Prevalence consequence and significance of reverse cleavage by human embryos viewed with the use of the Embryoscope time lapse video system

This study investigated the prevalence and significance of reverse cleavage by human embryos observed via time-lapse monitoring. Embryos showing reverse cleavage were associated with compromised subsequent development and implantation potential.

Yanhe Liu, M.Sc., Vincent Chapple, M.B., B.S., F.R.A.N.Z.C.O.G., M.R.Med., Peter Roberts, Ph.D., Phillip Matson, Ph.D.

Volume 102, Issue 5, Pages 1295-1300


To investigate the prevalence and potential causes of reverse cleavage (RC) by human early-cleavage embryos and its associations with embryonic development and implantation after transfer.

Clinical retrospective cohort study.

Private fertility treatment center.

A total of 126 consecutive in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment cycles, with 353 IVF and 436 ICSI embryos cultured in the Embryoscope until day 3.


Main Outcome Measure(s):
Embryo assessment on day 3, incidence of abnormal division, embryo morphokinetic parameters, and fetal heart beat.

RC, referring to either blastomere fusion or failed cytokinesis, occurred up to three times per individual embryo in 27.4% of embryos during the first three cleavage cycles. A higher incidence was associated with GnRH antagonist cycles compared with agonist cycles (odds ratio [OR] 1.683), or with ICSI compared with IVF (OR 1.600). After ICSI, sperm progressive motility was associated with RC (area under the receiver operating characteristic curve: 0.573). Compared with RC-negative embryos, a lower proportion of RC-positive embryos reached 6-cell stage or beyond by day 3 (47.7% vs. 71.7%), and were more likely to have multinucleation at the 4-cell stage (10.1% vs. 5.0%). Embryos showing RC had significantly poorer performance in both conventional grading and morphokinetic parameters, and they implanted less (0/22 vs. 29/131) than those not showing RC.

RC significantly compromised embryo development, culminating in poor implantation potential. For each embryo, it can occur on more than one occasion at any stage during the first 3 days of culture. It is associated with factors affecting both oocyte and sperm.

  • Shvetha Zarek

    Thank you to the authors for a very interesting study! This was a retrospective cohort analysis of 126 ART cycles which culminated in 353 IVF and 436 ICSI embryos that were cultured with the use of the time monitoring system, the EmbryoScope. The authors postulate that given that blastocyst transfer is associated with increased risk to offspring compared to cleavage stage transfer, that it is crucial to identify morphokinetic features that differentiate day three embryos in order to select the best cleavage stage embryo. They identify reverse cleavage (RC), defined as blastomere fusion (type I) and failed cytokinesis (type II) as a risk factor for poor quality embryos. They report that RC occurred in 27.4% of embryos and sometimes occurred up to three times in an embryo. GnRH antagonist compared to GnRH agonist cycles and ICSI compared to IVF was associated with a higher risk of RC, (odds ratio [OR] 1.683), and (OR 1.600) respectively. RC embryos had significantly poorer performance in both conventional grading and morphokinetic analysis. The take home message of clinical relevance is that none of the RC embryos were able to achieve a clinical pregnancy with a fetal cardiac activity. This is a very intriguing concept and aids in understanding in mechanisms that result in poor development of embryos and suggests that transfer of an RC embryo will not result in a clinical pregnancy. However, given that most RC embryos demonstrate poorer conventional grading, it is likely that better conventional graded embryos would be chosen for embryo transfer anyway without the information of RC. However, if a couple has only poor quality embryos, with RC, this study aids in counseling that the likelihood of a pregnancy is very, very low. Larger studies are warranted to confirm that RC embryos are unable to achieve a clinical pregnancy. In addition, it would have been very useful to know if these RC embryos would have continued growth to blastocyst stage. Thank you to the authors for a thought provoking study!

Translate »