An investigation of antiphospholipid antibody associated obstetric complications

I aimed to assess the involvement of 'phospholipid antibodies' (aPL) in the pathology of antiphospholipid syndrome (aPS), with an emphasis on pregnancy complications and placental pathology. Using an immunofluorescent technique I demonstrated binding of affinity purified aPL to normal term placenta; further experiments suggested binding to placental proteins. I established assays for prothrombin (aPT) and β2Glycoprotein-I (a-β2GPI) antibodies, and studied a variety of non pregnant patients (PAPS, SLE, and infection). An associations between IgG and IgM a-β2GPI with aPS was demonstrated, but aPT were less specific. In serial samples from aPS patients with thrombotic/ neurological events, a-β2GPI levels were reasonably constant. In pregnant aPS patients, the antibody levels fluctuated. Women who became aPL negative before 12 weeks, proceeded with normal pregnancies. Other women having mixed pregnancy outcomes, had a peak in aPL levels, and the overall trend was that aPL remained positive at =20 weeks gestation. In a low risk pregnant population, the prevalence of aCL was approximately 3%, a-β2GPI 3.5% and aPT 3-6%. aPL were not always associated with an adverse outcome and are unsuitable preclinical markers of pregnancy complications in general obstetric populations. Women with persistent abnormal uterine artery Doppler in mid-gestation, were more likely to express aCL than healthy controls. There was no increase in the prevalence of aPL in pregnancies with unexplained biochemical markers of obstetric problems. In non-pregnant PAPS and SLE patients, thrombin generation, FVIIa and FXIIa were significantly increased, and this was ameliorated by oral anticoagulants (except FXIIa). Increased activation markers were observed in normal and aPS pregnancies, despite heparin and aspirin prophylaxis. β2GPI and annexin V (AV) were expressed by the placenta, from the 7th week, and throughout gestation, in normal, and aPS pregnancies. The immuno localisation of β2GPI and AV in term aPS pregnancies was similar to normal, but abnormal staining patterns were detected in aborted first trimester aPS placentas. Extractable β2GPI was reduced in term aPS placentas. The villous placenta and placenta bed are both exposed to maternal circulation during pregnancy, thus allowing access of aPL to target antigens. aPL are associated with coagulation activation, and arc capable of binding to cellular antigens. In pregnancy, the aPL antibody spectrum, individual cellular response to challenge, and the procoagulant environment probably interact to determine the clinical consequence of aPL

A prospective study of implantation, maternal cardiovascular function and pregnancy outcome

Events at embryonic implantation play a key role in the establishment of successful pregnancy. Not only is delayed implantation associated with an increased incidence of early pregnancy loss, but may also be associated with impaired trophoblastic invasion and uteroplacental insufficiency. Furthermore, uteroplacental vascular mal-adaptation may also be affected by pre-existing maternal cardiovascular function and associated with maternal cardiovascular maladaptation during pregnancy. There is limited understanding of events surrounding human implantation because of the difficulties in conducting prospective studies from prior to pregnancy and an inability to study events at the trophoblast-decidual interface in vivo. The primary objective of this study was to test the feasibility of being able to conduct and complete a prospective study from prior to pregnancy to the postpartum period combining measures of ovulation, implantation, ultrasound measurements of fetal size and cardiovascular changes during pregnancy. The secondary objective was to investigate ovulation and implantation timing using digital home ovulation and pregnancy test kits along with cardiovascular changes in relation to various pregnancy complications and fetal growth to determine the power for a future prospective study. This was a prospective cohort feasibility study of 143 women planning to conceive. Pre-pregnancy cardiovascular function was investigated in all women. We observed ovulation, implantation timing in 101 pregnancies and investigated the relationship between implantation timing, embryonic and fetal growth, birthweight and length of gestation in the 69 viable pregnancies. Longitudinal cardiovascular changes in viable pregnancies were examined in relation both to previous obstetric history and index pregnancy outcome. Normal pregnancy was associated with profound cardiovascular changes, beginning from 6 weeks of gestation. Delayed implantation was associated with early pregnancy loss and a smaller first trimester fetal size. The incremental rise in cardiac output from before pregnancy to its peak in the second trimester was associated with birthweight. It is feasible to conduct and complete a prospective study from prior to pregnancy to the postpartum period. Larger prospective studies of this nature will enable an understanding of the events surrounding implantation including the ‘cause and effect’ relationship of cardiovascular function with pregnancy complications such as preeclampsia and fetal growth restriction

Natural killer cell profiling in women with recurrent pregnancy loss

Natural Killer (NK) cells are cells of our immune system that protect us against all kinds of pathogens. However, during pregnancy, these cells seem to have an important function to protect the embryo so that it can develop properly. In order to gain more insight into the characteristics of NK cells in women with recurrent pregnancy loss, this dissertation focused on NK cell receptor profiles. First of all, a literature search was done to see which receptors have been studied before in women with recurrent pregnancy loss and which receptors have not yet, so that an overview could be created to see which receptors are still underexposed. Next, NK cell receptor profiles were examined in blood and menstrual blood from healthy women to see whether NK cells have different characteristics in the womb than in the bloodstream. In addition, NK cell receptor profiles were compared between women with recurrent pregnancy loss and women with a previous healthy pregnancy and it was also examined whether there was a genetic difference in one specific receptor between these women. Furthermore, other systems that interact with NK cells, such as the circulatory system and the metabolic system of these women, were also investigated. Finally, a literature review was conducted to see whether immunotherapy had an effect on the success of life birth in women with a history of recurrent pregnancy loss and immunological problems. These therapies are sometimes already used, but it is still insufficiently known whether and, if so, for whom this treatment works. Because there are only a few studies on this topic, it is too early to draw firm conclusions. In summary, all the results of this thesis show that it is important to increase awareness and understanding of immunological problems in women with recurrent miscarriages.<br/

Abortions in First Trimester Pregnancy, Management, Treatment

Tujuan dari penelitian: 1. Mendeskripsikan penerepan pendekatan Client Centered dalam mengatasi kepribadian introvert pada siswa kelas XI IPS MA Al Hidayah Kudus Tahun Pelajaran 2016/2017. 2. Mendeskripsikan kepribadian introvert pada konseli siswa kelas XI IPS MA Al Hidayah Kudus setelah diberikan konseling dengan pendekatan Client Centered. Pendekatan client centered adalah pendekatan yang berpusat pada diri klien, yang mana seorang konselor hanya memberikan konseling serta mengawasi klien pada saat mendapatkan pemberian konseling tersebut agar klien dapat berkembang atau keluar dari masalah yang dihadapinya. Introvert merupakan tipe kepribadian individu yang mempunyai kecenderungan menutup diri dari dunia luar. Jenis penelitian yang digunakan adalah peneltian kualitatif studi kasus. Penelitian dilakukan di MA NU Al Hidayah Kudus Tahun Pelajaran 2016/2017, dengan dua subjek penelitian (ABS, DAS). Metode pengumpulan data yang digunakan: 1. Wawancara, 2. Observasi, 3. Dokumentasi dan 4. Home Visit. Analisis data yang digunakan adalah: analisis sistem Bacon. Hasil penelitian: 1. Konseli I (ABS) faktor yang menyebabkan memiliki kepribadian intovert: 1. Tidak percaya diri. ABS yang berusia 16 tahun dan saat ini tengah duduk di kelas XI IPS MA NU Al Hidayah Kudus merasa kurang percaya diri dengan bentuk kaki yang dimiliki membuat ABS menjadi pibadi yang tidak percaya diri dalam pergaulan, sehingga membuat konseli sering mendapatkan perlakuan yang tidak menyenangkan dari siswa-siswi lain. Konseli memang terlahir dengan keadaan yang tidak sempurna karena cacat fisik pada salah satu kakinya atau yang biasa disebut sebagai (Clubfoot) atau kaki pengkor. 2. Perlakuan diskriminasi. Karena bentuk fisik yang dimiliki oleh konseli yang berbeda, konseli mendapatkan perlakuan diskrinasi dari siswa-siswi lain. 2. Konseli II (DAS) faktor yang menyebabkan konseli memiliki kepribadian introvert: 1. Rendahnya kemampuan interaksi konseli. Konseli sering berpindah tempat tinggal sejak usia sekolah dasar membuat kemampuan interaksi DAS kurang. Di sekolah, konseli banyak diperhatikan oleh siswa-siswi di sekolah karena secara fisik DAS merupakan siswa yang berpenampilan menarik. Tetapi kurang interaksi sosial, konseli lebih banyak memilih menyendiri dan tidak terlihat aktif dalam hubungan pertemanan yang sering terjalin pada anak usia sekolah atau remaja awal. 2. Perceraian kedua orang tua konseli. Perceraian yang ditimbulkan karena keuangan keluarga yang memburuk membuat konseli harus bekerja keras untuk membiayai sekolahnya semakin membuat konseli tidak memiliki waktu untuk bersosialisasi dengan teman sebayanya. Setelah pelaksanaan tiga kali konseling client centered terhadap kedua konseli diperoleh keterangan bahwa, konseli I (ABS) telah mampu menerima kekurangan dirinya yang memiliki keterbatasan pada kakinya. ABS telah percaya diri dan mampu bersosialisasi dengan baik. Konseli II (DAS) telah menyadari bahwa kehidupan yang ia alami harus tetap berjalan, dan DAS juga telah memahami bahwa makna kehidupan adalah terus bekerja dan bahagia atas apa yang dimilikinya sekarang. Berdasarkan kesimpulan di atas peneliti dapat memberikan saran: 1. Kepala sekolah: Dalam penelitian ini menunjukkan bahwa konseling individual sangat membantu siswa dalam memberikan mengatasi perilaku introvert siswa. Sehingga diharapkan kepala sekolah dapat mendukung adanya layanan konseling indivual ini dengan memfasilitasi guru pembimbing dalam memberikan layanan konseling individual. 2. Guru bimbingan dan konseling: Diharapkan guru bimbingan dan konseling dapat menjadikan hasil penelitian sebagai acuan dalam memberikan pelayanan konseling individual dengan konseling client centered. 3. Siswa: Diharapkan siswa dapat bergaul dengan baik dan semakin meningkatkan hubungan interpersonal. 4. Penelitian selanjutnya: Diharapkan peneliti selanjutnya dapat mengembangkan penelitian yang sejenis dengan menggunakan layanan konseling yang lebih varatif, sehingga didapatkan komparasi yang berbeda dengan penelitian ini

Increased Anti-HSP60 and Anti-HSP70 Antibodies in Women with Unexplained Recurrent Pregnancy Loss

　Vascular dysfunction has been reported in women with recurrent pregnancy loss (RPL). We investigated the severity of vascular dysfunction in non-pregnant women with RPL and its correlation with anti-heat shock protein (HSP) antibodies that are known to induce arteriosclerosis. We measured the serum anti-HSP60 antibodies, anti-HSP70 antibodies, and anti-phospholipid antibodies (APA) in 68 women with RPL and 29 healthy controls. Among the women with RPL, 14 had a diagnosis of antiphospholipid syndrome (APS), and in the remaining 54, the causes for RPL were unexplained. Compared to the controls, the brachial-ankle pulse wave velocity (baPWV), carotid augmentation index (cAI), and uterine artery pulsatility index (PI) were all significantly higher in the women with both APS and unexplained RPL. Compared to the controls, the anti-HSP60 antibody levels were significantly higher in the APA-positive group of women with unexplained RPL, and the anti-HSP70 antibody levels were significantly higher in APS and APA-positive group of women with unexplained RPL. However, the anti-HSP60 and anti-HSP70 antibody levels did not correlate with the values of baPWV or cAI. Our results demonstrated anti-HSP60 and anti-HSP70 antibodies are increased in women with unexplained RPL. Further studies are needed to elucidate the roles of anti-HSP antibodies and their pathophysiology in unexplained RPL

Abortions in First Trimester Pregnancy, Management, Treatment

The miscarriages’ investigation should include a familiar history, gynecological examination and a full laboratory testing including hormonal control, as well as karyotype, maternal immune control and thrombophilia testing. If the physician suspects the cause of abortions is chromosomal due to heredity, a special blood test (karyotype) for the pair is recommended. Chromosomal abnormalities are the most common reason for first trimester abortions, and are impossible to be prevented. Based on the above data, abortion and the subsequent possible infertility should not be considered as a personal failure for the woman and the treating physician. Nowadays, medical advancement provides many options combined with psychological support can actually reduce the miscarriages’ risk

Control of human trophoblast function

The trophoblast, i.e. the peripheral part of the human conceptus, exerts a crucial role in implantation and placentation. Both processes properly occur as a consequence of an intimate dialogue between fetal and maternal tissues, fulfilled by membrane ligands and receptors, as well as by hormone and local factor release. During blastocyst implantation, generation of distinct trophoblast cell types begins, namely the villous and the extravillous trophoblast, the former of which is devoted to fetal-maternal exchanges and the latter binds the placental body to the uterine wall. Physiological placentation is characterized by the invasion of the uterine spiral arteries by extravillous trophoblast cells arising from anchoring villi. Due to this invasion, the arterial structure is replaced by amorphous fibrinoid material and endovascular trophoblastic cells. This transformation establishes a low-resistance, high-capacity perfusion system from the radial arteries to the intervillous space, in which the villous tree is embedded. The physiology of pregnancy depends upon the orderly progress of structural and functional changes of villous and extravillous trophoblast, whereas a derangement of such processes can lead to different types of complications of varying degrees of gravity, including possible pregnancy loss and maternal life-threatening diseases. In this review we describe the mechanisms which regulate trophoblast differentiation, proliferation, migration and invasiveness, and the alterations in these mechanisms which lead to pathological conditions. Furthermore, based on the growing evidence that proper inflammatory changes and oxidative balance are needed for successful gestation, we explain the mechanisms by which agents able to influence such processes may be useful in the prevention and treatment of pregnancy disorders

Spontaneous pregnancy loss mediated by abnormal maternal inflammation in rats is linked to deficient uteroplacental perfusion

Abnormal maternal inflammation during pregnancy is associated with spontaneous pregnancy loss and intrauterine fetal growth restriction. However, the mechanisms responsible for these pregnancy outcomes are not well understood. In this study, we used a rat model to demonstrate that pregnancy loss resulting from aberrant maternal inflammation is closely linked to deficient placental perfusion. Administration of LPS to pregnantWistar rats on gestational day 14.5, to induce maternal inflammation, caused fetal loss in a dose-dependent manner 3-4 h later, and surviving fetuses were significantly growth restricted. Pregnancy loss was associated with coagulopathy, structural abnormalities in the uteroplacental vasculature, decreased placental blood flow, and placental and fetal hypoxia within 3 h of LPS administration. This impairment in uteroplacental hemodynamics in LPS-treated rats was linked to increased uterine artery resistance and reduced spiral arteriole flow velocity. Pregnancy loss induced by LPS was prevented by maternal administration of the immunoregulatory cytokine IL-10 or by blocking TNF-α activity after treatment with etanercept (Enbrel). These results indicate that alterations in placental perfusion are responsible for fetal morbidities associated with aberrant maternal inflammation and support a rationale for investigating a potential use of immunomodulatory agents in the prevention of spontaneous pregnancy loss. Copyright © 2011 by The American Association of Immunologists, Inc