研究開発・学会発表

Study question:

Can the difference in size between male and female pronuclei (PN) be one of the indicators to tell normal embryos?

 

Summary answer:

Yes, the birth of healthy babies derives from zygotes having similar sized male and female pronuclei, when this measurement is achieved immediately before PNMBD.

 

What is known already:

The size of a male pronucleus is known to be larger than a female pronucleus, however, observation of the size is generally made about 16-20 hours after fertilization, although the PN continues to grow until PNMBD.

 

Study design, size, duration:

Retrospective cohort study involving 71 frozen-thawed single blastocyst transfers observed by time lapse system (Embryo Scope) from June 2013 to December 2014.

 

Participants/materials, setting, methods:

Time lapse recordings were performed and the areas of male and female pronuclei were retrospectively analyzed by measuring vertical and horizontal diameter of pronuclei. The measurements were taken
4 hours before the PNMBD, which is equivalent to 16-20 hours after insemination or ICSI, and right before the PNMBD. The difference in square measurements between the 2PNs in embryos resulting in clinical pregnancy and live born babies were compared to those of embryos from failed pregnancies.

 

Main results and the role of chance:

71 frozen-thawed blastocysts were transferred after observation with a time-lapse system. The hCG, gestational sack (GC), fetus heart beat (FHB) positive rates were 74.2% (52/71), 63.4% (45/71) and 57.7% (41/71) respectively. Among the 41 cycles with positive FHB, 36 cases were delivered without any chromosomal abnormality, 4 cases miscarried and one case lost contact. The average difference in area (±SD) between 2 pronuclei 4 hours before and immediately before PNMBD among patients resulting in the birth of healthy babies were 39.9 µm2 (±37.8) and 11.6 µm2 (±15.5) respectively,　whereas the average difference in those resulting in unsuccessful birth were 62.8 µm2 (±43.0) and
62.8 µm2 (±53.3) respectively. Statistically significant differences were obtained between patients with successful and unsuccessful births both 4 hours before (p=0.012) and immediately before (p<0.001) the PNMBD. In addition, the average difference among patients with successful birth was significantly smaller when the measurement was achieved immediately before PNMBD than 4 hours before PNMBD (p<0.001). This difference was not detected among patients with unsuccessful birth.

 

Limitations, reasons for caution:

The analysis of PNs is restricted to 2D in this study. 3D analysis will show more precise data when 3D analysis becomes possible. The birth of babies derived from natural conception, which occurs during frozen-thawed HRT cycles, cannot be eliminated in this study, although the occurrence is very small.

Wider implications of the findings:

As the size of pronuclei immediately before PNMBD was similar in embryos resulted in the birth of healthy babies, a large difference in size between the 2PN may indicate the presence of aneuploidy, which could be a useful tool in deselecting embryos.

Trial registration number:

Not applicable