Abstract
Objective: To explore the use of a new molecular work-up based on the stepwise use of Quantitative Fluorescence PCR (QF-PCR) extended to eight chromosomes and single nucleotide polymorphism array (SNP-array) in chorionic villi obtained by chorionic villi sampling (CVS) offered to women experiencing an early pregnancy loss.Methods: During a 3-year period (January 2016–December 2018), CVS was offered to women experiencing an early pregnancy loss before the evacuation of the products of conception (POC) to retrieve chorionic villi, irrespective of the number of previous losses. A new molecular work-up was prospectively assayed encompassing a first QF-PCR round (with the 21, 18, 13, 7, X, and Y chromosomes), a second QF-PCR round (with the 15, 16, and 22 chromosomes), and a high resolution SNP-array in those cases with normal QF-PCR results. A control group in which POC were collected after surgical uterine evacuation was used to be compared with the intervention group.Results: Around 459 women were enrolled in the intervention group (CVS) and 185 in the control group (POC after uterine evacuation). The QF-PCR testing success rates were significantly higher in the intervention group (98.5%: 452/459) as compared to the control group (74%: 109/147; p < 0.001), while the chromosomal anomaly rate at the two QF-PCR rounds was similar between the two groups: 52% (234/452) in the intervention and 42% (46/109) in the control group (p = 0.073). The SNP-array was performed in 202 QF-PCR normal samples of the intervention group and revealed 67 (33%) atypical chromosomal anomalies (>10 Mb), 5 (2.5%) submicroscopic pathogenic copy number variants, and 2 (1%) variant of uncertain significance (VOUS).Conclusion: Eighty-two percent of women experiencing an early pregnancy loss opted for a CVS. The testing success rates were higher in the intervention group (CVS; 98%) as compared to the control group (POC; 74%). The overall yields were 52% by QF-PCR (including three complete hydatiform moles), and 16% by SNP-array, including 15% atypical chromosomal anomalies and 1.1% submicroscopic pathogenic copy number variants.
Highlights
Pregnancy loss is defined as a non-viable, intrauterine pregnancy in the first trimester with either an empty gestational sac or a gestational sac containing an embryo or a fetus without fetal heart activity (Nice.org.uk, 2012)
We address early pregnancy loss from three novel approaches: (a) We performed chorionic villi sampling (CVS) with a transcervical forceps before uterine evacuation; (b) we applied a new stepwise molecular work-up based on the use of Quantitative Fluorescence PCR (QF-PCR) extended to eight chromosomes and single nucleotide polymorphism array (SNP-array); and (c) we offered this work-up to women after their first early pregnancy loss, since a single early gestational loss has been shown to have a great emotional impact (Stergiotou et al, 2016; Farren et al, 2018)
This is an interventional trial in which two rounds of QF-PCR and SNP-array were applied to chorionic villi retrieved by CVS before uterine evacuation of products of conception (POC)
Summary
Pregnancy loss is defined as a non-viable, intrauterine pregnancy in the first trimester with either an empty gestational sac or a gestational sac containing an embryo or a fetus without fetal heart activity (Nice.org.uk, 2012). This is the most common form of pregnancy loss, occurring in 15–20% of clinical pregnancies (Zinaman et al, 1996). It is clearly associated with maternal age, increasing from 10% of pregnancies at 20 years to 75% at 40 years (Andersen et al, 2000) due to a rise in chromosomally abnormal pregnancies along maternal age (Grande et al, 2012). Maternal cellcontamination leads to a false-negative result in 22% of the samples (Lathi et al, 2014) decreasing to 53% of the rate of correct diagnoses in POC samples
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