Chorionic villous vascularization related to phenotype and genotype in first trimester miscarriages in a recurrent pregnancy loss cohort.

STUDY QUESTION: Is there an association between chorionic villous vascularization, ultrasound findings and corresponding chromosome results in early miscarriage specimens from a cohort of recurrent pregnancy loss patients? SUMMARY ANSWER: We did not find a significant difference in vascularization scores of chorionic villi between embryonic, yolk sac or empty sac miscarriages, or between euploid and noneuploid miscarriages. WHAT IS KNOWN ALREADY: At least half of first trimester miscarriages are due to embryopathogenesis associated with chromosome errors and/or major congenital anomalies, resulting in an empty sac, a yolk sac or an embryonic miscarriage. Absent and decreased chorionic villous vascularization is usually present in these pregnancies. STUDY DESIGN, SIZE, DURATION: For this retrospective study, 60 hematoxylin and eosin slides of miscarriage tissue of less than 10 weeks gestational age were collected from an academic institution. All patients were seen in consultation between July 2004 and October 2009. PARTICIPANTS, SETTING, METHODS: Chorionic villous vascularization was determined using a previously published classification. The results were validated and compared with the ultrasound findings and corresponding chromosome results. MAIN RESULTS AND THE ROLE OF CHANCE: There were 53 embryonic miscarriages, 5 yolk sac miscarriages and 2 empty sac miscarriages. Chromosome results were obtained in 59 of the 60 miscarriages; 37.3% were euploid and 62.7% were noneuploid. Validation of the vascularization score between observers was reasonable to good (Kappa 0.47-0.76), and 59% of the cases were classified as avascular. The vascularization score did not differ between euploid or noneuploid miscarriages, or between embryonic, yolk sac or empty sac miscarriages. Avascular villi were seen more frequently in miscarriages trisomic for chromosome 16, when compared with miscarriages with other trisomies (6 out of 7 versus 8 out of 22, P = 0.04). LIMITATIONS, REASONS FOR CAUTION: Unfortunately, the number of samples in the study was limited. WIDER IMPLICATIONS OF THE FINDINGS: Avascular villi may indicate abnormal early placentation as a part of embryopathogenesis. Further study is warranted to determine whether a genetic cause can be found to explain these results.

Early pregnancy placental bed and fetal vascular volume measurements using 3-D virtual reality.

In this study, a new 3-D Virtual Reality (3D VR) technique for examining placental and uterine vasculature was investigated. The validity of placental bed vascular volume (PBVV) and fetal vascular volume (FVV) measurements was assessed and associations of PBVV and FVV with embryonic volume, crown-rump length, fetal birth weight and maternal parity were investigated. One hundred thirty-two patients were included in this study, and measurements were performed in 100 patients. Using V-Scope software, 100 3-D Power Doppler data sets of 100 pregnancies at 12 wk of gestation were analyzed with 3D VR in the I-Space Virtual Reality system. Volume measurements were performed with semi-automatic, pre-defined parameters. The inter-observer and intra-observer agreement was excellent with all intra-class correlation coefficients >0.93. PBVVs of multiparous women were significantly larger than the PBVVs of primiparous women (p = 0.008). In this study, no other associations were found. In conclusion, V-Scope offers a reproducible method for measuring PBVV and FVV at 12 wk of gestation, although we are unsure whether the volume measured represents the true volume of the vasculature. Maternal parity influences PBVV.

An immunological basis for chronic histiocytic intervillositis in recurrent fetal loss.

PROBLEM: Chronic histiocytic intervillositis (CHIV) is a rare type of placental pathology that is associated with reproductive loss at all gestational ages. The aim of the study was to investigate the relationship between the severity of CHIV and the outcome of pregnancy and to compare the immune response between CHIV patients and controls to explore an immunological origin of CHIV. METHOD OF STUDY: Microscopic slides were reviewed and scored according to a previously published grading system in 30 pregnancies of 22 CHIV patients. Partner-specific mixed lymphocyte reactions, cytotoxic T-lymphocyte precursor frequencies (CTLpf), and anti-HLA antibodies were determined in four patients and seven controls. RESULTS: Higher CHIV scores are associated with worse pregnancy outcome. CHIV patients demonstrated a higher CTLpf against their partner compared to non-complicated pregnancies (P = 0.03). The CTLpf was extremely high in 75% of the patients. Antipaternal HLA antibodies were only present in 75% of the CHIV patients compared to none of the controls (P = 0.02). CONCLUSION: CHIV scores seem to be associated with the severity of adverse pregnancy outcome. High antipaternal cellular (T-cell) and humoral (B-cell) response to partner-specific CTLpf and the presence of anti-HLA antibodies directed to the partner suggest an immunologic origin of CHIV.