Cytokines and immuno-endocrine factors in recurrent miscarriage (original) (raw)
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Recurrent miscarriage: pathophysiology and outcome
Current Opinion in Obstetrics & Gynecology, 2005
Purpose of review This article reviews new concepts in the aetiology of recurrent miscarriage, presents new outcome data and evaluates new modalities of treatment for unexplained recurrent miscarriage. Recent findings Preimplantation genetic diagnosis has been considered an option for couples who have structural chromosomal abnormalities or unexplained recurrent miscarriage. The association between thrombophilias and adverse pregnancy outcome is further reviewed. In relation to this, there is increasing support for the use of thromboprophylaxis in improving pregnancy outcome in women with inherited thrombophilias. Nonrandomized studies have shown that the reduction in insulin levels with metformin in insulin-resistant individuals may reduce miscarriage risk by restoring normal haemostasis and improving the endometrial milieu. With respect to immunological concepts there is now evidence to suggest that, in addition to a suppression of maternal cell-mediated immunity, some elements of the innate immune system are activated in successful pregnancies. Summary With the exception of aspirin and heparin for the prevention of recurrent miscarriage in women with the antiphospholipid syndrome, no other suggested therapies for this heterogeneous group of patients have been evaluated in randomized controlled trials. These include thromboprophylaxis for inherited thrombophilias and use of insulin sensitizers in women with insulin resistance and/or polycystic ovarian syndrome. The role of the innate immune system in pregnancy was recently highlighted, and use of nonspecific therapies to suppress the maternal immune response to pregnancy should be reassessed.
Recurrent miscarriage: an overview
Reviews in Gynaecological Practice, 2003
Recurrent miscarriage (RM) is a clinical condition of heterogeneous aetiology. Classification of recurrent pregnancy loss is a crucial tool in the investigation and exploration of pathophysiological mechanisms. Some of the previous causes of RM, such as polycystic ovaries, and endocrinopathies are now viewed with scepticism, paving the way for a modern, refined and evidence-based approach. While the antiphospholipid syndrome continues to be a prominent feature in RM, the traditional thrombotic pathogenetic mechanism has been extrapolated, encompassing the direct effect of anticardiolipin antibodies on trophoblast invasion. Furthermore, the emergence of other thrombophilias, have gained more consideration as aetiological factors. At the molecular and biological phases, more light has been shed on immunological influences and the role of a hostile endometrium. The fate of normal and abnormal embryos has challenged traditional concepts of RM, giving birth to the paradigm of nature's quality control.
Evidence of a TH 1 type response associated with recurrent miscarriage
Fertility and Sterility, 2000
To determine whether the T(H) 1 cytokine interferon (IFN)-gamma is associated with miscarriage whereas the T(H) 2 cytokine interleukin (IL)-10 is associated with successful pregnancy. Controlled clinical study. Healthy volunteers in an academic setting. Group 1 comprised 10 nonpregnant women; group 2, 10 first-trimester primigravid women; group 3, 10 first-trimester primigravid women suffering spontaneous abortion; and group 4, 10 first-trimester pregnant women with a history of miscarriage. All women were pregnant at the time of sampling, but 5 miscarried later in the first trimester. None of the patients received any medication. Serum levels of IL-10 and IFN-gamma. Levels of IL-10 were significantly raised in normal pregnancy. Levels of IFN-gamma were raised in the recurrent-miscarriage group as compared with normal pregnancy. When patients in group 4 were divided into those whose pregnancies went to term and those who miscarried, we found that successful pregnancy was associated with a statistically significant increase in IL-10, whereas miscarriage was associated with significantly increased levels of IFN-gamma. These results support the view that miscarriage is associated with a T(H) 1 type response.
Recurrent miscarriage: current concepts in diagnosis and treatment
Journal of Reproductive Immunology, 2010
Please cite this article in press as: Toth, B., et al., Recurrent miscarriage: current concepts in diagnosis and treatment. Please cite this article in press as: Toth, B., et al., Recurrent miscarriage: current concepts in diagnosis and treatment. Please cite this article in press as: Toth, B., et al., Recurrent miscarriage: current concepts in diagnosis and treatment.
Role of genetic factors in recurrent miscarriages -A review
Role of genetic factors in recurrent miscarriages - A review, 2022
Recurrent miscarriage is classically defined as three or more consecutive pregnancy losses in about 1-5% of couples trying to conceive. However, several researchers have amended this to two or more because of the recent increase in childless miscarriages. Recurrent miscarriage is a clinical challenge for clinicians because there are many possible causes, and diagnostic testing is expensive and time-consuming. Established causes of recurrent miscarriage are antiphospholipid antibodies, uterine anomalies, and abnormal chromosomes in either partner, particularly translocations. Uterine anatomical abnormalities, endocrine abnormalities, infections, immunologic factors, environmental factors, metabolic or hormonal disorders, sperm quality, and maternal and paternal age have each been linked. Among them, the genetic factor plays a significant role in recurrent miscarriage. Approximately 70% of miscarriage conceptions with sporadic spontaneous miscarriage reveal some chromosome abnormality. Specifically, recurrent miscarriage can be caused by a structural or numerical defect in the parents' or fetus' chromosomes. Recurrent miscarriage has been linked to several genes, including those involved in oxidative stress, angiogenesis, clotting, and inflammation. Despite several wellknown etiologic factors, the etiology of recurrent miscarriage is unknown in over half of all instances. The current review aims to analyse the role of the genetic basis of recurrent miscarriages.
Recurrent miscarriage and factors that effects its: A review
2024
Spontaneous abortion is a commonly occurring issue during human pregnancy. The definition provided by the WHO in 1977 is universally accepted. Recurrent pregnancy loss is a multifaceted health issue that lacks a universally agreed-upon definition. The lack of agreement in definitions encompasses not only the varying number of spontaneous abortions (two or three) that are considered recurrent pregnancy losses but also the different types of pregnancies and the gestational age at which the miscarriage occurs. The prevalence among clinical pregnancies is approximately less 15%, but when early pregnancy losses are included, it rises to 17–22%. The only two etiologic causes that all authors agree on are uterine abnormalities and paternal balanced chromosomal rearrangements. Numerous alternative risk variables have been proposed.
Abnormal cytokine levels in non-pregnant women with a history of recurrent miscarriage
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2004
To compare cytokine levels in serum from non-pregnant women with a history of recurrent miscarriage with those found in non-pregnant women with no such history. Two patient groups were enrolled into the study. Group 1 comprised 25 non-pregnant women with no history of recurrent miscarriage. Group 2 comprised 50 non-pregnant women who had a history of at least three previous miscarriages. Fifteen of these women have since become pregnant again--10 had a successful pregnancy and five miscarried. Serum levels of IL-4, IFN gamma, IL-12 and IL-18 were measured. Results showed IFN gamma ( 0.68 +/- 0.72 versus 0.45 +/- 0.29 P < 0.05) and IL-12 levels (66 +/- 25 versus 51 +/- 24 P < 0.05) were significantly higher in Group 2 compared to Group 1. Levels of IL-18 were significantly lower in Group 2 patients (318 +/- 140 versus 246 +/- 219 P < 0.05). Of the 15 women who became pregnant, those who miscarried again had significantly higher IL-18 levels when not pregnant than those women whose next pregnancies went successfully to term (547 +/- 20 versus 274 +/- 129 P < 0.05). These results suggest that women with a history of recurrent miscarriage can have abnormal cytokine expression even when not pregnant. This may influence the potential for future successful immune modulatory therapy.
PHARMACOLOGY, MEDICAL REPORTS, ORTHOPEDIC, AND ILLNESS DETAILS (COMORBID), 2022
Miscarriage occurs when the fetus is unable to survive outside the womb and the results of conception are expelled. Although the issue of RPL is still controversial, current information about the suggested treatment offers effective treatment to improve reproductive quality and can provide appropriate therapy in a woman with RPL based on the etiology. The time restriction until the fetus is pronounced viable or capable of surviving outside the womb varies by country. According to the World Health Organization, over 21.6 million abortions occurred worldwide in 2008, with almost all of these cases occur in developing countries. The risk of miscarriage increases most significantly at the age of 35 years. Women aged 35 years have twice the risk of miscarriage compared to women aged < 35 years. Antiphospholipid syndrome is a risk factor for recurrent miscarriage, which occurs in about 15% of patients. The reason of recurrent miscarriage can be linked to both fetal and maternal factors...
Human Reproduction, 1994
A total of 500 consecutive women (mean age 32.9 years; SD 5 years) presenting with a history of recurrent miscarriages (median 4; range 3-17) were investigated for the presence of antiphospholipid antibodies (APA), polycystic ovaries (PCO), hypersecretion of luteinizing hormone (LH) and chromosome abnormalities in order to detect an underlying cause of their pregnancy losses. All women had details of their previous reproductive history, investigations and treatment documented: 76% of the women had experienced only early pregnancy losses (miscarriage < 13 weeks gestation); 32% had a history of subfertility; and significant parental chromosome rearrangements were present in 3.6% of couples. An ultrasound diagnosis of PCO was made in 56% of women, 58% of whom were demonstrated to hypersecrete LH, based on early morning urinary LH analysis. Circulating APA were found in 14% of women. An underlying cause of recurrent miscarriage-genetic, endocrine or autoimmune-was found in >50% of couples. Women in the latter two groups are being recruited to randomized treatment trials which are discussed.
Genetics of Recurrent Miscarriage: Challenges, Current Knowledge, Future Directions
Frontiers in Genetics, 2012
Recurrent miscarriage (RM) occurs in 1-3% of couples aiming at childbirth. Due to multifactorial etiology the clinical diagnosis of RM varies. The design of genetic/"omics" studies to identify genes and biological mechanisms involved in pathogenesis of RM has challenges as there are several options in defining the study subjects (female patient and/or couple with miscarriages, fetus/placenta) and controls. An ideal study would attempt a trio-design focusing on both partners as well as pregnancies of the couple. Application of genetic association studies focusing on pre-selected candidate genes with potential pathological effect in RM show limitations. Polymorphisms in ∼100 genes have been investigated and association with RM is often inconclusive or negative. Also, implication of prognostic molecular diagnostic tests in clinical practice exhibits uncertainties. Future directions in investigating biomolecular risk factors for RM rely on integrating alternative approaches (SNPs, copy number variations, gene/protein expression, epigenetic regulation) in studies of single genes as well as whole-genome analysis.This would be enhanced by collaborative network between research centers and RM clinics.