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Raj Rai

Publications and source records attributed to Raj Rai.

10 recordsLinked to original sources
PubMed2006

Recurrent miscarriage.

Many human conceptions are genetically abnormal and end in miscarriage, which is the commonest complication of pregnancy. Recurrent miscarriage, the loss of three or more consecutive pregnancies, affects 1% of couples trying to conceive. It is associated with psychological morbidity, and has often proven to be frustrating for both patient and clinician. A third of women attending specialist clinics are clinically depressed, and one in five have levels of anxiety that are similar to those in psychiatric outpatient populations. Many conventional beliefs about the cause and treatment of women with recurrent miscarriage have not withstood scrutiny, but progress has been made. Research has emphasised the importance of recurrent miscarriage in the range of reproductive failure linking subfertility and late pregnancy complications and has allowed us to reject practice based on anecdotal evidence in favour of evidence-based management.

Abortion, Habitual↗
PubMed2006

Impaired expression of endometrial differentiation markers and complement regulatory proteins in patients with recurrent pregnancy loss associated with antiphospholipid syndrome.

Antiphospholipid syndrome (APS), characterized by circulating antiphospholipid (aPL) antibodies, is a major cause of early pregnancy failure and placental insufficiency. In this study, we examined whether impaired endometrial differentiation before conception contributes to the high incidence of pregnancy complications in APS. Timed secretory endometrial biopsies were obtained from a cohort of women with recurrent pregnancy loss (RPL). Real-time quantitative (RTQ)-PCR was used to determine the expression levels of transcripts that encode for decidual markers, proinflammatory cytokines and complement regulatory proteins. Expression of decidual markers such as prolactin (PRL), tissue factor (TF) and signal transducer and activator of transcription 5 (Stat5), but not insulin-like growth factor-binding protein 1 (IGFBP-1), was significantly lower in samples obtained from aPL(+) patients (n = 24) when compared with aPL(-) group (n = 58) (P < 0.05). The abundance of transcripts encoding for interferon gamma (IFNgamma), tumour necrosis factor alpha (TNFalpha) or Stat1 did not differ significantly between both groups (P >/= 0.05). However, analysis of transcripts that encode for complement regulatory proteins showed a marked decrease in decay-accelerating factor (DAF/CD55) levels in aPL(+) patients (P = 0.005), which was mimicked at protein level as demonstrated by immunohistochemistry. In summary, patients with RPL have distinct endometrial gene expression profiles depending on the presence or absence of circulating aPL antibodies. In APS, impaired endometrial differentiation and lower DAF/CD55 expression before conception may compromise implantation and predispose to complement-mediated pregnancy failure.

Abortion, Habitual↗
PubMed2006

Anti-inflammatory and immunosuppressive drugs and reproduction.

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

Adult↗
PubMed2006

Heparin prevents programmed cell death in human trophoblast.

Heparin is used clinically for the prevention of pregnancy complications associated with prothrombotic disorders, especially antiphospholipid antibody syndrome. Recent studies have suggested that heparin may exert direct effects on placental trophoblast, independently of its anticoagulant activity. We now demonstrate that heparin abrogates apoptosis of primary first trimester villous trophoblast in response to treatment with the pro-inflammatory cytokines interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. This multifunctional glycosaminoglycan also inhibited apoptosis induced by other agents, including staurosporin, broad-spectrum kinase inhibitor and thrombin. Furthermore, heparin attenuated caspase-3 activity, a hallmark of apoptosis, in human first trimester villous and extravillous trophoblast cell lines treated with peptidoglycan, a Toll-like receptor-2 agonist isolated from Staphylococcus aureus. The ability of heparin to antagonize cell death induced by such diverse apoptotic signals suggested that it acts as a survival factor for human trophoblast. We demonstrate that heparin, like epidermal growth factor (EGF) and heparin-binding EGF (HB-EGF), elicits phosphorylation of the EGF receptor and activation of the phosphatidyl inositol 3-kinase (PI3K)-, the extracellular signal-related kinase 1/2 (ERK1/2)- and the c-Jun NH2 terminal kinase (JNK)-signal transduction pathways in primary villous trophoblast. In summary, we have demonstrated that heparin activates multiple anti-apoptotic pathways in human trophoblast. Our results suggest that heparin may be useful in the management of at-risk patients, even in the absence of an identifiable thrombophilic disorder.

Apoptosis↗
PubMed2005

Natural killer cells and reproductive failure--theory, practice and prejudice.

The relationship between peripheral blood natural killer (NK) cells and reproductive failure is one of the most controversial areas in reproductive medicine. Amidst much publicity, peripheral blood NK cell testing is being promoted as a useful diagnostic test to guide the initiation of a variety of immunosuppressive therapies amongst patients with either recurrent miscarriage or infertility. We contend (i) that at present there is no scientific basis for the introduction of NK cell testing into routine clinical practice, and (ii) that the use of immunosuppressant agents based on the results of such testing may potentially be harmful.

Abortion, Habitual↗
PubMed2003

Is miscarriage a coagulopathy?

PURPOSE OF REVIEW: Pregnancy is a hypercoaguable state. The hypothesis has been developed that many cases of recurrent miscarriage and of later pregnancy complications are caused by a defective maternal haemostatic response leading to thrombosis of the uteroplacental vasculature and subsequent fetal loss. The evidence upon which this hypothesis is based is reviewed. RECENT FINDINGS: The majority of studies report an increased prevalence of genetic thrombophilic mutations in the female partner of couples with recurrent miscarriage. It is important to note, however, that this is not a uniform finding. A sub-group of women with recurrent miscarriage has been demonstrated to be in a prothrombotic state before pregnancy, and that women in such a state are at an increased risk of miscarriage in future untreated pregnancies. Furthermore, the long-term health implications of this hypercoaguability have been highlighted in a large retrospective study reporting an increased risk of ischaemic heart disease among women with a history of pregnancy loss. SUMMARY: Although recurrent miscarriage is a heterogeneous condition and no single abnormality will account for all cases of pregnancy loss, the relationship between abnormalities in the haemostatic pathways and pregnancy outcome is increasingly recognized. The challenges we face are how to discriminate between women with a thrombophilic defect who are destined to miscarry from those whose pregnancy will be successful, the pathology of pregnancy loss associated with thrombophilic defects, the role of the fetal genotype in determining pregnancy outcome, and the management of women with thrombophilic defects both during and beyond their reproductive years.

Abortion, Habitual↗
PubMed2002

High serum luteinizing hormone and testosterone concentrations do not predict pregnancy outcome in women with recurrent miscarriage.

OBJECTIVE: To investigate the relationship between Day 8 serum luteinizing hormone (LH) and testosterone (T) concentrations, and body mass index (BMI) with pregnancy outcome in women with recurrent miscarriage. DESIGN: Prospective observational study. SETTING: National recurrent miscarriage clinic. PATIENT(S): Three hundred forty-four women (median age 32 years; range 18-44) with a history of recurrent first trimester miscarriage (median 4; 3-14; <12 weeks gestation) who conceived spontaneously and who received no pharmacological treatment during pregnancy were studied. All women were antiphospholipid antibody negative and had a normal peripheral karyotype as did their partners. INTERVENTION(S): Outcome of untreated pregnancies. MAIN OUTCOME MEASURE(S): Day 8 serum LH and T concentrations and BMI were correlated with pregnancy outcome. RESULT(S): One hundred and ninety-two (55.8%) women had a live birth and 152 (44.2%) women miscarried. Polycystic ovarian morphology was diagnosed in 174 women (50.6%). There was no significant relationship between follicular phase LH concentrations and pregnancy outcome. Pregnancy outcome was similar in women with normal and high serum T concentrations. BMI value was not significantly different between women who had a live birth and those who miscarried. CONCLUSION(S): The analysis of this large cohort of women with recurrent miscarriage demonstrates that prepregnancy Day 8 serum LH and T concentrations, and BMI do not have a statistically significant relationship with pregnancy outcome.

Abortion, Habitual↗
PubMed2002

Antiphospholipid antibodies and infertility.

Antiphospholipid antibodies (aPL) are an established cause of recurrent pregnancy loss. As defective embryonic implantation is a common link between unexplained infertility and recurrent miscarriage, interest has focused on the potential relationship between aPL and implantation failure after in vitro fertilization and embryo transfer (IVF-ET). This review critically examines the published data to determine whether women undergoing IVF-ET should be routinely screened for aPL. Although most studies have reported an increased prevalence of aPL among women undergoing IVF-ET, prospective studies examining the effect of aPL on the outcome of IVF-ET demonstrate that these antibodies do not significantly affect either the implantation or ongoing pregnancy rates. The increased prevalence of aPL among women with infertility is therefore likely to be part of a generalized autoimmune disturbance associated with infertility. Hence routine screening for aPL among women undergoing IVF-ET is not warranted and therapeutic interventions should be used only in well designed randomized controlled trials.

Abortion, Habitual↗
PubMedDate not supplied

Thrombophilia and pregnancy loss.

Thrombophilia is defined as a tendency to thrombosis. The association between specific thrombophilic defects--both inherited and acquired--and pregnancy loss is a rapidly developing field. However, apart from antiphospholipid antibodies (aPL), an acquired thrombophilic defect, the role of other defects in the haemostatic pathways remains to be established. In this invited review we discuss the recent advances in our understanding of aPL related pregnancy loss, the association between genetic thrombophilic mutations and pregnancy outcome and the role of whole blood haemostasis testing in the investigation of women with recurrent miscarriage.

Abortion, Habitual↗