P-786 Perinatal outcomes of assisted reproduction technology (ART) pregnancies after transfer of mosaic blastocysts: a single centre matched cohort study
Authors: Pozzoni M , Corti L , Papale M , Alteri A , Vanni V.S , Pagliardini L , Rabellotti E , Girardelli S , Viganò P , Candiani M , Cavoretto P 
Published: June 2022

Study question

Do viable pregnancies after transfer of mosaic blastocysts present different perinatal outcomes as compared to those deriving from transfer of euploid blastocysts?

Summary answer

Pregnancies from transfer of mosaic vs. euploid blastocysts showed an increased rate of fetal structural malformations and postpartum haemorrhages (PPH).

What is known already

The incidence of mosaicisms in the trophoectoderm is a relatively frequent event and most true embryo mosaicisms result in spontaneous intrauterine demise. The confirmation of the mosaic aneuploidy in the fetus is related to the type and grade of the aneuploidy with higher risk for chromosomes 13, 14, 15, 16, 18 and 21 and X monosomy. On the other hand, selected mosaic blastocysts have been transferred with subsequent birth of healthy neonates. However, the risk of abnormal obstetric outcomes after transfer of mosaic embryos remains to be completely elucidated.

Study design, size, duration

Explorative cohort study between 2016 and 2021 including consecutive viable ART pregnancies developing from transfer of mosaic blastocysts (n = 39 cases). Transfer of available mosaic embryos was considered for patients with a poor response to ovarian stimulation or recurrent implantation failures and no available euploid blastocysts, after genetic counselling. Cases were matched for maternal age, parity and body mass index to women with viable pregnancies after transfer of euploid blastocysts (n = 39, controls) and followed-up until delivery.

Participants/materials, setting, methods

All patients recruited at San Raffaele, Scientific Institute of Milan, underwent a prenatal genetic testing by trophoectoderm biopsy and next-generation sequencing analysis. Patients with a viable fetus at 12 weeks gestation were included and underwent detailed ultrasound assessment at 12, 20 and 32 weeks including fetal biometry and anatomical survey. Frequency of adverse pregnancy and perinatal outcomes including maternal, fetal and delivery complications were compared between patients who received a mosaic versus a euploid blastocyst.

Main results and the role of chance

No difference in indications to preimplantation diagnosis was found between cases and controls. In the group who transferred mosaic embryos, median rate of mosaicisms was 35% (IQR 30%-40%) and they were characterized by heterogeneous anomalies including complex aneuploidies (n = 12), autosomal monosomies (n = 13), trisomies (n = 8) and duplications/deletions (n = 6). Invasive testing was performed in 62.0% of mosaics (5 chorion villous samplings; 19 amniocenteses; 2 anomalies: confined placental mosaicism trisomy 15 after transfer of mosaic monosomy 6 and fetal microduplication 6p after transfer of mosaic deletion 10p) vs 2.5% of controls (p &lt; 0.001). Structural malformations were observed in 6 neonates in the study group (tanatophoric skeletal dysplasia, complex central nervous system anomaly, congenital diaphragmatic hernia, cerebral arteriovenous fistulae, pyeloureteral junction stenosis, diffuse haemangiomatosis) compared to 1 in controls (pulmonary stenosis) (p = 0.04). One neonate per group was followed-up for future surgery. PPH rate was significantly higher in cases vs controls (15 vs 7; p = 0.04). Neonatal survival at hospital discharge was not different in the two groups (p = 0.30). No significant differences were recorded in rates of preterm birth, small or large for gestational age, fetal growth restriction, miscarriage, preeclampsia and median birthweight centile or gestational age at birth.

Limitations, reasons for caution

Data from our exploratory study should be interpreted cautiously given the limited sample size which makes it challenging to infer a causal relationship between the association found and transfer of mosaic blastocysts.

Wider implications of the findings

The higher rates of structural malformations and PPH in ART pregnancies after transfer of mosaic embryos strongly suggest the need for strict monitoring of these patients. First and second trimester ultrasound screening for structural defects, and preventive measures to minimize bleeding at delivery should be implemented.

Trial registration number

not applicable