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

OBJECTIVE: 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.

DESIGN: Clinical retrospective cohort study.

SETTING: Private fertility treatment center.

PATIENT(S): 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.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Embryo assessment on day 3, incidence of abnormal division, embryo morphokinetic parameters, and fetal heart beat.

RESULT(S): 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.

CONCLUSION(S): 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.