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PubMed2005

Roles of methylenetetrahydrofolate reductase C677T polymorphism in repeated pregnancy loss.

Congenital thrombophilia in repeated pregnancy lost (RPL) has been noted for years. Methylenetetrahydrofolate reductase (MTHFR) gene is an interesting gene, mentioned for its possible roles in RPL. There is considerable controversy regarding the clinical role of MTHFR C677T polymorphism as a risk factor of RPL. Here, a summative analysis is performed on the recent previous reports on the MTHFR C677T and its correlation to RPL. The metanalysis was performed to assess the correlation between the pattern of MTHFR C677T polymorphism and RPL. From available eight case-control studies, 752 patients and 625 controls are evaluated. The overall frequencies of 4G allele for the patients and controls are 31.5 and 33.5, respectively. According to this study, 53.1% of subjects with T allele have RLP while 55.3% of subjects without T allele have RLP. From overall risk estimation, the subjects with T alleles have 0.96 times lower risk to RLP. According to this analysis, the pattern of MTHFR C677T polymorphism might not represent a useful marker of increased risk for RPL. In addition, there was no association between pattern of MTHFR C677T polymorphism and ethnicity of the patients in this study.

Abortion, Habitual↗

PubMed1990

Interactions between endogenous virus loci ev6 and ev21. 1. Immune response to exogenous avian leukosis virus infection.

The effects of ev6, ev21, sex, and hatch, were studied with respect to avian leukosis virus (ALV) viremia, cloacal shedding, and antibody response among RPL-40 virus-infected White Leghorns that carried ev6 and ev21 in all combinations. Among the four possible ev genotypes, chickens that carried only ev21 were the most immunologically tolerant to RPL-40 infection. Incidence of RPL-40 viremia was lowest among hatchmates that lacked both ev genes. Analysis of variance indicated significant interactions between ev6 and ev21 with respect to all responses. Among ev21+ slow-feathering (SF) chickens, the incidence of viremia and shedding of RPL-40 was reduced in the presence of ev6 when compared with ev6- hatchmates. Conversely, among ev21- rapid-feathering (RF) chickens, ev6 significantly enhanced the incidence of RPL-40 viremia when compared with ev6- hatchmates. The endogenous virus, ev6, markedly reduced recovery of the endogenous virus (EV21) from plasmas of slow-feathering chickens. When both flocks were terminated at 21 wk of age, significantly more ev21+ SF females had died from or developed RPL-40-induced tumors than ev21- hatchmates.

Animals↗

PubMed1995

[Identification of patients at risk of post-infarction heart rupture. Clinical and therapeutic characteristics of 121 consecutive cases and review of the literature].

In patients with acute myocardial infarction (AMI) since a decrease of deaths due to arrhythmia control and pump failure, rupture of the left ventricle free wall (RPL) has gained increasing importance as a cause of death. Of 4987 patients hospitalised for AMI from January 1969 to December 1993, RPL occurred in 121 patients (2.4%) and 17.6% of total deaths from AMI are the result of this complication. RPL was found more often in women > 75 years old, with a history of hypertension and sustaining a first coronary event. Cardiac rupture occurred after transmural myocardial necrosis, usually (60%) following an anterior AMI. RPL was an early phenomenon (in 40% it occurred within the first 24 hours and in more than 80% within 5 days from symptoms onset). Although RPL is widely considered catastrophic and unexpected, in the greater number of patients it is possible to recognise symptomatic markers (pain, emesis and agitation) indicative of impending rupture. A prompt diagnosis and the consideration that rupture is usually a stuttering process must point out an aggressive approach, which can allow a surgical treatment of RPL with a likely prognosis.

Age Factors↗

PubMed1997

Autoimmune causes of recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is the loss of 3 or more spontaneous and consecutive pregnancies. There are many causes, such as genetic, anatomic, hormonal, medical and immunologic causes. Two theories, the alloimmune and the autoimmune theories, explain the immunologic cause. The Antiphospholipid Antibody (APA) Syndrome is considered as the autoimmune cause of RPL. It involves two antibodies, Lupus anticoagulant (LAC) and the anti-cardiolipin antibody (ACA). The rate of LAC is 7% and of ACA is 15%, among pregnant women. These two antibodies are believed to cause thrombosis in the maternal circulation, leading to the events that lead to the fetal losses. Women with these antibodies, along with other factors, are believed to be at high risk for RPL. The diagnostic criteria for the APA syndrome include elevated LAC or ACA serum levels and clinical findings of thrombosis, thrombocytopenia and RPL. Presently, the medical treatment of the APA syndrome includes heparin, low-dose aspirin, and immunoglobulins. There must also be an active attempt to search for other causes of RPL among patients with APA syndrome, such as anatomic, endocrinologic, anatomic and medical problems. Management of RPL should also include extensive counseling for the patient and her family.

Abortion, Habitual↗

PubMed1984

Factors related to subsequent reproductive outcome in couples with repeated pregnancy loss.

Specific factors in a couple's history may influence the recurrence risk following repeated pregnancy loss (RPL). Couples with RPL were contacted several years following evaluation and information concerning subsequent pregnancies was obtained. Linear regression analysis was utilized to determine which factors in the history were significant predictors of pregnancy outcome following evaluation. A family history of RPL or a "genetic defect" was a highly significant predictor of subsequent unsuccessful pregnancies. Surgical, but not medical, treatment for RPL was a significant predictor of eventual successful outcome. The number of abortions prior to evaluation for RPL, presence of a liveborn child, maternal age at evaluation, and intercurrent infertility all failed to be significant predictors of pregnancy outcome after evaluation.

Abortion, Habitual↗

PubMed1994

Identification of the core residues of the epitope of a monoclonal antibody raised against glycoprotein D of herpes simplex virus type 1 by screening of a random peptide library.

Random peptide libraries (RPL) displayed on the surface of a filamentous bacteriophage can be used to identify peptide ligands that interact with target molecules. We have used a 15-amino acid residue RPL displayed on bacteriophage M13 to identify the core residues within the epitope of a monoclonal antibody (mAb) A16 which interacts with a continuous epitope restricted to amino acid residues 9 to 19 in the N-terminal region of glycoprotein D of herpes simplex virus type 1 (gD-1). The single peptide sequence obtained after three rounds of selection contained identical residues at three positions compared to the authentic gD-1 sequence. Synthetic peptides were prepared based on the sequence of the original epitope and the phage-derived epitope. The binding constants (Ka) with mAb A16 were determined using surface plasmon resonance (SPR) biosensor technology. The RPL-derived peptide and peptide 9-19 of gD-1 had approximately the same affinity for mAb A16. This suggests that those residues within the epitope that are essential for binding were identified. The synthesis of shorter versions of the RPL-derived peptide restricted the binding region to seven amino acid residues. These results show that minimal information retrieved from the screening of an RPL combined with peptide synthesis can characterize the epitope of an mAb with high resolution. Immunization of mice with the phage-derived peptide protected against a challenge with a lethal dose of herpes simplex virus type 1 equally well as the gD-1 derived peptide.

Amino Acid Sequence↗

PubMed2001

Hyperbaric oxygenation after portal vein emobilization for regeneration of the predicted remnant liver.

BACKGROUND: Liver failure often develops after extensive liver resection. Preoperative portal vein embolization to induce compensatory hypertrophy in the predicted remnant liver decreases clinical complications after hepatectomy. The aim of this study was to examine whether hyperbaric oxygenation (HBO) after portal vein embolization increases compensatory hypertrophy of the predicted liver remnant. We performed portal vein ligation and HBO in rats to investigate whether HBO after portal vein embolization increases compensatory hypertrophy of the predicted remnant liver. METHODS: Rats were divided into four groups that underwent (1) laparotomy only (control group); (2) right portal vein ligation (RPL group); (3) RPL followed by HBO at 2 atm (HBO-2 atm group; 1 h/day, 5 days/week for 2 weeks); or (4) RPL followed by HBO at 3 atm (HBO-3 atm group). Laparotomy was repeated after 2 weeks in each group; serum levels of albumin and hepatocyte growth factor (HGF) were measured, and the ratio of the weights of nonligated to ligated hepatic segments and the percentage of hepatocytes expressing proliferating cell nuclear antigen (PCNA) in ligated hepatic segments were determined. RESULTS: In rats that had received HBO after RPL, serum levels of HGF, weight ratios of nonligated to ligated hepatic segments, and the percentage of PCNA-positive hepatocytes in nonligated liver were significantly higher than those in the control group. Furthermore, rats that had undergone 3-atm HBO after RPL had significantly higher serum levels of HGF and percentages of PCNA-positive hepatocytes in nonligated hepatic segments. CONCLUSIONS: Preoperative HBO after portal vein embolization may be useful for inducing compensatory hypertrophy of the predicted remnant liver.

Animals↗

PubMed1988

Hyporeactivity to mitogens of retroplacental blood lymphocytes in human pregnancy.

Retroplacental blood lymphocytes (RPL) obtained from women without complications at the term delivery were studied for proliferative response to mitogens and surface phenotype and were compared with autologous peripheral blood lymphocytes (PBL). Proliferation of RPL induced by phytohemagglutinin (PHA) was significantly lower than that of PBL in 11 of 13 cases. Also RPL proliferated poorly in response to concanavalin A (Con A) in 8 of 10 cases. On the other hand, flow cytometry analysis of T cell subsets revealed that RPL contain comparable or higher number of CD3+ cells and CD4+ cells and similar numbers of CD8+ cells as compared with PBL in most cases. These results indicate that T cell proliferative response in retroplacental space is impaired, which could be due to a functional defect of RPL.

Antigens, Surface↗

PubMed2006

Y-chromosome microdeletions and recurrent pregnancy loss.

OBJECTIVE: To determine the prevalence of Y-chromosome microdeletions in recurrent pregnancy loss (RPL) couples as compared with couples with male factor infertility and fertile couples. DESIGN: Controlled clinical study. SETTING: Andrology laboratory and RPL clinic. PATIENT(S): Seventeen men from RPL couples, 18 men from couples with a live birth and no history of miscarriages, and 10 men from couples with male factor infertility. INTERVENTION(S): Buccal smears for Y-chromosome microdeletion testing. MAIN OUTCOME MEASURE(S): The DNA was tested for microdeletions in the proximal AZFc region by polymerase chain reaction (PCR). RESULT(S): Fourteen of the 17 men (82%) tested had microdeletions in one or more of the four segments studied. Two of the 10 male factor infertility patients (20%) had microdeletions in 2 different segments. None of the 18 fertile men had any microdeletions in the 4 segments of the proximal AZFc region studied. CONCLUSION(S): The prevalence of the Y-chromosome microdeletions in the proximal AZFc region was much higher in men from RPL couples than from fertile or infertile couples. Although these patients are from a tertiary referral center that may skew the population and findings, one may consider Y-chromosome microdeletion testing particularly of the AZFc region in the evaluation of RPL couples when all other tests fail to reveal the etiology.

Abortion, Habitual↗

PubMed2006

Pregnancy-associated plasma protein-A polymorphism and the risk of recurrent pregnancy loss.

Pregnancy-associated plasma protein-A (PAPP-A)/insulin-like growth factor-binding protein-4 (IGFBP4) protease is a member of the metzincin family of metalloproteases, known as a sensitive biomarker of adverse pregnancy outcomes. Recently, a missense A/C (Tyr/Ser) polymorphism (dbSNP: rs7020782) in the PAPPA gene has been reported. To examine the association between recurrent pregnancy loss (RPL) and this polymorphism, a case-control study of 215 cases with two or more pregnancy losses (PLs) and 420 fertile controls was performed. Genotyping of the PAPPA polymorphism was determined by allelic discrimination using fluorogenic probes and the 5' nuclease assay. Sixty-nine cases (32.1%) were heterozygous and 11 cases (5.1%) were homozygous for the C allele of PAPPA; the respective figures were 127 (30.2%) and 11 (2.6%) in the controls. Women carrying the C allele had a tendency to increased risk of RPL (AA genotype [reference]; AC genotype: odds ratio [OR], 1.17; 95% confidence interval [CI], 0.82-1.68; CC genotype: OR, 2.06; 95% CI, 0.87-4.90), but it was not significant. Women with three or more PLs had a similar tendency (AA genotype [reference]; AC genotype: OR, 1.04; 95% CI, 0.66-1.64; CC genotype: OR, 2.20; 95% CI, 0.82-5.91). The risk of RPL with at least one PL after 9 weeks' gestation significantly increased in women carrying the C allele (AA genotype [reference]; AC genotype: OR, 1.54; 95% CI, 0.95-2.49; CC genotype: OR, 2.83; 95% CI, 1.00-8.05; AC+CC genotypes: OR, 1.65; CI, 1.04-2.62). This is the first report on the PAPPA gene polymorphism in women with RPL, demonstrating some association between the investigated polymorphism and the risk of RPL.

Abortion, Habitual↗

PubMed2004

Nerve-sparing retroperitoneal lymphadenectomy using hydro-jet dissection: initial experience.

BACKGROUND AND PURPOSE: Nerve-sparing retroperitoneal lymphadenectomy (RPL) is performed in a significant number of patients to preserve ejaculation after treatment for testicular cancer. Identification and preservation of the sympathetic nerves may be challenging. Hydro-Jet technology has been utilized for various surgical applications. A small high-pressure stream of water is used to delineate surgical planes, with preservation of vascular and neural structures. We have examined the utility of this technology for RPL in a porcine model and in human subjects. MATERIALS AND METHOD: A Helix Hydro-Jet device (Erbe, USA) was used for all procedures. A high-pressure water-jet stream is directed through a small nozzle with a 120-microm inner radius for soft-tissue dissection. The upper pressure limit (range 0-2175 psi) is set using a digital monitor. The jet is initiated using a foot pedal, and the actual pressure is monitored. A pressure of 360 to 400 psi was used for experimental studies, which was decreased to 255 to 300 psi for human use. Three pigs underwent RPL using this technique. Subsequently, RPL was performed in five men with testicular cancer, being primary in two and postchemotherapy in three. The primary diagnosis was seminoma in one and non-seminomatous cancer in four. The patient with seminoma had a residual mass after chemotherapy. RESULTS: The procedures were completed successfully in all subjects. There were no intraoperative or postoperative complications. Hydro-Jet dissection permitted tissue selectivity, with preservation of vascular structures and sympathetic nerves. The soft tissue and lymphatics were removed with the high-pressure water stream assisted by blunt dissection. The nerve fibers were grossly resistant to the pressure used and were isolated individually. Dissection around the great vessels appeared to be safe, and no injury was observed with direct application of the jet. Lumbar arteries and veins and accessory vessels could be isolated safely. The estimated blood loss was minimal in animals and 300 to 800 mL in humans. CONCLUSIONS: Hydro-Jet dissection demonstrated tissue selectivity using a pressure range of 255 to 300 psi in humans. The vascular structures and sympathetic nerves were preserved. Our initial experience with this device for nerve-sparing RPL is encouraging.

Adult↗

PubMed2002

Antiphospholipid antibodies (APA) and recurrent pregnancy loss: treating a unique APA positive population.

BACKGROUND: Recurrent pregnancy loss (RPL) has been associated with antiphospholipid antibodies (APA) including anticardiolipin and lupus anticoagulant. Therapy using heparin and aspirin has been shown to significantly improve the live birth rate. We evaluated whether other APA should be considered as a basis for treatment in women with RPL. We also assessed the efficacy of heparin and aspirin therapy compared with aspirin alone in these women. METHODS: A two-centred, prospective, cohort evaluation of 79 women with two or more consecutive pregnancy losses who underwent a complete evaluation for RPL that was negative except for positive APA. Women with RPL and APA to cardiolipin (CL), phosphatidyl serine (PS) and/or lupus anticoagulant (LAC) treated with heparin and aspirin (group 1) were compared with those with other positive APA (to phosphatidyl inositol, phosphatidyl glycerol and/or phosphatidyl ethanolamine) treated with heparin or aspirin (group 2) or treated with aspirin alone (group 3). RESULTS: There were no significant differences in patients' demographics between groups. There were 19 viable infants born to 25 women (76%) in group 1, 18 viable infants born to the 28 women (64%) in group 2, and 12 viable infants born to the 26 women (46%) in group 3. Only the comparison between group 1 and group 3 reached statistical significance (P = 0.03). CONCLUSION: APA other than CL, PS and LAC may be associated with RPL.

Abortion, Habitual↗

PubMed2004

Association of CYP1A1 gene polymorphism with recurrent pregnancy loss in the South Indian population.

BACKGROUND: We investigated the relationship between idiopathic recurrent pregnancy loss (RPL) and genetic polymorphisms in phase I and phase II detoxification genes which include CYP1A1, CYP2D6, GSTM1, GSTP1 and GSTT1. METHOD: A case-control study comprised 160 females with RPL and 63 healthy controls with a successful reproductive history. RESULTS: The CYP1A1 variant allele was present at frequencies of 0.61 and 0.44 in cases and controls, respectively (odds ratio=1.93; P=0.023, 95% confidence interval 1.10-3.38). The CYP2D6 variant allele was present at a frequency of 0.17 in females with RPL, while in the control population the frequency was 0.16. The GSTM1 and GSTT1 null genotypes were present at frequencies of 0.39 and 0.26 in RPL cases, whereas in controls the frequencies were 0.37 and 0.17, respectively. The mutant GSTP1 frequencies in case and control women were 0.38 and 0.40, respectively. We report a significant association of the CYP1A1*2A allele with RPL which is confirmed by logistic regression analysis. No association was observed for the other polymorphisms or in their combinations studied. CONCLUSIONS: The present study suggests the occurrence of the CYP1A1*2A allele as a probable risk factor in idiopathic recurrent miscarriages.

Abortion, Habitual↗

PubMed2003

Glutathione S-transferase M1 and T1 polymorphisms and the risk of recurrent pregnancy loss.

The aetiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in two genes, glutathione S-transferases (GST) M1 and T1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. A case-control study of 115 cases with RPL and 160 controls was conducted. All cases and controls were women resident in Sapporo, Japan and the surrounding area. They were genotyped for polymorphisms of GSTM1 and GSTT1 using PCR-based methods. We found that 65.2% of the cases with RPL and 45.6% of the controls had the GSTM1 null genotype [odds ratio (OR) = 2.23, 95% confidence interval (CI) = 1.36-3.66]. On the other hand, 47.0% of the cases and 49.4% of the controls had the GSTT1 null genotype (OR = 0.95; 95% CI = 0.58-1.55). The results suggest that women with GSTM1 null polymorphism may therefore have an increased risk of RPL.

Abortion, Habitual↗

PubMed2003

A polymorphism in the CYP17 gene relates to the risk of recurrent pregnancy loss.

The CYP17 gene encodes the enzyme cytochrome P450c17alpha, which mediates both 17alpha-hydroxylase and 17,20-lyase activity in the steroid biosynthesis pathway. A T-->C polymorphism in the 5' promoter region of CYP17 has been described. To examine the association between recurrent pregnancy loss (RPL) and a polymorphism in CYP17, a case-control study of 117 cases with RPL and 164 controls was conducted. This polymorphism was investigated by PCR/restriction fragment length polymorphism using DNA from peripheral lymphocytes. The T-->C transition in the variant allele (A2) creates a new recognition site for the restriction enzyme MspA1, which permits designation of the wildtype allele (A1) and A2. Women with the A2 allele of CYP17 had an increased risk of RPL [A1/A1 genotype (reference); A1/A2 genotype: odds ratio (OR), 1.68; 95% confidence interval (CI), 0.94-3.01; A2/A2 genotype: OR, 2.37; 95% CI, 1.16-4.83; P trend, 0.016]. Additionally, there was a similar tendency for the increased risk of primary RPL [A1/A1 genotype (reference); A1/A2 genotype: OR, 2.14; 95% CI, 1.14-4.01; A2/A2 genotype: OR, 2.50; 95% CI, 1.16-5.41; P trend, 0.015]. These results suggest that possession of the A2 variant of CYP17 may predispose to an increased risk of RPL with a gene dosage effect.

Abortion, Habitual↗

PubMed2004

Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not involved in the risk of recurrent pregnancy loss.

The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.

Abortion, Habitual↗

PubMed1984

Evidence for an inhibitory influence of rat placental lactogen on prolactin release in vitro.

Incubation of placental tissue from Day 11 pregnant rats for increasing periods of time resulted in proportionately more rat placental lactogen (rPL) release. The amount of placental tissue incubated correlated directly with the amount of rPL released into the medium. When placentas were coincubated with anterior pituitaries from ovariectomized rats, prolactin release was significantly inhibited. When media from incubations which had contained varying numbers of Day 11 placentas for 24 h were added to vials containing anterior pituitaries, prolactin release was inhibited, proportionate to the amount of rPL in the media. Media from incubations of Day 9 placentas, which contained very little rPL, had no effect on prolactin release. When medium containing anterior pituitary tissue was incubated for 24 h, pituitaries removed, and the medium incubated with placental tissue for an additional 24 h, there was no difference in prolactin levels compared to incubation medium not containing placental tissue. Addition of a trypsin inhibitor to the medium containing placental tissue did not augment the amount of prolactin remaining after a 24-h incubation. Thus it would appear that the placenta does not release a substance into the medium that destroys prolactin. This suggests that secretions from the placenta, presumably rPL, can exert a negative feedback on prolactin secretion at the level of the anterior pituitary.

Animals↗

PubMedDate not supplied

Reduction of interleukin-2-receptor expression on retroplacental blood lymphocytes in human pregnancy.

Retroplacental blood lymphocytes (RPL) in human pregnancy were studied for proliferative response induced by recombinant interleukin-2 (rIL-2) and anti-Tac positive cells before and after PHA stimulation for 24 hr and compared with peripheral blood lymphocytes (PBL) of the same donor. Proliferation of RPL induced by IL-2 was significantly lower than that of PBL in all of six cases. In addition, flow cytometry analysis of IL-2 receptors (IL-2R) revealed that IL-2R expression of RPL after stimulation with PHA for 24 hr was significantly less than that of PBL in three of four cases and that RPL showed significantly fewer IL-2R than PBL even at resting state in one case. These results suggest that RPL seem likely to be composed of reduced numbers of lymphocytes bearing IL-2R of non-Tac protein and to have impaired capacity for the acquisition of high-affinity receptors for IL-2.

Female↗