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Ole B Christiansen

Publications and source records attributed to Ole B Christiansen.

13 recordsLinked to original sources
PubMed2006

Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage.

Recurrent miscarriage (RM; > or =3 consecutive early pregnancy losses) affects around 1% of fertile couples. Parental chromosomal anomalies, maternal thrombophilic disorders and structural uterine anomalies have been directly associated with recurrent miscarriage; however, in the vast majority of cases the pathophysiology remains unknown. We have updated the ESHRE Special Interest Group for Early Pregnancy (SIGEP) protocol for the investigation and medical management of RM. Based on the data of recently published large randomized controlled trials (RCTs) and meta-analyses, we recommend that basic investigations of a couple presenting with recurrent miscarriage should include obstetric and family history, age, BMI and exposure to toxins, full blood count, antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies), parental karyotype, pelvic ultrasound and/or hysterosalpingogram. Other investigations should be limited to particular cases and/or used within research programmes. Tender loving care and health advice are the only interventions that do not require more RCTs. All other proposed therapies, which require more investigations, are of no proven benefit or are associated with more harm than good.

Abortion, Habitual↗
PubMed2006

Inflammation and miscarriage.

Most relevant studies in animals and humans indicate that some degree of systemic or uterine inflammation is necessary both for normal implantation and pregnancy. However, if inflammation becomes too excessive it might cause pregnancy complications such as fetal resorption/miscarriage. The main regulator of the correct level of inflammation at the feto-maternal interface seems to be the uterine CD16(-) CD56(bright) natural killer (NK) cells. Trophoblast debris, apoptotic cells and progesterone probably stimulate/regulate the production of inflammatory cytokines from these cells. Miscarriage of karyotypically normal embryos may occur when the level of inflammation at the feto-maternal interface falls outside the optimal range. This may be caused by an insufficient influx of CD56(bright) NK cells into the decidua, too little soluble histocompatibility leukocyte antigen (HLA)-G secretion from the trophoblast, hypersecretion of inflammatory cytokines due to the presence of high-production polymorphisms, presence of maternal HLA-DR alleles associated with high tumor necrosis factor (TNF)-alpha production, or maternal mannose-binding lectin deficiency.

Abortion, Habitual↗
PubMed2006

Future directions of failed implantation and recurrent miscarriage research.

Recurrent implantation failure is today the major reason for women completing several IVF/intracytoplasmic sperm injection attempts without having achieved a child, and is probably also the explanation for many cases of unexplained infertility. Most causes of recurrent miscarriage are still poorly elucidated, but from a theoretical point of view recurrent implantation failure and recurrent miscarriage are suggested to have partly overlapping causes. Recent research has indeed documented that both syndromes can be caused by the same embryonic chromosomal abnormalities and the same maternal endocrine, thrombophilic and immunological disturbances. Consequently, many treatments attempting to normalize these abnormalities have been tested or are currently used in women with both recurrent implantation failure and recurrent miscarriage. However, no treatment for the two syndromes is at the moment sufficiently documented to justify its routine use. In this review, an overview is given regarding present knowledge about causes that may be common for recurrent implantation failure and recurrent miscarriage, and suggestions are put forward for future research that may significantly improve understanding and treatment options for the syndromes.

Abortion, Habitual↗
PubMed2006

Research methodology and epidemiology of relevance in recurrent pregnancy loss.

With respect to recurrent pregnancy loss (RPL), unfortunately there is very little consensus about which investigations are useful for identifying causes and evaluating the prognosis, and also about which treatments are effective. In this review, arguments are given for the claim that this lack of consensus may mainly be because studies in the field of RPL have yielded very heterogeneous results. This heterogeneity, in the authors' belief, is caused by the scientists' lack of appreciation, when they do research, of important epidemiological knowledge about RPL (e.g., about the multifactorial background for most of the RPL cases and the importance of matching/adjusting for a series of prognostic variables when groups are mutually compared). Furthermore, many studies in RPL contain methodological flaws that are sometimes severe. A series of important epidemiological features of RPL is highlighted in the review and the most important methodological pitfalls, many of them specific for RPL research, are discussed. Advice is given about to how to avoid the pitfalls in order that the validity of the studies can improve for the benefit of the patients.

Abortion, Habitual↗
PubMed2006

Evidence-based investigations and treatments of recurrent pregnancy loss.

PURPOSE OF REVIEW: The majority of investigations and treatments offered to women with recurrent pregnancy loss are not evidence-based. In this review a critical analysis is given of the current management of recurrent pregnancy loss often recommended in meta-analyses and guidelines. RECENT FINDINGS: Our knowledge of genetic, endocrine, thrombophilic and immunological causes of recurrent pregnancy loss has been improved significantly, primarily by the introduction of modern laboratory techniques. Most clinical trials in this area, however, are still subject to serious methodological flaws. SUMMARY: At present, the clinician must base their clinical practice on the few high-quality observational studies and intervention trials available rather than on meta-analyses, as there is a scarcity of good clinical trials. More high-quality clinical studies are urgently needed in this area.

Abortion, Habitual↗
PubMed2005

Evidence-based investigations and treatments of recurrent pregnancy loss.

OBJECTIVE: To give an overview of currently used investigations and treatments offered to women with recurrent pregnancy loss (RPL) and, from an evidence-based point of view, to evaluate the usefulness of these interventions. DESIGN: Ten experts on epidemiologic, genetic, anatomic, endocrinologic, thrombophilic, immunologic, and immunogenetic aspects of RPL discussed methodologic problems threatening the validity of research in RPL during and after an international workshop on the evidence-based management of RPL. CONCLUSION(S): Most RPL patients have several risk factors for miscarriage, and an extensive investigation for all major factors should always be undertaken. There is an urgent need for agreement concerning the thresholds for detecting what is normal and abnormal, irrespective of whether laboratory tests or uterine abnormalities are concerned. A series of lifestyle factors should be reported in future studies of RPL because they might modify the effect of laboratory or anatomic risk factors. More and larger randomized controlled trials, including trials of surgical procedures, are urgently needed, and to achieve this objective multiple centers have to collaborate. Current meta-analyses evaluating the efficacy of treatments of RPL are generally pooling very heterogeneous patient populations and treatments. It is recommended that future meta-analyses look at subsets of patients and treatment protocols that are more combinable.

Abortion, Habitual↗
PubMed2005

Linkage disequilibrium between human leukocyte antigen (HLA) class II and HLA-G--possible implications for human reproduction and autoimmune disease.

A line of investigation indicates that one or several genes in the human major histocompatibility complex (MHC) influences reproductive success. Studies have revealed associations between human leukocyte antigen (HLA) class II genes and risk of recurrent spontaneous abortion (RSA) and pre-eclampsia. However, these genes are not expressed at the feto-maternal interface. Furthermore, associations between polymorphisms in the nonclassical HLA class Ib gene, HLA-G, and reproductive outcome have been demonstrated. HLA-G is expressed by extravillous trophoblast during pregnancy, making it a more obvious candidate gene for a possible influence on pregnancy outcome. HLA-G has immunomodulatory functions. We have studied linkage disequilibrium between HLA class II genes, primarily HLA-DRB1 alleles, and HLA-G alleles in women with RSA and their partners (n = 103) and in control women and their partners (n = 92). We found a significant linkage disequilibrium between HLA-DR3 and HLA-G*010102 in both the RSA and control populations. For all four studied HLA loci, the alleles in the haplotype HLA-DRB1*03.DQA1*05.DQB1*02.G*010102 was in clear linkage disequilibrium. This HLA haplotype has repeatedly been associated with different autoimmune diseases but also with RSA. The G*010102 allele includes a 14-bp sequence polymorphism in the 3' untranslated region of the gene, which has been associated with differences in HLA-G mRNA alternative splicing and stability. This 14-bp polymorphism has also been associated with RSA, pre-eclampsia, and outcome of in vitro fertilization. Implications of HLA polymorphism--and other polymorphic genes in the MHC for pregnancy outcome--and for autoimmune diseases during pregnancy are discussed.

Abortion, Habitual↗
PubMed2005

Intravenous immunoglobulin in the prevention of recurrent miscarriage: does it work?

Immunological disturbances play a role in the majority of patients with recurrent miscarriage (RM) and therefore treatment with intravenous immunoglobulin (IvIg) has been tested in patients with RM in several trials. Seven placebo-controlled trials that were extremely heterogeneous with respect to patient characteristics and treatment procedures were carried out. One trial found that IvIg significantly improved pregnancy outcome in all patients whereas the remaining trials could either detect no treatment effect at all or only an effect in subsets of patients. In a meta-analysis, the pooled odds ratio for a new live birth in IvIg- versus placebo-treated patients with RM after a birth (secondary RM) was 1.60 (95% CI = 0.70-3.66). IvIg seems to be efficacious in patients with repeated second trimester intrauterine fetal deaths since it significantly (p < 0.01) increased the live birth rate in this subset compared with placebo. In most trials the design was suboptimal with regard to detecting any treatment effect of IvIg in RM due to low doses or starting the treatment late. A new large placebo-controlled trial should be conducted in RM patients with secondary RM or repeated second trimester fetal deaths and sufficient IvIg doses should be given with optimal timing.

Abortion, Habitual↗
PubMed2004

HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms.

The expression and importance of the non-classical human leukocyte antigen (HLA) class Ib gene, HLA-G, at the feto-maternal interface have been recognized. The HLA-G molecule is almost monomorphic and expressed in both membrane-bound and soluble isoforms. It has been shown to inhibit NK-mediated cell lysis and influence cytokine expression. Recently, a possible boarder immunoregulatory function of HLA-G also in adult life has been recognized. HLA-G gene polymorphism has been linked to differences in gene expression profile of alternatively spliced HLA-G transcripts and levels of specific HLA-G mRNA isoforms. On this background it is of general interest to further elucidate any associations between HLA-G polymorphism and protein expression. We have HLA-G genotyped 85 individuals attending IVF treatment, and further studied sHLA-G1/HLA-G5 and interleukin-10 (IL-10) in serum samples. In 21% of the serum samples sHLA-G1/HLA-G5 could be detected. There was no correlation between sHLA-G1/HLA-G5 and IL-10 concentrations in serum. Soluble HLA-G1/HLA-G5 was not detected in any samples homozygous for a 14-bp insertion polymorphism in exon 8 of the 3'-untranslated region (3'UTR) of the HLA-G gene ( P=0.03; Fisher's exact test). Polymorphisms in the 5'-upstream regulatory region (5'URR) of the HLA-G gene were also studied. In conclusion, this study indicates that polymorphisms in the 3'UTR and the 5'URR of the HLA-G gene may influence the expression of sHLA-G of possible importance in pathological pregnancies and also in organ transplantation.

3' Untranslated Regions↗
PubMed2004

Active or passive immunization in unexplained recurrent miscarriage.

Controversy exists as to whether active immunotherapy with allogeneic lymphocyte transfusions (ALT) or passive immunotherapy with intravenous immunoglobulin (IvIg) improve the chance of live birth in women with unexplained recurrent miscarriages (RM). Meta-analyses of the placebo-controlled trials carried out as Cochrane reviews have concluded than none of the different forms of immunotherapy has proved effective in the total RM population. However, the included trials have generally been small and very heterogenous with respect to the clinical histories of patients and the immunization protocols. Thus, other meta-analyses which have looked at the efficacy in subgroups of RM patients have reported that ALT and IvIg may be effective in women with primary RM and secondary RM, respectively. In RM clinics in Denmark, ALT with donor lymphocytes or IvIg immunotherapy have been tested in several placebo-controlled trials since 1986 in which greater doses than used in other trials have been administered, and both treatments are now used for routine therapy. Our results have convinced us that using the correct immunization protocols on the right subsets of RM patients is effective, but we admit that new placebo-controlled trials focusing on subsets of RM patients are now urgently needed. Furthermore, treated patients should be extensively monitored for changes in a series of immune parameters that may predict pregnancy success and be of importance for our understanding of the mechanisms of action of immunotherapy in RM.

Abortion, Habitual↗
PubMed2002

Low serum level of mannan-binding lectin is a determinant for pregnancy outcome in women with recurrent spontaneous abortion.

OBJECTIVE: The purpose of this study was to investigate the genetic background for the previously reported finding of an increased frequency of low levels of mannan-binding lectin in couples with unexplained recurrent spontaneous abortion and to evaluate the impact of low mannan-binding lectin levels on future pregnancy outcome. STUDY DESIGNS: Mannan-binding lectin levels were measured in 217 women with unexplained recurrent spontaneous abortion and 111 of their husbands and were compared with corresponding measurements in 104 couples with uncomplicated reproductive histories and 210 blood donors. An investigation of the genetic polymorphism, which is largely responsible for serum mannan- binding lectin levels, was done by polymerase chain reaction methods with DNA from a subset of the patients and control subjects. Information was collected about the outcome of the patients' next pregnancies, together with perinatal data concerning the patients' first birth that occurred before or after being assigned to the study. RESULTS: Among women with recurrent spontaneous abortion, 18.9% of the women had mannan-binding lectin levels of </= 100 ng/mL compared with 12.2% of control subjects ( P =.02). An investigation of mannan-binding lectin levels and genetic analyses gave no evidence that paternal mannan- binding lectin deficiency plays a role for recurrent spontaneous abortion. Patients with mannan-binding lectin levels of </=100 ng/mL had a higher abortion rate than patients with normal mannan- binding lectin levels (P <.05). The median birth weight of children who were born at term of women with recurrent spontaneous abortion was 287 g less in women with mannan-binding lectin levels of </= 100 ng/mL than that of patients with normal mannan-binding lectin levels (P =.04). CONCLUSION: Low maternal serum mannan-binding lectin levels exhibit a negative impact on pregnancy outcome in women with unexplained recurrent spontaneous abortion.

Abortion, Habitual↗
PubMed2002

A randomized, double-blind, placebo-controlled trial of intravenous immunoglobulin in the prevention of recurrent miscarriage: evidence for a therapeutic effect in women with secondary recurrent miscarriage.

BACKGROUND: Previous trials of intravenous immunoglobulin (IvIg) treatment of women with recurrent miscarriage (RM) have provided diverging results. This may be due to different inclusion criteria and suboptimal treatment protocols in some trials. METHODS: According to a computer-generated list, 58 women with at least four unexplained miscarriages were randomly assigned to receive infusions of high doses of IvIg or placebo starting as soon as the pregnancy test was positive. RESULTS: In the intention-to-treat analysis, a 45% live birth rate was found in both allocation groups. In patients with secondary RM, 50% in the treatment group and 23% in the placebo group had successful pregnancies (P = not significant). When data from the present and a previous placebo-controlled trial of the same treatment were combined, 15/26 (58%) of the patients with secondary RM in the treatment group versus 6/26 (24%) in the placebo group had successful outcomes (P < 0.02). Only 7% of the karyotyped abortuses were abnormal. CONCLUSIONS: IvIg may improve pregnancy outcome in patients with secondary RM. A new placebo-controlled trial focusing on this subgroup should be conducted to confirm the results.

Abortion, Habitual↗