Is the rabbit a natural model of fetal growth restriction? Morphological and functional characterization study using diffusion-weighted MRI and stereology.

INTRODUCTION: Rabbits are routinely used as a natural model of fetal growth restriction (FGR); however, no studies have confirmed that rabbits have FGR. This study aimed to characterize the fetoplacental unit (FPU) in healthy pregnant rabbits using diffusion-weighted MRI and stereology. A secondary objective of the study was to describe the associations among findings from diffusion-weighted MRI (DW-MRI), fetal weight measurement and histological analysis of the placenta. METHODS: Pregnant rabbits underwent DW-MRI under general anesthesia on embryonic day 28 of pregnancy. MR imaging was performed at 3.0 T. The apparent diffusion coefficient (ADC) values were calculated for the fetal brain, liver, and placenta. The placenta was analyzed by stereology (volume density of trophoblasts, the maternal blood space and fetal vessels). Each fetus and placenta were weighed. Two groups of fetuses were defined according to the position in the uterine horn (Cervix group versus Ovary group). RESULTS: We analyzed 20 FPUs from 5 pregnant rabbits. Fetuses and placentas were significantly lighter in the Cervix group than in the Ovary group (34.7 ± 3.7 g vs. 40.2 ± 5.4 g; p = 0.02). Volume density analysis revealed that the percentage of fetal vessels, the maternal blood space and trophoblasts was not significantly affected by the position of the fetus in the uterine horn. There was no difference in ADC values according to the position of the fetus in the uterine horn, and there was no correlation between ADC values and fetal weight. DISCUSSION: The findings of a multimodal evaluation of the placenta in a rabbit model of FGR suggested is not a natural model of fetal growth restriction.

Perinatal outcomes between immediate vs deferred selective termination in dichorionic twin pregnancies with fetal congenital anomalies: a French multicenter study.

BACKGROUND: Because selective termination for discordant dichorionic twin anomalies carries a risk of pregnancy loss, deferring the procedure until the third trimester can be considered in settings where it is legal. OBJECTIVE: To determine whether perinatal outcomes were more favorable following deferred rather than immediate selective termination. STUDY DESIGN: A French multicenter retrospective study from 2012 to 2023 on dichorionic twin pregnancies with selective termination for fetal conditions, which were diagnosed before 24 weeks gestation. Pregnancies with additional risk factors for late miscarriage were excluded. We defined 2 groups according to the intention to perform selective termination within 2 weeks after the diagnosis of the severe fetal anomaly was established (immediate selective termination) or to wait until the third trimester (deferred selective termination). The primary outcome was perinatal survival at 28 days of life. Secondary outcomes were pregnancy losses before 24 weeks gestation and preterm delivery. RESULTS: Of 390 pregnancies, 258 were in the immediate selective termination group and 132 in the deferred selective termination group. Baseline characteristics were similar in both groups. Overall survival of the healthy co-twin was 93.8% (242/258) in the immediate selective termination group vs 100% (132/132) in the deferred selective termination group (P<.01). Preterm birth <37 weeks gestation was lower in the immediate than in the deferred selective termination group (66.7% vs 20.2%; P<.01); preterm birth <28 weeks gestation and <32 weeks gestation did not differ significantly (respectively 1.7% vs 0.8%; P=.66 and 8.26% vs 11.4%; P=.36). In the deferred selective termination group, an emergency procedure was performed in 11.3% (15/132) because of threatened preterm labor, of which 3.7% (5/132) for imminent delivery. CONCLUSION: Overall survival after selective termination was high regardless of the gestational age at which the procedure was performed. Postponing selective termination until the third trimester seems to improve survival, whereas immediate selective termination reduces the risk of preterm delivery. Furthermore, deferred selective termination requires an expert center capable of performing the selective termination procedure on an emergency basis if required.

Assisted reproductive technology in France: The reproductive rights of LGBT people.

BACKGROUND: In 2021, France authorized ART with sperm donor for female couples and single women. OBJECTIVES: We summarize here the possibilities of ART among LGBT people in France to date, pointing out the main restrictions for LGBT reproductive rights, requiring future legislative changes. RESULTS: Despite the latest modification of the French bioethics laws which notably opens ART to female couples, French legislation still excludes most LGBT people from parenthood through ART, especially gay men and transgender people in most cases. Surrogacy, ROPA, co-parenting and directed sperm donation are banned. CONCLUSIONS: Legalize ROPA and overcome gender issues for trans people are necessary. A French model of surrogacy is to be considered.

Perinatal outcomes of severe, isolated intrauterine growth restriction before 25 weeks' gestation: A retrospective cohort study.

OBJECTIVE: To evaluate the perinatal outcome associated with severe and isolated intrauterine growth restriction (IUGR) diagnosed before 25 weeks and to describe factors related to fetal death. METHODS: This retrospective study included singleton pregnancies with an estimated fetal weight (EFW) ≤ 3rd centile between 21 + 0 and 24 + 6 weeks' gestation referred between 2013 and 2020. All fetuses with morphological or chromosomal abnormalities were excluded. We constituted three groups based on perinatal outcomes to highlight poor prognostic factors: live birth, fetal death and termination of pregnancies (TOP). RESULTS: We included 98 pregnancies with an overall survival rate of 61.2% (60/98). There were 63.2% (62/98) live births, 24.5% (24/98) TOP, and 12.2% (12/98) fetal death. Of the live births, 27.4% (17/62) of fetuses were born before 32 weeks, and two died in the neonatal period (2/62; 3.2%). The fetal death rate was higher with the presence of an EFW below the first percentile (83.3% of fetal death Vs 33.8% of live births; p = 0.002), Doppler abnormalities (83.3% of fetal death Vs 6.4% of live births; p<0.001), and oligoamnios (41.9% of fetal death Vs 11.3% of live births; p = 0.05). CONCLUSION: Severe growth restriction detected before 25 weeks was associated with poor perinatal outcomes. There were more often EFW <1st percentile, abnormal Doppler and oligoamnios in cases of fetal death compared to live births.

Genetic studies in isolated bilateral clubfoot detected by prenatal ultrasound.

OBJECTIVE: To evaluate the contribution of genetic investigations in case of isolated bilateral clubfoot detected by routine prenatal ultrasound. Pathogenic Copy Number Variations is about 3.9% in fetuses with isolated clubfoot (uni- or bilateral). We hypothesize that this rate could be higher in a homogenous group of fetuses with bilateral clubfoot. METHODS: This retrospective single-center study included all women referred to our fetal-medicine center between 2013 and 2020 after ultrasound detection of isolated bilateral clubfoot. Genetic counseling was offered in which the woman was offered an amniocentesis for CMA and targeted investigation for Prader-Willi Syndrome (PWS), Steinert's disease and Spinal Muscular Atrophy (SMA). RESULTS: 34 women were referred, 18 of them consented to undergo genetic studies by amniocentesis (18/34; 52.9%). Pathogenic copy number variations (CNVs) were found in 2/18 (11.1%) of cases. One of these CNVs was directly linked to the clubfoot pathology (a deletion in 5q31.1 containing PITX1 gene). Four fetuses (4/18, 22.2%) had variants of unknown significance (VUS). No PWS, SMA or Steinert's disease was found. No case diagnosed with isolated clubfoot prenatally had additional anomalies postnatally. CONCLUSIONS: In the case of bilateral isolated clubfoot detected at the antenatal ultrasound, invasive prenatal testing should be offered, and if accepted, a CMA should be done, as pathogenic variations were observed in up to 11.1% of women who got amniocentesis. The findings of this study do not support the systematic recommendation of molecular studies for PWS, SMA, Steinert's disease.

Magnetic Resonance Imaging Angiography of Physiological and Pathological Pregnancy Placentas Ex Vivo: Protocol for a Prospective Pilot Study.

BACKGROUND: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are 2 major pregnancy complications due to abnormal placental vasculogenesis. Data on whole fetoplacental vasculature are still missing; hence, these pathologies are not well understood. Ex vivo magnetic resonance imaging (MRI) angiography has been developed to characterize the human placental vasculature by injecting a contrast agent within the umbilical cord. OBJECTIVE: The primary objective of this study is to compare the placental vascular architecture between normal and pathological pregnancies. This study's secondary objectives are to (1) compare texture features on MRI between groups (normal and pathological), (2) quantitatively compare the vascular architecture between both pathological groups (pathological IUGR, and pathological PE), (3) evaluate the quality of the histological examination in injected placentas, and (4) compare vascularization indices to histological characteristics. METHODS: This is a prospective controlled study. We expect to include 100 placentas: 40 from normal pregnancies and 60 from pathological pregnancies (30 for IUGR and 30 for PE). Ex vivo MR image acquisition will be performed shortly after delivery and with preparation by injection of a contrast agent in the umbilical cord. The vascular architecture will be quantitatively described by vascularization indices measured from ex vivo MRI angiography data. Comparisons of vascularization indices and texture features in accordance with the group and within comparable gestational age will be also performed. After MR image acquisition, placental histopathological analysis will be performed. RESULTS: The enrollment of women began in November 2019. In view of the recruitment capacity of our institution and the availability of the MRI, recruitment should be completed by March 2022. As of November 2021, we enrolled 70% of the intended study population. CONCLUSIONS: This study protocol aims to provide information about the fetal side of placental vascular architecture in normal and pathological placenta through MRI. TRIAL REGISTRATION: Clinicaltrials.gov NCT04389099; https://clinicaltrials.gov/ct2/show/NCT04389099. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35051.

Thrombotic thrombocytopenic purpura and severe preeclampsia: a clinical overlap during pregnancy and a possible coexistence.

In pregnant women, Thrombotic Thrombocytopenic Purpura (TTP) mimics severe preeclampsia because of the overlapping of these symptoms. We report the case of a 28-years-old woman who presented severe thrombocytopenia (platelets at 34 G/L) at 31 gestational weeks. The day after, she showed anaemia, worsening thrombocytopenia (platelets at 6 G/L) and an isolated increase of AST (91 UI/L). Plasmapheresis was performed without improvement. Secondary, she presented hypertension and proteinuria at 15 g/24 hours and elevated liver enzymes (AST 116 UI/L). A cesarean section was performed on day four for suspected HELLP syndrome. We observed in postpartum a progressive increase of platelets and regression of hepatic cytolysis. The sFlt1/PlGF ratio was elevated at 855, the results of ADAMTS13 activity were below 5 %, and the ADAMTS13 gene was mutated. TTP and HELLP syndrome can co-exist and can complicate one another. TTP lead to placental malperfusion. Further studies are needed to confirm the diagnosis value of the sFlt-1/PlGF ratio in TTP pregnant women.

Utility of chromosomal microarray analysis for the exploration of isolated and severe fetal growth restriction diagnosed before 24 weeks' gestation.

OBJECTIVE: This study aimed to evaluate the utility of chromosomal microarray analysis (CMA), for the genetic exploration of isolated and severe intrauterine growth restriction (IUGR) diagnosed before 24 weeks gestation (WG). METHODS: This retrospective study included singleton fetuses diagnosed with severe IUGR without structural anomalies before 24 WG referred between 2013 and 2021 who underwent prenatal genetic analysis. IUGR was defined by estimated fetal weight ≤3rd centile for gestational age. Genetic analysis, including QF-PCR and CMA, was systematically offered as part of the etiologic evaluation. RESULTS: Of 101 referred fetuses, CMA and QF-PCR were performed in 67 fetuses. Among these 67 cases, a total of 10.5% (7/67) chromosomal abnormalities were detected. CMA detected three pathogenic copy number variants (CNV) (3/67, 4.5%) and three variants of unknown signification (VUS) (3/67, 4.5%). Karyotype detected one chromosomal abnormality. All of the QF-PCR were normal. Two fetuses with pathogenic CNV shows Doppler abnormalities. CONCLUSION: Our study found that in fetuses with severe, isolated, and very early-onset growth restriction, the rate of pathogenic CNV detected by CMA was 4.5%. Although this cohort is too small to draw a definitive conclusion, the presence of Doppler abnormalities couldn't exclude the possibility of genetic abnormalities.

Is cell-free fetal DNA testing a safe option for women in a high-risk population after combined first-trimester testing?

OBJECTIVES: Our study aimed to examine the relevance of cell-free fetal DNA (cfDNA) testing on the screening of chromosomal defects and the issue of pregnancies in patients with a risk over 1:50 after the first-trimester combined test. METHODS: This is a retrospective monocentric study. We included all consecutive patients with a singleton pregnancy between January 2015 and December 2020 attending our fetal medicine center because the estimated risk for trisomy 21 after the first-trimester combined screening was over 1:50. The patients could either choose to have invasive testing or cell-free DNA testing. We collected data about the patient, the tests results (cfDNA, karyotype) and the pregnancy outcome (born alive, medical termination, miscarriage or intrauterine fetal death). RESULTS: We included 98 patients with an estimated risk for trisomy 21 over 1:50. We found a total of 14 major chromosomal abnormalities (14/98; 14.3%), of which: thirteen trisomies 21 and one triploidy 69, XXY. A cfDNA testing was chosen by 34 (34/98; 34.7%) patients. Among the pathological results of invasive testing, 5 (5/64; 7.8%) couldn't be targeted by cfDNA testing. Two of them were placental mosaicism, one a triploidy 69, XXY, and two defects inherited from a parent and considered benign. There was no miscarriage linked to an invasive test in the population study. CONCLUSION: In our monocentric cohort, a third of the patients choose cfDNA in a case of a risk over 1:50 after combined testing. Even if this cohort is too small to draw definitive conclusions, cfDNA could be safe in a high-risk population after combined testing. None of the chromosomal abnormalities found at the karyotype and non-detectable by cfDNA was a loss of information that impacted pregnancy follow-up. Further study could explore the input of Genome-Wide cfDNA and chromosomal micro-array in this population.

Labor induction in indicated moderate to late preterm birth.

Introduction: The primary objective of this study was to evaluate the success of labor induction for indicated moderate and late preterm birth. As secondary objectives, the mode of delivery was assessed.Material and methods: This is an observational study conducted in a tertiary care unit between 2013 and 2015. All patients who underwent labor induction for indicated preterm birth between 32+0 and 36+6 weeks of gestation (as premature rupture of membranes, preeclampsia, intrauterine growth restriction, fetomaternal alloimmunization, or intrahepatic cholestasis) were included. The main outcome was the success of labor induction defined by repeated uterine contractions associated with cervical dilation >3 cm. The secondary outcomes were mode of delivery and neonatal outcomes.Results: Among 824 women who gave birth during the study period, 105 (12.7%) underwent induction of labor for indicated preterm birth. Labor induction was successful in 90.5% of cases (95/105), and 72.4% of the women (76/105) delivered vaginally. The success rate did not differ significantly in cases of moderate (32+0 to 33+6 weeks), compared with late (34+0 to 36+6 weeks) preterm birth (87.5 versus 90.7%, p = .56). The vaginal delivery rate was significantly lower in moderate compared to late preterm birth (37.5 versus 75.3%, p = .03).Conclusion: The success of labor induction and consecutive vaginal delivery were high in case of moderate and late preterm birth. Labor induction can be considered as an effective option for medical indications.

Variable phenotypic expression of Apert syndrome in monozygotic twins.

Apert syndrome in monozygotic twins can lead to different phenotypic expression of the disease in the two fetuses. Apert syndrome can be associated with congenital left diaphragmatic hernia and cleft palate.

Predictors of successful manual rotation for occiput posterior positions.

OBJECTIVE: To identify predictors of the success of manual rotation of fetuses in an occiput posterior position. METHODS: A prospective, observational, single-center study included all women with a singleton pregnancy at term with a fetus in an occiput posterior position for whom manual rotation was attempted from December 1, 2013, to April 30, 2015 at a tertiary care maternity unit in Nancy, France. Occiput posterior position was confirmed by ultrasonography, and success of manual rotation was defined by the occiput anterior position of the fetus after the attempt. RESULTS: Occiput posterior position was diagnosed in 233 (9.2%) of the 2522 deliveries during the study period and the majority of cases were managed successfully by manual rotation (167 [71.7%]). Factors associated with successful rotation were fetal engagement (adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.05-4.56), spontaneous labor (aOR 1.85, 95% CI 1.01-3.43), and no failure to progress (aOR 2.01, 95% CI 1.02-3.94). Successful manual rotation was associated with lower rates of cesarean (P<0.001) and instrumental (P<0.001) deliveries. CONCLUSION: Study findings suggested that manual rotation, especially after fetal engagement, succeeded more often when performed systematically than when it was attempted after failure to progress.