OBJECTIVE: Monochorionic twins (MC) have higher risk of perinatal morbi-mortality compared to singletons and dichorionic twins (DC). Selective fetal growth restriction (sFGR) increases the chances of adverse outcome. Hepatic arterial buffer response (HABR) is an important mechanism for maintaining liver perfusion. We hypothesised that HABR is active in monochorionic diamniotic twins (MCDA) with sFGR where restricted fetus may have liver hypoperfusion. The objective of this study is to test whether the HAV-ratio is diminished in pregnancies affected by selective fetal growth restriction pointing to activation of HABR in the growth-restricted fetus.
METHODS: sFGR was defined according to a consensus definition. Hepatic artery (HA) peak systolic velocity (PSV) was measured and its correlation with fetal Dopplers and pregnancy characteristics were determined. A ratio using HA-PSV (HAV-ratio) was calculated and its association with sFGR was established. Further analysis of HA-PSV was performed comparing z-scores between normal and growth restricted fetuses.
RESULTS: We included 202 MCDA pregnancies, 160 (79 %) normal and 42 (21 %) with sFGR. HAV-ratio was significant different between groups. The mean HAV-ratio was 1.01 (±0.20) for normal twins and 0.77 (±0.25) for sFGR. Furthermore, HA-PSV z-scores was significant increased in in growth-restricted fetus (0.94±1.45), while in normal fetuses was -0.16 (±0.97).
CONCLUSIONS: Our findings demonstrate that, in pregnancies with sFGR, HAV-ratio is significantly lower than in normal MCDA pregnancies. The lower HAV-ratio is due to an increase in HA PSV in the growth restricted fetus. This observation indicates an activation of HABR in the small fetus.

BACKGROUND: The aim of the study was to explore patients\' perspectives on diagnosis and treatment options for complicated monochorionic multiple gestations, and experiences with fetoscopic laser photocoagulation.
METHODS: This is a prospective cohort study of patients undergoing laser photocoagulation. Participants were interviewed during pregnancy and the postpartum period. Qualitative analysis was performed.
RESULTS: Twenty-seven patients who were candidates for laser photocoagulation were included. All elected to have laser photocoagulation. Patients chose surgery with goals of improving survival, decreasing the risk of preterm delivery, and improving the long-term health of their fetuses. They demonstrated accurate knowledge of the risks and benefits of treatment. Most (74%) felt that laser photocoagulation represented their only viable clinical option. Few seriously considered pregnancy termination or selective reduction (7% and 11% respectively). Postpartum, patients expressed no regrets about their decisions for surgery, but many felt unprepared for the challenges of preterm delivery.
CONCLUSIONS: Participants weighed treatment options similarly to fetal specialists. They acknowledged but did not seriously consider treatments other than fetoscopic laser photocoagulation and were highly motivated to do whatever they could to improve outcomes for their fetuses.

BACKGROUND: Accurate prenatal recognition of discordant fetal growth in twins is critical for deciding suitable management strategies. We explored the predictive value of the level of maternal second-trimester placental growth factor (PLGF) as a novel indicator of discordant fetal growth.
METHODS: A total of 860 women pregnant with twins were enrolled, including 168 women with monochorionic twins (31 cases of discordant fetal growth and 137 without) and 692 with dichorionic twins (79 cases of discordant fetal growth and 613 without). Maternal second-trimester PLGF concentrations were measured via immunofluorescence.
RESULTS: Maternal second-trimester PLGF levels were significantly lower in women pregnant with twins who subsequently developed discordant fetal growth than in those who did not (monochorionic twin pregnancy: P < 0.001; dichorionic twin pregnancy: P < 0.001). A 3-4 fold difference in median PLGF concentrations was detected between the two groups with both monochorionic and dichorionic twin pregnancies. Maternal second-trimester PLGF levels were significantly correlated with birth weight differences (monochorionic twin pregnancy: r =  - 0.331, P < 0.001; dichorionic twin pregnancy: r =  - 0.234, P < 0.001). A receiver operating characteristic curve was used to evaluate the predictive efficiency. In monochorionic twin pregnancies, the area under the curve (AUC) was 0.751 (95% confidence interval [CI]: 0.649-0.852), and the cutoff value was 187.5 pg/mL with a sensitivity of 77.4% and specificity of 71.0%. In dichorionic twin pregnancies, the AUC was 0.716 (95% CI; 0.655-0.777), and the cutoff value was 252.5 pg/mL with a sensitivity of 65.1% and specificity of 69.6%. Based on the above cutoff values, univariate and multivariate logistic regression analyses were performed to calculate the odds ratios (OR) for the PLGF levels. After adjustment for potential confounding factors, low PLGF concentrations still significantly increased the risk of discordant fetal growth (monochorionic twin pregnancy: adjusted OR: 7.039, 95% CI: 2.798-17.710, P < 0.001; dichorionic twin pregnancy: adjusted OR: 4.279, 95% CI: 2.572-7.120, P < 0.001).
CONCLUSIONS: A low maternal second-trimester PLGF level is considered a remarkable risk factor and potential predictor of discordant fetal growth. This finding provides a complementary screening strategy for the prediction of discordant fetal growth and offers a unique perspective for the subsequent research in this field.

OBJECTIVE: Hepatic arterial buffer response (HABR) is an important defence mechanism for maintaining liver blood flow. It is suspected that HABR is active in monochorionic diamniotic twins (MCDA) with twin-to-twin transfusion syndrome (TTTS) where donor compensates a setting of volume depletion and the recipient an overload. The present study investigates whether in TTTS, HABR is active in donor and/or recipient individually and try to determine if the activation of HABR is a direct response to TTTS.
METHODS: Hepatic artery (HA) peak systolic velocity (PSV) was measured in normal MCDA fetuses and TTTS. Correlation with relevant fetal Dopplers and characteristics were determined. Z-scores for HA-PSV (HAV-Z) were calculated and its association with TTTS in donors and recipients were determined as well as changes in HAV-Z after laser treatment.
RESULTS: In this study 118 MCDA were included, 61.9 % normal and 38.1 % TTTS. Of the TTTS 22 required laser treatment. A total of 382 scans were performed in normal group and 155 in TTTS. Our data demonstrates that in donors HAV-Z was 2.4 Z-scores higher compared to normal fetuses (β=2.429 95 % CI 1.887, 2.971; p<0.001) and after laser treatment HAV-Z reduced (β=-1.829 95 % CI -2.593, -1.064; p<0.001). There was no significant difference between recipients and normal (β=-0.092 95 % CI -0.633, 0.449; p=0.738).
CONCLUSIONS: HABR is active in TTTS, promoting an increased hepatic blood flow in donors. The activation is direct response to TTTS as shown by the reduction in HAV-Z after laser. This finding provides important insights into the pathophysiology of TTTS.

The Twin Reversed Arterial Perfusion (TRAP) Sequence is an extremely rare complication of monochorionic twin pregnancies, with one severely malformed twin (the \"acardiac\") lacking autonomous placental blood supply and being perfused by the co-twin (the \"pump\"), through arterio-arterial (and sometimes also veno-venous) vascular anastomoses located on the placental surface. The prognosis is poor: mortality is 100% in the acardiac twin because of its severe malformations and about 50-55% in the pump twin, mainly due to heart failure and prematurity. So, the goal of perinatal management of the TRAP twin pregnancy is to deliver a healthy and near-term pump twin without heart failure or fetal hydrops. Intuitively, the earlier the diagnosis, the better the outcome. Herein, we report two cases of monochorionic monoamniotic (MCMA) twin pregnancies complicated by the TRAP Sequence, which are of interest since the objective of early diagnosis was achieved by means of transvaginal and 3D ultrasound, two techniques which revealed themselves as being useful to this purpose but are underused in the literature. The second aim of this study is to provide an overview of literature data about the diagnosis, prognosis establishment, and management of this rare condition, which are still debated and unclear due to negligible poor-quality evidence.

BACKGROUND: The optimal approach and therapy method for the acardiac twin with a reverse arterial perfusion sequence has not yet been established. The aim of this study was to determine the clinical practice patterns among international fetal therapy units in their management of these cases.
METHODS: A survey was sent to fetal centers across the world via email between December 2020 and December 2021.
RESULTS: Responses were obtained from 77% contacted centers. The most frequent ultrasound variables used in the evaluation of twin reverse arterial perfusion sequence include echocardiographic assessment of the pump twin and umbilical artery Doppler waveforms in the acardiac and pump twins, in 90% and 80% of the centers, respectively. Most centers in Europe and Latin America propose an in utero intervention in all cases. Most centers in Europe and Latin America prefer interstitial laser ablation, whereas radiofrequency ablation (RFA) is preferred in North America. The earliest gestational age for an intervention is on mean 13 weeks in Europe, which is earlier than the other geographic areas (p = 0.001).
CONCLUSIONS: Most centers agreed that antenatal evaluation should include echocardiography along with the UA Doppler waveform measurements, and the most frequently used interventions were interstitial laser ablation or RFA at a median between 14 and 26 weeks.

OBJECTIVE: To compare outcomes of monochorionic diamniotic (MCDA) twin pregnancies by in vitro fertilization (IVF) vs. spontaneously conceived counterparts.
METHODS: Retrospective comparison. Data about MCDA twin pregnancies, conceived spontaneously or by IVF, attending the Twin Pregnancy Care Unit of Sant\'Anna Hospital in Turin (Italy) between January 1st 2010 and March 31st 2022, were collected retrospectively. Obstetric, fetal, and neonatal outcomes of MCDA twin pregnancies by IVF were compared to those of spontaneously conceived counterparts. Data were described by univariate and multivariate analysis.
RESULTS: 541 MCDA twin pregnancies were included in the study, among which 45 conceived by IVF and 496 spontaneously conceived. Women with IVF twins were older than those who conceived spontaneously (36.7 ± 5.7 vs. 32.1 ± 5.2 years; p<0.001). No significant difference in the prevalence of pregnancy complications between the two groups was found, except for an increased incidence of hypertensive disorders among IVF pregnancies (17.8 vs. 8.5 %; p=0.039), which resulted nonsignificant after adjusting for maternal age and parity (aOR 1.9, 95 % CI 0.8-4.6). Data about 1,046 live born babies (90 conceived by IVF and 956 spontaneously) were also collected: perinatal outcomes did not differ between the two groups.
CONCLUSIONS: Our results suggest that MCDA twin pregnancies following IVF are not at increased risk of adverse outcomes compared to spontaneous MCDA twin pregnancies.

Maternal cardiac function plays a crucial role in placental function and development. The maternal hemodynamic changes in twin pregnancy are more pronounced than those in singleton pregnancy, presumably due to a greater plasma volume expansion. In view of the correlation between maternal cardiac and placental function, it is plausible that chorionicity could influence maternal cardiac function. The aim of this study was to compare the longitudinal maternal hemodynamic changes between uncomplicated dichorionic (DC) and monochorionic (MC) twin pregnancies and in comparison to singleton pregnancies.
Included in the study were 40 MC diamniotic and 35 DC diamniotic uncomplicated twin pregnancies. These were compared with a group of 294 healthy singleton pregnancies from a previous cross-sectional study. All participants underwent a hemodynamic evaluation using an Ultrasound Cardiac Output Monitor (USCOM®), at three different stages in pregnancy (11-15 weeks, 20-24 weeks and 29-33 weeks). The following parameters were recorded: mean arterial pressure (MAP), stroke volume (SV), stroke volume index (SVI), heart rate, cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI), stroke volume variation, Smith-Madigan inotropy index (INO) and potential-to-kinetic-energy ratio (PKR).
In the first trimester, DC and MC twin pregnancies showed lower MAP, SVR and PKR and higher CO and SV in comparison to singleton pregnancy. In the second trimester, maternal CO (8.33 vs 7.30 L/min, P = 0.03) and CI (4.52 vs 4.00 L/min/m2 , P = 0.02) were significantly higher in MC compared with DC twin pregnancy. In the third trimester, compared with in singleton pregnancy, women with MC twin pregnancy showed significantly higher PKR (24.06 vs 20.13, P = 0.03) and SVRI (1837.20 vs 1698.48 dynes × s/cm5 /m2 , P = 0.03), and significantly lower SV (78.80 vs 88.80 mL, P = 0.01), SVI (42.79 vs 50.31 mL/m2 , P < 0.01) and INO (1.70 vs 1.87 W/m2 , P = 0.03); these differences were not observed between DC twin and singleton pregnancies.
Maternal cardiovascular function undergoes significant change during uncomplicated twin pregnancy and chorionicity influences maternal hemodynamics. In both MC and DC twin pregnancy, hemodynamic changes are detectable as early as the first trimester, showing higher maternal CO and lower SVR compared with singleton pregnancy. In DC twin pregnancy, the maternal hemodynamics remain stable during the rest of pregnancy. In contrast, in MC twin pregnancy, the rise in maternal CO continues in the second trimester in order to sustain the greater placental growth. There is a subsequent crossover, with a reduction in cardiovascular performance during the third trimester. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

OBJECTIVE: Hepatic arterial buffer response (HABR) is an important regulatory process for hepatic blood flow. Its activity has been described in some fetal adverse conditions but in twin-to-twin transfusion syndrome (TTTS) it is unknown if such response is present. The aim of this study is to test the hypothesis that HABR operates in monochorionic diamniotic twins (MCDA) with TTTS.
METHODS: Hepatic artery pulsatility index (PI) and peak systolic velocity (PSV) were measured prospectively in 64 MCDA pregnancies. 43 without TTTS (group 1) and in 21 pregnancies with TTTS (group 2). We calculated ratios for PI (HAPI-ratio) and PSV (HAV-ratio) between recipient and donor in group 2 or bigger and smaller fetus in group 1 and compared groups. The association of HAV-ratio and HAPI ratio with TTTS, relation with other fetal Dopplers and reliability of measurement by a single operator were investigated.
RESULTS: HAV-ratio and HAPI-ratio appears to be independent from fetal Dopplers, estimated weight and gestational age. In group 2, HAV-ratio is lower than group 1 (p<0.001, 95% CI 0.443-0.643). In group 1 the mean HAV-ratio is 1.014 (±0.021) while in group 2 is 0.47 (±0.035). HAPI-ratio is lower in group 2 than in group 1 although this difference was not significant (p=0.066, 95% CI -0.007-0.231). A good reliability of measurements of hepatic artery PSV and PI was demonstrated by intraclass correlation coefficient analysis (ICC 0.971 95% CI 0.963-0.977, p<0.001 and ICC 0.694 95% CI 0.596-0.772, p<0.001, respectively).
CONCLUSIONS: Monochorionic pregnancies with TTTS are associated with lower HAV-ratios. This could be explained by an active HABR.

To evaluate the prevalence, subtypes and postnatal outcomes of congenital heart defects (CHD) in a cohort of monochorionic diamniotic (MCDA) twin pregnancies complicated by selective fetal growth restriction (sFGR), and to compare this population with a cohort of uncomplicated MCDA pregnancies evaluated during the same period.
This was a retrospective analysis of all consecutive MCDA pregnancies referred between 2009 and 2018, including those complicated by sFGR (Group A) and those without complications (Group B). All neonates delivered in our center were screened for CHD before discharge. Discharge letters for all those delivered elsewhere were retrieved. Pregnancies with complications other than sFGR and those without perinatal follow-up were excluded. Pregnancies in Group A were divided into three types according to the Gratacós system of sFGR classification.
A total of 870 MCDA twin pregnancies were included: 296 in Group A and 574 in Group B. In Group A, the prevalence of CHD was 3.7% (22/592 twins), with no significant difference in CHD frequency between the three types of sFGR (Type I, 3.7%; Type II, 3.2%; Type III, 4.2%; P = 0.55). Of four Type-III sFGR pregnancies with CHD, one had pulmonary stenosis (PS) in the larger twin and isolated coarctation of the aorta in the smaller cotwin, and three had PS in the larger twin only. No Type-III sFGR pregnancies in which only the smaller twin was affected by CHD were observed. Of 11 CHD cases in the larger twin, 10 (91%) were right ventricular outflow tract abnormalities (RVOTA), and one (9%) was a ventricular septal defect. In the smaller twins, 11 cases of CHD were observed, covering a broad spectrum of cardiac abnormalities. In Group B, the CHD prevalence was 1.1% (13/1148 twins), which was similar to that in the general population, according to the EUROCAT registry for the same period and geographical area of the study (0.96%; P = 0.579). The CHD prevalence was significantly higher in Group A compared with Group B (3.7% vs 1.1%; P = 0.0002; odds ratio, 3.57 (95% CI, 1.78-7.22)). In all pregnancies with CHD in the study population, the anomaly was discordant.
In MCDA twin pregnancy, sFGR was associated with a three-fold higher prevalence of CHD. Women with such pregnancies should be referred to a tertiary care hospital for pre- and postnatal cardiac evaluation, treatment and long-term follow-up. In larger twins, the only major CHD observed was RVOTA, while a broad spectrum of CHD was noted in smaller twins. The higher risk of CHD in MCDA pregnancies appears to be due to the typical complications of the monochorionic pregnancy, rather than to the monochorionic nature of the pregnancy itself. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.