speed and stiffness measurements were performed in 50 non-pregnant patients without gynaecological pathology using SWE transvaginal ultrasound. We performed the evaluation in the midsagittal plane of the uterine cervix with measurements at 0.5, 1 and 1.5 cm from external cervical os, at both anterior and posterior cervical lips. RESULTS: We evaluated 44 patients by SWE and obtained a total average velocity of 3.48 ± 1.08 m/s and stiffness of 42.39 ± 25.33 kPa. We found differences in speed and stiffness according to the cervical lip and depth evaluated; thus, we observed a velocity of 2.70 m/s at 0.5 cm of depth in the anterior lip and 3.53 m/s at 1.5 cm of depth in the posterior lip (p < 0.05). We observed differences according to parity, obtaining a wave transmission speed of 2.67 m/s and 4.41 m/s at the cervical canal of nulliparous and multiparous patients, respectively (p < 0 0.002). We observed differences according to patient age (from a speed of 2.75 m/s at the cervical canal in the age group of 20-35 years to 5.05 m/s in the age group > 50 years) (p < 0.008). We did not observe differences in speed or stiffness according to the phase of the menstrual cycle, BMI, smoking status or the presence or absence of non-HPV infections. CONCLUSIONS: The wave transmission speed and stiffness of the uterine cervix evaluated by SWE varies according to the cervical lip and depth of the evaluation as well as according to the parity and age of the patient.

Influence of the disengagement of the forceps on levator ani muscle injuries in instrumental delivery: A multicenter study.

INTRODUCTION: Forceps use is the main risk factor for levator ani muscle (LAM) injuries. We believe that the disengagement of the forceps branches before delivery of the fetal head could influence LAM injuries, so we aimed to determine the influence of the disengagement of the forceps on the occurrence of LAM avulsion during forceps delivery. MATERIAL AND METHODS: A prospective, observational, multicenter study was conducted with 261 women who underwent forceps delivery. The women were classified according to whether the branches of the forceps had been disengaged before delivery of the fetal head. LAM avulsion was defined using a multislice mode (3 central slices). RESULTS: In all, 255 women completed the study (160 without disengagement and 95 with disengagement). LAM avulsions were observed in 37.9% of women in the group with disengagement and in 41.9% of women in the group without disengagement. The crude OR (without disengagement vs with disengagement) for avulsion was 0.90 (95% CI 0.49-1.67, P = 0.757) and an adjusted OR of 0.82 (95% CI 0.40-1.69, P = 0.603). CONCLUSIONS: We did not observe a statistically significant reduction in the LAM avulsion rate with disengagement of the forceps branches before delivery of the fetal head.

A simple model to predict the complicated operative vaginal deliveries using vacuum or forceps.

BACKGROUND: Complicated operative vaginal deliveries are associated with high neonatal morbidity and maternal trauma, especially if the procedure is unsuccessful and a cesarean delivery is needed. The decision to perform an operative vaginal delivery has traditionally been based on a subjective assessment by digital vaginal examination combined with the clinical expertise of the obstetrician. Currently there is no method for objectively quantifying the likelihood of successful delivery. Intrapartum ultrasound has been introduced in clinical practice to help predict the progression and final method of delivery. OBJECTIVE: The aim of this study was to compare predictive models for identifying complicated operative vaginal deliveries (vacuum or forceps) based on intrapartum transperineal ultrasound in nulliparous women. STUDY DESIGN: We performed a prospective cohort study in nulliparous women at term with singleton pregnancies and full dilatation who underwent intrapartum transperineal ultrasound evaluation prior to operative vaginal delivery. Managing obstetricians were blinded to the ultrasound data. Intrapartum transperineal ultrasound (angle of progression, progression distance, and midline angle) was performed immediately before instrument application, both at rest and concurrently with pushing. Intrapartum evaluation of fetal biometric parameters (estimated fetal weight, head circumference, and biparietal diameter) was also carried out. An operative vaginal delivery was classified as complicated when 1 or more of the following complications occurred: ≥3 tractions needed; third- to fourth-degree perineal tear; severe bleeding during episiotomy repair (decrease of ≥2.5 g/dL in the hemoglobin level); or significant traumatic neonatal lesion (subdural-intracerebral hemorrhage, epicranial subaponeurotic hemorrhage, skeletal injuries, injuries to spine and spinal cord, or peripheral and cranial nerve injuries). Six predictive models were evaluated (information available in Table 2). RESULTS: We recruited 84 nulliparous patients, of whom 5 were excluded because of the difficulty of adequately evaluating the biparietal diameter and head circumference. A total of 79 nulliparous patients were studied (47 vacuum deliveries, 32 forceps deliveries) with 13 cases in the occiput-posterior position. We identified 31 cases of complicated operative vaginal deliveries (19 vacuum deliveries and 12 forceps deliveries). No differences were identified in obstetric, neonatal, or intrapartum characteristics between the 2 study groups (operative uncomplicated vaginal delivery vs operative complicated vaginal delivery), with the following exceptions: estimated fetal weight (3243 ± 425 g vs 3565 ± 330 g; P = .001), biparietal diameter (93.2 ± 2.1 vs 95.2 ± 2.3 mm; P = .001), head circumference (336 ± 12 vs 348 ± 6.4 mm; P = .001), sex (female 62.5% vs 29.0%; P = .010), newborn weight (3258 ± 472 g vs 3499 ± 383 g; P = .027), and number of tractions (median, interquartile range) (1 [1-2] vs 4 [3-5]; P < .0005). To predict complicated operative deliveries, all 6 of the studied models presented an area under the receiver-operating characteristics curve between 0.863 and 0.876 (95% confidence intervals, 0.775-0.950 and 0.790-0.963; P < .0005). The results of the study met the criteria of interpretability and parsimony (simplicity), allowing us to identify a binary logistic regression model based on the angle of progression and head circumference; this model has an area under the receiver-operating characteristics curve of 0.876 (95% confidence interval, 0.790-0.963; P < .0005) and a calibration slope B of 0.984 (95% confidence interval, 0.0.726-1.243; P < .0005). CONCLUSION: The combination of the angle of progression and the head circumference can predict 87% of complicated operative vaginal deliveries and can be performed in the delivery room.

Utility of intrapartum transperineal ultrasound to predict cases of failure in vacuum extraction attempt and need of cesarean section to complete delivery.

OBJECTIVES: We aim to evaluate the predictive capacity of intrapartum transperineal ultrasound (ITU) to predict cases of failure in fetal extraction in operative deliveries with vacuum. Prospective, observational study performed on 61 nulliparous women, ≥ 37 weeks, singleton pregnancies at full dilatation who underwent transperineal ultrasound before placement of vacuum to complete fetal extraction. Working on the transperineal longitudinal plane, we evaluated the following: Angle of Progression (AoP), Progression Distance (PD) and head direction. In the transverse plane, midline angle (MLA) and head-perineum distance were assessed. Vacuum extractions were classified as easy (EG) (three or less vacuum pulls), difficult (DG) (more than three vacuum pulls) or impossible (IG) (delivery completed by cesarean section). Occipito-posterior presentations were not evaluated. RESULTS: Fifty-two patients were studied (26-EG, 19-DG and 7-IG). No differences in obstetric, intrapartum or neonatal characteristics were observed between study groups, with the following exceptions: weight at birth (3147 g-EG, 3523 g-DG and 3588 g-IG) and number of vacuum pulls (1.4-EG, 4.4-DG and 4.1-IG; p < 0.0005). The AoP pushing was 133.1° ± 13.6-EG, 112.8° ± 12.8-DG and 99.1° ± 8.9-IG (p < 0.0005); "head-up" direction was identified in 84.6% of EG, 36.8% of DG and 28.6% of IG (p < 0.001); PD were 37.0 ± 10.4 mm, 33.3 ± 23.3 mm and 20.8 ± 9.5 mm (p < 0.0005); MLA were 35.0° ± 19.6, 55.3° ± 24.4 and 76.0° ± 23.2 (p = 0.003); and head-perineum distances were 41.8 ± 6.6 mm, 49.2 ± 9.8 mm and 48.0 ± 3.4 mm (p = 0.072), respectively. CONCLUSION: We have observed that the presence of an AoP with pushing <105°, a PD <25 mm, a "head-down" direction and a >45° MLA are very unfavorable ITU parameters which can be used to identify cases of high risk of fetal extraction failure in vacuum-assisted deliveries.

Contribution of "modified genetic sonography" to the combined test as a screening method for chromosomal abnormalities.

OBJECTIVES: We propose to assess the contribution of "modified genetic sonography" (MGS) to the combined test (CT) as a method of stepwise sequential screening (1st step: CT, 2nd step: MGS) for chromosome abnormalities in the general population of pregnant women. METHODS: Prospective study. During a 4 year study period (July 2005-June 2009) 16,548 pregnancies underwent a CT combined with MGS (major malformation and nuchal fold) as a screening method for chromosome abnormalities. We assessed sensitivity and false positive rate (FPR) (95% CI). RESULTS: We offered a chromosome abnormalities screening test to 96.6% of pregnancies (15,995 cases). 14,160 cases are analyzed (1st step: CT, 2nd step: MGS) including 49 chromosome abnormalities and 35 Down's syndrome (DS). The sensitivity of CT for DS was 77.1% [95% CI, 63.2-91] (27/35) and 77.5% for all chromosome abnormalities [95% CI, 65.8-89.2] (38/49) with a FPR of 4.4% [95% CI, 4.1-4.7]. If MGS was combined with CT, the sensitivity for DS was 91.4% [95% CI, 82.1-99] (32/35) and 93.8% for all chromosome abnormalities [95% CI, 87-99] (46/49) for a FPR of 5.1% [95% CI, 4.7-5.5]. CONCLUSIONS: The addition of an MGS to combined first-trimester screening test for aneuploidy improved sensitivity by 14.3% while only increasing the FPR by 0.7%.

Influencia de la visita puerperal temprana en la detección y evolución de la depresión posparto / Influence of early postpartum home visits on the detection and clinical course of postpartum depression

Objetivos. Nos proponemos determinar y valorar la influencia de la visita puerperal temprana (VPT) domiciliaria en la disminución de la incidencia de depresión posparto en nuestro medio. Material y métodos. Cuatrocientos treinta pacientes con embarazo y partos sin complicaciones que se aleatorizan en dos grupos homogéneos (grupo con VPT y grupo control). Se utilizó la hospital anxiety and depresión scale para valorar la depresión posparto a los 7 y 30 días. Resultados. Se observó un score positivo para depresión puerperal a los 7 días del parto en un 10,2%. En el grupo de VPT se observó una disminución de incidencia de la depresión puerperal (0,9%) frente al grupo control (3,7%). Conclusión. La incidencia de depresión posparto en nuestra área es similar a la esperada. La visita puerperal temprana parece ser útil en la detección de patología psiquiátrica y disminuye la evolución de los síntomas(AU)

Objectives. The aim of this study was to determine the influence of early postpartum home visits in reducing the incidence of puerperal depression in our environment. Material and methods. A total of 430 patients with uncomplicated pregnancy and delivery were randomized to two homogeneous groups (one group receiving an early postpartum home visit and a control group). The hospital anxiety and depression scale was used to assess puerperal depression at 7 and 30 days. Results. At 7 days, 10.2% of the patients had a positive score for puerperal depression. At 30 days, the incidence of puerperal depression was lower in the group receiving an early home visit (0.9%) than in the control group (3.7%). Conclusion. The incidence of postpartum depression in our setting was similar to the expected incidence. Early postpartum home visits seem to be useful in detecting this disorder and in reducing symptoms(AU)

Preliminary molecular genetic analysis of the Receptor Interacting Protein 140 (RIP140) in women affected by endometriosis.

BACKGROUND: Endometriosis is a complex disease affecting 10-15% of women at reproductive age. Very few genes are known to be altered in this pathology. RIP140 protein is an important cofactor of oestrogen receptor and many other nuclear receptors. Targeting disruption experiments of nrip1 gene in mice have demonstrated that nuclear receptor interacting protein 1 gene (nrip1), the gene encoding for rip140 protein, is essential for female fertility. Specifically, mice null for nrip1 gene are viable, but females are infertile because of complete failure of mature follicles to release oocytes at ovulation stage. The ovarian phenotype observed in mice devoid of rip140 closely resembles the luteinized unruptured follicle (LUF) syndrome that is observed in a high proportion of women affected of endometriosis or idiopathic infertility. Here we present a preliminary work that analyses the role of NRIP1 gene in humans. METHODS: We have sequenced the complete coding region of NRIP1 gene in 20 unrelated patients affected by endometriosis. We have performed genetic association studies by using the DNA variants identified during the sequencing process. RESULTS: We identified six DNA variants within the coding sequence of NRIP1 gene, and five of them generated amino acid changes in the protein. We observed that three of twenty sequenced patients have specific combinations of amino-acid variants within the RIP140 protein that are poorly represented in the control population (p = 0.006). Moreover, we found that Arg448Gly, a common polymorphism located within NRIP1 gene, is associated with endometriosis in a case-control study (59 cases and 141 controls, Pallele positivity test = 0.027). CONCLUSION: Our results suggest that NRIP1 gene variants, separately or in combinations, might act as predisposing factors for human endometriosis.