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Pregnancy is a high-risk situation in sickle cell patients, both for the mother and the foetus. It considerably increases the risk of an acute complication (vaso-occlusive crisis, acute chest syndrome, infection, thrombosis) of sickle cell disease. In addition, this condition increases the risk of placental vascular complications (in utero growth retardation, pre-eclampsia, retroplacental haematoma and in utero foetal death).

In this study, we aimed to analyze the value of annexin-A5 anticoagulant ratio (A5R) and non-criteria antibodies for the diagnosis of APS in patients with clinical seronegative APS. Three groups were defined, including 21 seronegative APS patients with unexplained obstetrical adverse events or thrombosis history, 15 confirmed APS patients with triple aPL positivity, and a control group of 20 healthy patients without any history of thrombosis or pregnancy complications. Seronegative APS patients have similar levels of A5R in comparison to healthy controls (202% [171%-238%] versus 191% [178%-221%]; p = 0.65), whereas triple-positive APS patients have significantly more reduced A5R in comparison to both seronegative and healthy patients (149% [138%-158%] versus 202% [171%-238%] and 191% [178%-221%], respectively, p 0.001). The non-criteria aPL were found in 24% of seronegative APS: anti-PE IgM in 3 cases (14%) and anti-PS/PT IgG and anti-PS/PT IgM in 1 (5%) case each. The frequency of non-criteria APL was significantly more frequent in comparison to healthy controls (p = 0.048). All triple-positive APS patients have at least one non-criteria aPL, and the non-criteria aPL were significantly more frequent in these patients compared to seronegative APS and healthy controls (p 0.001). Whereas A5R levels do not allow to discriminate seronegative APS from healthy controls, our results demonstrate that non-criteria aPL can help to APS diagnosis in clinical seronegative APS.Key points• Annexin-A5 resistance testing does not help for the diagnosis of seronegative APS.• The non-criteria antiphospholipid antibodies can contribute to APS diagnosis in patients without conventional antibodies.

Villitis of unknown etiology (VUE) is characterized by lympho-histiocytic infiltrates, which are predominant within the villous stroma. VUE can be of low grade i.e. affecting less than 10 contiguous villi or high grade with either patchy or diffuse subgroups (the later concerning more than 30 % of distal villi). Several other placental lesions could be associated with VUE, in particular in diffuse subgroups, such as diffuse perivillous fibrin deposition and chronic intervillositis. One of the most characteristic features of VUE is the late onset of fetal growth restriction after 32 weeks of gestation, and earlier detection of villitis should first raise an infectious origin. High grade VUE has been associated with fetal growth restriction, prematurity, fetal deaths, recurrent pregnancy loss, central nervous system injury and is characterized by relatively high risk of recurrence (25-50 %). Prospective and well-designed studies are necessary to determine the real prevalence of these adverse pregnancy events associated with VUE. Data about the management of VUE are extremely scarce and thus no recommendation based on the literature review could be actually done.

Introduction Recurrent miscarriages are defined as three or more early miscarriages before 12 weeks of gestation. The aim of this study was to describe a cohort of women with unexplained recurrent miscarriages, evaluate several potential biomarkers of immune origin and describe the outcome of pregnancies under immunomodulatory therapies METHODS: Women having a history of at least 3 early miscarriages without any etiology were recruited from 3 university hospitals. Results Among 101 women with recurrent miscarriages, overall, 652 pregnancies have been included in the analysis. Women which experienced miscarriages were older (33.3 ± 5.4 versus 31.9 ± 6.7; p = 0.03), with history of more pregnancies (4 (2-6) versus 3.5 (1-5.75); p 0.0008), and less frequently the same partner (406 (74%) versus 79 (86%); p=0.01). There was no difference in the level and frequencies of biomarkers of immune origin (NK, lymphocyte, gammaglobulins and blood cytokine levels and endometrial uNK activation status), except the higher rates of positive antinuclear antibodies in women with live birth (12 (13%) versus 36 (7%); p=0.03). Among the 652 pregnancies, 215 (33%) have been treated and received either aspirin/low weighted molecular heparin (LMWH) and/or combined to different lines of immunomodulatory treatment. Patients with pregnancy under treatment had a significantly higher rate of cumulative live birth rate that those with untreated ones (43.0% vs 34.8%; p = 0.04). When compared to patients with untreated pregnancies, patients with steroids during the pregnancy had twice more chances to obtain live birth (OR 2.0, CI95% 1.1 - 3.7, p = 0.02). Conclusions Unexplained recurrent miscarriages could have improved obstetrical outcome under immunomodulatory therapies and in particular steroids.

International audience; Objective: Severe preeclampsia may require the delivery of the placenta to avoid life-threatening complications for the mother. Before 26 weeks of gestation, this often results in perinatal death. A decrease in soluble fms-like tyrosine kinase 1 (sFlt1), an anti-angiogenic factor central to the pathophysiology of the maternal syndrome, has been reported after LDL- apheresis. The present study tested whether LDL-apheresis could be used to allow women with early and severe preeclampsia to reach a gestational age where the baby had a viable chance of survival.Study Design: A phase II prospective study. Adult women were included if they had very early (

INTRODUCTION The antiphospholipid syndrome (APS) (1) is defined by the development of vascular thrombosis, or pregnancy morbidity in the presence of persistent antiphospholipid antibodies (aPL). Antinuclear antibodies (ANA) can be detected in primary APS patients without any clinical systemic autoimmune disease. The presence of ANA antibodies could confer a specific phenotype in primary APS. OBJECTIVE To evaluate the characteristics of APS patients with antinuclear antibodies without other autoimmune disease (ANA positive APS patients) in comparison with primary APS without ANA or secondary APS patients with associated systemic lupus erythematosus (SLE). METHODS Clinical and biologic data from 195 APS were retrospectively collected and patients were classified as primary APS with positive ANA (ANA-positive APS), primary APS without any ANA (ANA-negative APS), and SLE-associated APS (SLE-APS). RESULTS Fourty patients (21%) were classified into ANA-positive APS group, 77 (39%) in ANA-negative APS and 78 (40%) in SLE-APS. In ANA-positive APS patients, 20 patients (51%) had arterial thrombosis, 14 (41%) had veinous thrombosis and 19% had obstetrical complications. There was no difference between the three groups for the frequency of thrombotic manifestations and obstetrical complications. ANA-positive APS patients had more non-criteria manifestations than ANA-negative APS (48% versus 25%; P≤0.01). ANA-positive APS had more triple aPL positivity (59% versus 18%; P

Introduction The effect of coronavirus disease (COVID-19) on pregnancy outcome in women with sickle cell disease (SCD) is unknown. Objectives To analyze the severity of the SARS-CoV-2 infection in pregnant women with SCD and its impact on pregnancy. Methods This retrospective cohort study included SCD pregnant women tested positive for COVID-19 between March 2020 – February 2021. The primary endpoint was the severity of the COVID-19 infection. Secondary endpoints were pregnancy complications and fetal outcomes. Results During the study period among 82 pregnant women with SCD, 8 have presented symptoms suggestive of COVID-19 and were tested positive. A common mild clinical presentation was observed in 6 women (75%), one woman was asymptomatic and one required oxygen. The latter was admitted to the Intensive Care Unit and a cesarean section was performed in the context of an ongoing vaso-occlusive crisis and acute chest syndrome together with incidental preeclampsia. Labor was induced in another patient who developed a vaso-occlusive crisis after COVID-19 remission. Fetal outcomes were good with an average Apgar score of 10 and normal umbilical blood pH at birth. Two newborns were small-for-gestational-age as expected on the ultrasound follow-up before occurrence of COVID-19. Conclusion COVID-19 infection in our population of pregnant women with SCD had typical presentation and rarely triggered a sickle cell crisis or other complications. Fetal outcomes were good and did not seem to be directly influenced by the SARS-CoV-2 virus. Further studies are required to confirm these observations as compared to the population of women with SCD without COVID-19 infection.

Introduction In retrospective cohort study of women with unexplained recurrent implantation failure (RIF) and miscarriage (RM), we analyzed the efficacy and safety of intralipid therapy to obtain a live birth. Patients and methods Women with unexplained RM and/or RIF were included from 2015 to 2018 from three French university hospitals. Results Among 187 women treated for unexplained recurrent miscarriages and implantation failures, 26 women with median age of 36 years (29−43) received intralipid therapy. Among these 26 women, 10 women with a median age of 33 years (31−40) had a history of spontaneous recurrent miscarriages, with a median of 5 (4–8) previous miscarriages. Live births occurred in 7 (70 %) pregnancies under intralipids and were significantly more frequent than in women with recurrent miscarriages who did not receive intralipid therapy (n = 20, p = 0.02). Age, number of previous miscarriages, and additional therapies did not significantly differ between the two groups. Among the 26 included women, 16 had a history of recurrent implantation failures, with median age of 37 years (29−43) and median 9.5 (3–19) embryo transfers. Clinical pregnancy occurred in 9 (56 %) women receiving intralipids after embryo transfers under intralipids among which 5 (55 %) resulted in a live birth. Comparing successful pregnancies under intralipids with those with fetal loss, no significant differences have been noted. Conclusion Intralipids could be an effective and safe therapy in women with unexplained recurrent miscarriages and infertility.

International audience; Background: Endometriosis is a multifactorial pathology dependent on intrinsic and extrinsic factors, but the immune deregulation seems to play a pivotal role. In endometriosis-associated infertility this could raise the benefit of immunomodulatory strategies to improve the results of ART. In this review, we will describe (1) sera and peritoneal fluid cytokines and immune markers; (2) autoantibodies; (3) immunomodulatory treatments in endometriosis with infertility.Methods: The literature research was conducted in Medline, Embase and Cochrane Library with keywords: "endometriosis", "unexplained miscarriage", "implantation failure", "recurrent implantation failure » and « IVF-ICSI », « biomarkers of autoimmunity", "TNF-α", "TNF-α antagonists", "infliximab", "adalimumab", "etanercept", "immunomodulatory treatment", "steroids", "intralipids", "intravenous immunoglobulins", "G-CSF", "pentoxyfylline".Results: Several studies analyzed the levels of pro-inflammatory cytokines in sera and peritoneal fluid of endometriosis-associated infertility, in particular TNF-α. Various autoantibodies have been found in peritoneal fluid and sera of infertile endometriosis women even in the absence of clinically defined autoimmune disease, as antinuclear, anti-SSA and antiphospholipid autoantibodies. In few uncontrolled studies, steroids and TNF-α antagonists could increase the pregnancy rates in endometriosis-associated infertility, but well-designed trials are lacking.Conclusion: Endometriosis is characterized by increased levels of cytokines and autoantibodies. This suggests the role of inflammation and immune cell deregulation in infertility associated to endometriosis. The strategies of immunomodulation to regulate these immune deregulations are poorly studied and well-designed studies are necessary.

ObjectiveTo compare characteristics, pregnancies and treatments during pregnancies of seronegative and seropositive antiphospholipid syndrome (APS), to analyse factors associated with obstetrical outcome.Patients and methodsInclusion criteria were: (1) thrombotic and/or obstetrical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies (APL); (3) at least one persistent non-conventional APL among IgA anticardiolipin antibodies, IgA anti-B2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-phosphatidylethanolamine G/M and anti-phosphatidylserine/prothrombin G/M antibodies. The exclusion criteria were: (1) systemic lupus erythematosus ( SLE) or SLE-like disease; and (2) other connective tissue disease.ResultsA total of 187 women (mean 33±5 years) with seronegative APS were included from 14 centres in Austria, Spain, Italy, Slovenia and France and compared with 285 patients with seropositive APS. Seronegative APS has more obstetrical rather than thrombotic phenotypes, with only 6% of venous thrombosis in comparison to seropositive APS. Cumulative incidence of adverse obstetrical events was similar in seronegative and seropositive APS patients, although higher rates of intrauterine deaths (15% vs 5%; p=0.03), of preeclampsia (7% vs 16%, p=0.048) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) were noted in seropositive APS. The cumulative incidence of adverse obstetrical events was significantly improved in treated versus untreated seronegative APS (log rankConclusionSeveral non-criteria APL can be detected in patients with clinical APS features without any conventional APL, with various rates. The detection of non-criteria APL and thus the diagnosis of seronegative APS could discuss the therapeutic management similar to seropositive APS, but well-designed controlled studies are necessary.

Objective To describe the course over time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in French women from the beginning of the pandemic until mid-April, the risk profile of women with respiratory complications, and short-term pregnancy outcomes. Methods We collected a case series of pregnant women with COVID-19 in a research network of 33 French maternity units between March 1 and April 14, 2020. All cases of SARS-CoV-2 infection confirmed by a positive result on real-time reverse transcriptase polymerase chain reaction tests of a nasal sample and/or diagnosed by a computed tomography chest scan were included and analyzed. The primary outcome measures were COVID-19 requiring oxygen (oxygen therapy or noninvasive ventilation) and critical COVID-19 (requiring invasive mechanical ventilation or extracorporeal membrane oxygenation, ECMO). Demographic data, baseline comorbidities, and pregnancy outcomes were also collected. Results Active cases of COVID-19 increased exponentially during March 1–31, 2020; the numbers fell during April 1–14, after lockdown was imposed on March 17. The shape of the curve of active critical COVID-19 mirrored that of all active cases. By April 14, among the 617 pregnant women with COVID-19, 93 women (15.1 %; 95 %CI 12.3–18.1) had required oxygen therapy and 35 others (5.7 %; 95 %CI 4.0–7.8) had had a critical form of COVID-19. The severity of the disease was associated with age older than 35 years and obesity, as well as preexisting diabetes, previous preeclampsia, and gestational hypertension or preeclampsia. One woman with critical COVID-19 died (0.2 %; 95 %CI 0−0.9). Among the women who gave birth, rates of preterm birth in women with non-severe, oxygen-requiring, and critical COVID-19 were 13/123 (10.6 %), 14/29 (48.3 %), and 23/29 (79.3 %) before 37 weeks and 3/123 (2.4 %), 4/29 (13.8 %), and 14/29 (48.3 %) before 32 weeks, respectively. One neonate (0.5 %; 95 %CI 0.01–2.9) in the critical group died from prematurity. Conclusion COVID-19 can be responsible for significant rates of severe acute, potentially deadly, respiratory distress syndromes. The most vulnerable pregnant women, those with comorbidities, may benefit particularly from prevention measures such as a lockdown.

Resume Contexte et problematique Le syndrome des antiphospholipides (SAPL) est defini par une thrombose ou une complication obstetricale (≥ 3 fausses couches spontanees ou une mort fœtale ou une prematurite

Chronic intervillositis is a rare condition, which is associated with severe obstetrical outcome and high recurrence rate. Obstetrical adverse events are intrauterine growth restriction, recurrent early miscarriages, intrauterine deaths and prematurity by placental insufficiency. The determination of the extension and the intensity of the chronic intervillositis are not currently standardized. High rates of recurrence have been described, but actually there is no reliable predictive biomarker. No treatment is currently validated, but the use of immunomodulatory drugs could be justified by the possible autoimmune or allo-immune origin. The treatment should be particularly discussed in patients with recurrent and severe obstetrical adverse events and in the presence of severe and massive histological lesions.

Resume Environ 1 a 3 % des femmes en âge de procreer presentent des fausses couches precoces recidivantes, definies par ≥ 3 pertes fœtales avant 14 semaines de gestation. Environ la moitie de ces fausses couches precoces inexpliquees pourraient etre en relation avec une cause genetique. Bien que le depistage preimplantatoire soit utilise en medecine de la reproduction dans de nombreux pays, cette technique est interdite en France en dehors du cadre precis du « diagnostic preimplantatoire », concernant les couples a risque de transmission de maladie genetique grave. Dans les autres cas, une reponse allo-immune du fait d’un defaut d’induction de tolerance vis-a-vis des antigenes paternels pourrait etre a l’origine de la perte fœtale, bien que l’on manque actuellement de marqueur disponible en routine pour affirmer l’origine immunitaire de la perte fœtale. Plusieurs traitements immunomodulateurs ont fait l’objet d’etudes ouvertes ou randomisees chez les patientes presentant des fausses couches precoces inexpliquees, parmi lesquels les corticoides, le G-CSF, les immunoglobulines, les intralipides et les antagonistes du TNF-α. Les donnees disponibles ne permettent pas actuellement de proposer des recommandations, mais des etudes sont necessaires pour determiner des strategies pour ces patientes.

Resume Le syndrome des antiphospholipides (SAPL) est defini par l’association des manifestations thrombotiques et/ou d’une morbidite obstetricale associees a la presence d’anticorps antiphospholipides persistants (APL). L’association de l’aspirine a dose antiagregante avec une heparine de bas poids moleculaire (HBPM) a dose prophylactique a permis d’ameliorer considerablement le pronostic obstetrical au cours du SAPL primaire obstetrical. Plusieurs facteurs pourraient etre associes a la survenue de complications obstetricales chez les patientes presentant un SAPL. L’existence d’une thrombose arterielle ou veineuse anterieure, d’un lupus associe, d’un SAPL avec un anticoagulant circulant (ACC) ou une triple positivite des antiphospholipides (ACC lupique avec un anticorps anticardiolipide et un anticorps anti-β2GP1) est associee a un mauvais pronostic obstetrical. En revanche, le SAPL obstetrical comportant des fausses couches precoces isolees est le plus souvent associe aux anticardiolipides isoles et son pronostic obstetrical est meilleur. Il faut noter qu’il n’y a pas de definition reellement etablie de SAPL obstetrical refractaire, qui pourrait etre defini par une perte fœtale malgre un traitement par aspirine et HBPM bien conduit, en l’absence d’autres etiologies retrouvees et la frequence de SAPL refractaire ainsi defini serait de 20–39 %. Plusieurs traitements associes a la combinaison aspirine–HBPM ont ete utilises dans le SAPL obstetrical tel que les corticoides, l’hydroxychloroquine, les immunoglobulines intraveineuses et les echanges plasmatiques, d’autres traitements tel que l’eculizumab ou les statines pouvant avoir egalement un interet clinique, bien que des etudes soient necessaires pour demontrer l’efficacite et la place de ces differentes strategies.

Introduction Le syndrome des antiphospholipides (SAPL) seronegatif constitue une nouvelle entite avec la presence de caracteristiques cliniques de SAPL, en l’absence d’anticorps antiphospholipides conventionnels. Patients et methodes Nous avons realise un appel a observation europeen de patientes avec au moins un critere clinique de SAPL obstetrical (criteres de Sydney), en l’absence d’anticorps antiphospholipides conventionnels mais avec la presence d’au moins un anticorps antiphospholipides non criteria parmi : anticorps anti-annexine V, anti-phosphatidylethanolamine (anti-PE), anti-prothrombine/phosphatidylserine (anti-PS/PT), et/ou anti-beta2-glycoproteine 1 Immunoglobuline A (anti-β2GpI IgA). Resultats Nous avons inclus 187 patientes issues de 12 centres universitaires europeens (Italie, Autriche, Espagne, France), d’un âge median de 32 ans [18–44], dont 80 % de femmes caucasiennes (n = 150). Au moins un critere clinique de SAPL (criteres de Sydney) etait present chez toutes les femmes, avec 35 % de patientes ayant presente au moins 3 fausses couches precoces (n = 66), 32 % ayant un antecedent d’au moins une mort fœtale in utero (n = 60), 23 % ayant un antecedent d’au moins une naissance prematuree avant 34 semaines d’amenorrhee (SA) liee a une eclampsie, preeclampsie severe ou insuffisance placentaire (n = 43). Neuf patientes avaient un antecedent de thrombose veineuse profonde (5 %). Les anticorps non conventionnels presents chez toutes les femmes etaient : des anticorps anti-annexine V dans 23 % des cas (n = 43), anti-PE dans 62 % (n = 56) (IgG pour 34 %, et IgM 76 %), des anti-PS/PT dans 52 % (n = 98) (IgG pour 67 % et/ou IgM pour 70 %) et anti-β2GpI IgA dans 2 % (n = 1). Vingt-huit pour cent de patientes presentaient une positivite de plusieurs antiphospholipides non criteria (n = 53). Au moins une grossesse apres la mise en evidence de ces anticorps est survenue chez 79 % des patientes (n = 148). Un traitement pendant la grossesse etait prescrit dans 86 % de cas (n = 127) par : aspirine seule (n = 37 ; 29 %) ; association d’aspirine et d’HBPM (n = 82 ; 65 %), corticotherapie a faible dose (n = 16 ; 13 %) et/ou hydroxychloroquine (n = 17 ; 13 %). Une grossesse vivante etait obtenue dans 57 % des cas (n = 84) avec un terme median de 38 SA. Une complication maternelle et/ou fœtale etait notee dans 38 % des grossesses (n = 57) : preeclampsie ou HELLP syndrome (n = 11 ; 7 %), retard de croissance intra-uterin (n = 5 ; 3 %), oligoamnios (n = 2 ; 1 %) et pertes fœtales (n = 37 ; 25 %) (causes maternelles anatomiques, infectieuses, hormonales ou materno-paternelles chromosomiques exclues), sans aucun cas de thrombose. Conclusion Le SAPL seronegatif est donc une reelle entite clinique associee aux anticorps antiphospholipides non criteria. Le pronostic obstetrical de ces patientes est impacte avec des complications maternofœtales pour plus d’un tiers des grossesses dans notre serie europeenne. Cette etude plaide pour la recherche systematique des anticorps antiphospholipides non criteria en cas de SAPL clinique seronegatif afin d’encadrer et de traiter au mieux les grossesses pour en ameliorer leur devenir. Des etudes prospectives sont necessaires pour confirmer et approfondir ces donnees.

We aimed to compare the proportion of peripheral blood natural killer (NK) cells (CD3–CD56+) and T-cell large granular lymphocytes (CD8+CD57+) during preconception in a homogenous group of women with unexplained well-defined recurrent miscarriage (RM) and repeated implantation failure (RIF) vs healthy controls in relation to pregnancy outcomes. This case–control study followed by a literature review and meta-analysis was conducted in three university hospitals. Patients and controls were consecutively recruited from December 2015 to October 2017. In total, 115 women were included in the study: 54 with RM, 41 with RIF and 20 healthy controls with ≥ 2 term births. Percentages of CD3–CD56+ and CD8+CD57+ cells and sub-populations of CD3–CD56+ cells did not differ between cases and controls. The results for women with subsequent miscarriage did not differ from those with live births. The meta-analysis of the literature showed higher NK-cell proportions in RM [mean difference 3.47 (95% CI 2.94–4.00); p

Introduction Le syndrome des anti-phospholipides (SAPL) est une pathologie auto-immune caracterisee par la presence d’au moins un evenement clinique (thrombose et/ou complication obstetricale) et la presence persistante d’anticorps antiphospholipides (APL). De nombreux patients remplissent le critere clinique malgre la negativite repetee de la recherche d’anticoagulant circulant ou des anticorps anti B2-GP1 ou anti-cardiolipine. Cette constatation a conduit a l’emergence du terme « syndrome des anti-phospholipides seronegatifs ». Des anticorps antiphospholipides, dit non conventionnels (APL NC) ont ete decrits, mais leur valeur diagnostique reste a ce jour peu evaluee. L’objectif de l’etude etait de decrire la prevalence des APL NC chez des patients presentant au moins un critere clinique du SAPL et de determiner la prise en charge et l’evolution. Patients et methodes Il s’agissait d’une etude retrospective ayant inclus tous les patients ayant eu une recherche d’APL NC entre le 01/01/2016 et le 31/05/2019. Tous les patients ont beneficie de la recherche d’APL conventionnels qui etaient negatifs. Les anticorps non conventionnels recherches etaient : anti-annexine V IgG et IgM, anti-phosohatidylethanolamide (PE) IgG et IgM, anti phosphatidyl/prothrombine (PS/PT) IgG et IgM. Resultats Au total 391 patients ont eu une recherche d’APL NC, parmi lesquels 275 patients (70 %) avaient un critere clinique SAPL et dont 137 patients (35 %) avaient au moins un APL NC positif. Ces APL NC etaient anti-annexine V (n = 21), anti-PE (n = 117), anti-PS/PT (n = 44). Les criteres cliniques positifs chez les 275 patients etaient une thrombose arterielle ou veineuse (n = 159), une complication obstetricale (n = 103), ou les deux (n = 13). La prevalence de thromboses ou de complications obstetricales etait comparable entre les groupes APL NC positifs (66 %) et APL NC negatifs (72 %), (p = 0,26). Les patients avec un APL NC etaient significativement plus jeunes (âge median 40 ans contre 42 ans chez les patients APL NC negatifs, p = 0,0082), plus frequemment des femmes (88 % contre 75 % chez les patients APL NC negatifs, p = 0,012), avec moins de facteurs de risque cardio-vasculaires (30 % vs 45 % respectivement, p = 0,007). En revanche il n’y avait pas de difference en termes de facteurs de risque de thrombose veineuse, ni difference de frequence de maladies auto-immunes associees. Dans notre serie, 172 patients presentaient au moins un episode de thrombose arterielle ou veineuse dont 46 (26 %) avaient un APL NC positif. Parmi ces patients avec APL NC positifs, 12 % ont presente au moins une rechute contre 40 % chez les patients APL NC negatifs (difference non significative, p = 0,1), alors que les durees de traitement apres le premier episode etaient comparables (mediane 18 et 16 mois respectivement, p = 0,76), ainsi que le nombre d’episode (medianes 1 et 1 respectivement, p = 0,21). Par ailleurs, 116 patientes presentaient au moins 1 critere obstetrical dont 49 (42 %) avaient une APL NC positif. Il n’y avait pas de difference significative entre les patientes APL NC positives et les patientes APL NC negatives en termes de nombre d’episode (medianes 4 et 4 respectivement, p = 0,47), de maladie auto-immunes associees (24 % et 20 % respectivement, p = 0,65), ou de facteur de risque cardio-vasculaires associes (22 % et 30 % respectivement, p = 0,39). Conclusion La recherche d’anticorps anti-phospholipides a permis d’identifier une population specifique, a predominance feminine, plus jeunes et presentant moins de facteurs cardio-vasculaires, par rapport aux autres patients. Cependant nous n’avons pas trouve d’association entre la positivite des APL NC et la probabilite de recidive de la maladie thrombotique ou obstetricale. Cette population pourrait faire l’objet d’etudes prospectives pour mieux connaitre son profil evolutif et les specificites de traitement necessaires.

To retrospectively evaluate the diagnostic performance of magnetic resonance (MR) imaging for the diagnosis of adnexal torsion in a series of patients with an equivocal adnexal mass at ultrasonography (US) in the context of acute or subacute pelvic pain.The institutional ethics committee approved the study and waived informed consent. All patients with acute or subacute pelvic pain who were undergoing MR examination for the exploration of an equivocal adnexal mass (January 2007 to December 2012) with surgical exploration or clinical and radiologic follow-up of at least 3 months were retrospectively included (n = 58). The prospective interpretations were recorded. Additionally, three radiologists who were blinded to the clinical, US, and surgical data retrospectively and independently reviewed MR images. Features associated with adnexal torsion were identified by using univariate and recursive partitioning multivariate analysis.Twenty-two patients (38%) had a diagnosis of adnexal torsion. The accuracy of MR imaging at the time of prospective interpretation was 80.6% (25 of 31 patients) and 85.1% (23 of 27 patients) in acute and subacute torsion, respectively. The accuracy of image interpretation by each retrospective reader was 83.9% (26 of 31 patients), 90.3% (28 of 31 patients), and 83.9% (26 of 31 patients) in the context of acute pelvic pain and 92.6% (25 of 27 patients), 88.9% (24 of 27 patients), and 81.5% (22 of 27 patients) in the context of subacute pelvic pain for readers 1, 2, and 3, respectively. At multivariate analysis, the whirlpool sign (odds ratio = 6.5 [95% confidence interval: 1.36, 31.0], P = .01) and a thickened tube (10 mm) (odds ratio = 8.2 [95% confidence interval: 1.2, 56.8], P = .03) were associated with adnexal torsion, with substantial interreader agreement (κ = 0.71-0.84 and 0.82-0.86, respectively). The presence of adnexal hemorrhagic content was associated with nonviable ovaries in seven of 10 patients (70%) and with viable ovaries in 12 of 45 patients (27%) (P = .009).MR imaging is an accurate technique for the diagnosis of adnexal torsion in patients who have an adnexal mass with acute or subacute pelvic pain.

Approximately 1 to 3% of women have recurrent early miscarriages, defined as ≥3 pregnancy losses before 14 weeks of gestation. The immune deregulation and tolerance rupture could be the origin of these miscarriages in at least 30% of these women. Chronic intervillositis of unknown etiology (CIUE) is a rare placental lesion characterized by intrauterine deaths, growth restriction and high recurrence rate. In cases with recurrent obstetrical adverse events and intrauterine deaths, we previously reported the benefit of hydroxychloroquine combination to prednisone. Even few data raised the potential value of TNF antagonists in early recurrent miscarriages, these cases show its potential value in the setting of recurrent refractory chronic intervillositis and unexplained miscarriages.

Introduction Adult onset Still’s disease is a rare affection classified among non-hereditary autoinflammatory diseases. We here report a case of AOSD revealed during pregnancy with a life-threatening presentation along with a review of 19 cases from literature. Case A 38-years old woman was treated in our department for diffuse systemic sclerosis and associated Sjogren syndrome. She was pregnant and presented with acute fever and arthralgias. Laboratory data revealed mild liver cytolysis but a large screening for infectious and auto-immune diseases was negative and hepato-biliar imaging was normal. Ferritin levels were at 41 000 ng/mL with glycosylated ferritin less than 5%. The diagnosis of AOSD was stated and because of persistent fever and polyarthralgias, after exclusion of active infection, steroids were started (prednisone 1 mg/kg) associated with colchicine, which allowed clinical remission and C-reactive protein significant decrease. Conclusion Pregnancy-revealed AOSD appears to be a specifical subset of the disease with a systemic course, flares on first and second trimester, obstetrical complications such as prematurity and IUGR sometimes leading to life-threatening situations requiring parenteral corticotherapy and intravenous immunoglobulins.

Introduction La maladie de Still est une pathologie rare classee parmi les maladies auto-inflammatoires non hereditaires. La presentation clinique peut aller d’une eruption pseudo-urticarienne avec arthralgies jusqu’a un tableau de syndrome d’activation macrophagique pouvant engager le pronostic vital. Les mecanismes physiopathologiques responsables restent indetermines mais semblent impliquer les interleukines 1b, 6 et 18. Plusieurs cas de maladie de Still revelee pendant la grossesse ont ete rapportes, sans que l’on sache s’il existe un sur-risque d’evenement obstetrical. Nous rapportons un cas de maladie de Still revele pendant la grossesse suivi d’une revue de 19 cas de la litterature. Observation Nous rapportons le cas d’une patiente de 38 ans, qui consulta dans le service en mai 2016 a 12 semaines de grossesse pour une fievre d’apparition recente sans autre symptome. Le bilan biologique realise revela une cytolyse hepatique moderee (ASAT et ALAT a 4xN), et un large bilan a la recherche d’une cause infectieuse ou auto-immune revient negatif. La fievre et la cytolyse regresserent spontanement en 3 jours. Deux mois plus tard, elle fut hospitalisee pour une fievre intense, une odynophagie et des douleurs abdominales. Le bilan retrouva une cytolyse hepatique plus marquee (ASAT et ALAT a 10xN) avec cholestase, elevation de la bilirubine conjuguee et syndrome inflammatoire avec CRP a 53 mg/L. Un dosage de la ferritine retrouva des valeurs moderement elevees a 657 ng/mL. Un bilan etiologique etendu a la recherche d’une cause infectieuse revint une nouvelle fois negative, les symptomes regresserent de nouveau sans traitement specifique. Un mois plus tard, a 28 semaines de grossesse, elle fut re-hospitalisee pour fievre et arthromyalgies, syndrome inflammatoire avec CRP a 163 mg/L, cytolyse hepatique a 2xN, avec une ferritinemie a 371 mg/L. Un scanner cervico-thoraco-abdomino-abdominal revela un epanchement pericardique modere non compressif ainsi qu’une hepatomegalie homogene. Devant la fievre persistante et les symptomes articulaires, apres exclusion d’une infection active, une corticotherapie d’epreuve fut debutee (Prednisone 1 mg/kg/jour) et permit une remission clinique et diminution du syndrome inflammatoire biologique. Au decours de la decroissance de la corticotherapie, a 12,5 mg/jour en association a la colchicine, les symptomes reapparurent et une immunotherapie a doses immunomodulatrices fut decidee. Juste avant la mise en route du traitement, la patiente developpa une agranulocytose attribuee a la colchicine, compliquee d’un sepsis severe a point de depart urinaire et une extraction fœtale fut decidee a 34 semaines de grossesse. La fievre et les arthralgies persisterent avec une cholestase et un syndrome inflammatoire majeurs (GGT 15xN, CRP a 320 mg/L), la ferritine s’eleva a 41,000 ng/mL et un dosage de la ferritine glycosylee revient inferieur a 5 %. Le diagnostic de maladie de Still put etre pose selon les criteres de Yamaguchi et de Fautrel, la corticotherapie reprise en association avec l’anakinra (100 mg/j) permettant une remission clinique et biologique rapide. La maladie de Still peut etre revelee par la grossesse comme rapporte pour la premiere fois en 1982. Nous avons rassemble 19 cas provenant de la litterature medicale. Les patientes avaient entre 19 et 38 ans (âge median 28,6). Parmi 18 grossesses, la premiere poussee de la maladie de Still survenait a 16,77 semaines de grossesse, et pour la majorite des patientes entre le premier et le deuxieme trimestre de grossesse. La presentation clinique associait arthromyalgies et arthrites, fievre irreguliere et pharyngite. Les taux de ferritinemie se situaient entre 1/311 et 41/424 ng/mL. La plupart des patientes recevaient une corticotherapie (n = 16/20), et deux furent traitees par immunoglobulines intraveineuses. Toutes les patientes avaient une forme systemique sans forme chronique articulaire. Il n’y avait pas de predominance particuliere entre les formes monocycliques et polycycliques. Les complications obstetricales etaient frequentes (n = 11/20) avec au premier plan des naissances prematurees (n = 10/20) parmi lesquelles 3 etaient dues a une rupture prematuree des membranes potentiellement imputable a la corticotherapie systemique. Trois naissances furent compliquees de retard de croissance intra-uterin, deux grossesses d’oligohydroamnios, et une de mort fœtale in utero. Conclusion La maladie de Still revelee par la grossesse semble etre une forme specifique associant une presentation systemique, des poussees aux premiers et deuxiemes trimestres de grossesse, des complications obstetricales comme la prematurite et des RCIU, engageant parfois le pronostic vital et necessitant corticotherapie systemique et immunoglobulines intraveineuses.

Introduction Les patients presentant les symptomes du syndrome des antiphospholipides (SAPL) sans repondre aux criteres biologiques de Sydney, c’est-a-dire en l’absence d’anticorps antiphospholipides (aPL), sont classes « SAPL seronegatifs ». D’autres marqueurs biologiques tels que les anticorps non conventionnels (anticorps anti-phosphatidylserine/prothrombine (aPS/PT), anti-phosphatidylethanolamine (aPE) ou anti-annexine-A5 (aA5)) ont montre un interet predictif du risque de thrombose. Par exemple, la presence d’aPE est un facteur de risque de fausse couche precoce, plus fort (OR = 4) que les anticorps anticardiolipine (aCL) et anti-β-2-Glycoproteine I (aβ2-GPI) et un facteur de risque independant de thrombose veineuse (OR = 6, p = 0,005). L’Annexine-A5, proteine au role majeur dans les mecanismes de fibrinolyse, d’apoptose, d’inflammation, forme a la surface cellulaire une couche protegeant les lipides des mecanismes activant la coagulation. Le test evaluant la resistance a l’activite anticoagulante de l’Annexine-A5 (R-A5) semble correle au nombre d’aPL du SAPL detectes. Rand et al. ont montre la correlation entre la multi-positivite des aPL, la diminution du ratio anticoagulant de l’Annexine-A5 (A5R) et le developpement d’evenements thrombotiques. La detection d’anticorps non conventionnels et la diminution du R-A5 pourraient etre de nouveaux outils diagnostics des cas de SAPL seronegatifs. Nous avons etudie l’interet de la valeur de l’A5R et des anticorps non conventionnels dans le diagnostic des SAPL seronegatifs. Patients et methodes De janvier 2016 a decembre 2017, trois groupes ont ete definis, comprenant 21 patients SAPL seronegatifs avec des manifestations thrombotiques ou obstetricales en accord avec les criteres de Sydney, 15 patients SAPL presentant les trois criteres biologiques appeles « SAPL triple-positifs » et un groupe controle de 20 patients sains sans antecedent thrombotique ou de complication obstetricale et sans presence d’anticorps antiphospholipides. Le R-A5 a ete decrit par Rand et al. en 2004. L’activite anticoagulante de l’Annexine-A5 est exprimee en ratio, A5R = temps de coagulation en presence d’Anx-A5/temps de coagulation en l’absence d’Anx-A5 × 100 %. Tous les sujets ont ete testes pour les anticorps non conventionnels (aA5, aPE, aPS/PT). Resultats Les patients SAPL seronegatifs ont des valeurs similaires de A5R au groupe controle : 202 % [171 %–238 %] versus 191 % [178 %–221 %] ; p = 0,65, alors que les patients SAPL triple-positifs ont une diminution significative de l’A5R en comparaison aux groupes SAPL seronegatifs et controles sains (149 % [138 %–158 %] versus 202 % [171 %–238 %] et 191 % [178 %–221 %], respectivement ; p Discussion Dans cette etude nous avons etudie l’interet du dosage des anticorps non conventionnels et du R-A5 dans le diagnostic des patients presentant la symptomatologie du SAPL sans critere biologique en l’absence d’etiologie retrouvee. Nous avons montre que les anticorps non conventionnels etaient significativement plus frequents dans le SAPL seronegatif et triple-positif. La sensibilite et la specificite restent a determiner sur une plus grande cohorte. Rodriguez-Garcia et al. [1] ont montre que les patients SAPL seronegatifs avaient une morbidite similaire aux patients SAPL. La prise en charge devrait donc etre identique chez ces patients SAPL seronegatifs. L’identification de nouveaux biomarqueurs est necessaire pour classer ces patients et retenir le diagnostic de SAPL. Notre etude confirme la diminution de l’A5R chez les patients triple-positifs. De plus, contrairement aux anticorps circulants de type lupique (ACC), nous n’avons observe aucun impact du traitement anticoagulant sur les valeurs de l’A5R. Par ailleurs aucun SAPL seronegatif ne presentait d’IgG/M aA5, or nous les avons observes chez 87 % des SAPL triple-positifs. La presence d’aA5 IgG/M chez les SAPL triple-positifs et a l’inverse leur absence chez les SAPL seronegatifs et chez les controles sains, pourrait expliquer les valeurs plus basses d’A5R chez les SAPL triple-positifs. Conclusion Pour conclure, bien que le R-A5 ne permette pas de differencier les SAPL seronegatifs des controles sains, les aPL non conventionnels peuvent nous aider pour leur diagnostic.

Introduction L’equilibre immunitaire est essentiel dans l’implantation embryonnaire et dans le maintien de la grossesse. La rupture de cet equilibre pourrait etre responsable d’echecs d’implantation (EI) et de fausses couches spontanees (FCS) inexpliquees a repetition. Parmi les cellules immunitaires impliquees, les lymphocytes Natural Killers (CD3-CD56 + ) et les grands lymphocytes granuleux T (CD3 + CD8 + CD57 + ) peuvent occuper une place importante. L’objectif de ce travail etait d’evaluer la frequence des lymphocytes CD3-CD56+ et T CD3 + CD8 + CD57+ sanguins en preconception chez les femmes presentant des FCS et des EI a repetition. Patients et methodes Le pourcentage des lymphocytes CD3-CD56 + et T CD3 + CD8 + CD57+ sanguins et les sous-populations des lymphocytes CD3-CD56+ immature (CD3-CD56brightCD16-), mature (CD3-CD56dimCD16 + ) et activee (CD3-CD56dimCD16 + CD57 + ) ont ete analyses par cytometrie en flux chez 54 femmes avec des FCS et 41 femmes avec des EI a repetition et compares aux 20 femmes temoins âgees de moins de 45 ans ayant eu ≥ 2 grossesses normales menees a terme. Resultats Les pourcentages des lymphocytes CD3-CD56+ et CD3 + CD8 + CD57+ n’etaient pas differents entre le groupe FCS ou EI et les controles (9,4 % [2,5–31,6], 9,4 % [4,3–29,3] et 10,6 % [3,4–20,2], (p = 0,43) et 5,4 % [0,4–14,4] et 4,3 % [0,0–18,4] vs 3,8 % [0,3–9,7], p = 0,22, respectivement). De la meme facon, la frequence des sous-populations de CD3-CD56+ n’etait pas differente entre le groupe FCS ou EI et les controles (CD3-CD56brightCD16- : 6,7 % [0,0–19,6], 8,1 % [0,0–23,0] et 5,8 % [2,0–18,9], p = 0,18 ; CD3-CD56dimCD16 + : 93,3 % [80,4–100,0], 91,9 % [77,0–100,0] et 94,3 % [81,1–98,0], p = 0,18 ; CD3-CD56dimCD16 + CD57 + : 48,6 % [17,7–85,0], 49,6 % [18,2–80,9] et 45,2 % [28,2–77,2], p = 0,75). Les resultats des femmes avec des fausses couches ulterieures n’etaient pas statistiquement differents des femmes ayant eu ulterieurement des naissances vivantes dans le groupe FCS et le groupe EI (9,8 % [3,2–31,6] vs. 9,4 % [4,1–15,6], p = 0,7 ; 7,8 % [5,2–26,6] vs. 9,6 % [4,4–18,8], p = 0,39, respectivement). Conclusion La proportion de lymphocytes CD3-CD56 + et CD3 + CD8 + CD57+ sanguins dans la periode pre-conceptionnelle ne reflete pas le risque d’echec d’implantation ou de fausse couche. D’autres etudes prospectives sont necessaires afin d’identifier des marqueurs sanguins fiables de desequilibre immunologique dans les FCS et EI a repetition.

Objective To investigate the gestational age-specific outcomes and the different etiologies of megacystis diagnosed at screening ultrasound. Methods A retrospective single-center study was conducted between 1989 and 2009. We identified all consecutive cases of megacystis prenatally diagnosed during routine ultrasound screening. Outcome, final diagnosis, and renal function were recorded. Results Eighty-four patients were included. An isolated lower urinary tract obstruction was observed in 38/84 (45.2%), ureterovesical reflux in 9/84 (10.7%), an associated congenital abnormality in 32/84 (38.1%) and a normal bladder in 5/84 (6%). Increased gestational age at diagnosis was correlated with an increased rate of live born children (P

We present here a rare case that involved the long-term coexistence of 2 mature, functional, and equilibrated immune systems in a single child after fetofetal transfusion between dizygotic twins. A dichorionic diamniotic pregnancy complicated by twin anemia-polycythemia sequence resulted in the demise of 1 twin. The detection of abnormal vessels on the dichorionic plate strongly suggested the existence of functional vascular anastomoses leading to blood chimerism in the survivor. Genetic, phenotypic, and immunologic analyses at 2 years revealed chimeric lymphoid and myeloid cells in the surviving twin, although no tissue mosaicism was detected, which indicates that early transfusion led to mutual immune tolerance.

To describe and analyze the benefit of immunomodulatory drugs for recurrent miscarriages and implantation failures. The literature research was conducted in Medline, Embase and Cochrane Library concerning recurrent miscarriages and implantation failures and steroids, progesterone, intralipids, TNF-α antagonists, G-CSF, hydroxychloroquine, intravenous immunoglobulins, endometrial scratching. Using meta-analysis, modest benefit was found for progesterone to obtain a live birth, with odds ratio at 1.38 (95% CI: 1.07-1.77) and significant heterogeneity (P = 0.01, I(2) = 78%). In early ≥3 miscarriages, patients treated by TNF-α antagonists (adalimumab or etanercept; n = 17) combined with low-dose aspirin, heparin and intravenous immunoglobulins have a live births of 71% (12/17), vs 19% with aspirin+heparin (4/21) (P = 0.0026). Sixty-eight patients with unexplained recurrent miscarriage were randomized to receive either G-CSF (filgastrim, Neupogen, 1 μ/kg/day SC, n = 35) after the ovulation until the 9th weeks of gestation or placebo (n = 33). Among patients treated with G-CSF, 29/35 (82.8%) have live birth and 16/33 (48.5%) of controls (P = 0.006). Among 200 women with recurrent miscarriages and implantation failure treated with intralipids, the pregnancy rate was 52%, with pregnancy ongoing/live birth rate at 91%. The physiopathological rational for immunotolerance failure in this topic raise the need to demonstrate the efficacy of immunomodulatory drugs, define the patients subsets and develop treatment strategies.

To investigate the gestational age-specific outcomes and the different etiologies of megacystis diagnosed at screening ultrasound.A retrospective single-center study was conducted between 1989 and 2009. We identified all consecutive cases of megacystis prenatally diagnosed during routine ultrasound screening. Outcome, final diagnosis, and renal function were recorded.Eighty-four patients were included. An isolated lower urinary tract obstruction was observed in 38/84 (45.2%), ureterovesical reflux in 9/84 (10.7%), an associated congenital abnormality in 32/84 (38.1%) and a normal bladder in 5/84 (6%). Increased gestational age at diagnosis was correlated with an increased rate of live born children (P0.01). No cases of megacystis diagnosed in the first trimester were born alive. When diagnosis of posterior urethral valves (PUV) was made in the third trimester, the ultimate survival rate was 11/13 (84.6%) compared with 3/12 (25%) for a diagnosis made in the second trimester (P = 0.02).Lower urinary tract obstruction is the main etiology of megacystis. Megacystis can also be part of more complex malformations. Outcome of megacystis detected in the first trimester is poor. PUV detected in the third trimester had a better overall survival rate than PUV detected in the second trimester.

We report the association of gigantomastia during pregnancy and a lactating adenoma in ectopic breast tissue of the vulva in a context of myasthenia in a 27-year-old primigravid woman. We discuss the pathophysiologic condition and management of gigantomastia that involves ectopic breast tissue during pregnancy.

Objective To report the fatal outcome of a woman with Turner syndrome (TS) undergoing assisted reproductive technology (ART). Design Case report. Setting Reproductive medicine center. Patient(s) A 33-year-old woman with TS. Intervention(s) Screening before oocyte donation and treatment of aortic dissection occurring at term pregnancy. Main Outcome Measure(s) Evaluation of cardiovascular risk. Result(s) After a normal cardiac screening, a woman with TS got pregnant as a result of oocyte donation. At 16 weeks of gestation, a bicuspid aortic valve was detected and associated with moderate aortic root dilation. Aortic dissection was diagnosed at 38 weeks of gestation, which required emergent cesarean delivery and aortic root replacement. Despite surgical treatment, early maternal death was recorded. Conclusion(s) Careful cardiac screening and close follow-up before and during pregnancy are necessary in patients with TS.

Background Preterm prelabor rupture of membranes (PPROM) before 34 weeks of gestation complicates 1% of pregnancies and accounts for one-third of preterm births. International guidelines recommend expectant management, along with antenatal steroids before 34 weeks and antibiotics. Up-to-date evidence about the risks and benefits of administering tocolysis after PPROM, however, is lacking. In theory, reducing uterine contractility could delay delivery and reduce the risks of prematurity and its adverse short- and long-term consequences, but it might also prolong fetal exposure to inflammation, infection, and acute obstetric complications, potentially associated with neonatal death or long-term sequelae. The primary objective of this study is to assess whether short-term (48 h) tocolysis reduces perinatal mortality/morbidity in PPROM at 22 to 33 completed weeks of gestation. Methods A randomized, double-blind, placebo-controlled, superiority trial will be performed in 29 French maternity units. Women with PPROM between 220/7 and 336/7 weeks of gestation, a singleton pregnancy, and no condition contraindicating expectant management will be randomized to receive a 48-hour oral treatment by either nifedipine or placebo (1:1 ratio). The primary outcome will be the occurrence of perinatal mortality/morbidity, a composite outcome including fetal death, neonatal death, or severe neonatal morbidity before discharge. If we assume an alpha-risk of 0.05 and beta-risk of 0.20 (i.e., a statistical power of 80%), 702 women (351 per arm) are required to show a reduction of the primary endpoint from 35% (placebo group) to 25% (nifedipine group). We plan to increase the required number of subjects by 20%, to replace any patients who leave the study early. The total number of subjects required is thus 850. Data will be analyzed by the intention-to-treat principle. Discussion This trial will inform practices and policies worldwide. Optimized prenatal management to improve the prognosis of infants born preterm could benefit about 50,000 women in the European Union and 40,000 in the United States each year. Trial registration ClinicalTrials.gov identifier: NCT03976063 (registration date June 5, 2019).