HLA-G and Recurrent Pregnancy Loss

Placentation is an immunological compromise where maternal immune system cells and trophoblastic cells interact to reach an equilibrium condition. Although the cross talk between the two systems is complex and not completely understood, Human Leukocyte Antigen G (HLA-G), expressed on trophoblastic cell surfaces, seems to be one of the main molecules involved in the modulation of both local and systemic maternal immune response. The prevalence of recurrent pregnancy loss (RPL), probably underestimated, is 5% of all women who achieve pregnancy, and about 40–60% percent of RPL cases are unexplained. There is an immunological analogy between allograft rejection and miscarriage, and the purpose of this review is to describe how the HLA-G pathway alterations are involved in disrupting the immunologic balance and in increasing the risk of recurrent pregnancy loss

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

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

Adverse perinatal outcome and placental abnormalities in pregnancies with major fetal congenital heart defects: A retrospective case‐control study

Objective The placental development has been shown to be compromised in pregnancies affected by fetal congenital heart defects (CHD). This study aimed to investigate the frequency of complications related to utero‐placental insufficiency in pregnancies with and without major CHD. Method This retrospective case‐control study was conducted at a Fetal Echocardiography Center in Milan. The following outcomes were compared between the two groups: preeclampsia (PE), small for gestational age (SGA), placental disorders and preterm birth (PTB). The logistic regression analysis was adjusted for maternal age, parity, co‐morbidities and mode of conception. Results The CHD group (n = 480) showed significantly increased incidence of PE (2.9% vs 0.9%; aOR, 6.50; 95% CI, 1.39‐30.41; P = .017) as compared to the control group (n = 456). Placental disorders occurred more frequently in the CHD than in controls, but the increased risk showed only a borderline significance (4.5% vs 3.3%; aOR, 2.56; 95% CI, 0.99‐1.02; P = .046). There was a significantly higher risk of SGA in CHD than in controls (8.7% vs 3.9%; aOR, 3.37; 95% CI, 1.51‐7.51; P = .003). PTB occurred in 65/477 (13.6%) cases and in 39/447 (8.7%) controls (P = .022) (aOR, 2.17; 95% CI, 1.24‐3.81; P = .007). Conclusion Major CHD are significantly associated with the risk of PE, SGA and PTB

Evaluation of uterine arteries doppler and estrogen milieu in oocyte donation pregnancies

Introduction: The number of oocyte donation (OD) cycles have dramatically increased. While OD pregnancies face increased risks of obstetrical complications, especially pregnancy-induced hypertension and pre-eclampsia (PE), little is known about the physiology and the physiopathology of placentation. Method: We performed a prospective cohort study to analyze uterine arteries Doppler Pulsatility index (PI) and serum maternal 17 \u3b2 \u2013 estradiol at 11+0-13+6 weeks\u2019 gestation. Three groups of singleton pregnancies were studied: OD, in vitro fertilization pregnancies with autologous oocytes from fresh cycles (Autologous IVF) and spontaneous pregnancies. Outcomes were collected to include only physiological pregnancies. Results: The analysis by weeks showed a decreased uterine arteries PI between 11 and 13+6 weeks with a similar trend in all groups, but mean uterine artery PI at 11-13+6 weeks were significantly lower in OD recipients compared to Spontaneous Pregnancies and Autologous IVF (1.415 (DS 0.486) vs. 1.679 (DS 0.456) vs. 1.706 (DS 0.481) - p < 0.05). In spontaneous pregnancies,maternal serum levels of 17 \u3b2 \u2013 estradiol grows between 11 and 13+6 weeks, with mean level of 2423 pg/ml at 11.5 weeks, 2521 pg/ml at 12.5 weeks and 4654 pg/ml at 13.5 weeks. Interestingly, in the same cohort we found a higher value in female fetuses with a mean of 3204 pg/ml (DS 1634) compared to the mean value of male fetuses of 2436 pg/ml (DS 1170) with a ratio female/male of 17 \u3b2 \u2013 estradiol maternal serum concentration of 1,31 (IC95%: 1.04 \u2013 1.65). Maternal serum levels of 17 \u3b2 \u2013 estradiol in OD - oocyte recipients were significantly lower than in IVF and spontaneous pregnancies (1705.33 (DS 380.61) vs. 2121.50 (DS 1387.62) vs. 2844.93 (1516,29) p < 0.05). Conclusion: Mean uterine artery PI and 17-\u3b2 estradiol at 11-13+6 weeks were significantly lower in OD recipients compared to Spontaneous Pregnancies and Autologous IVF. Oocyte donation has a significant impact on placentation in the first trimester of pregnanc

Risk of spontaneous preterm birth in singleton pregnancies conceived after IVF/ICSI treatment: meta-analysis of cohort studies

Objective: Preterm birth (PTB) is more common in pregnancies conceived by in-vitro fertilization (IVF) as compared with those conceived naturally. However, the extent to which this is attributed to spontaneous labor or to iatrogenic indications has not been determined. The aim of this study was to quantify the risk of spontaneous PTB (sPTB) in singleton pregnancies resulting from IVF or intracytoplasmic sperm injection (ICSI) treatment as compared with that in spontaneously conceived pregnancies. Methods: An electronic search of PubMed/MEDLINE, Scopus and Web of Science to September 2017 and manual search of reference lists identified articles comparing the risk of sPTB in IVF/ICSI vs spontaneously conceived singleton pregnancies. Inclusion criteria were singleton conception with IVF/ICSI, PTB defined as delivery before 37 weeks' gestation and cohort design with clear distinction between spontaneous and indicated PTB. The primary outcome was sPTB < 37 weeks. Relevant secondary outcomes were also analyzed, including sPTB < 34 and < 32 weeks, preterm prelabor rupture of membranes, stillbirth, perinatal mortality, neonatal sepsis, respiratory distress syndrome and gastrointestinal morbidity. A meta-analysis provided the estimation of risk of sPTB in IVF/ICSI pregnancies. Results: In total, 674 records were identified from the search, of which 15 met the inclusion criteria and were included in the meta-analysis. A pooled crude analysis of the primary outcome generated a total sample size of 61 677 births, including 8044 singletons conceived after IVF/ICSI and 53 633 conceived spontaneously. A pooled crude data analysis showed a significant increase in the incidence of sPTB < 37 weeks in singleton IVF/ICSI pregnancies compared with those conceived spontaneously (810/8044 (10.1%) vs 2932/53 633 (5.5%); odds ratio (OR), 1.75; 95% CI, 1.50\u20132.03; I2 = 39%). A subgroup analysis of studies matching for maternal age and parity confirmed the finding (OR, 1.63; 95% CI, 1.30\u20132.05; I2 = 33%). A pooled crude analysis of secondary outcomes showed a significant increase in the incidence of sPTB < 34 weeks in pregnancies conceived after IVF/ICSI compared with those conceived spontaneously (37/1012 (3.6%) vs 24/1107 (2.2%); OR, 1.78; 95% CI, 1.03\u20133.08; I2 = 6%) and did not show any significant difference for any of the other secondary outcomes analyzed. The quality of evidence, rated using the GRADE criteria, was low for the outcome sPTB < 37 weeks and very low for sPTB < 34 weeks. Conclusions: The risk of sPTB in singleton pregnancies resulting from IVF/ICSI is significantly greater than that in spontaneously conceived singletons. These findings should be interpreted with caution given the low quality of the available evidence. Copyright \ua9 2017 ISUOG. Published by John Wiley & Sons Ltd

Nuchal translucency measurement, free &#946;-hCG and PAPP-A concentrations in IVF/ICSI pregnancies : systematic review and meta-analysis

So far, data on the effect of assisted reproductive technologies (ART) on the components of first trimester combined screening for Down syndrome are still controversial. A systematic search of the literature was performed in order to identify the effect of ART, particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with fresh embryo transfer, on the nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A measurements. Moreover, a meta-analysis and a descriptive graphical representation of the ratios between ART and spontaneous pregnancies (controls) values of median of the multiple of median (m0MoM) were performed. Free beta-human chorionic gonadotrophin test showed slightly higher values in the ICSI group than controls (RR\ua0=\ua01.09, 95%CI: 1.03\u20131.16) but not in the IVF group (RR\ua0=\ua01.03, 95%CI: 0.94\u20131.12). Pregnancy-associated plasma protein-A values for IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI 0.85, 0.80\u20130.90; 0.82, 0.74\u20130.89 and 0.83, 0.79\u20130.86, respectively). The nuchal translucency measurement did not show any statistical differences between study groups (IVF and ICSI) and controls (RR\ua0=\ua01.00, 95%CI: 0.94\u20131.08 and RR\ua0=\ua01.01, 95%CI: 0.97\u20131.05, respectively). These results may be due to alterations in the placentation of ART pregnancies. Differentiating further subgroups of ART pregnancies may explain the differences in biomarker concentrations, in prenatal behavior and in obstetric outcomes between ART and spontaneous pregnancies

Neurodevelopmental outcome of children with spina bifida aperta repaired prenatally vs postnatally: systematic review and meta-analysis

OBJECTIVE: To assess the neurodevelopmental outcome of children with spina bifida aperta (SBA) treated prenatally as compared to those treated postnatally. METHODS: We performed a systematic review of the literature in PubMed/MEDLINE, EMBASE, Web of Science and The Cochrane Library, comparing the neurological outcome of infants with SBA treated prenatally vs postnatally. Only randomized controlled trials (RCTs) and non-randomized prospective controlled studies were included. The primary outcome assessed was neurodevelopmental impairment at the age of 1 year or later. Secondary outcomes were preterm birth, need for ventriculoperitoneal (VP) shunt by 12 months of age, absence of signs of hindbrain herniation at the first postnatal magnetic resonance imaging (MRI) evaluation and independent ambulation evaluated at 30 months. RESULTS: Of 11 359 studies identified through the electronic search, six met the inclusion criteria and were assessed in full text and two, one RCT and one prospective cohort study, were ultimately included in the meta-analysis. Sensitivity analysis did not show any difference between the outcomes of the RCT alone and those of the pooled RCT and prospective cohort study. This allowed neurodevelopmental assessment of 213 children between 14 and 53 months of age. Neurodevelopment was assessed by the Bayley Scales of Infant Development II (BSID-II) mental development index corrected for chronological age, with a cut-off of ≥ 70 (representing no more than 2 SD below the mean). The presence of neurodevelopmental impairment was similar between children who underwent prenatal (25/105 (23.8%)) and those who had postnatal (30/108 (27.8%)) repair of SBA (odds ratio (OR), 0.82 (95% CI, 0.43-1.56); P = 0.54), although the risk of prematurity was higher in the prenatal-repair group (OR, 17.62 (95% CI, 7.60-40.87); P < 0.0001). For every two fetuses operated on before birth, there was, compared with those operated on after birth, one additional premature birth (number needed to harm = 2 (95% CI, 1-3)). The need for VP shunt placement by 12 months of age was lower in the prenatal-repair group (45/109 (41.3%)) than in children that had postnatal repair (93/112 (83.0%); OR, 0.14 (95% CI, 0.08-0.26); P < 0.0001). Data on neurodevelopmental impairment in children with a shunt were available only for patients from the prenatal-surgery group of the RCT; in this subgroup, the likelihood for impairment was similar between children who did (7/39 (17.9%)) and those who did not (4/48 (8.3%)) have shunt placement (P = 0.21). At first postnatal MRI evaluation, no signs of hindbrain herniation were detected in 28/88 (31.8%) children who were operated on prenatally compared with 4/89 (4.5%) who had postnatal repair (OR, 9.45 (95% CI, 3.12-28.64); P < 0.0001). Independent ambulation at 30 months was achieved by 41/109 (37.6%) children who underwent prenatal repair compared with 21/111 (18.9%) who had postnatal repair (OR, 2.59 (95% CI, 1.39-4.86); P = 0.003). CONCLUSION: The risk of neurodevelopmental impairment in infants with SBA was similar between those who underwent prenatal and those who had postnatal surgical repair, despite an increased risk of prematurity in the prenatally repaired group. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.status: publishe

Congenital heart defects in IVF/ICSI pregnancy : systematic review and meta-analysis

OBJECTIVE: There is no consensus in current practice guidelines on whether conception by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) techniques is an indication for performing a fetal echocardiogram. The aim of the study was to assess whether congenital heart defects (CHD) occur more often in pregnancies conceived after IVF/ICSI as compared with those conceived spontaneously. METHODS: A systematic search for studies was conducted of PubMed/MEDLINE, EMBASE and Scopus from inception to September 2017. The search included the following medical subject heading (MeSH) terms alone or in different combinations: 'IVF', 'IVF/ICSI', 'ART pregnancy', 'assisted conception', 'birth defect', 'congenital heart defects' and 'congenital malformation or abnormalities'. Studies comparing neonatal incidence of CHD in pregnancies conceived after IVF/ICSI and those conceived spontaneously were included. Studies reporting on other types of assisted reproductive technology (ART) or lacking information concerning termination of pregnancy were excluded. Chromosomal abnormalities were excluded in all analyzed studies. A meta-analysis of selected cohort studies was conducted to estimate the pooled odds ratio (OR) with 95% CI using a random-effects model. Statistical heterogeneity among the studies was evaluated with the I2 statistic and Q-test. RESULTS: Forty-one studies were identified for review including six case-control and 35 cohort studies. Data of eight selected cohort studies were used for meta-analysis. A total of 25\u2009856 children conceived from IVF/ICSI techniques and 287\u2009995 children conceived spontaneously, involving both singleton and multiple gestations, were included in the analysis. Total CHD events were 337/25\u2009856 (1.30%) and 1952/287\u2009995 (0.68%) in the IVF/ICSI and spontaneous conception groups, respectively. The risk of CHD was significantly increased in the IVF/ICSI group as compared with the spontaneous conception group (pooled OR, 1.45; 95%\u2009CI, 1.20-1.76; P\u2009=\u20090.0001; I2 \u2009=\u200944%; P\u2009=\u20090.08). In the subgroup of singleton IVF pregnancies, a significant difference was also obtained (OR, 1.55; 95%\u2009CI, 1.21-1.99; P\u2009=\u20090.0005; I2 \u2009=\u200936%; P\u2009=\u20090.18) and also multiple confounding factors adjusted ORs showed statistical significance (pooled OR, 1.29; 95%\u2009CI, 1.03-1.60; P\u2009=\u20090.02; I2 \u2009=\u20090%; P\u2009=\u20090.43). CONCLUSION: Fetuses conceived with IVF/ICSI methods are at an increased risk of developing CHD compared with those conceived spontaneously. However, this finding deserves further investigation due to heterogeneity of both ART procedures and cardiac defects

An observational multicentre study on the efficacy and safety of assisted reproductive technologies in women with rheumatic diseases.

The aim was to determine whether assisted reproductive technologies (ARTs) confer additional risk in rheumatic patients (in terms of disease flare and fetal-maternal complications) and whether, if performed, their efficacy is affected by maternal disease