The Prevalence of Common Mutations in Thrombophilic Patients in Iranian Population with Recurrent Miscarriage

Background and Aims: To date, several factors have been reported in recurrent miscarriage. Genetic mutations are the most important causative factors in women. Fetal thrombotic vasculopathy is a new described placental alteration with varying degrees of involvement and often associated with adverse prenatal outcomes. The diagnosis is made histologically and so is postnatal, which makes it a challenge in clinical practice. The aim of the present study is investigation of the common mutations in women with recurrent miscarriage. Materials and Methods: A cross-sectional study was conducted on 100 women with a history of recurrent miscarriage fetus in 2018. In these patients, several genes such as MTHFR, F2, F5 Leiden, PAI1, F13 and FGB were analyzed by sequencing techniques. The most common mutations in these genes were sequenced and analyzed. Results: According to statistical results obtained, MTHFR gene (C677T, A1298C) has the highest rate (50 %) of common mutations (p=0.001). After that F2 (G20210A) and F5 Leiden (G1691A) have the highest statistical values (each one 20%). In addition to these genes, there are other unknown mutations which have not been studied in terms of pathogenicity. Other genes have a smaller percentage of aborted fetus infrequently. Conclusions: Common polymorphisms in the thrombophilic system are likely to result in abortion in these subjects, due to impaired coagulation of the mother and the fetus. Investigating the presence of common mutations and examining their association with other mutations in the thrombophilia as a prognostic in patients with recurrent miscarriage is necessary

Do Doppler Changes Reflect Pathology of Placental Vascular Lesions in IUGR Pregnancies?

Objectives Doppler assessment of uteroplacental (UP) and fetoplacental (FP) circulation detects abnormal waveforms in intrauterine growth-restricted (IUGR) pregnancies. Similarly, histopathology also reveals lesions of vascular compromise in IUGR placenta. We evaluated an association between Doppler and histopathological (HP) assessment of the maternal and fetal circulation in IUGR. Methods IUGR cases with both Doppler and histopathology assessment were selected from our database. Doppler patterns recorded UP and FP insufficiency. The HP vascular lesions were classified as maternal vascular underperfusion and fetal thrombotic vasculopathy (FTV). IUGRs were grouped based on (i) presence of preeclampsia (PE), (ii) clinical onset (early vs late) of IUGR (early onset [EO]/late onset), and (iii) gestational age (term, T/preterm, PT). Results Abnormal Doppler waveforms were present in 69 of the total 88 IUGR cases (78.4%). The most frequent pattern was fetoplacental insufficiency (FPI) (66%) which was combined with uteroplacental insufficiency (UPI) in 49%. HP showed vascular lesions in 52.3% and most frequent was FTV (38%). PE-associated IUGR (n = 49) had higher UPI pattern (75.5% vs 43.6%, P = .004), while normotensive IUGR had higher FPI pattern (28.2% vs 8.2%, P = .01). EO-IUGR (n = 55) and PT-IUGR (n = 52) had significant abnormal Doppler waveforms ( P < .05) with higher combined patterns and brain sparing. Doppler was more sensitive for fetal vascular lesions than maternal (75.8% vs 66.7%). However, 42% of cases with normal Doppler findings showed HP vascular lesions. Conclusion IUGR pregnancies harbor significant vascular compromise. Fetal circulatory lesions were more common in IUGR pregnancies. In a significant number of cases with normal Doppler report, vascular lesions were identified on histopathology, emphasizing placental examination in all cases of IUGR.

Fetal thrombotic vasculopathy: A case report and literature review

Summary Introduction: Fetal thrombotic vasculopathy is a recently described placental alteration with varying degrees of involvement and often associated with adverse perinatal outcomes. The diagnosis is made histologically and therefore is postnatal, which makes it a challenge in clinical practice. Method: Case report and review of literature on the subject. Results: The present case refers to a pregnant woman presenting fetal growth restriction, with poor obstetrical past, and sent late to our service. Even with weekly assessments of fetal vitality (fetal biophysical profile and Doppler velocimetry) and prenatal care, the patient progressed with fetal death at 36 weeks and 1 day. There was no association with inherited and acquired thrombophilia. Pathological examination of the placenta revealed fetal thrombotic vasculopathy. Conclusion: The fetal thrombotic vasculopathy may be associated with adverse perinatal outcomes including fetal death, but much remains to be studied regarding its pathogenesis. Diagnosis during pregnancy is not possible and there is still no proven treatment for this condition. Future studies are needed so that strategies can be developed to minimize the impact of fetal thrombotic vasculopathy.