The question of whether Day 6 embryos are more likely to be female originates in In Vitro Fertilization (IVF) during the process of selecting the most viable embryo for transfer. During an IVF cycle, embryos are cultured until they reach the blastocyst stage. The timing of this development is an important metric used by embryologists to gauge an embryo’s developmental potential. This timing, specifically whether the blastocyst forms on Day 5 or Day 6, has prompted scientific investigation into whether this difference correlates with the sex of the embryo.
The Embryo Development Timeline in IVF
Embryo development begins with fertilization, considered Day 0. By Day 3, the embryo should be in the cleavage stage, consisting of six to eight cells. The next major hurdle occurs around Day 4, when the cells compact into a morula before differentiating into the two distinct cell types of the blastocyst stage.
A blastocyst is an embryo that has formed a fluid-filled cavity (the blastocoel) and has differentiated into the Inner Cell Mass (ICM), which becomes the fetus, and the Trophectoderm (TE), which forms the placenta. A Day 5 blastocyst reaches this advanced state five days after fertilization. A Day 6 blastocyst takes an additional 24 hours to achieve the same developmental milestone.
The embryologist grades a blastocyst based on its degree of expansion and the quality of both the ICM and TE layers. This grading helps determine the embryo’s potential for implantation. While Day 5 embryos are generally preferred because they have demonstrated faster development, Day 6 embryos are an expected part of the culture process, representing those that are still viable but are slightly slower to reach the necessary stage for transfer or cryopreservation.
Analyzing the Scientific Evidence for Sex Bias
The belief that Day 6 embryos may be more likely to be female is a statistical observation rooted in the finding that male embryos tend to develop faster than female embryos. Multiple studies indicate that male embryos (XY) show a tendency to reach the blastocyst stage and achieve higher morphological grades earlier than female embryos (XX). This means that a slightly higher proportion of the highest-quality Day 5 blastocysts may be male.
Conversely, the slower-developing population of embryos that reach the blastocyst stage on Day 6 is observed to have a subtle skew toward female embryos. This skew is not definitive, and the difference is not large enough to be a reliable method for sex selection. For instance, one study evaluating thousands of screened embryos found the overall population was split nearly evenly (45.9% male and 54.1% female). While the association is biologically plausible, the correlation is not strong enough to predict the sex of an individual embryo based solely on its Day 5 or Day 6 designation.
Biological Factors Affecting Embryo Development Speed
The mechanisms for this difference in developmental speed trace back to the genetic makeup of male and female embryos. Male embryos (XY) appear to have a metabolic advantage allowing for faster cell division. Studies suggest male embryos prioritize genes associated with energy metabolism, fueling a quicker growth rate in the earliest stages.
Female embryos (XX) must undergo X-chromosome inactivation (XCI) early in development to silence one of the two X chromosomes. This process balances the dosage of X-linked genes between the sexes, as males only have one copy. The requirement to initiate and complete XCI is thought to introduce a slight developmental delay in female embryos compared to their male counterparts. This intrinsic genetic difference provides a molecular explanation for the pattern of male embryos showing a propensity for faster development.
Clinical Outcomes and Viability of Day 6 Embryos
Success in an IVF cycle is more dependent on the quality of the embryo than the exact day it reaches the blastocyst stage. While Day 5 blastocysts generally show a higher potential for implantation and live birth rates compared to Day 6 blastocysts, the difference does not render Day 6 embryos non-viable. Studies consistently show that Day 6 blastocysts, especially those with good morphological grades, result in high success rates when transferred.
The slightly lower clinical outcomes observed with Day 6 embryos are likely because developmental delay can sometimes mark underlying issues, such as a higher risk of chromosomal abnormality (aneuploidy). However, when embryos undergo preimplantation genetic testing (PGT) and are confirmed to be chromosomally normal, the live birth rates of Day 5 and Day 6 blastocysts become comparable. Day 6 embryos are valued in the IVF process because they increase the number of viable embryos available for transfer or cryopreservation, maximizing the chance of achieving a pregnancy.