Ultrasound diagnosis of placental and umbilical cord anomalies in singleton pregnancies resulting from in-vitro fertilization.

INTRODUCTION: placental anomalies can affect fetal and maternal outcome due to severe maternal hemorrhage potentially resulting in hysterectomy and cord accident including abruption that can determine fetal damage or death. The aims of our study are to determine if the rate of placental and umbilical cord anomalies are more common in IVF singleton pregnancies compared to spontaneous pregnancies; to evaluate the role of ultrasound in screening for these anomalies and to investigate if oocyte donor fertilization is an additional risk factor for the development of these anomalies. METHODS: this was a prospective cohort study involving two tertiary centers. Patients with a singleton pregnancy conceived with IVF and patients presenting with a spontaneous conception were recruited between 1st May 2019 to 31st March 2021. A total of 634 pregnancies were enrolled in the study. All patients underwent similar antenatal care, which included ultrasound examinations at 11-14, 19-22 and 33-35 weeks. Ultrasound findings of placental and/or umbilical cord abnormalities were recorded using the same protocol for both groups and confirmed after birth. RESULTS: IVF pregnancies had a significantly higher risk of low-lying placenta, placenta previa, bilobed placenta and velamentous cord insertion (VCI) compared with spontaneous pregnancies. In the heterologous subgroup there was a significant increased incidence of placenta accreta spectrum (PAS) disorders than in spontaneous pregnancies. All these anomalies were identified prenatally on ultrasound imaging and confirmed at birth. DISCUSSION: IVF pregnancies in general and those resulting from donor oocyte in particular are at higher risk of placental and umbilical cord abnormalities compared to spontaneous pregnancies. These anomalies can be diagnosed accurately at the mid-trimester detailed fetal anomaly scan and our findings support the need for a targeted ultrasound screening of these anomalies in IVF pregnancies.

Greater estimated fetal weight and birth weight in IVF/ICSI pregnancy after frozen-thawed vs fresh blastocyst transfer: prospective cohort study with novel unified modeling methodology.

OBJECTIVE: To compare, using a unified approach, standardized estimated fetal weight (EFW) trajectories from the second trimester to birth and birth-weight (BW) measurements in in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies obtained after frozen-thawed vs fresh blastocyst transfer (BT). METHODS: This was a secondary analysis of a prospective longitudinal cohort study performed at the Fetal Medicine and Obstetric Departments of San Raffaele Hospital in Milan, Italy, from January 2016 to December 2020. Eligible for inclusion were singleton viable gestations conceived by autologous IVF/ICSI conception after fresh or frozen-thawed BT that underwent standard fetal biometry assessment at 19-41 weeks and had BW measurements available. All ultrasound assessments were performed by operators blinded to the employment of cryopreservation. Patients with twin gestation, significant pregestational disease, miscarriage, major fetal abnormalities and use of other types of medically assisted reproduction techniques were excluded. EFW and BW Z-scores and their trajectories were analyzed using general linear models (GLM) and logistic regression with a unified modeling methodology based on the Fetal Medicine Foundation fetal and neonatal population weight charts, adjusting for major confounders. Differences between prenatal EFW and postnatal BW centiles in the two groups were assessed and compared using contingency tables, χ2 test and conversion of prenatal to postnatal centiles. RESULTS: A total of 631 IVF/ICSI pregnancies were considered, comprising 263 conceived following fresh BT and 368 after frozen-thawed BT. A total of 1795 EFW observations were available (n = 715 in fresh BT group and n = 1080 in frozen-thawed BT group; median of three observations per patient). EFW and BW < 10th centile were significantly more frequent in the fresh than in the frozen-thawed BT group (P = 0.003 and P < 0.001, respectively). EFW and BW > 90th centile were significantly more frequent in the frozen-thawed vs fresh BT group (P = 0.034 and P = 0.002, respectively). GLM showed significantly decreasing EFW Z-scores with advancing gestational age (GA) in both groups. The effect of GA was assumed to be equal in the two study groups, as no significant interaction effect was found. Smoothed mean EFW Z-scores from 19 weeks of gestation to term and smoothed mean BW Z-scores were both significantly higher in the frozen-thawed compared with the fresh BT group (EFW Z-score, 0.70 ± 1.29 vs 0.28 ± 1.43; P < 0.001; BW Z-score, 0.04 ± 1.08 vs -0.31 ± 1.28; P < 0.001). Mean smoothed EFW Z-score values in the frozen-thawed vs fresh BT groups were 1.01 ± 0.12 vs 0.60 ± 0.08 at 19-27 weeks, 0.36 ± 0.07 vs -0.06 ± 0.04 at 28-35 weeks and -0.66 ± 0.01 vs -0.88 ± 0.02 at 36-41 weeks. Mean smoothed BW Z-score values in the frozen-thawed vs fresh BT groups were -0.80 ± 0.14 vs -1.20 ± 0.10 at 28-35 weeks and 0.22 ± 0.16 vs -0.24 ± 0.14 at 36-41 weeks. Assessment of EFW and BW concordance showed a significantly greater rate of postnatal confirmation of prenatally predicted small-for-gestational age (SGA) < 10th centile in the fresh compared with the frozen-thawed BT group (P < 0.001), whereas the rate of postnatal confirmation of large-for-gestational age (LGA) > 90th centile was significantly higher in the frozen-thawed vs the fresh BT group (P < 0.001). Logistic regression analysis showed that the smoothed rate of EFW < 3rd centile was about 6-fold higher in the fresh vs frozen-thawed BT group (P < 0.001), whereas the smoothed rates of EFW 90th -97th centile and > 97th centile were nearly double in the frozen-thawed compared with the fresh BT group (P < 0.05 and P < 0.001, respectively). CONCLUSIONS: Robust novel unified prenatal-postnatal modeling in IVF/ICSI pregnancies after frozen-thawed or fresh BT from 19 weeks of gestation to birth showed non-divergent growth trajectories, with higher EFW and BW Z-scores in the frozen-thawed vs fresh BT group. The mean EFW Z-scores in both IVF/ICSI groups were greater than those expected for natural conceptions, being highest in the midtrimester and decreasing with advancing gestation in both groups, becoming negative after 32 weeks in the fresh and after 35 weeks in the frozen-thawed BT group. Mean BW Z-scores were negative in both groups, with lower values in preterm fetuses, and increased with advancing gestation, becoming positive at term in the frozen-thawed BT group. IVF/ICSI conceptions from frozen-thawed as compared to fresh BT presented increased rate of LGA and reduced rate of SGA both prenatally and postnatally. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prospective longitudinal cohort study of uterine arteries Doppler in singleton pregnancies obtained by IVF/ICSI with oocyte donation or natural conception.

STUDY QUESTION: Do uterine arteries Doppler studies show different pulsatility index (UtA-PI) measurements in IVF/ICSI pregnancies with oocyte donation (OD) as compared to natural conceptions? SUMMARY ANSWER: In IVF/ICSI pregnancies with OD, UtA-PI is reduced by an average of about 40% as compared to pregnancies with natural conception. WHAT IS KNOWN ALREADY: OD pregnancies present worse pregnancy outcomes as compared to natural conception, particularly for increased incidence of pre-eclampsia (PE). Recent evidence shows that IVF/ICSI pregnancies with frozen blastocyst transfer also present higher prevalence of PE and 15% lower UtA-PI as compared to pregnancies after fresh blastocyst transfers. STUDY DESIGN, SIZE, DURATION: Prospective, longitudinal matched cohort study performed in the Fetal Medicine and Obstetric Departments of San Raffaele Hospital in Milan, between 2013 and 2018. The analysis is based on 584 Doppler observations collected from 296 women with different method of conception (OD n = 122; natural conception n = 174). PARTICIPANTS/MATERIALS, SETTING, METHODS: IVF/ICSI viable singleton pregnancies with OD and natural conception control pregnancies matched for BMI and smoking, performing repeated UtA-PI measurements at 11-34 weeks. Miscarriages, abnormalities, twins, significant maternal diseases and other types of ARTs were excluded. Log mean left-right UtA-PI was used for analysis with linear mixed model (LMM) and correction for significant confounders. Pregnancy outcome was also analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: Participants after OD were older and more frequently nulliparous (mean age: OD 43.4, 95% CI from 42.3 to 44.6; natural conception 35.1, 95% CI from 34.5 to 35.7; P-value < 0.001; nulliparous: OD 96.6%; natural conception 56.2%; P-value < 0.001). Mean pulsatility index was lower in OD (UtA-PI: natural conception 1.22; 95% CI from 1.11 to 1.28; OD 1.04; 95% CI from 0.96 to 1.12; P-value < 0.001). A significant effect of parity, gestational age (GA) modeled with a cubic polynomial and BMI was described in the LMM. The mean Log UtA-PI was on average 37% lower in OD as compared to natural conception pregnancies at LMM (P-value < 0.001). We also found a significant interaction between longitudinal UtA-PI Doppler and GA. Therefore, at 11 weeks' gestation the Log UtA-PI was 42% lower and, at 34 weeks, the differences reduced to 32%. GA at delivery and birth weight were statistically lower in OD group; however, birthweight centile was not statistically different. Preeclampsia was 11-fold more common in the OD group (0.6% and 6.6%, P-value = 0.003). No other significant difference in pregnancy outcome was shown in the study groups (gestational diabetes mellitus, small or large for GA). LIMITATIONS, REASONS FOR CAUTION: It was not possible to properly match for maternal age and to blind the assessment given the major differences between cohorts; however, we did not find significant within-groups effects related to maternal age. Future research is needed to reassess outcomes and correct them for maternal characteristics (e.g. cardiovascular function). WIDER IMPLICATIONS OF THE FINDINGS: This finding reproduces our previous discovery of lower UtA-PI in frozen as compared to fresh blastocyst transfer. The vast majority of OD is obtained by the use of cryopreservation. We speculate that increased uterine perfusion may be the physiological response to compensate dysfunctions both in the mother and in the placenta. STUDY FUNDING/COMPETING INTEREST(S): This is a non-funded study. The authors do not declare competing interest. TRIAL REGISTRATION NUMBER: N/A.

External validation of a simple risk score based on the ASPRE trial algorithm for preterm pre-eclampsia considering maternal characteristics in nulliparous pregnant women: a multicentre retrospective cohort study.

OBJECTIVE: To validate the performance of a first-trimester simple risk score based on the ASPRE trial algorithm for pre-eclampsia. DESIGN: Multicentre retrospective cohort analysis. SETTING: Four Italian hospitals. POPULATION: Unselected nulliparous women at 11-13 weeks of gestation from January 2014 through to January 2018. METHODS: Model performance was evaluated based on discrimination and calibration. MAIN OUTCOME MEASURES: Delivery before 37 weeks of gestation with a diagnosis of pre-eclampsia. RESULTS: Based on 73 preterm pre-eclampsia cases and 7546 controls (including 101 cases of late pre-eclampsia), the area under the receiver operating characteristics curve was 0.659 (95% CI 0.579-0.726). The sensitivity was 32.9% (95% CI 22.1-43.7) at a false-positive rate of 8.8%. The positive likelihood ratio was 3.74 (95% CI 2.67-5.23), the positive predictive value was 3.49% (95% CI 2.12-4.86%) and the negative predictive value was 99.3% (95% CI 99.1-99.5%). The sensitivity and positive likelihood ratio were approximately 40% lower than in the original study. The calibration analysis showed a good agreement between observed and expected risks (P = 0.037). Comparison with the Fetal Medicine Foundation (FMF) algorithm yielded a difference in the area under the curve of 0.084 (P = 0.007). CONCLUSIONS: In our Italian population, the simple risk score had a lower performance than expected for the prediction of preterm pre-eclampsia in nulliparous women. The FMF algorithm applied to the same data set resulted in a better prediction. TWEETABLE ABSTRACT: Simple risk score predicts preterm pre-eclampsia in Italy.

Hypoxic events during non-obstetric abdominal surgery in pregnant women.

OBJECTIVE: Every year 0.5-2% of women undergo non-obstetric surgery in pregnancy. Hypoxic events with short-term and long-term consequences are one of the most frequent complications in surgery. There is only limited data available regarding the impact of these events. This review aims to analyze the current literature on hypoxic events occurring in non-obstetric abdominal surgery in pregnant women, focused on maternal and fetal outcomes. MATERIALS AND METHODS: We performed a non-systematic review of the literature, through a PubMed search using the key words "hypoxemia", "non-obstetric surgery", "surgical procedures", "pregnancy", "pregnant women" and "outcome". RESULTS: There is little data available regarding maternal and fetal outcomes after hypoxic episodes during non-obstetric surgery in pregnancy. In these cases, conservative intrauterine resuscitation maneuvers or immediate delivery should be taken into account. Perimortem cesarean section can be lifesaving for both mother and fetus when maternal collapse is non responsive to resuscitation procedures. Inaccurate information regarding maternal and fetal outcomes is due to the lack of robust data and the heterogeneity of the causes underlying maternal respiratory complications during surgery. CONCLUSIONS: Non-obstetric surgery during pregnancy must be performed when indicated. An expert multidisciplinary team, composed of obstetricians, surgeons, and anesthesiologists need to be included, giving appropriate attention to the physiological changes of respiratory, cardiovascular, and gastrointestinal system that occur during pregnancy. The shortest operative time and peri-operative assistance should be ensured. Complications, such as hypoxic events in pregnant patients need adequate assistance. Multidisciplinary cooperation, continuous training and simulation for anesthesiology and resuscitative procedures can guarantee this.

Impact of TRREMS on symptoms of obstructed defecation due to rectocele: predictive factors and outcomes.

BACKGROUND: The aim of this study was to evaluate the impact of the transanal repair of rectocele and rectal mucosectomy with a single circular stapler (TRREMS) on the treatment of obstructed defecation due to rectocele and to identify the predictive factors for unsuccessful results. METHODS: Consecutive patients with obstructed defecation symptoms (ODS) associated with rectocele who had the TRREMS procedure were included. Each patient was assessed by echodefecography, manometry, and colonic transit time as well as the Cleveland Clinic constipation score (CCS) before therapy and at follow-up after 6 months. Reduction in the CCS score was calculated as a ratio. Factors correlated with a decrease in the CCS were analyzed in a univariate analysis. RESULTS: A total of 81 patients were included. Nineteen patients had postoperative complications that were not severe: 7 (8.6%) had tenesmus, 6 (7.4%) stenosis (4 treated with digital dilatation and 2 with endoscopic stricturectomy), 4 (4.9%) residual mucosal prolapse treated with rubber band ligation, 1 (1.2%) early bleeding, and 1(1.2%) thrombosis. Seventy-nine (97.5%) patients had a significant clinical response with significant reduction of the CCS constipation score from median 13 (range 17-10) to 4 (range, 8-2) (p = 0.0001); only 2 patients (2.5%) had an unsatisfactory response, complaining of straining and vaginal digitation during the evacuatory effort. Patients with anismus previously treated with biofeedback had a lower reduction ratio of the CCS score compared with patients without anismus (61.2 ± 2.8% versus 70.9% ± 1.5, p = 0.0006). There were no significant differences in the reduction of the CCS according to age, parity, type of delivery, previous hysterectomy, post-menopausal status, rectal mucosal prolapse and/or associated rectal intussusception, grade of rectocele and presence of complications. CONCLUSIONS: The TRREMS procedure significantly improved evacuation disorders in this study. Appropriate selection of patients is key for the success of this approach. Anismus even if previously treated with biofeedback, was the main predictive factor of unsuccessful treatment.

Post-abortion long-acting reversible contraception in a sample of Italian women: intrauterine device versus subdermal implant.

Long-acting reversible contraceptives (LARC) represent an especially effective kind of post-abortion contraception. We aimed at assessing satisfaction, discontinuation, efficacy, and tolerability associated with either levonorgestrel intrauterine device (L-IUCD), the copper intrauterine device (C-IUCD) and implant (IMP) after termination of pregnancy (TOP). We recorded baseline data about the patients and performed phone surveys at 3, 6 and 12 months after insertion to assess the bleeding profile. Furthermore, women were inquired about possible adverse events, satisfaction, and discontinuation at 12 months after insertion. LARC continuers (>12 months after TOP) were divided into three groups: L-IUCD (n = 47), C-IUCD (n = 6) and IMP (n = 36). Satisfaction rates among L-IUCD users were higher than among IMP users (100% vs. 72.2%, p < .05). A higher, yet not significant, share of patients decided to withdraw contraception in IMP group (3.6% in IUCD group and 12.2% in IMP group). The bleeding profile was significantly more favorable among L-IUCD users than among IMP users. Finally, the reported rate of treatment-associated adverse events did not differ significantly among the groups. L-IUCD insertion after TOP is associated with higher satisfaction and lower discontinuation rates than IMP. Such pattern could be attributed to a more favorable bleeding profile.

cAMP efflux from human trophoblast cell lines: a role for multidrug resistance protein (MRP)1 transporter.

Cyclic adenosine 3'-5'-monophosphate (cAMP) is a second messenger, which exerts an important role in the control of human first-trimester trophoblast functions. In the present study we demonstrate the existence of a mechanism that is able to extrude cAMP from trophoblast-derived cell lines, and show evidence indicating the involvement of multidrug resistance protein (MRP) 1, a transporter belonging to the ATP-binding cassette family, in cAMP egress. MRP1 is expressed in trophoblast cell lines and cAMP efflux is highly reduced by the MRP1 inhibitor, MK-571. In addition, interleukin-1beta and estrone are able to enhance MRP1 gene expression and influence extracellular cAMP concentration. The occurrence of a MRP1-dependent cAMP efflux is also shown in human first-trimester placenta explants. Extracellular cAMP could represent a source for adenosine formation, which in turn could regulate cAMP-dependent responses in placental tissue. Evidence is provided that adenosine receptor subtypes are present and functional in human trophoblast-derived cells. A role for cAMP egress mechanism in the fine modulation of the nucleotide homeostasis is therefore suggested.

Orofacial cleft in Southern Italy.

AIM: Cleft lip and palate or orofacial cleft (OFC) is one of the most common congenital malformations. The average incidence is around 1 every 1 000 live births. Different types of cleft lip and palate exist: cleft lip (CL), cleft lip and alveolus (CLA), cleft lip, alveolus and palate (CLP), and cleft palate only (CPO). Genetic studies on human samples have demonstrated that OFC has a heterogeneous genetic background and environmental factors also contribute to disclose this malformation. Because of the complex aetiology of OFC, studies on different and homogeneous populations can be useful in detecting environmental and genetic factors involved in the onset of this disease. The aim of the present study is to evaluate the relation between gender, type of cleft and affected side in a group of patients in Southern Italy. METHODS: Six hundred and fifty patients were enrolled in this retrospective study. They were operated at the Dental Clinic of the Second University of Naples in the period 1980-2002. Gender, type of cleft and affected side were analysed by means of the "Test for comparing two proportions". RESULTS: Among the analysed variables it was statistically demonstrated that overall CLP is more frequent in males as well as bilateral CLP whereas overall CPO is more frequent in females as well as right microform of CL. CONCLUSION: The identification of gender related subtypes of cleft is in accordance with data reported in similar studies on different populations and confirms that OFC is an heterogeneous disease even in a homogeneous ethnic group.

Correlation among amniotic fluid index (AFI), cesarean section rate, and labor length in inducted pregnancies beyond 41 weeks' gestation with unfavorable cervix.

This paper evaluated how the pregnancy after 41 completed weeks' gestation with amniotic fluid index (AFI) > 6 has a slower response to the prostaglandin E2 (PGE2) induction. Eighty-one post-term pregnancies (41 completed gestations' weeks) with unfavorable cervix were considered in this follow-up. Induction was performed by means of intracervical PGE2 gel (Dinoprostone 0.5 mg). After 12 hours, if the cervix was still unfavorable, then another gel administration followed. Cases that had oxytocin administration were excluded from the study. The median time of spontaneous delivery in the overall series was 25 hours, 14 minutes. We had 18 cases of cesarean section (22.2%). In the group of pregnancies with AFI > 6 (60 cases) and in the group with AFI < or =6 (21 cases), the median time of spontaneous delivery was 29 hours, 25 minutes and 23 hours, 39 minutes, respectively (p-value = 0.02). The rate of cesarean sections was 26.67 and 9.52, respectively in the two groups (p-value >0.05). Two out of four cases of cesarean sections for fetal distress belonged to the group of AFI > 6. All the 14 cases of cesarean section for dystocia belonged to the group with AFI > 6. Considering just patients who did not deliver within 12 hours (57 cases), median time of spontaneous delivery was 33 hours and 24 hours 40 minutes for group AFI > 6 (42 cases) and AFI < or =6 (15 cases), respectively (p-value = 0.0009). Thirty-one cases out of 57 had another PGE2 gel administration. Adjusted odds ratio was 0.33 (0.16-0.65, 95% C.I.) for AFI < or =6 versus AFI > 6.