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.     

The effect of thrombophylaxis on pregnancy outcome in patients with recurrent pregnancy loss associated with factor V Leiden mutation

Objective To observe the effect of thrombophylaxis on pregnancy in women with a history of unexplained recurrent pregnancy loss also carrying the factor V Leiden mutation.
Methods Between 1 January and 31 December 1996, activated protein C (APC) resistance and factor V Leiden mutation were prospectively measured in 56 nonpregnant women, with a history of two or more unexplained recurrent pregnancy losses. During the same study period, seven women carrying the factor V Leiden mutation conceived, and were subsequently followed throughout their pregnancy. Subcutaneous low molecular weight heparin (LMWH, enoxaparin, 40 mg/day) and oral low dose aspirin (100 mg/day) were administered throughout the pregnancies, starting at early first trimester. Ultrasound and Doppler umbilical and fetal middle cerebral arterial flow studies were performed in the second and third trimesters, and the course and outcome of the pregnancies were documented.
Results Activated protein C resistance and factor V Leiden were found in 20 (36%) and 12 (21%) women of the study, respectively. Five of the seven pregnancies occuring progressed uneventfully to term with normal fetal growth, normal Doppler flow studies and uneventful neonatal outcome. Two of the seven women had early missed abortions.
Conclusions Thrombophylaxis, beginning in early pregnancy, in women with unexplained recurrent pregnancy loss associated with factor V Leiden mutation, seems to be safe and allow normal fetal development and good neonatal outcome. To prove the efficacy of thrombophylaxis by LMWH and low dose aspirin in this setting prospective controlled studies seem to be justified.     

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.     

Increased resistance to activated protein C and factor V Leiden in recurrent abortions. Review of other hypercoagulability factors

Objective To evaluate hereditary and acquired hemostatic abnormalities associated with recurrent spontaneous early (first-trimester) abortions.

Method A group of 56 Greek women with two or more unexplained primary spontaneous abortions, and a reference group of 148 women without a history of recurrent abortions, were screened for hypercoagulability. A randomly selected population of first-trimester pregnant women was also chosen for factor V Leiden genetic screening.

Results A total of 21% of the women with recurrent abortions, compared with 12% of the reference group, showed increased activated protein C resistance. Fourteen per cent had positive lupus anticoagulant, compared with 11.5% of the reference group. For the rest of the parameters, there was no difference between the two groups. Of 22 women studied for factor V Leiden, one was homozygous and one was heterozygous. Results were compared using Fisher' exact test and two-tailed Student' t tests.

Conclusions Increased activated protein C resistance appears to be an important factor in women with recurrent abortions. These data indicate the need for routine investigation of activated protein C resistance in women with recurrent abortions.     

Increased resistance to activated protein C and factor V Leiden in recurrent abortions. Review of other hypercoagulability factors.

OBJECTIVE: To evaluate hereditary and acquired hemostatic abnormalities associated with recurrent spontaneous early (first-trimester) abortions. METHOD: A group of 56 Greek women with two or more unexplained primary spontaneous abortions, and a reference group of 148 women without a history of recurrent abortions, were screened for hypercoagulability. A randomly selected population of first-trimester pregnant women was also chosen for factor V Leiden genetic screening. RESULTS: A total of 21% of the women with recurrent abortions, compared with 12% of the reference group, showed increased activated protein C resistance. Fourteen per cent had positive lupus anticoagulant, compared with 11.5% of the reference group. For the rest of the parameters, there was no difference between the two groups. Of 22 women studied for factor V Leiden, one was homozygous and one was heterozygous. Results were compared using Fisher's exact test and two-tailed Student's t tests. CONCLUSIONS: Increased activated protein C resistance appears to be an important factor in women with recurrent abortions. These data indicate the need for routine investigation of activated protein C resistance in women with recurrent abortions.     

Hormonal treatment of recurrent spontaneous abortions

A retrospective study with 79 pregnant women was conducted. All of them were diagnosed as spontaneous abortion. The patients were separated in two group and the women have been treated in two schemes--51%--Utrogestan and 49%--Utrogestan and Profasi. The medication was applied only into the first trimester of the pregnancy. The duration of the therapy was 15.0 +/- 12.34 days. The mean gestational age in this study was 7.6 +/- 3.0 gestational weeks. Women with a first pregnancy and spontaneous abortion were excluded from the study. The number of this hormonal treated pregnancy was 2.84 +/- 1.13. 10.2% of the followed women had 3 and more than 3 miscarriages. The followed group of women was historically and clinically heterogenic. For that reason we think that many other factors could play a role in the optimum outcome of this pregnancy. The criteria for positive result we accepted the vital embryo/fetus on the time of dehospitalization. From these pregnancy only 3 terminated with miscarriage--3.79%. The rest of 96.2% went at home with intact pregnancy. The authors try to find a theoretical support for use of micronized progesterone Utrogestan--there could be some changes in the cellular and humoral immunity at repeated abortions, related to the change of the cytokine production. It could be find an ability to realize a readjustment of the endocrine system of the mother and to control the immune reaction in the fetoplacental unit.     

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     

Chromosome abnormalities in 118 couples with recurrent spontaneous abortions

Cytogenetic studies were carried out on 118 couples with recurrent spontaneous abortions. Four major chromosomal abnormalities were found including two 13/14 Robertsonian translocations, one t(7;12) and one t(1;10) reciprocal translocation. The incidence of chromosomal abnormalities in this study was 3.39%, which is lower than the mean value of the published data. The clinical significance of balanced translocations in recurrent reproductive loss is discussed.     

Pregnancy outcome following recurrent spontaneous abortions

OBJECTIVE: The purpose of the present study was to examine the association between spontaneous consecutive recurrent abortions and pregnancy complications such as hypertensive disorders, abruptio placenta, intrauterine growth restriction and cesarean section (CS) in the subsequent pregnancy. METHODS: A population-based study comparing all singleton pregnancies in women with and without two or more consecutive recurrent abortions was conducted. Deliveries occurred during the years 1988-2002. Stratified analysis, using a multiple logistic regression model was performed to control for confounders. RESULTS: During the study period 154,294 singleton deliveries occurred, with 4.9% in patients with history of recurrent consecutive abortions. Using a multivariate analysis, with backward elimination, the following complications were significantly associated with recurrent abortions-advanced maternal age, cervical incompetence, previous CS, diabetes mellitus, hypertensive disorders, placenta previa and abruptio placenta, mal-presentations and PROM. A higher rate of CS was found among patients with previous spontaneous consecutive recurrent abortions (15.9% versus 10.9%; OR = 1.6; 95% CI, 1.5-1.7; P < 0.001). Another multivariate analysis was performed, with CS as the outcome variable, controlling for confounders such as placenta previa, abruptio placenta, diabetes mellitus, hypertensive disorders, previous CS, mal-presentations, fertility treatments and PROM. A history of recurrent abortion was found as an independent risk factor for CS (OR = 1.2; 95% CI, 1.1-1.3; P < 0.001). About 58 cases of inherited thrombophilia were found between the years 2000-2002. These cases were significantly more common in the recurrent abortion as compared to the comparison group (1.2% versus 0.1%; OR = 11.1; 95% CI, 6.5-18.9; P < 0.001). CONCLUSION: A significant association exists between consecutive recurrent abortions and pregnancy complications such as placental abruption, hypertensive disorders and CS. This association persists after controlling for variables considered to coexist with recurrent abortions. Careful surveillance is required in pregnancies following recurrent abortions, for early detection of possible complications.     

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.     

Thrombophilia and antithrombotic therapy in women with recurrent spontaneous abortions

OBJECTIVE: To investigate the association between thrombophilia and recurrent spontaneous abortions (RSAs) and to evaluate the efficacy of anticoagulant treatment. STUDY DESIGN: All couples with a history of RSAs were studied by immunologic tests and determination of coagulation factors. Low-molecular-weight heparin and low-dose aspirin daily during pregnancy were used in 29 selected cases with acquired and inherited thrombophilia. The control group included 23 women with a history of RSAs and tests positive for thrombophilia who declined to receive medication during pregnancy. RESULTS: All couples with a history of RSAs were studied by immunologic tests and determination of coagulation factors. Low-molecular-weight heparin and low-dose aspirin daily during pregnancy were used in 29 selected cases with acquired and inherited thrombophilia. The control group included 23 women with a history of RSAs and tests positive for thrombophilia who declined to receive medication during pregnancy. CONCLUSION: All couples with RSAs require screening for thrombophilia. Low-molecular-weight heparin and low-dose aspirin daily during pregnancy appear to have a favorable effect on pregnancy outcome in selected women with RSAs and acquired or inherited thrombophilia.     

Progesterone profiles in luteal-phase defects associated with recurrent spontaneous abortions

Purpose: Histologically documented luteal-phase defects (LPD) have been detected in 20–40% of women with recurrent spontaneous abortions. In 28 patients with recurrent spontaneous abortions, luteal-phase serum progesterone (P) levels (days 19, 21, 23, 25) and endometrial biopsies were evaluated. Methods: On the basis of endometrial biopsy findings, the patients were separated into two groups: Group 1, recurrent spontaneous abortions with LPDs (n=18); and Group 2, recurrent spontaneous abortions with normal biopsies (n=7). The data are shown in the table below. Conclusions: This study demonstrated that the P values found in Group 1 were significantly lower than those in Group 2, almost throughout the luteal phase. The results also indicate a close relationship between the P profile in the luteal phase and endometrial biopsy.     

The prevalence of recurrent spontaneous abortions, cancer, and congenital anomalies in the families of couples with recurrent spontaneous abortions or gestational trophoblastic tumors.

This study extends our previous work on the genetics of recurrent spontaneous abortion and of gestational trophoblastic tumors in an ethnically homogeneous population of Chinese in Taiwan by comparing the prevalence of recurrent spontaneous abortions, cancer, and congenital anomalies in the first-, second-, and third-degree relatives of the index couples to that of normally fertile couples from the same population. The rationale for this study was to provide another test for our hypothesis that genes linked to the major histocompatibility complex are responsible for the diseases in the index couples. If they are, these genes should segregate with a higher frequency in the relatives of the index couples than in the relatives of normally fertile couples and lead to a higher prevalence of these diseases in the extended families. Such a difference was found and adds support to our hypothesis that major histocompatibility complex-linked genes affect growth, development, and susceptibility to cancer.     

Obstetric implications of activated protein C resistance and factor V Leiden mutation

An increasing number of reports have focused on activated protein C resistance (APCR) as it has been shown not only to be the most common genetic factor predisposing patients to thromboembolic disease but the most common identifiable cause overall. More than 90 percent of the cases of APCR are caused by the factor V Leiden mutation, in which a guanine to adenine substitution in the factor V gene at nucleotide position 1691 results in a glutamine to arginine switch at position 506. Recent studies have also pointed to evidence of an association between APCR/factor V Leiden mutation and hypertensive disorders of pregnancy, first and second trimester miscarriage, placental infarction, and placental abruption.