L. Mandia

Pregenesys pre-eclampsia markers consensus meeting: What do we require from markers, risk assessment and model systems to tailor preventive strategies?

The Pregenesys Consensus Meeting held in Cambridge on 13 July 2009 was organized by the Pregenesys Consortium to review and critically discuss current knowledge regarding early markers of preeclampsia, to identify priorities and opportunities for future research, to consider issues that may need to be addressed in future recommendations and to highlight key issues in cost effectiveness and national policies concerning prediction and early screening for the risk of developing preeclampsia. This report summarizes the outcome of the Consensus Meeting and draws attention to issues for further investigation with specific regard to single versus multiple markers, early versus late risk identification, and the long-term effects on both maternal and perinatal health and the need to include these in any future cost-benefit assessment.

Lactate detection in the brain of growth-restricted fetuses with magnetic resonance spectroscopy

OBJECTIVE The objective of the study was to determine the feasibility of detecting fetal brain lactate, a marker of fetal metabolic acidemia, using a noninvasive technique, proton magnetic resonance spectroscopy ((1)H MRS), in intrauterine growth-restricted (IUGR) fetuses. STUDY DESIGN In vivo human fetal brain lactate detection was determined by (1)H MRS in 5 fetuses with IUGR. Oxygenation and acid-base balance data were obtained at birth. RESULTS (1)H MRS analysis showed the presence of a lactate peak in the brain of the most severely affected IUGR fetus, with abnormal umbilical artery Doppler and fetal heart rate tracing. This finding was consistent with the low oxygen content and high lactic acid concentration observed in umbilical blood obtained at delivery. CONCLUSION (1)H MRS allows the noninvasive detection of cerebral lactate in IUGR fetuses. Lactate detected by (1)H MRS may represent a possible marker of in utero cerebral injury or underperfusion.

First trimester placental markers in oocyte donation pregnancies.

INTRODUCTION This study investigates the hypothesis that placenta works differently in oocyte donation (OD) compared to spontaneous pregnancies. To verify this hypothesis we examine the first trimester maternal serum levels of free β-hCG and pregnancy-associated plasma protein-A (PAPP-A). Then we evaluated for potential differences of Down syndrome screening between OD pregnancies, in vitro fertilization/intracytoplasmic sperm injection pregnancies with autologous oocytes (IVF/ICSI) and spontaneous pregnancies. METHODS We analyze 13624 spontaneously conceived pregnancies (Controls), 171 oocyte donation pregnancies (OD IVF/ICSI) and 76 IVF pregnancies with autologous oocytes (Autologous IVF/ICSI). Furthermore, we collect a cohort of 802 spontaneously conceived age-matched pregnancies, in order to evaluate how older uteri contribute to explain the changes in markers concentrations (Age-matched controls We compare the multiples of the median (MoM) of free β-hCG and PAPP-A and nuchal translucency. RESULTS Free β-hCG levels are significantly higher both in OD IVF/ICSI pregnancies (1.44 ± 1.06 MoM) and Autologous IVF/ICSI (1.48 ± 1.02 MoM) compared to Controls (1.15 ± 0.84 MoM; p < 0.05) and Age-matched Controls (1.18 ± 0.98 MoM; p < 0.05). PAPP-A levels do not significantly differ among the four groups. Significantly lower nuchal translucency is detected in Controls (1.41 ± 0.36 mm) compared to OD IVF/ICSI (1.46 ± 0.44 mm; p < 0.05), in Autologous IVF/ICSI (1.51 ± 0.34 mm; p < 0.05) and Age-matched Controls (1.44 ± 0.42 mm; p < 0.05). DISCUSSION Oocyte donation pregnancies (OD IVF/ICSI) are significantly related to altered maternal serum placenta marker levels. These alterations might be due to the IVF technique.

OP13.06: Fetal borderline cerebral lateral ventriculomegaly: a retrospective analysis of 74 cases

S. Boito1, A. Righini2, L. Ramenghi3, L. Mandia1, P. Ficarazzi1, R. Fogliani1, G. Pardi1 1Obstetrics and Gynecology Inst., IRCCS Policlinico, Mangiagalli and Regina Elena Foundation, University of Milan, Italy, 2Radiology and Neuroradiology, IRCCS Policlinico, Mangiagalli and Regina Elena Foundation, University of Milano, Italy, 3Neonatal Intensive Care Unit, IRCCS Policlinico, Mangiagalli and Regina Elena, University of Milan, Italy

OP15.01: Absolute uterine artery blood flow volume is increased in twin human pregnancies compared to singletons

Objectives: To compare (1) absolute and (2) weight-specific blood flow volume of uterine arteries (UtA) in normal twin pregnancies to normal singleton pregnancies. Methods: Twelve twin pregnancies (10 dichorionic, two monochorionic) with normal UtA PI and normal weight at birth were included. UtA diameter and time-averaged maximum velocity were obtained to calculate flow (mL/min) and UtA flow/EFW (mL/min/kg) in each UtA. UtA flow was estimated by the formula Q = hV · πD2/4; a patient-specific coefficient, h, was obtained by an ad hoc mathematical model. Total UtA flow was calculated as a sum of right and left vessel flow volume. Twins’ UtA flow was expressed per unit EFW considering the sum of the two EFWs. Twins were compared to 48 normal age-matched singletons. Results: Gestational age at exam was similar in twins and in singletons (25.9 ± 6.4 vs. 25.2 ± 6.2 weeks, NS). UtA flow (mL/min) was significantly increased in twins (509.3 ± 240.7 mL/min) compared to singletons (337.2 ± 257.0 mL/min) (P = 0.04). UtA flow (mL/min) exponentially increased along gestation in twins and in singletons. The twins’ trend was above the third interquartile range of singletons’ reference values. UtA diameter was significantly increased in twins (0.33 ± 0.07 cm) than in singletons (0.28 ± 0.05 cm), while no differences in UtA mean velocity were observed (77.5 ± 29.9 vs. 76.7 ± 29.1 cm/sec, respectively, NS). UtA flow per EFW did not differ between twins and singletons (384.4 ± 198.6 vs. 460.9 ± 302.9 mL/min/kg, respectively, NS). Conclusions: (1) UtA flow volume (mL/min) in twin pregnancies was significantly increased. This was determined by larger vessel diameter, compared to singletons. (2) Each twin proved to share an amount of UtA flow per unit estimated fetal weight not significantly different from singletons.

Uterine artery Doppler pulsatility index at 11–38 weeks in ICSI pregnancies with egg donation

Abstract Background: Uterine artery Doppler pulsatility index (UtA-PI) may be different in pregnancies with egg donation (ICSI-ED) as compared to conceptions with autologous intra-cytoplasmatic sperm injection (autologous ICSI) and to spontaneous conceptions (SC). Methods: One hundred and ninety-four pregnant women with different modes of conception (MC) were prospectively evaluated: 53 ICSI-ED, 36 autologous ICSI and 105 SC. To evaluate the effects of different MC on PI, multivariable linear regression (MLR) models predicting UtA-PI were fitted after adjustment for maternal age, body mass index, race, parity, smoking status and gestational age. Results: In the first trimester, at MLR, autologous ICSI was not associated with a significantly different UtA-PI [estimate (EST) 0.01; 95% confidence interval (CI) −0.19, 0.2; P=0.9] when compared to SC. Conversely, MC by ICSI-ED was associated with lower first trimester UtA-PI (EST −0.32; CI −0.55, −0.08; P=0.01) when compared to SC. At MLR, MC by autologous ICSI and by ICSI-ED were not associated with significant differences in the second and third trimester UtA-PI when compared to SC. Conclusion: ICSI-ED conception presented lower UtA-PI when compared to SC at 11+0–13+6 weeks but not at later assessments. Correction of UtA-PI measurement specifying the origin of oocyte may be useful in first trimester screening.

OP01.06: Reduction of uterine artery blood flow volume is correlated to reduced fetal mass in pregnancies with abnormal uterine resistance index

Total vascular resistance (dyne s/cm5) 1623 (1287–3125) 1163 (944–1785) 0.008 Stroke volume (mL) 69 (36–81) 67 (57–86) 0.95 Cardiac output (L/min) 5.40 (4.4–7.0) 6.1 (4.0–8.1) 0.08 Ejection fraction (%) 69 (64–83) 71 (65–79) 0.59 Midwall fractional shortening (% of predicted value) 118 (94–126) 122 (106–140) 0.04 Isovolumetric relaxation time (ms) 78 (50–90) 60 (45–75) 0.006 24 h ambulatory heart rate (bpm) 74 (61–82) 79 (76–92) 0.003 24 h ambulatory systolic blood pressure (mmHg) 117 (104–136) 106 (101–121) 0.031 24 h ambulatory diastolic blood pressure (mmHg) 75 (65–88) 66 (56–73) 0.012 24 h ambulatory mean arterial pressure (mmHg) 87 (79–104) 79 (72–87) 0.016

OP09.19: Three‐dimensional assessment of placenta volume during the first half of pregnancy

Objective: This study examines the role of virtual reality in the visualization of 3D data volume sets of ambiguous genitalia as acquired by 3D ultrasound. Methods: In 2005 in three patients referred to our department for prenatal ultrasound assessment ambiguous genitalia were diagnosed. Postpartum diagnosis was one case of Russell-Silver syndrome, one case of an XY-female with normal labia majora and an enlarged clitoris and a case with an unusual type of cloacal malformation with an enlarged clitoris, prominent preputium and single urogenital sinus. Prenatally, patients were examined by 2D and 3D ultrasound and subsequently the images obtained at 3D ultrasound were visualized in the Barco I-Space virtual reality system. Results: In these cases, prenatal diagnosis was impossible with 2D ultrasound. 3D ultrasound provided an impression of ambiguity, however this was incorrect in two cases. In the I-Space, a better impression of genital ambiguity was established. Particularly the bi-ocular depth perception provided by the I-space was useful when faced with the task of differentiating a micropenis from an enlarged clitoris. Conclusions: The presence of ambiguous genitalia in a baby post partum presents a major diagnostic dilemma that few clinicians would attempt on a purely visual basis without resorting to palpation and physical examination. Prenatal ultrasound of such a condition can at best only alert to a condition that will need further examinations post partum, thus unfortunately raising parents’ anxiety level. A 3D virtual reality technique that improves depth perception can improve visualisation of difficult anatomical structures such as ambiguous genitalia.

P07.05: Uterine artery blood flow volume growth rate in uncomplicated human pregnancies

Objective: 1) To study uterine artery (UtA) flow (ml/min) growth rate along gestation in normal human pregnancies; 2) to evaluate longitudinal changes of UtA flow expressed per unit estimated fetal weight (EFW) (ml/min/kg). Methods: A cohort of twelve singleton uneventful human pregnancies, with a normal mean UtA PI, was included in this longitudinal study. UtA was evidenced by power-Doppler mode and sampled 10–15 mm prior to bifurcation. UtA diameter was measured on a perpendicular view after removing power-Doppler. UtA PI and velocity were measured with a Doppler beam angle < 30◦. The average of three consecutive diameters and velocities was considered. UtA flow was estimated by the formula Q = hV · πD2/4; h coefficient (0.5) was obtained by an ad hoc mathematical model. UtA total flow (ml/min) (right plus left UtA flow) was then expressed per EFW (ml/min/kg). Using linear interpolation, including random effects for the intercept and the slope of gestational age for each fetus, a linear mixed effects model was fitted. Results: Forty-seven ultrasound examinations were performed. Ultrasound exams were performed at 14.3,b1.2 weeks and every 4 weeks until delivery. Each case was definitively included in the study after recording normal perinatal and neonatal outcomes. UtA total flow (ml/min) showed a significant correlation to gestational age (133.6 ml/min at 15 weeks; 415.9 ml/min at 35 weeks) (p < 0.001), with a linear increase of 14.1 ml/min per week (right UtA 5.4 vs. left UtA 8.7 ml/min per week, p NS). UtA flow per unit EFW (ml/min/kg) showed a significant reduction from 780.3 ml/min/kg at 15 weeks to 144.1 ml/min/kg at 35 weeks (reduction rate 40.3 ml/min/kg per week). Conclusions: UtA flow (ml/min) significantly increased along gestation in this longitudinal cohort of normal pregnancies. UtA flow per unit EFW (ml/min/kg) significantly decreased longitudinally, since UtA flow (ml/min) growth rate was lower than fetal weight gain rate along gestation.

Ultrasound in Infertility Setting: Optimal Strategy to Evaluate the Assessment of Tubal Patency

Tubal patency is a key element in women who are undergoing assisted reproductive techniques (ART), in order to attempt or exclude intrauterine insemination (IUI) cycles. Amongst the different procedures that can be used, without resorting to laparoscopy that remains the gold standard, hystero-salpingo-contrast sonography (HyCoSy) is an acceptable, time-efficient, and well tolerated option; it can be performed with administration of saline and air simultaneously or alternately (air/saline-HyCoSy), or with some other contrast agents, like SonoVue (sulfur hexafluoride microbubbles). In this paper, we describe two different studies: in the first one, our aim is to compare the efficiency of air/saline-HyCoSy with HyCoSy performed with contrast media (SonoVue), considering hysterosalpingography (HSG) and laparoscopy (LPS) as reference tests; in the second one, we estimate the pregnancy rate of a cohort of infertile women selected to undergo IUI cycles after tubal bilateral patency demonstration with air/saline-HyCoSy, to understand if this technique can be used as an efficient screening procedure in a Reproductive Unit.