[Uterine transplant: Clinical and ethical challenges in Switzerland]. / La greffe utérine en Suisse: les défis à venir.

Uterine transplant is a novel treatment option for women with absolute uterine infertility. Sixty uterine transplants have been performed worldwide to date. The first live birth happened in 2014 and since then 20 children have been born after this procedure. The procedure has several challenges: The donor is usually a woman alive. Surgery is long and complex for both the donor and the recipient, with a high risk of complications. Embryos have to be obtained through IVF. Pregnancies are at high risk for complications and require cesarean delivery, and transplant is temporary (the transplanted uterus is removed after pregnancy in order to allow discontinuation of immunosuppressive therapy). Uterine transplant is a new hope for women with absolute uterine infertility but a high-risk experimental procedure for the donor, the recipient and the newborns and raises major ethical questions.

La transplantation utérine est une possibilité nouvelle offerte aux femmes présentant une infertilité utérine absolue. Environ 60 greffes utérines ont été réalisées dans le monde. La première naissance a été obtenue en 2014 et depuis 20 enfants ont vu le jour. La «donneuse¼ est le plus souvent une donneuse vivante. Les étapes chirurgicales sont longues et le risque de complications élevé. L'entrée dans un tel programme nécessite l'obtention préalable d'embryons par fécondation in vitro. Les grossesses obtenues sont à haut risque et la naissance se fait par césarienne. La greffe est transitoire car le greffon sera retiré afin d'interrompre le traitement immunosuppresseur. Eût égard aux risques qu'elle fait courir aux «donneuses¼, aux «receveuses¼ et aux enfants obtenus, cette procédure expérimentale soulève de nombreuses questions éthiques.

[Clinical value of angiogenic and anti-angiogenic marker assay in preeclampsia]. / Intérêt du dosage des marqueurs angiogéniques et antiangiogéniques dans la prise en charge de la prééclampsie.

Preeclampsia is a disease which originates in the placenta and is specific to human pregnancy. It is one of the main causes of maternal and perinatal morbidity and mortality. The introduction of assays for angiogenic and anti-angiogenic markers reflecting placental dysfunction, which lies at the root of preeclampsia, is a turning point in the management of women with suspected preeclampsia or with an atypical form of the disease. The sFlt1/PlGF ratio assay, which has been covered by health insurance since July 2019, is a valuable diagnostic aid : the disease can be ruled out, with a high negative predictive value, when the ratio is low, thus avoiding unnecessary hospital admission and premature delivery. A high ratio can help to confirm the diagnosis of preeclampsia, albeit with a lower positive predictive value.

La prééclampsie est une pathologie d'origine placentaire spécifique à la grossesse humaine. C'est l'une des principales causes de morbi-mortalité maternelle et périnatale. L'utilisation du dosage de marqueurs angiogéniques et antiangiogéniques qui reflètent la dysfonction placentaire, cause de la prééclampsie, représente une évolution majeure dans la prise en charge des femmes présentant une suspicion de prééclampsie. Le ratio sFlt1/PlGF, pris en charge par les caisses d'assurance depuis juillet 2019, permet d'assister la démarche diagnostique. Le rule out permet, lorsque le ratio est bas, d'exclure la pathologie avec une haute valeur prédictive négative et ainsi d'éviter une hospitalisation inutile ou une naissance prématurée. En revanche, le rule in a une moindre performance (faible valeur prédictive positive) pour confirmer la pathologie.

[Hypertensive disorders of pregnancy]. / Troubles hypertensifs de la grossesse.

Hypertensive disorders of the pregnancy represent a major cause of maternal and fetal morbidity and mortality worldwide. Immediate and future complications are already well known, but recently gestational hypertension emerged as an equally serious risk factor for future maternal health. This article so offers a review of knowledge and recent changes about the diagnosis, treatment and long-term follow-up of hypertensive troubles of the pregnancy which are useful to know for the general practitioner. It also describes the ambulatory follow-up that has been implemented in the University hospitals of Geneva.

Les troubles hypertensifs de la grossesse représentent une des principales causes de morbidité et de mortalité materno-fœtales. On connaissait déjà les complications immédiates et futures de la prééclampsie pour la mère et son enfant, mais l'hypertension gestationnelle transitoire a récemment émergé comme un facteur de risque tout aussi sérieux pour la santé maternelle future. Cet article propose donc une revue des connaissances et des changements récents sur le diagnostic, le traitement et le suivi au long terme des troubles hypertensifs gestationnels, qui sont utiles à connaître pour l'interniste généraliste. Il décrit également le suivi ambulatoire qui a été mis en place aux Hôpitaux universitaires de Genève.

[Obstetrics]. / Obstétrique.

During the past year, we have renewed interest in old well-known problems. New studies and guidelines have been issued about lung maturation in cases of preterm delivery after 37 weeks of gestation. Short term benefits have been proven but the number of cases needed to treat to prevent one case of respiratory complications is high and with possible neurological long-term effects. Also, several studies have shown the benefits of including the ultrasound measurement of the inferior segment of the uterus in order to attempt vaginal delivery after caesarean section with the lowest risk for uterine rupture, while others studies have shown the best procedure to close the uterus during cesarean section. And finally, we will discuss about an old friend: aspirin to reduce the risk of pre-eclampsia.

Au cours de l'année écoulée, l'intérêt pour de vieux problèmes bien connus de notre spécialité médicale a été renouvelé. De nouvelles études et lignes directrices ont été publiées concernant la maturation pulmonaire en cas d'accouchement prématuré après 37 semaines de gestation. Bien qu'un bénéfice à court terme ait été prouvé, le nombre de cas à traiter pour prévenir une complication respiratoire néonatale est élevé, avec des effets neurologiques potentiels à long terme. Afin de promouvoir la tentative d'accouchement vaginal après césarienne sans augmenter le risque de rupture utérine, différents travaux indiquent qu'il faut intégrer la mesure du segment inférieur de l'utérus dans la discussion de la voie d'accouchement. D'autres ont montré la meilleure procédure pour fermer l'utérus pendant la césarienne. Enfin, nous allons parler d'une vieille amie : l'aspirine pour réduire le risque de prééclampsie.

Preeclamptic plasma induces transcription modifications involving the AP-1 transcriptional regulator JDP2 in endothelial cells.

Preeclampsia is a pregnancy disorder characterized by hypertension and proteinuria. In preeclampsia, the placenta releases factors into the maternal circulation that cause a systemic endothelial dysfunction. Herein, we investigated the effects of plasma from women with preeclamptic and normal pregnancies on the transcriptome of an immortalized human umbilical vein endothelial cell line. The cells were exposed for 24 hours to preeclamptic or normal pregnancy plasma and their transcriptome was analyzed using Agilent microarrays. A total of 116 genes were found differentially expressed: 71 were up-regulated and 45 were down-regulated. In silico analysis revealed significant consistency and identified four functional categories of genes: mitosis and cell cycle progression, anti-apoptotic, fatty acid biosynthesis, and endoplasmic reticulum stress effectors. Moreover, several genes involved in vasoregulation and endothelial homeostasis showed modified expression, including EDN1, APLN, NOX4, and CBS. Promoter analysis detected, among the up-regulated genes, a significant overrepresentation of genes containing activation protein-1 regulatory sites. This correlated with down-regulation of JDP2, a gene encoding a repressor of activation protein-1. The role of JDP2 in the regulation of a subset of genes in the human umbilical vein endothelial cells was confirmed by siRNA inhibition. We characterized transcriptional changes induced by preeclamptic plasma on human umbilical vein endothelial cells, and identified, for the first time to our knowledge, JDP2 as a regulator of a subset of genes modified by preeclamptic plasma.

B-type natriuretic peptide measurement for early diagnosis of acute pulmonary edema during pregnancy.

Calcium-channel blockers administered to pregnant women as tocolytic agents can cause acute pulmonary edema. The first signs of this severe complication can be atypical and so delay introduction of appropriate therapy. We describe three cases in whom B-type natriuretic peptide measurements proved to be relevant in early diagnosis and monitoring of pregnant women with acute pulmonary edema. B-type natriuretic peptide measurement in this setting could contribute to timely diagnosis and improve follow-up.

Postpartum septic arthritis of pubic symphysis due to Sneathia sanguinegens, Sneathia vaginalis, and Mageeibacillus indolicus: Contribution of clinicalmetagenomics.

Sneathia sanguinegens, Sneathia vaginalis, and Mageeibacillus indolicus have been recently described in the female genital tract. We present the first case of a postpartum septic arthritis of the pubic symphysis due to these organisms, identified by next generation sequencing.

Decidual soluble factors participate in the control of HIV-1 infection at the maternofetal interface.

BACKGROUND: Maternofetal transmission (MFT) of HIV-1 is relatively rare during the first trimester of pregnancy despite the permissivity of placental cells for cell-to-cell HIV-1 infection. Invasive placental cells interact directly with decidual cells of the uterine mucosa during the first months of pregnancy, but the role of the decidua in the control of HIV-1 transmission is unknown. RESULTS: We found that decidual mononuclear cells naturally produce low levels of IL-10, IL-12, IL-15, TNF-α, IFN-α, IFN-γ and CXCL-12 (SDF-1), and large amounts of CCL-2 (MCP1), CCL-3 (MIP-1α), CCL-4 (MIP-1ß), CCL-5 (Rantes), CXCL-10 (IP-10), IL-6 and IL-8. CCL-3 and CCL-4 levels were significantly upregulated by in vitro infection with R5 HIV-1 but not X4. Decidual CD14+ antigen presenting cells were the main CCL-3 and CCL-4 producers among decidual leukocytes. R5 and X4 HIV-1 infection was inhibited by decidual cell culture supernatants in vitro. Using HIV-1 pseudotypes, we found that inhibition of the HIV-1 entry step was inhibited by decidual soluble factors. CONCLUSION: Our findings show that decidual innate immunity (soluble factors) is involved in the control of HIV-1 infection at the maternofetal interface. The decidua could thus serve as a mucosal model for identifying correlates of protection against HIV-1 infection.

The role of sFlt1/PlGF ratio in the assessment of preeclampsia and pregnancy-related hypertensive disorders.

Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Early recognition of the disease may be challenging. Complications may precede the onset of clinical symptoms and medical intervention is often delayed. Moreover, in the absence of specific clinical signs, many patients will present symptoms mimicking the disease without ever being diagnosed with preeclampsia. This situation may, however, lead to medical interventions and cause unnecessary stress for the patient. For many years, research tried to evaluate the significance of serum biomarkers as early indicators of preeclampsia. Among many, the sFlt-1/PlGF ratio, given its performance, aroused the greatest interest. This article reviews current knowledge on the subject, focusing on a Swiss perspective.

Steroid profiling in preeclamptic women: evidence for aromatase deficiency.

OBJECTIVE: Experimental data have revealed the critical role played by 2-methoxy-estradiol, a metabolite of 17ß-estradiol, in the pathophysiology of preeclampsia. We used gas chromatography/mass spectrometry to measure a whole panel of hormonal steroids in the plasma from women during the third trimester of their pregnancy. STUDY DESIGN: The population study consists of 24 pregnant patients with different outcomes: normal, or complicated by isolated preeclampsia or by severe preeclampsia with Hemolysis Enzyme Liver Low Platelets (HELLP) syndrome. RESULTS: 17ß-estradiol was reduced by 50% in isolated preeclampsia, and by 70% in severe preeclampsia with HELLP syndrome (normal: 8.54 ± 0.9 ng/mL; isolated preeclampsia: 4.65 ± 1.0 ng/mL; severe preeclampsia with HELLP syndrome: 2.64 ± 0.4 ng/mL), as is estrone. Downstream, 2-methoxy-estradiol was decreased only in severe preeclampsia with HELLP syndrome. The concentrations of estrone and 17ß-estradiol precursors were comparable between groups, suggesting that placental aromatase is deficient in preeclampsia. CONCLUSION: The gradual decrease of estrogen levels with increasing severity of preeclampsia suggests an impairment of placental steroidogenesis.

Impact of previous uterine artery embolization on fertility.

PURPOSE OF REVIEW: To describe data on the effects of uterine artery embolization (UAE) on fertility. RECENT FINDINGS: UAE is used to treat postpartum hemorrhage (PPH) and fibroids. This effective therapy is replacing surgery in many cases. One of the main goals of UAE is to preserve the uterus and therefore fertility (pregnancies, menses and ovarian reserve). Pregnancies after this technique have been described. The main complications encountered during these pregnancies are not only PPH but also miscarriages and cesarean deliveries after UAE for fibroids. Conflicting results varying from completely well tolerated to serious complications such as definitive negative effect on endometrium and ovary function have been reported. Nevertheless, the series differ in that they included women of different ages and used different material for vessel occlusion (definitive microparticles of varying sizes, temporary pledgets of gelatine sponge, etc.). We discuss the impact of these differences on uterus vascularization and fertility. SUMMARY: UAE is an effective treatment for PPH and fibroids. Pregnancy is possible after UAE. Recurrent PPH is a serious and frequent complication. Synechia is also a potential complication. Desire of childbearing should be considered when choosing embolization or surgery and, in case of embolization, the choice of material used. Further studies on future fertility after UAE are needed as well as information on fertility after surgery.

Impact of pelvic arterial embolization for intractable postpartum hemorrhage on fertility.

OBJECTIVE: This study was to determine the long-term outcomes of arterial pelvic embolization for intractable postpartum hemorrhage and particularly its effect on menses, fertility, and outcomes of subsequent pregnancies. STUDY DESIGN: Fifty-six consecutive patients who underwent emergency pelvic arterial embolization for severe postpartum hemorrhage between April 1995 and July 2005 were included in the study. Patients were contacted to obtain information about menses and fertility after pelvic arterial embolization. RESULTS: Thirty-four women (61.8%) were successfully contacted. One patient had a hysterectomy. Thirty women (91%) reported regular menses. Thirteen women (38.3%) had a total of 20 spontaneous pregnancies. Eight pregnancies ended during the first trimester. The 12 other pregnancies (60%) were all normal and all patients delivered vaginally healthy babies with normal weight for gestational age. CONCLUSION: The current study suggests that fertility is not adversely affected by arterial pelvic embolization for intractable postpartum hemorrhage and that women can conceive after the procedure with normal pregnancy outcomes.

Hormonal Changes Associated With Intra-Uterine Growth Restriction: Impact on the Developing Brain and Future Neurodevelopment.

The environment in which a fetus develops is not only important for its growth and maturation but also for its long-term postnatal health and neurodevelopment. Several hormones including glucocorticosteroids, estrogens and progesterone, insulin growth factor and thyroid hormones, carefully regulate the growth of the fetus and its metabolism during pregnancy by controlling the supply of nutrients crossing the placenta. In addition to fetal synthesis, hormones regulating fetal growth are also expressed and regulated in the placenta, and they play a key role in the vulnerability of the developing brain and its maturation. This review summarizes the current understanding and evidence regarding the involvement of hormonal dysregulation associated with intra-uterine growth restriction and its consequences on brain development.

How should women with pre-eclampsia be followed up? New insights from mechanistic studies.

Understanding of the maternal syndrome of pre-eclampsia has greatly improved over the past 5 years. Specifically, the notion has emerged that the placenta is a source of antiangiogenic factors, such as soluble fms-like tyrosine kinase 1, that can progressively impair the mother's vascular and glomerular function throughout pregnancy. This impairment can be harmless during normal pregnancy, but in cases of defective placentation, concentrations of antiangiogenic factors increase to a level that compromises vital vascular functions in the short term and jeopardizes long-term maternal and fetal outcomes. In both pre-eclamptic and healthy pregnancies, the transient imbalance between angiogenic and antiangiogenic factors elicited by pregnancy acts as a 'stress test' for the endothelium, particularly in the glomerular capillary bed. Women who do not pass this test (i.e. those who develop pre-eclampsia or gestational hypertension) should be screened for glomerular disease, and their cardiovascular risk should be carefully monitored throughout life.

Abnormal steroidogenesis and aromatase activity in preeclampsia.

INTRODUCTION: Estrogens and progesterone play critical roles in angiogenesis and vasodilation. Moreover, placental aromatase deficiency is detected in women with preeclampsia (PE) at delivery. We hypothesized that abnormal steroidogenesis occurs much earlier than typical PE diagnosis. Thus, we investigated whether the circulating steroid profile was already disturbed at 24-29 weeks of gestation in women with subsequent PE, and compared the profile with that of women with "placental" small gestational age (SGA) without PE. METHODS: We selected nulliparous women (n = 90) from the MOMA trial, including women with PE (n = 25), SGA (n = 25), and controls (NP; n = 40), for plasma steroid profiling by gas chromatography/mass spectrometry and to measure placental growth factor and soluble fms-like tyrosine kinase-1. Placental aromatase expression was evaluated in a new set of women. RESULTS: Compared with that of controls, the women with PE had a significantly lower estrone/androstenedione ratio, and exhibited a decreasing trend for estradiol and estrone levels. Lower estriol levels were observed in the SGA group compared to the NP group. Compared with that of controls, the women with PE and SGA had significantly higher levels of 20α-dihydroprogesterone (20α-DHP) and 20α-DHP/progesterone ratios. Pregnenolone sulfate levels were lower in the PE group than in the NP and SGA groups. Decreased expression of aromatase was observed in the PE group compared to the control group. DISCUSSION: Preeclampsia appears to be characterized by specific steroidogenesis dysregulation long before PE diagnosis, highlighting potential new biomarkers of PE.

Spontaneous uterine artery rupture during pregnancy in a woman with sickle cell disease: a case report.

BACKGROUND: Spontaneous rupture of uterine vessels during pregnancy is rare and usually involves uteroovarian veins. Presenting symptoms include acute-onset abdominal pain and maternal hypovolemic collapse due to hemoperitoneum. An atypical case of subacute uterine artery rupture at 27 weeks of gestation occurred in a woman with sickle cell disease. CASE: A 28-year-old, nulliparous woman with sickle cell disease was admitted at 27 weeks of gestation for sharp abdominal pain radiating to the right flank. The first diagnosis included acute renal colic and a sickling vasoocclusive crisis. One week after admission the patient experienced paroxysmal, diffuse abdominal pain associated with acute fetal distress requiring an emergency cesarean section. Laparotomy revealed an 800-mL hemoperitoneum. Active bleeding from a ruptured uterine artery was observed and successfully treated by selective suture. CONCLUSION: Spontaneous rupture of the uterine artery during pregnancy may present as a 2-step process.

From Pregnancy to Preeclampsia: A Key Role for Estrogens.

Preeclampsia (PE) results in placental dysfunction and is one of the primary causes of maternal and fetal mortality and morbidity. During pregnancy, estrogen is produced primarily in the placenta by conversion of androgen precursors originating from maternal and fetal adrenal glands. These processes lead to increased plasma estrogen concentrations compared with levels in nonpregnant women. Aberrant production of estrogens could play a key role in PE symptoms because they are exclusively produced by the placenta and they promote angiogenesis and vasodilation. Previous assessments of estrogen synthesis during PE yielded conflicting results, possibly because of the lack of specificity of the assays. However, with the introduction of reliable analytical protocols using liquid chromatography/mass spectrometry or gas chromatography/mass spectrometry, more recent studies suggest a marked decrease in estradiol levels in PE. The aim of this review is to summarize current knowledge of estrogen synthesis, regulation in the placenta, and biological effects during pregnancy and PE. Moreover, this review highlights the links among the occurrence of PE, estrogen biosynthesis, angiogenic factors, and cardiovascular risk factors. A close link between estrogen dysregulation and PE occurrence might validate estrogen levels as a biomarker but could also reveal a potential approach for prevention or cure of PE.

[Recurrent miscarriage]. / Echecs répétés de grossesse.

Repetitive spontaneous first trimester miscarriage as well as second and third trimester in utero fetal death are considered as recurrent pregnancy losses. They represent 1% of all pregnancies. Repetitive fetal loss with alive fetus should also be counted as such. An explanation is found for less than 50% of such patients. Most recurrent first trimester fetal losses are of chromosomal, hormonal, immunological, uterine or environmental origin. The most frequent causes for in utero fetal death are renovascular syndromes, hormonal or immunological pathologies, hereditary thrombophilias, red cell or platelet allo-immunisation and chromosomal anomalies. Second trimester miscarriage is generally due to a cervical incompetence, uterine malformations or infections.