Risk of hypertensive disorders of pregnancy linked to trophectoderm biopsy in new study

Published 08 February 2021

A large single-centre study has found a two-fold higher risk of pregnancy-related hypertension following blastocyst biopsy and frozen transfer than in non-biopsied controls. Dublin embryologist Joyce Leyden, an ESHRE young ambassador, reports.

Following several studies with mixed results examining maternal and neonatal complications following PGT, a new study has found a higher incidence of hypertensive disorders of pregnancy (HDP) after trophectoderm biopsy in FET cycles.(1) The results once again raise the question of whether techniques to find the perfect euploid embryo are worth potential obstetric and neonatal risks.

This was a large cohort study, conducted in a single US centre, which found an almost two-fold higher risk of HDP following trophectoderm biopsy in FET cycles than in non-biopsied FET cycles. However, other previously noted complications, such as placenta previa, placenta accreta, and placental abruption, were examined but did not result in any significant differences between the two groups.
Similarly, there were no significant differences found in fetal birthweight, gestational age, major birth defects or fetal growth restriction (FGR). Thus, despite the placenta playing a pivotal role in fetal growth, the authors suggest that trophectoderm biopsy does not have a negative impact on the development of the fetus.

The authors report that behind their study lies a ‘concern’ of the potential detrimental effect of trophectoderm biopsy on outcomes. In 2019, for example, another US study found a statistically significant increase in the risk of pre-eclampsia in IVF with PGT pregnancies over IVF without PGT, with an incidence of 10.5% versus 4.1%.(2) However, with relatively small numbers these differences were no longer significant when the data were limited to only FET cycles.

The authors of this latest study, while noting that trophectoderm biopsy seems not to adversely affect embryo development and implantation potential, advise that disruption via biopsy to obtain cells for analysis may damage the embryo and result in abnormalities of placentation. It is the trophectoderm, they add, which ultimately gives rise to the placenta.

Trophectoderm biopsy has become routine in PGT-A cycles in recent years, showing higher implantation and pregnancy rates when compared with cleavage stage blastomere biopsy. It is similarly common practice that trophectoderm biopsy cycles are also freeze-all, followed by FET once the ploidy status of the embryos is known. As the authors of this study propose, trophectoderm cells are the precursors of the placenta, and it is not implausible that trophectoderm agitation and biopsy may have an adverse effect on placentation, which may not ‘manifest until later in pregnancy’.

This well designed study adjusted for variables overlooked in previous similar publications: suitable control group, singleton live birth outcomes, autologous oocytes, embryo stage and method of cryopreservation. As described by the authors ‘this is the largest study to date to provide a detailed report on obstetric and perinatal outcomes with respect to trophectoderm biopsy in FET cycles’.

However, they too recognise that a larger multicentre study is now warranted to further investigate these findings. Moreover, freeze-all cycles have recently been associated with a small risk of pregnancy-associated hypertension; a 2019 study concluded that the absence of a corpus luteum increased the risk of pre-eclampsia.(3)

In the USA alone around 40% of all IVF cycles are now accompanied by PGT.(4) Whilst some cycles are performed because of advanced maternal age or recurrent pregnancy loss, there are many performed simply as an adjuvant option. With the potential obstetric risks highlighted in this study, combined with the negative add-on status of PGT-A, caution may well be appropriate when offered with trophectoderm biopsy, in particular to patients at higher risk of placental disorders.

1. Makhijani R, Bartels CB, Godiwala P, et al. Impact of trophectoderm biopsy on obstetric and perinatal outcomes following frozen–thawed embryo transfer cycles. Hum Reprod 2021; 36: 340-348. doi:10.1093/humrep/deaa316
2. Zhang WY, Versen-Hoynck FV, Kapphahn KI, et al. Maternal and neonatal outcomes associated with trophectoderm biopsy. Fertil Steril 2019; 112: 283–290.
3. von Versen-Hoynck F, Schaube AM, Chi YY, et al. Increased preeclampsia risk and reduced aortic compliance with in vitro fertilization cycles in the absence of a corpus luteum. Hypertension 2019; 73: 640-649.
4. Munné S. Status of preimplantation genetic testing and embryo selection. Reprod Biomed Online 2018; 37: 393-396.

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