The absence of factor V Leiden mutation in Malays with recurrent spontaneous abortions

OBJECTIVES: The objectives of this study were to investigate the prevalence of factor V Leiden mutation in Malay women with recurrent spontaneous abortion and to clarify the contribution of the factor V Leiden mutation to recurrent miscarriages in these women. DESIGN: A prospective case control study between June 1999 and April 2000. SETTING: Hospital University Science of Malaysia, Kubang Kerian, Kelantan, and Maternal and Child Health Clinic, Pasir Mas, Kelantan, Malaysia. SAMPLES: A total of 46 Malay women with a history of three or more first or second trimester miscarriages were studied. The control group consisted of 46 parous women without obstetric complications. METHODS: Diagnosis of factor V Leiden mutation was made by examination of factor V Leiden allele product following Mnl I digestion of factor V Leiden alleles amplified by polymerase chain reaction. RESULTS: None of the 46 women with recurrent spontaneous abortion carried the mutation. Also, we found no subject carrying the factor V Leiden alleles in the control group. CONCLUSION: These results suggest that that there is no association between the factor V Leiden mutation and recurrent spontaneous abortion in the Malay population.     

Pregnancy outcome in women with factor V Leiden and recurrent miscarriage

We compared the outcome of 25 untreated pregnancies among women with recurrent miscarriage (RM) at <12 weeks' gestation who were heterozygous for factor V Leiden with women with unexplained RM. The livebirth rate was lower among pregnancies in carriers of factor V Leiden (12/25; 48%) compared with pregnancies in women with unexplained RM (175/307; 57%), but the difference did not reach statistical significance. The best possible treatment regimen to improve livebirth rate in this group of women needs to be assessed in the form of a randomised controlled trial.     

Factor V Leiden mutation in pregnancy

Normal maternal adaptation to pregnancy significantly increases the risk for thrombus formation. Inherited thrombophilias further increase risk for deep venous thrombosis and adverse outcome in pregnancy. Factor V Leiden mutation is the most common inherited thrombophilia, occurring in approximately 5% of the White and 1% of the Black populations. Nurses should be knowledgeable about screening for and diagnosis of factor V Leiden mutation, risk reduction counseling, recommended care of the affected patient, and implications of anticoagulant therapy during the perinatal period.     

Clinical factors associated with pregnancy outcome in women with recurrent pregnancy loss

Abstract

The aim of this prospective cohort study was to evaluate clinical factors associated with pregnancy outcomes in women with recurrent pregnancy loss (RPL). Women with a history of two or more pregnancy losses underwent workups for clinical factors of RPL and their pregnancies were followed-up with informed consent. Two hundred eleven (81.5%) of 259 women with RPL became pregnant. The multivariable analyses demonstrated that age (p?<?.01, OR 0.9, 95%CI 0.97–0.83), uterine abnormality (p?<?.05, OR 0.3, 95%CI 0.11–0.8), and protein C (PC) deficiency (p?<?.01, OR 0.14, 95%CI 0.03–0.6) were independent factors for becoming pregnancy in women with RPL. The number of previous pregnancy loss (p?<?.01, OR 0.57, 95%CI 0.43–0.75) and natural killer (NK) cell activity ≥33% (p?<?.01, OR 0.31, 95%CI 0.13–0.73) were independent factors for live birth in the subsequent pregnancy. Advanced age, the presence of uterine abnormality, and PC deficiency were risk factors for reduced pregnancy rate in women with RPL. Increased number of previous pregnancy loss and high NK cell activity were risk factors for miscarriage in the subsequent pregnancy. These results involve important information and are helpful for clinical practitioners.     

Homozygous factor V Leiden mutation in a woman with multiple adverse pregnancy outcomes

We report a case with one intrauterine fetal death (IUFD) at 32 weeks of gestation, one premature delivery at the same week, and one abortion of unknown etiology at 12 weeks of gestation. We discuss that the presence of homozygosity for Factor V Leiden may be associated with placental insufficiency in this woman. Application of anticoagulant therapy may have been beneficial in her current pregnancy. Received: 1 February 2000 / Accepted: 9 May 2000     

Primary habitual abortions are associated with high frequency of factor V Leiden mutation

OBJECTIVE: To analyze the prevalence of the mutation G1691A in factor V gene (Leiden mutation), of mutation C677T in the methylenetetrahydrofolate reductase (MTHFR) gene, and of polymorphism in G20210A in the prothrombin gene in women with recurrent abortions; further, to identify a subgroup at higher risk of being carriers of these mutations. DESIGN: Prospective case control evaluation. SETTING: University clinic. PATIENT(S): Eighty-four women with 3 or more consecutive miscarriages were compared with 69 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Polymerase chain reactions were performed to identify the mutations G1691A in factor V and C677T in MTHFR genes and the polymorphism G20210A in the prothrombin gene. RESULT(S): In women with primary habitual abortions, 27.8% carried the Leiden mutation. No difference was observed in the prevalence of mutation C677T in the MTHFR gene or in polymorphism G20210A in the prothrombin gene. CONCLUSION(S): The Leiden mutation may play a considerable role for women having primary recurrent abortions.     

Factor V Leiden mutation. Successful outcome of a pregnancy after heparin therapy

Several reports have highlighted the significant correlation between maternal thromboembolism pathologies, such as factor V Leiden mutation, and the occurrence of gestational pathologies. The main causes of thromboembolism pathologies are the inherited coagulopathies. The most common genetic predispositions include autosomal dominant inheritance coagulative factors deficiencies, such as antithrombin III (AT III), C protein (CP), S protein (SP), G20210A mutation, hyperomocystinemia and the activated C protein resistance, caused by factor V Leiden mutation. Maternal thromboembolism as an inherited coagulopathy expression, may be associated with high fetal-maternal morbidity and mortality rate. Nowadays, a wide screening is not possible, but the patients with previous or familiar deep venous thrombosis episodes should at least undergo very careful examinations. In the present case the patient's knowledge of her own status as a factor V Leiden mutation carrier , the prophylactic therapy performed, and the frequent fetal and maternal monitoring allowed us to avoid the recurrence of the dramatic events occurring during her first pregnancy.     

The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus

OBJECTIVE: We sought to estimate the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden (FVL) mutation without a personal history of thromboembolism, and to evaluate the impact of maternal and fetal FVL mutation carriage or other thrombophilias on the risk of adverse outcomes. METHODS: Women with a singleton pregnancy and no history of thromboembolism were recruited at 13 clinical centers before 14 weeks of gestation from April 2000 to August 2001. Each was tested for the FVL mutation, as was the resultant conceptus after delivery or after miscarriage, when available. The incidence of thromboembolism (primary outcome), and of other adverse outcomes, was compared between FVL mutation carriers and noncarriers. We also compared adverse outcomes in a secondary nested carrier-control analysis of FVL mutation and other coagulation abnormalities. In this secondary analysis, we defined carriers as women having one or more of the following traits: carrier for FVL mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations. Carriers of the FVL mutation alone (with or without activated protein C resistance) were compared with those having one or more other coagulation abnormalities and with controls with no coagulation abnormality. RESULTS: One hundred thirty-four FVL mutation carriers were identified among 4,885 gravidas (2.7%), with both FVL mutation status and pregnancy outcomes available. No thromboembolic events occurred among the FVL mutation carriers (0%, 95% confidence interval 0-2.7%). Three pulmonary emboli and one deep venous thrombosis occurred (0.08%, 95% confidence interval 0.02-0.21%), all occurring in FVL mutation noncarriers. In the nested carrier-control analysis (n = 339), no differences in adverse pregnancy outcomes were observed between FVL mutation carriers, carriers of other coagulation disorders, and controls. Maternal FVL mutation carriage was not associated with increased pregnancy loss, preeclampsia, placental abruption, or small for gestational age births. However, fetal FVL mutation carriage was associated with more frequent preeclampsia among African-American (15.0%) and Hispanic (12.5%) women than white women (2.6%, P = .04), adjusted odds ratio 2.4 (95% confidence interval 1.0-5.2, P = .05). CONCLUSION: Among women with no history of thromboembolism, maternal heterozygous carriage of the FVL mutation is associated with a low risk of venous thromboembolism in pregnancy. Neither universal screening for the FVL mutation, nor treatment of low-risk carriers during pregnancy is indicated. LEVEL OF EVIDENCE: II-2.     

Endocrinopathies associated with recurrent pregnancy loss

Repeated pregnancy wastage is defined as the loss of three consecutive pregnancies at less than 20 weeks of gestation andfetal weight less than 500 g. This article provides guidelines to evaluate endocrinopathies associated with recurrent abortions. Thyroid disorder, although usually obvious, has a high frequency in the female population and should be evaluated and treated, if revealed. Recent studies indicate that thyroid antibodies, even in the absence of abnormal thyroid function tests, may be related to pregnancy loss. Diabetes mellitus should be controlled. Luteal phase defects should be sought and, when consistently documented, treated with clomiphene citrate or progesterone supplementation. Bromocriptine may be added to the treatment of a patient with hyperprolactinemia prior to testing for luteal phase defect. An understanding of the stress and anxiety in these couples should always be considered and included in the treatment style of the physician.     

The immunophenotype of patients with recurrent pregnancy loss

OBJECTIVE: The aim of the study was to estimate the alterations in the phenotype of lymphocytes of women with unexplained pregnancy failures in comparison with healthy women. MATERIALS AND METHODS: Fourteen women with unexplained habitual miscarriages and 18 healthy, fertile women with the history of successful pregnancies were included in the study. The lymphocytes were isolated from peripheral blood and stained with monoclonal antibodies. The expression of selected surface molecules was estimated using the flow cytometric method. RESULTS: We found that the percentage of T CD4(+) lymphocytes, CD3(-)16/56(+) cells, and T CD8(+)11b(-) cells was significantly higher in patients with recurrent pregnancy loss in comparison with healthy women. The percentage of B-1 CD19(+)5(+) lymphocytes was also significantly higher in women with unexplained habitual miscarriages in comparison with healthy women. Furthermore, we found higher expression of CD25 molecule on T CD3(+) and T CD4(+) lymphocytes in the study group, when compared to controls. Moreover, the percentages of B CD19(+) and T suppressor CD8(+)11b(+) lymphocytes were lower in women with pregnancy failures in comparison with the control group. The percentage of T CD3(+) lymphocytes and T CD8(+) cells did not differ in both studied groups. Similarly, the expression of CD25 antigen and HLA-DR molecule on T CD8(+) did not differ in the study group, when compared to controls. CONCLUSION: Our results can suggest that the immunological alterations may be involved in the etiopathogenesis of unexplained recurrent pregnancy loss.     

Maternal carriership of factor V Leiden associated with pathological uterine artery Doppler measurements during pregnancy

To determine whether increased vascular resistance in the uterine artery is associated with carriership of factor V Leiden, a retrospective study was undertaken of 231 pregnant women who were monitored with Doppler velocimetry of the uterine arteries. These women had been part of a prospective study of 2480 pregnant women in whom factor V Leiden had been analysed. When compared with non-carriers of factor V Leiden, carriers had a tendency towards an increased proportion of pathological Doppler measurements, including a significant increase in bilateral uterine artery notches (7/33 vs 16/198, relative risk 3.1; 95% CI 1.2–8.1). This suggests an increased vascular resistance in the uteroplacental circulation among carriers of factor V Leiden.     

The impact of male factor on recurrent pregnancy loss

PURPOSE OF REVIEW: The present paper reviews the current literature on the impact of male factor on recurrent pregnancy loss. RECENT FINDINGS: Most clinicians focus their evaluation of recurrent pregnancy loss on the female, without much, if any, consideration of the other half of the couple - the male. Yet, the male contributes one-half of the genes for the embryo. Recent literature demonstrates that the male contributes to recurrent pregnancy loss due to genetic factors, semen factors or due to other factors such as age. SUMMARY: Recurrent pregnancy loss results as a factor of a couple. This paper emphasizes the contribution of the male to implantation failure, miscarriage, and congenital anomalies suggested by recent literature. The current data are preliminary. With further investigation, evaluation of the male may be considered a routine part of the evaluation in the near future.     

Anatomic factors associated with recurrent pregnancy loss

Anatomic uterine defects appear to predispose women to reproductive difficulties, including first- and second-trimester pregnancy losses, higher rates of preterm labor and birth, and abnormal fetal presentation. These anatomic abnormalities can be classified as congenital, including müllerian and diethylstilbestrol-related abnormalities, or acquired, such as intrauterine adhesions or leiomyomata. In women with three or more consecutive spontaneous abortions who underwent hysterosalpingography or hysteroscopic examination of their uteri, mullerian anomalies have been found in 8 to 10%. Women with mullerian anomalies may be predisposed to recurrent pregnancy loss because of inadequate vascularity to the developing embryo and placenta, reduced intraluminal volume, or cervical incompetence. The reproductive history of most women with a müllerian anomaly is poor, especially for women with a uterine septum, the most common mullerian anomaly. Recurrent pregnancy losses resulting from a uterine septum, bicornuate uterus, intrauterine adhesions, and fibroids are amenable to surgical correction. Women with müllerian anomaly and a history of second-trimester pregnancy losses may benefit from a prophylactic cervical cerclage.     

Environmental toxins associated with recurrent pregnancy loss

Couples experiencing recurrent pregnancy loss are often concerned that toxins within the environment have contributed to their reproductive difficulty. Questions posed by these couples to their health care providers are difficult to answer because scientifically accurate information regarding the reproductive impact of potential environmental toxins and other teratogens is not readily available. Heavy metals such as lead and mercury, organic solvents, alcohol, and ionizing radiation are confirmed environmental teratogens, and exposure could contribute to pregnancy loss. Caffeine, cigarette smoking, and hyperthermia are suspected teratogens, and the teratogenic impact of pesticides remains unknown. The teratogenic potential of multiple other environmental factors has been studied and is reviewed. Before definitive conclusions can be drawn regarding the teratogenicity of environmental exposures, several clinical factors need to be addressed, including gestational age at the time of exposure, the amount of toxin reaching the conceptus, the duration of exposure, the impact of other factors or agents to which the mother or her conceptus is simultaneously exposed, and the physiological status of the mother and conceptus. In addition, in a given population, the interrelationship between frequency of exposures,frequency of effects, and recognizability of adverse outcomes, such as spontaneous abortion, should be considered.