Do Receptors Get Pregnant Too? Adrenergic Receptor Alterations in Human Pregnancy

In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.     

Does hyaluronan improve embryo implantation?

PURPOSE OF REVIEW: Taking into consideration the increasing interest on hyaluronan and its biological as well as physiological properties, this review will focus on the role of this molecule in human embryo implantation. RECENT FINDINGS: Several studies have been performed up to date in order to assess whether the addition of hyaluronan in the human embryo culture system can improve pregnancy and implantation rates, including one retrospective and six randomized controlled trials. On the one hand, four of those studies showed significant increase in clinical pregnancy and/or implantation rates after using embryo transfer medium containing high concentration of hyaluronan. On the other hand, three studies did not demonstrate any significant improvement in clinical pregnancy and implantation rates. However, regardless of statistical significance, almost all studies demonstrate higher pregnancy and implantation rates after using embryo transfer medium containing high concentration of hyaluronan. SUMMARY: Up to date, the results regarding the role of hyaluronan in human embryo implantation are still conflicting and, thus, further prospective randomized clinical trials are necessary to draw solid conclusions.     

The sick placenta-the role of malaria

The human placenta is an ideal site for the accumulation of Plasmodium falciparum malaria parasites, and as a consequence serious health problems arise for the mother and her baby. The pathogenesis of placental malaria is only partially understood, but it is clear that it leads to a distinct epidemiological pattern of malaria during pregnancy. The objectives of this review are: (1) To review recent data on the epidemiology of malaria in pregnancy, with emphasis on placental malaria; (2) to describe the pathological changes and immunological factors related to placental malaria; and (3) to discuss briefly the functional consequences of this infection for the mother and her baby. The review attempts to bring together local events at the maternal-fetal interface which encompass immunological and pathological processes which relate to the epidemiological pattern of malaria in pregnancy in areas of both high and low malaria transmission. An integrated understanding of the epidemiological, immunological and pathological processes must be achieved in order to understand how to control malaria in pregnancy. The yearly exposure of at least 50 million pregnancies to malaria infection makes it the commonest and most recurrent parasitic infection directly affecting the placenta. These statistics and our limited understanding of its pathogenesis suggest the research priorities on this subject.     

The safety and efficacy of insulin analogs in pregnancy.

Diabetes during pregnancy is accompanied by increasing needs for maternal insulin and ongoing biological changes that cause maternal insulin requirements to reach higher and lower extremes throughout the day than in non-pregnant patients. As maternal hyperglycemia increases the risk of fetal and maternal morbidity, it is essential for the mother to maintain normoglycemia during pregnancy. With the advent of insulin analogs that feature improved absorption and physiological profiles over human insulin, the achievement of normoglycemia throughout pregnancy has become more attainable. This review provides a discussion of the application of the insulin analogs to diabetes during pregnancy and compares the benefits of rapid-acting insulin analogs with long-acting insulin analogs during pregnancy. This review further proposes a treatment protocol for achieving and maintaining normoglycemia throughout pregnancy.     

The involvement of HLA-E and -F in pregnancy

The human MHC class I genes, HLA-E, -F and -G are referred to as non-classical or class Ib genes and are distinguished from their close relatives (the classical HLA class I genes) by expression patterns and low allelic polymorphism. To date, most studies that relate these molecules to the immunology of pregnancy have concerned only HLA-G. However, recent advances have suggested potential unique roles as well for HLA-E and HLA-F in pregnancy. A notable advance was the observation that all three proteins are expressed on the surface of extravillous trophoblast that has invaded the maternal decidua. Given this expression site, possibly the only cell type in human development where this occurs, it is logical to hypothesize that all three antigens, each with its own unique receptor-ligand interaction(s), contribute collectively to enable the growth of the developing child. In this review, we examine and discuss the accumulated data on expression and function of HLA-E and HLA-F and attempt to relate what is known to the involvement of HLA-E and -F in human pregnancy.     

Microchimerism: Defining and redefining the prepregnancy context – A review

Bidirectional transplacental exchange characterizes human pregnancy. Cells exchanged between mother and fetus can durably persist as microchimerism and may have both short- and long-term consequences for the recipient. The amount, type, and persistence of microchimerism are influenced by obstetric characteristics, pregnancy complications, exposures to infection, and other factors. A reproductive-aged woman enters pregnancy harboring previously acquired microchimeric “grafts,” which may influence her preconception health and her subsequent pregnancy outcomes. Many questions remain to be answered about microchimerism with broad-ranging implications. This review will summarize key aspects of this field of research and propose important questions to be addressed moving forward.     

Apoptosis in the first trimester human placenta: the role in maintaining immune privilege at the maternal–foetal interface and in the trophoblast remodelling

Apoptosis has been proposed as a mechanism for maintaining immune privilege. Expression of Fas ligand (FasL) by the human trophoblast has been recently accepted as a mechanism providing protection against the lytic action of activated decidual immune cells expressing Fas receptor (FasR). Therefore, the purpose of this review was to determine the role of apoptosis in early pregnancy maintenance according to the latest literature. We used Medline literature search. The data suggest that apoptosis may serve as a previously unsuspected mechanism that induces tolerance of the foetal allograft against maternal immune system. Apoptosis of activated maternal immune cells occurs in the human decidua mainly through Fas–FasL or receptor for TNF-related apoptosis-inducing ligand (TRAIL-R)-TNF-related apoptosis-inducing ligand (TRAIL) signalling. This might be a defence mechanism against rejection of the foetal allograft by the maternal immune system. In addition, in this review contribution of programmed cell death to placental cell turnover and remodelling during first trimester of pregnancy is also discussed.     

A case report of human granulocytic anaplasmosis (ehrlichiosis) in pregnancy and a literature review of tick-borne diseases in the United States during pregnancy

There is paucity of data regarding tick-borne diseases during pregnancy. Here, we report a case of human granulocytic anaplasmosis during pregnancy with successful treatment and a favorable neonatal outcome. We also review diagnosis, treatment, and outcomes of published case reports from 1983 to 2010 of human granulocytic anaplasmosis, Lyme disease, babesiosis, and human monocytic ehrlichiosis in the United States. TARGET AUDIENCE: Obstetricians and Gynecologists and Family Physicians. LEARNING OBJECTIVES: After the completing the CME activity, physicians should be better able to diagnose tick-born diseases, implement best treatment options during the pregnancy, and assess the neonatal outcomes.     

血清标志物早期诊断异位妊娠研究进展

异位妊娠是妇产科常见的急腹症,近二十年发病率呈上升趋势,提高诊断技术可减少异位妊娠误诊率及漏诊率,为保守治疗及保留输卵管的再生育功能创造有利条件。目前异位妊娠早期诊断主要依靠超声和血清人绒毛膜促性腺激素β亚单位（β-hCG）化验检查,但在妊娠4～5周时,尚不能完全确定妊娠部位。近年用于诊断异位妊娠的血清标志物的研究有一定进展,就有关异位妊娠早期诊断的血清标志物——血清hCG、孕激素、血管内皮生长因子、妊娠相关血浆蛋白、激活素-抑制素的研究进展做文献综述。     

Ectopic pregnancy: an update

This review addresses recent publications that investigate etiology, epidemiology and different modalities in diagnosis and therapy for ectopic pregnancy. A significant proportion of recent work has focused in the development of new diagnostic tools to aid in the early detection of ectopic pregnancy. Diagnostic modalities have included systemic and local markers, vascular endothelial growth factor, vascular cell adhesion molecule-1, urokinase plasminogen activator receptor, cervical fetal fibronectin, and hormonal level determinations. In addition, magnetic resonance imaging, ultrasonography, color flow mapping and endometrial thickness have been evaluated. New studies have investigated controversial issues related to the cost of the medical versus surgical treatment and the use of different medications and techniques for the management of ectopic pregnancy. Most important of all, several lines of investigation have addressed the use of human chorionic gonadotropin, algorithms, and scoring systems as prognostic indicators of successful therapy and to determine the risk of complications. The management of cervical, interstitial and heterotopic pregnancy is evaluated in this review and a summary of recent proposed diagnostic tools and concepts in management is also presented.     

In vitro evidences of heparin's effects on embryo implantation and trophoblast development

Heparin seems to be effective in ameliorating pregnancy outcome in thrombophilic women with previous recurrent pregnancy loss, preeclampsia, intrauterine growth restriction and sudden fetal death. A prophylactic effect of heparin treatment has also been proposed in terms of prevention of adverse pregnancy outcomes recurrence in women with history of recurrent miscarriage, severe preeclampsia, placental abruption, low neonatal birth weight and intrauterine fetal death not related to thrombophilia, although literature in this field is quite controversial. The molecular mechanisms by which heparin might exert its potential therapeutic effects in human reproduction are still not fully understood. In this article we review the current knowledge in this research field, focusing on in vitro evidences of heparin's mechanisms of action in the processes of embryo implantation and trophoblast invasion.     

Events from ovulation to implantation studied by three-dimensional ultrasound

During the last decade transvaginal color Doppler has played an important role in increasing understanding of early human development. Although our knowledge of early pregnancy development has recently improved, little is known about the most critical period of human development: between conception and implantation. Recent advances in 3D ultrasound have made studies of follicular development, ovulation and uterine receptivity more accurate. The same method can be used for evaluation of the Fallopian tube patency and assessment of the ovarian and uterine causes of infertility which hamper processes of early human development. Storage capacities, reconstruction of the volume images and simultaneous viewing of all three orthogonal planes are the main advantages of this method. Introducing 3D ultrasound into assessment of early pregnancy has enabled visualization and volume estimation of the gestational sac, yolk sac and embryo. Switching on power Doppler superimposed to 3D gray scale can detect early vasculogenesis within the intervillous space and embryo/fetus. Here we review the potential application of this novel technique in monitoring the morphological and functional processes from ovulation towards implantation and early pregnancy.     

The human placental bed revisited

Pre-eclampsia, fetal growth restriction and spontaneous miscarriage have all been linked to abnormalities in trophoblast invasion into the placental bed. Despite intensive research our understanding of the mechanisms that control human trophoblast invasion in normal, let alone abnormal pregnancy, are still poorly understood. This is partly due to difficulties in obtaining "true" placental bed biopsies and most investigators have relied on in vitro models to try and understand the processes which control trophoblast invasion. The purpose of this article is to review the various studies which have attempted to sample the placental bed along with their success rate in doing so and secondly to review our current understanding of the morphological changes which occur in the placental bed in normal pregnancy, pre-eclampsia and spontaneous miscarriage.     

血清标志物早期诊断异位妊娠研究进展

异位妊娠是妇产科常见的急腹症,近二十年发病率呈上升趋势,提高诊断技术可减少异位妊娠误诊率及漏诊率,为保守治疗及保留输卵管的再生育功能创造有利条件。目前异位妊娠早期诊断主要依靠超声和血清人绒毛膜促性腺激素β亚单位（β-hCG）化验检查,但在妊娠4～5周时,尚不能完全确定妊娠部位。近年用于诊断异位妊娠的血清标志物的研究有一定进展,就有关异位妊娠早期诊断的血清标志物——血清hCG、孕激素、血管内皮生长因子、妊娠相关血浆蛋白、激活素-抑制素的研究进展做文献综述     

Vaping During Pregnancy: What Are the Potential Health Outcomes and Perceptions Pregnant Women Have?

The prevalence of electronic nicotine delivery systems, such as vaping, is a growing public health concern, and there is limited information on the use of these devices during pregnancy. The objective of this rapid review was to summarize the available literature on human studies of the potential maternal or fetal health effects of vaping or women's perceptions of vaping during pregnancy.A systematic search was completed in the following databases: Medline, EMBASE, Scopus, Web of Science, and CINAHL. A search strategy was developed combining the terms pregnancy and vaping. Findings were divided into two groups and summarized as: 1) Health outcomes following vaping during pregnancy; and 2) Perceptions pregnant women have related to vaping during pregnancy. A total of 760 articles were retrieved and, after applying the inclusion/exclusion criteria and screening, 19 studies were included. Five included studies provided evidence on potential health outcomes and 14 were focused on perceptions.There is emerging evidence that vaping during pregnancy may increase the risk of small for gestational age newborns. Pregnant women generally report that they used vaping products during pregnancy for smoking cessation and perceived that this was a healthier alternative to traditional cigarettes. Overall, there was consensus that there is a lack of information on maternal and fetal health outcomes following vaping during pregnancy. Based on the findings of this rapid review, there is an urgent need for high-quality studies in pregnant women to evaluate the potential in utero and long-term effects of exposure to prenatal vaping.     

Corticosteroids, pregnancy, and HELLP syndrome: a review

Corticosteroids are potent antiinflammatory and immunosuppressive drugs, which are used in the treatment of a wide range of medical disorders. During pregnancy, several corticosteroids are administered for maternal as well as fetal reasons. Prednisone and prednisolone show limited transplacental passage and are thus used for treatment of maternal disease. Dexamethasone and betamethasone, drugs that can easily cross the placenta, are more suitable for fetal indications. During the last decade, administration of corticosteroids was introduced in the treatment of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome), a severe form of preeclampsia unique to human pregnancy. Several randomized, controlled trials as well as other prospective and retrospective studies have been performed to investigate this beneficial effect of corticosteroids on biochemical measures and clinical signs. This review discusses the characteristics of corticosteroids in humans and details the use of corticosteroids during pregnancy. A review of literature on the effect of corticosteroids on HELLP syndrome is given and possible mechanisms of action are discussed.     

Strategies for investigating the maternal-fetal interface in the first trimester of pregnancy: What can we learn about pathology?

The pathologies of the pregnancy complications pre-eclampsia (PE) and fetal growth restriction (FGR) are established in the first trimester of human pregnancy. In a normal pregnancy, decidual spiral arteries are transformed into wide diameter, non-vasoactive vessels capable of meeting the increased demands of the developing fetus for nutrients and oxygen. Disruption of this transformation is associated with PE and FGR. Very little is known of how these first trimester changes are regulated normally and even less is known about how they are compromised in complicated pregnancies. Interactions between maternal and placental cells are essential for pregnancy to progress and this review will summarise the challenges in investigating this area. We will discuss how first trimester studies of pregnancies with an increased risk of developing PE/FGR have started to provide valuable information about pregnancy at this most dynamic and crucial time. We will discuss where there is scope to progress these studies further by refining the ability to identify compromised pregnancies at an early stage, by integrating information from many cell types from the same pregnancy, and by improving our methods for modelling the maternal-fetal interface in vitro.     

A proposed role for hCG in clinical obstetrics

The role of human chorionic gonadatropin (hCG) in the maintenance of early pregnancy is well known. Recent data suggests that hCG may play a role in the maintenance of the later stages of pregnancy as well, by directly and indirectly promoting uterine quiescence. If hCG acts as an endogenous tocolytic in normal pregnancy, then it may be an ideal candidate for therapy of preterm labor as well. We present compelling in vitro as well as in vivo data, which support the role of hCG in the maintenance of normal uterine quiescence. Additionally, we will present in vivo and in vitro data that confirms the ability of hCG to directly promote relaxation of uterine contractions. This review provides a basis for future study of the use of hCG in clinical obstetrics. Given the limited effectiveness of tocolytic therapies available at the time, hCG may provide a promising pharmacological approach to the pervasive problem of preterm labor in human pregnancy. While further work is needed, initial data strongly support this novel use of hCG in clinical obstetrics.     

Current aspects of blastocyst cryopreservation

Cryopreservation of human gametes and embryos has become an essential part of assisted reproduction. Successful cryopreservation of human blastocysts is increasingly relevant as extended in-vitro culture of human embryos becomes more common, permitting routine use of blastocyst transfer in IVF programmes. This reduces the number of embryos transferred, thereby reducing multiple pregnancies and maximizing cumulative pregnancy rates per oocyte retrieval. The superiority of blastocyst freezing over earlier stage freezing in terms of implantation per thawed embryo transferred improves overall expectations for the cryopreservation programme. Therefore, a reliable procedure for the cryopreservation of blastocysts is needed because, after transfer, only a small number of supernumerary blastocysts are likely to be available for cryopreservation. Since the early 1980s, two common techniques have been used in cryopreservation: the conventional slow cooling method and the more recent rapid procedure known as vitrification. Vitrification has become an attractive alternative to slow freezing, since it appears to result in significantly higher survival and pregnancy rates. The aim of this review is to focus on the cryopreservation of human blastocysts using slow and rapid protocols and to assess the impact of the crypreservation protocol used on the survival, implantation and pregnancy rates.