RESUMEN
OBJECTIVE: To study the influence of M2/ANXA5 for recurrent pregnancy loss (RPL), according to the timing of miscarriages and assess the male partner risk. DESIGN: Genetic association study. SETTING: Academic research center. PATIENT(S): Female patients from two academic centers in Germany and Bulgaria with two or more unexplained miscarriages were selected for this study. Male partners were available for a part of the German sample. Population controls were recruited from healthy individuals of respective populations. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of M2 carriage and odds ratios were calculated between patient and control groups, and RPL risk was evaluated. RESULT(S): The M2 haplotype in ANXA5 was associated with greater overall RPL risk in German and in Bulgarian women, and a trend of higher prevalence was seen for male partners of German RPL patients. The highest relative risk of M2 carriage was observed in women of both populations with "early" fetal losses between the 10th and 15th gestational weeks, which was significant in the meta-analysis. CONCLUSION(S): M2 carriage seems to have an RPL risk role mostly for early abortions, gestational weeks 10-15. In the first phase of pregnancy this correlates with vascular remodeling to accomplish the transition from high- to low-resistance blood vessels.
Asunto(s)
Aborto Espontáneo/genética , Anexina A5/genética , Padre , Haplotipos , Heterocigoto , Madres , Aborto Habitual/epidemiología , Aborto Habitual/genética , Aborto Espontáneo/epidemiología , Adulto , Bulgaria/epidemiología , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Alemania/epidemiología , Edad Gestacional , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Embarazo , Prevalencia , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
Polymorphism A1/A2 in the ß3 subunit of integrins αIIb/ß3 and αV/ß3 is implicated in the risk of development of embryonic and fetal recurrent pregnancy loss (RPL). In 191 women with RPL, polymorphism A1/A2 was statistically significantly associated with RPL at <10 weeks of gestation (29.3% versus 16.4% in controls), but it was much more pronounced in 67 women with RPL between 10 and 20 weeks of gestation (41.8%), illustrating its role in recurrent fetal loss.
Asunto(s)
Aborto Habitual/genética , Implantación del Embrión/genética , Integrina beta3/genética , Placentación/genética , Polimorfismo Genético , Aborto Habitual/patología , Adulto , Alelos , Antígenos de Superficie/genética , Antígenos de Superficie/metabolismo , Antígenos de Superficie/fisiología , Estudios de Casos y Controles , Pérdida del Embrión/genética , Pérdida del Embrión/patología , Femenino , Predisposición Genética a la Enfermedad , Edad Gestacional , Humanos , Infertilidad Femenina/genética , Infertilidad Femenina/patología , Integrina beta3/metabolismo , Integrina beta3/fisiología , Polimorfismo Genético/fisiología , Embarazo , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Subunidades de Proteína/fisiologíaRESUMEN
To investigate the impact of maternal-inherited thrombophilia: effects of factor V Leiden (FVL) and prothrombin gene mutation (FII 20210G>A) on the development of recurrent pregnancy loss in embryonic and postembryonic periods. A total of 153 patients were analysed for FVL and FII 20210G>A according to placenta gestation: 94 women with embryonic loss prior 10 weeks of gestation and 59 women with postembryonic (early fetal) loss occurring between 10 and 14 weeks of gestation. The control group consisted of 100 healthy women, with at least one uncomplicated full-term pregnancy. FVL prevalence was not significantly associated with pregnancy loss prior to 10 weeks of gestation (9.6%) compared with controls (7%) [odds ratio (OR) 1.41; 95% confidence interval (CI) 0.454-4.416, P > 0.05], but it was much more pronounced in women with postembryonic loss (10-14 weeks of gestation) - 18.6% (OR 3.05; 95% CI 1.010-9.387, P = 0.047). FII 20210G>A was significantly higher in both groups with embryonic (17%) and early fetal losses (16.9%) as compared to controls (3%) (OR 6.63; 95% CI 1.731-29.752, P = 0.003; OR 6.60; 95% CI 1.572-31.856, P = 0.006). FII 20210G>A is significantly associated with an increased risk of early recurrent pregnancy loss throughout the entire first trimester. FVL was significantly higher only in early fetal period after starting of the placentation process, but not associated with embryonic recurrent pregnancy loss. These results suggested that the first trimester should be viewed rather as a heterogeneous interval, with different relation to FVL in the embryonic and postembryonic fetal period. Genetic testing should be applied according to the diverse contribution of thrombophilic markers to embryonic and postembryonic period.