**7. Maternal and Neonatal Outcomes**

The wide use of PGT to implement assisted reproduction results, raises a concern about the potential risks of embryo biopsy, and extended embryo culture [10,180,181]. TE biopsy removes cells that are destined to form the placenta, increasing the risk of pathological placentation, potentially responsible for pre-eclampsia and reduced fetal growth. Therefore, the comparison of adverse obstetric and neonatal outcomes in pregnancies obtained from PGT IVF cycles and traditional IVF is mandatory.

In the study by Scott et al. [185], only 30% of biopsied embryos had sustained implantation and developed into live-born infants, versus 50% of non-biopsied controls. In contrast, sustained implantation rates were equivalent (51% vs. 54%) for biopsied and control blastocysts.

Zhang et al. [176] aimed to evaluate the existence of a correlation between TE biopsy and blastocysts quality. The authors found that, in high quality blastocysts, there were no differences in the survival and implantation rates, independently of the number of cells removed. However, blastocysts with grades B and C had significantly lower implantation rate, with an increasing number of TE cells removed. Implantation potential is negatively affected by the number of TE cell removed for the analysis in blastocysts with poor morphological score.

Additionally, a reduced cumulative HCG secretion after the biopsy procedure was suggested by Dokras et al. [186]. Moreover, the authors evidenced that the removal of less than 10 cells reduce the

HCG secretion (87.6 +/− 24.8 mIU/mL), but the difference was not significant. Oppositely, when a large biopsy was performed (greater than 10 cells), the HCG levels fell to 19.9 +/− 9.1 mIU/mL. This study indicates that blastocyst biopsy might impair the blastocysts development.

Forman et al. [10] reported neonatal and obstetric outcomes, when comparing SET after blastocyst biopsy and untested double embryo transfer in a randomized controlled trial. The delivery rates were similar (69% vs. 72%) through the fresh cycle and up to one frozen transfer, with a dramatic difference in multiple births (1.6% vs. 47%). The risk of preterm delivery, low birth weight, and admission to neonatal intensive care were significantly higher after untested two-embryos transfer. The improved obstetrical and neonatal outcomes suggest that PGT of a single euploid embryo might be a valid approach to patients requiring IVF.

On the other hand, a large study examining maternal and neonatal outcomes after TE biopsy documented a statistically significant increase in the risk of preeclampsia (10.5% vs. 5.8%) and placenta previa (4.1% vs. 1.4%) among pregnancies after IVF with PGT compared to those from IVF without PGT. The incidence of gestational diabetes, preterm premature rupture of membranes, and postpartum hemorrhage were similar. In addition, no differences were noted between the groups regarding neonatal outcomes, such as gestational age at delivery, preterm birth, low birth weight, neonatal intensive care unit admission, neonatal morbidities, or birth defects. [187].

The evaluation of 1721 children born after IVF cycles, including PGT at blastocyst stage combined with FTET, only showed an increased rate of cesarean section. In singletons, the cesarean section rate was as high as 80%, reached more than 90% in twins and it was significantly increased in PGT group when compared with controls [188].

Jing et al. [189] evaluated obstetric and neonatal outcomes from pregnancies that were obtained from FTET after TE and cleavage-stage biopsy for PGT. The results demonstrated that the incidence of gestational hypertension was significantly higher after blastocyst biopsy, as compared with cleavage-stage embryo (9.0% vs. 2.3%). Birth-weight and gestational age were higher after blastocyst-stage embryo transfer when compared to cleavage-stage in twins, but no significant differences were detected in the incidence of perinatal deaths, birth defects, neonates gender, and birth-weight for gestational age in both singletons and twins.
