José A. Sainz

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.

First trimester contingent test as a screening method for Down’s syndrome. A prospective study in the general population

Objectives: To evaluate the possibility of implementing a contingent test as a screening method for Down’s syndrome (DS) in the first trimester of pregnancy, and assess its sensitivity (Sen) and false positive rate (FPR). Methods: Prospective study covering a 4-year study period (July 2006–June 2010). Pregnant women were offered a combined test (CT) as the first step of a contingent test. An intermediate risk group is identified in the CT (1/101 and 1/1000) and offered an ultrasound assessment of secondary s (nasal bone, ductus venosus, tricuspid regurgitation). Results: CTs were performed on 10,452 pregnant women (24 cases of DS). In the intermediate risk group, which had 7 cases of DS, we performed secondary ultrasound marker assessment on 98.1% (1,017/1,036). The CT and the contingent test had a Sen of 83% (95% CI; 67.9–98) (20/24) and 70.8% (95% CI; 52.6–88.9) (17/24) with an FPR of 3% (95% CI; 2.7–3.3) (316/10,430) and 2% (95% CI; 1.7–2.3) (220/10,408), respectively. Conclusions: With the contingent test, we managed to reduce the FPR, but the Sen was too low for use as a screening method for DS.

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

Abstract 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.

Intrapartum transperineal ultrasound as a predictor of instrumentation difficulty with vacuum-assisted delivery in primiparous women

Abstract Objectives: To assess the capability of different intrapartum transperineal ultrasound parameters to predict the difficulty of vacuum extraction. This is a prospective observational study performed between 04/2012 and 03/2013 on 72 primiparous-women, ≥37-weeks with singleton pregnancies at full dilatation that underwent transperineal ultrasound before vacuum placement for foetal extraction. Working in a transperineal longitudinal plane we evaluated: progression-angle, progression-distance and head direction; in a transverse plane: midline-angle and head-perineum distance. The vacuum extractions were classified as easy-group (EG) (≤3 vacuum pulls), difficult/impossible-group (DG)(≥4 pulls). Occiput-posterior presentations were not assessed. Results: Fifty-two (52) patients were studied (26 patients per study group). No differences were observed in obstetric, neonatal or intrapartum characteristics between the study groups, with the following exceptions: new-born (NB) weight (3147 g versus 3540 g) and the number of vacuum pulls (1.4 EG versus 4.3 DG; p < 0.0005). The progression angle was 133.1° (123°–143°) in EG and 109.2° (97.2°–121.2°) in DG (p < 0.0005); up direction of foetal head was 88% versus 34.5% (p < 0.0005); progression distance was 37 mm (26.6–47.4) versus 29.9 mm (8.8–51; p = 0.003); midline angle was 35° (15.4°–54.6°) versus 59.7° (34.5°–84.9°; p = 0.0005); head-perineum distance was 41.9 mm (35.2–48.6) versus 48.9 mm (40.5–57.3; p = 0.017). The area under the Receiver Operating Characteristic (ROC) curve for the progression angle was 0.9 (95%CI, 0.82–0.99), and the midline angle was 0.8 (95%CI, 0.67–0.92). Conclusion: If previous to the placement of the vacuum cup the progression angle is ≤120°, the foetal head direction is horizontal or down, and the midline angle is ≥35°, there is an 85% chance that the delivery will require more than 4 vacuum pulls.

Analysis of middle cerebral artery peak systolic velocity in monochorionic twin pregnancies as a method for identifying spontaneous twin anaemia-polycythaemia sequence

Abstract A regular Doppler control evaluation of middle cerebral artery peak systolic velocity is needed in order to identify twin anaemia polycythaemia sequence in monochorionic twin pregnancies. Here, we present a clinical case of spontaneous TAPS, and we review the diagnostic criteria and management strategies for this syndrome.

Cribado prenatal de cardiopatías congénitas en población de bajo riesgo de defectos congénitos. Una realidad en la actualidad

INTRODUCTION We propose to demonstrate that it is possible to implement a valid (diagnostic sensitivity for major cardiac malformations 90%), and universal (applied to over 90% of pregnant women), prenatal screening method for congenital heart defects. MATERIALS AND METHODS Prospective study. A total of 12478 pregnant women were evaluated between January 2008 and December 2010. Congenital heart diseases were screened using fetal extended basic echocardiography (cardiac ultrasound). RESULTS The prevalence of birth defects in general and congenital heart disease was 2.5% (2.2-2.7%) and 0.9% (0.7-1%) respectively. Congenital heart disease had a higher rate of association with other structural abnormalities with 11.5% (5.6-17.4%), 21% for major congenital heart disease (9.9-32%), and chromosomal abnormalities of 15.9% (9.1-22.7%), with 32.6% for major congenital heart disease (19.8-45.3%). A fetal cardiac ultrasound assessment was performed on 99.2% of pregnant women. The fetal echocardiography is useful for the diagnosis of congenital heart disease in general, and major congenital heart disease, with a sensitivity of 42.8% (33.5-52.5%) and 90.4% (78.9-96.8%), respectively, and a specificity for both of 99.9% (99.8-99.9%). CONCLUSIONS It is possible to perform a valid prenatal and universal screening of major congenital heart disease.

Stepwise sequential screening for Down's syndrome (combined test associated with modified genetic sonography) in pregnant women with low risk for chromosomal disorders.

Abstract Objective: To assess the sensitivity (Sen) and false positive ratio (FPR) of stepwise sequential screening [1st step: combined test (CT), 2nd step: modified genetic sonography (major malformation and nuchal fold, MGS)] as a screening method for Down’s syndrome (DS) in the general population of pregnant women. Methods: Prospective study. During a 5-year study period (July 2005 to June 2010), 17,911 pregnant women were screened for DS using a stepwise sequential screening method (CT+MGS). We evaluated the Sen and FPR (95% CI) of the two chromosomal disorder screening methods for DS: CT and CT+MGS. Results: Seventeen thousand nine hundred and eleven cases were analysed, including 67 with chromosome abnormalities and 45 with DS. The Sen of CT for DS was 80% (95% CI; 68.3–91.7) (36/45) with a FPR of 4.2% (95% CI; 3.9–4.5) (752/17, 866). The Sen of CT+MSG for DS was 93.3 (95% CI; 85.9–99) (42/45) with a FPR of 4.8% (95% CI; 4.5–5.1) (860/17, 866). Conclusions: MGS coupled with CT increases the Sen of DS diagnosis by 13.3% (95% CI; 2.7–25.9), with an increase in FPR of 0.6% (95% CI; 0.5–0.7).

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%.

Intra and interobserver variability of intrapartum transperineal ultrasound measurements with contraction and pushing

Abstract The aim of this study was to evaluate the inter- and intraobserver correlation of the different intrapartum-transperineal-ultrasound-parameters(ITU) (angle of progression (AoP), progression-distance (PD), head-direction (HD), midline-angle (MLA) and head-perineum distance (HPD)) with contraction and pushing. We evaluated 28 nulliparous women at full dilatation under epidural analgesia. We performed a transperineal ultrasound evaluating AoP and PD in the longitudinal plane, and MLA and HPD in the transverse plane. Interclass correlation coefficients (ICC) with 95% CIs and Bland–Altman analysis were used to assess intra- and interobserver measurement’s repeatability. The ICC of the ITU for the same observer was adequate for all the parameters (p < .005) AoP 0.98 (95%CI, 0.96–0.99), PD 0.98 (95%CI, 0.97–0.99), MLA 0.99 (95%CI, 0.97–0.99), HPD 0.96 (95%CI, 0.88–0.99). The ICC of the ITU for interobserver was: AoP 0.93 (95%CI, 0.79–0.98), PD 0.92 (95%CI, 0.76–0.97), MLA 0.77 (95%CI, 0.42–0.92), HPD 0.47 (95%CI, −0.12–0.8). The HD had an interobserver correlation of 0.53 (95%CI, 0.1–0.9) (Kappa C). The mean difference of the AoP was 2.42°, of the PD 1 mm and 0.28° MLA (Bland–Altman test). ITU has an adequate intra- and interobserver correlation for its use with contraction and pushing under epidural analgesia. Impact statement What is already known on this subject: The intrapartum transperineal ultrasound parameters can be used with contraction and pushing under epidural analgesia. What the results of this study add to what we know: ITU may be used to evaluate the difficulty of instrumental delivery/to evaluate the difficulty of instrumentation in vaginal operative deliveries and this study concludes that ITU is reproducible during uterine contraction with pushing. What the implications are of these findings for clinical practice and/or further research: Therefore, ITU could be used without difficulty with an adequate intra- and interobserver correlation for the prediction of instrumentation difficulty in operative vaginal deliveries.

Levator ani muscle injuries associated with vaginal vacuum assisted delivery determined by 3/4D transperineal ultrasound

Abstract Objectives: To determine the rate of pelvic floor trauma, levator ani muscle (LAM) avulsion as well as the mean difference in levator hiatus area, after normal vaginal deliveries (NVD) and vacuum assisted deliveries (VD), assessed with three-dimensional transperineal ultrasound (3D-TpUS). Materials and methods: Prospective observational study with 151 nulliparous women with NVD or VD at ≥37 weeks between 9-2012 and 6-2013. 3D-TpUS was performed six months after every patient’s delivery, during which LAM, anteroposterior diameter, transverse diameter and levator hiatus area were assessed. Results: A total of 146 nulliparous were studied, comprising 73 NVD and 73 VD. No differences in obstetric, intrapartum or neonatal characteristics were observed between study groups, with the following exceptions: maternal age (28.1 ± 5.4 versus 30.4 ± 5.5; p = 0.008, OR = 1.1) and episiotomy rate (35.6% versus 97.3%; p = 0.011, OR = 4.3). LAM avulsion rate was 9.6% in NVD versus 34.2% in VD (p = 0.001, OR 3.99), while levator hiatus area at rest was 16.5 ± 3.2 versus 18.2 ± 3.9 (p = 0.016). Conclusions: Vacuum assisted deliveries present a higher rate of LAM avulsion, as well as a greater increase in levator hiatal area than in NVD.