Comparisons of cumulative live birth rates after embryo transfers at day 2/3 versus day 5/6: a French national study.

Research Question: Are there significant differences between cumulative live birth rates (CLBR) after short or extended embryo culture when comparisons are performed per cycle?

Design: This French national study included all IVF cycles performed from January 2016 to December 2019 with at least one cleaved embryo at day 2. The day 2/3 and day 5/6 groups were identified using the National Biomedicine Agency register. Only attempts involving the vitrification method were included.

Higher risk of pre-eclampsia and other vascular disorders with artificial cycle for frozen-thawed embryo transfer compared to ovulatory cycle or to fresh embryo transfer following fertilization.

Background: Risks of maternal morbidity are known to be reduced in pregnancies resulting from frozen embryo transfer (FET) compared to fresh-embryo transfer (-ET), except for the risk of pre-eclampsia, reported to be higher in FET pregnancies compared to -ET or natural conception. Few studies have compared the risk of maternal vascular morbidities according to endometrial preparation for FET, either with ovulatory cycle (OC-FET) or artificial cycle (AC-FET). Furthermore, maternal pre-eclampsia could be associated with subsequent vascular disorders in the offspring.

Clinical utility of periodic reinterpretation of CNVs of uncertain significance: an 8-year retrospective study.

Background: Array-CGH is the first-tier genetic test both in pre- and postnatal developmental disorders worldwide. Variants of uncertain significance (VUS) represent around 10~15% of reported copy number variants (CNVs). Even though VUS reanalysis has become usual in practice, no long-term study regarding CNV reinterpretation has been reported.

Fetal growth disorders following medically assisted reproduction: due to maternal context or techniques? A national French cohort study.

Research Question: What part do maternal context and medically assisted reproduction (MAR) techniques play in the risk of fetal growth disorders?

Design: This retrospective nationwide cohort study uses data available in the French National Health System database and focuses on the period from 2013 to 2017. Fetal growth disorders were divided into four groups according to the origin of pregnancy: fresh embryo transfer (n = 45,201), frozen embryo transfer (FET, n = 18,845), intrauterine insemination (IUI, n = 20,179) and natural conceptions (n = 3,412,868). Fetal growth disorders were defined from the percentiles of the weight distribution according to gestational age and sex: small and large for gestational age (SGA and LGA) if <10th and >90th percentiles, respectively.

Risk factors associated with preterm birth in singletons born after IVF: a national cohort study.

Research Question: What are the risk factors for prematurity other than intrauterine growth restriction in singletons after IVF?

Design: Data were collected from a national registry, based on an observational prospective cohort of 30,737 live births after assisted reproductive technology (fresh embryo transfers: n = 20,932 and frozen embryo transfer [FET] n = 9805) between 2014 and 2015. A population of not-small for gestational age singletons conceived after fresh embryo transfers and FET, and their parents, was selected. Data on a number of variables were collected, including type of infertility, number of oocytes retrieved and vanishing twins.

Putative founder effect of Arg338* AP4M1 (SPG50) variant causing severe intellectual disability, epilepsy and spastic paraplegia: Report of three families.

Bi-allelic variants affecting one of the four genes encoding the AP4 subunits are responsible for the "AP4 deficiency syndrome." Core features include hypotonia that progresses to hypertonia and spastic paraplegia, intellectual disability, postnatal microcephaly, epilepsy, and neuroimaging features. Namely, AP4M1 (SPG50) is involved in autosomal recessive spastic paraplegia 50 (MIM#612936).

Obstetrical outcomes and maternal morbidities associated with COVID-19 in pregnant women in France: A national retrospective cohort study.

Background: To the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic.

Methods And Findings: We conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births ≥22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI).

Endometriosis and assisted reproductive techniques independently related to mother-child morbidities: a French longitudinal national study.

Research Question: Does endometriosis increase obstetric and neonatal complications, and does assisted reproductive technology (ART) cause additional risk of maternal or fetal morbidity?

Design: A nationwide cohort study (2013-2018) comparing maternal and perinatal morbidities in three groups of single pregnancies: spontaneous pregnancies without endometriosis; spontaneous pregnancies with endometriosis; and ART pregnancies in women with endometriosis.

Results: Mean maternal ages were 30.0 (SD = 5.

Do in vitro fertilization, intrauterine insemination or female infertility impact the risk of congenital anomalies in singletons? A longitudinal national French study.

Study Question: Do IVF, IUI or female infertility (i.e. endometriosis, polycystic ovary syndrome [PCOS] and primary ovarian insufficiency [POI]) lead to an increased risk of congenital anomalies in singletons?

Summary Answer: After multivariable adjustments, the increased risks of congenital defects associated with IUI were no longer significant, but the underlying maternal infertility presented a potential emental risk, in addition to the risk associated with IVF.

Reproductive technologies, female infertility, and the risk of imprinting-related disorders.

Background: Epidemiological studies suggest that singletons born from assisted reproductive technologies (ART) have a high risk of adverse perinatal outcomes, specifically for imprinting disorders. Because ART processes take place at times when epigenetic reprogramming/imprinting are occurring, there is concern that ART can affect genomic imprints. However, little is currently known about the risk of imprinting defects according to the type of ART or the type of underlying female infertility.

Assessment of chimerism and immunomodulation to prevent post-transplantation relapse in childhood acute myeloblastic leukemia: is it the right approach?

Relapse of acute myeloblastic leukemia (AML) after first allogenic hematopoietic stem-cell transplantation (allo-HSCT) is a fatal complication. Sixty-five children transplanted for AML were included in a prospective national study from June 2005 to July 2008 to explore the feasibility of preemptive immune modulation based on the monitoring of blood chimerism. Relapse occurred in 23 patients (35%).

Familial pancreatic adenocarcinoma: A retrospective analysis of germline genetic testing in a French multicentre cohort.

The rate of genetic diagnosis of French patients with familial pancreatic ductal adenocarcinoma (PDAC) is not known. We report germline genetic testing data from 133 index cases meeting criteria for familial pancreatic cancer (FPC) as well as 87 'FPC-like' index cases who did not fulfilled strict FPC definition but were evocative for a PDAC predisposition. The overall rate of genetic diagnosis (in BRCA1, BRCA2, CDKN2A, and ATM genes) was 8.

Duplication of 10q24 locus: broadening the clinical and radiological spectrum.

Split-hand-split-foot malformation (SHFM) is a rare condition that occurs in 1 in 8500-25,000 newborns and accounts for 15% of all limb reduction defects. SHFM is heterogeneous and can be isolated, associated with other malformations, or syndromic. The mode of inheritance is mostly autosomal dominant with incomplete penetrance, but can be X-linked or autosomal recessive.

Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy.

Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of AP3B2 in 86 unrelated individuals with EOEE led to the identification of an additional family.

Haematological spectrum and genotype-phenotype correlations in nine unrelated families with RUNX1 mutations from the French network on inherited platelet disorders.

Background: Less than 50 patients with FPD/AML (OMIM 601309) have been reported as of today and there may an underestimation. The purpose of this study was to describe the natural history, the haematological features and the genotype-phenotype correlations of this entity in order to, first, screen it better and earlier, before leukaemia occurrence and secondly to optimize appropriate monitoring and treatment, in particular when familial stem cell transplantation is considered.

Methods: We have investigated 41 carriers of RUNX1 alteration belonging to nine unrelated French families with FPD/AML and two syndromic patients, registered in the French network on rare platelet disorders from 2005 to 2015.

GENESIS: a French national resource to study the missing heritability of breast cancer.

Background: Less than 20% of familial breast cancer patients who undergo genetic testing for BRCA1 and BRCA2 carry a pathogenic mutation in one of these two genes. The GENESIS (GENE SISter) study was designed to identify new breast cancer susceptibility genes in women attending cancer genetics clinics and with no BRCA1/2 mutation.

Methods: The study involved the French national network of family cancer clinics.

Pyrimidine 5'-nucleotidase deficiency associated to a polymalformative syndrome.

A pyrimidine 5'-nucleotidase deficiency in an adult is reported. Interestingly, the P5'N-1 deficiency was associated to a polymalformative syndrome and was characterized by a chronic, pancytopenic evolution with concomitant dyserythropoiesis.

A pure familial 6q15q21 split duplication associated with obesity and transmitted with partial reduction.

Familial transmission of chromosome 6 duplications is rare. We report on the first observation of a maternally-inherited pure segmental 6q duplication split into two segments, 6q15q16.3 and 6q16.

Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk.

To determine if the at-risk single-nucleotide polymorphism (SNP) alleles for colorectal cancer (CRC) could contribute to clinical situations suggestive of an increased genetic risk for CRC, we performed a prospective national case-control study based on highly selected patients (CRC in two first-degree relatives, one before 61 years of age; or CRC diagnosed before 51 years of age; or multiple primary CRCs, the first before 61 years of age; exclusion of Lynch syndrome and polyposes) and controls without personal or familial history of CRC. SNPs were genotyped using SNaPshot, and statistical analyses were performed using Pearson's χ(2) test, Cochran-Armitage test of trend and logistic regression. We included 1029 patients and 350 controls.

WWOX and severe autosomal recessive epileptic encephalopathy: first case in the prenatal period.

WWOX has been recently implicated in autosomal recessive spinocerebellar ataxia type 12 (SCAR12) and severe early-onset epileptic encephalopathy (EOEE). By array comparative genomic hybridization, we identified a 0.6 Mb homozygous deletion in 16q23.

Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.

Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008.