EMBRYOLOGY

Poor-quality blastocysts result in lower live birth rate – but do not lead to more adverse perinatal outcomes

Blastocyst LBR

Published 11 January 2024

Observational study of more than 10,000 women shows that the transfer of low-quality blastocysts isn’t associated with a higher risk of adverse birth outcomes. While the live birth rate (LBR) is lower, it is still ‘reasonable’ according to the authors.

In the era of single embryo transfer in clinical practice, the focus is on selecting the best embryo for transfer and low-quality blastocysts are routinely discarded by some clinics.

While it is known that low-quality blastocysts can lead to live births, the relatively small sample sizes and single-centre design of existing studies mean there is limited information on their potential. Even less is known about the impact of low-grade blastocysts on perinatal outcomes.

The results of a new study provide some clarity, along with a reassuring message for women.(1)

IVF patients should be informed that although low-quality embryos result in a lower LBR, it’s still ‘reasonable’ – and there’s no increase in the risk of adverse perinatal outcomes, say the authors.

The multi-centre, multi-national retrospective cohort study involved 10,018 women undergoing 10,964 single blastocyst transfer cycles in 14 clinics in Australia, China and New Zealand between 2009 and 2020.

The morphology and development of the inner cell mass (ICM) and trophectoderm (TE) of each blastocyst was graded ‘A’, ‘B’ or ‘C’, using the Gardner system.

Blastocysts with an A or B in both ICM and TE were classed as being of good quality (AA, AB, or BA; n=4,386). Those with a B in both ICM and TE were classed as moderate-grade (BB; n=3,735) and those with a C in either ICM or TE as low-grade (AC, CA, BC, CB, CC; n=2,843).

Day 5, 6 and 7 blastocysts were included, with the majority being Day 5. (90.7% of the good quality blastocysts were Day 5, vs 83.2% of the moderate quality blastocysts and 61.1% of the low-quality blastocysts.)

The LBR for the good-quality blastocyst group was 44.4%. This compares to a LBR of 38.6% (adjusted odds ratio (aOR ) 0.70, 95% CI 0.62–0.77) for the moderate-quality group and 30.2% (aOR 0.48, 95% CI 0.41–0.55) for the low-quality blastocysts.

For the very low-quality blastocysts (CC only), the LBR was 13.7%. This is close to the 16.7% LBR for CC blastocysts in another study.(2)

The results also suggest that the quality of the ICM is more important in achieving a live birth than the quality of the TE.

As might be expected, the LBR was lower in older women but it remained over 15% with low-grade blastocysts, even in the oldest quintile (≥38 years). This is ‘still high enough to justify the transfer of low-grade blastocysts,’ say the authors.

The results of the analysis of the association between blastocyst quality and perinatal outcomes were also reassuring.

The analysis of 4,132 singleton births found there was no significant difference between the low and good-grade blastocysts in any of the parameters studied (pre-term birth, birthweight Z-score, rates of very low birth weight, low birth weight, high birth weight, small for gestational age, large for gestational age).

In addition, perinatal outcomes were comparable between Day 5 and Day 6 low-grade blastocysts.

Finally, better-quality blastocysts were associated with higher clinical pregnancy rates but rates of pregnancy loss were similar in low, moderate and good-grade blastocysts.

Strengths of the study include its large sample size. And, by restricting the study population to single blastocyst transfers, the authors removed the need to trace the outcomes of individual embryos.

Among the limitations are the small size of some of the low-grade sub-groups and differences in blastocyst grading within, and between, clinics. Moreover, although the results were adjusted for confounding factors (institution, fresh/frozen transfer, female age, blastocyst developmental stage, blastocyst age and, in the case of perinatal outcomes, infant sex), the retrospective nature of the design means that some residual confounding could not be avoided.

The authors say that while low-grade blastocysts did not survive cryopreservation well in the past, vitrification has led to better preservation and so better reproductive outcomes.

Thus, the transfer of low-quality blastocysts could allow couples who do not have any good or moderate-grade blastocysts to avoid the delay, cost and psychological burden associated with starting a new stimulation cycle.

It will be important, however, to determine the added value of transferring low-grade blastocysts – especially for women with multiple failed transfers with good-quality blastocysts, say the authors.

They conclude that women undergoing IVF treatment should be informed that low-grade blastocysts result in lower, but ‘reasonable’, live birth rates. This is achieved without increasing the risk of adverse perinatal outcomes.

Indeed, even very low-quality blastocysts (CC) can result in live births. The perinatal outcomes of such embryos need to be investigated in a larger cohort, however, say the authors.

Suggestions for future research include developing criteria for embryos that should not be transferred. Other foetal outcomes and pregnancy complications, such as placentation, pre-eclampsia and hypertensive disorders, haemorrhage and placenta previa, should also be studied. The long-term follow-up of childhood outcomes is also required, say the authors.

1. Zou H, Kemper JM, Hammond ER, Xu F, Liu G, Xue L, et al. Blastocyst quality and reproductive and perinatal outcomes: a multinational multicentre observational study. Human Reproduction. 2023 Dec 1;38(12):2391–9. doi.org/10.1093/humrep/dead212
2. Li M, Yin M, Wu L, Yan Z, Lyu Q, Yan Z, et al. Pregnancy and neonatal outcomes of morphologically grade CC blastocysts: are they of clinical value? Arch Gynecol Obstet. 2020 Dec 1;302(6):1511–21. doi.org/10.1007/s00404-020-05741-w

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