By Kaylen Silverberg, MD
One of the most common questions that patients have about IVF concerns the differences between doing an embryo transfer on Day 3 or Day 5 following retrieval. Most of our patients are very comfortable reading the medical literature – either in journals or on the Internet, and they seem to all want Day 5 transfers, as they believe that there are studies that say that this will give them a better chance of having a baby. In fact, if you look at basic statistics that compare pregnancy rates between Day 3 and Day 5 transfers, it does look at first blush like Day 5 results are better. So why the controversy?
There are several possible explanations for the apparently higher pregnancy rates reported from Day 5 transfers. First of all, it could be that longer incubation of embryos in the laboratory allows healthier embryos to grow, while those that are not healthy stop growing. This would increase the likelihood that better quality embryos would be transferred into the patient’s uterus, potentially increasing the chance for pregnancy. Second, some people have suggested (without significant data to support their belief), that longer incubation in the laboratory can actually “rejuvenate” poor quality embryos. Delaying the transfer to Day 5 could, therefore, allow embryo quality to improve and perhaps result in a better chance for pregnancy. Third, it is possible that delaying the embryo transfer to Day 5 allows for better synchrony between the Day 5 embryo, or “blastocyst”, and the uterine lining, which could theoretically result in an improvement in pregnancy rates. Finally, it is possible that physicians advise patients with many good quality embryos on Day 3 to delay their transfer to Day 5. This may theoretically allow embryologists and physicians to get a better idea about the true health of the embryos, as many embryos that look healthy on Day 3 start to degenerate by Day 5. Putting patients with many excellent quality Day 3 embryos into the Day 5 group may artificially raise the pregnancy results in that group (while simultaneously lowering the pregnancy rates for the Day 3 group they were removed from), as most of the patients with many beautiful Day 3 embryos are young and have an outstanding prognosis for pregnancy anyway.
In science, and in clinical medical research, the best way to answer questions like these is to perform a prospective, randomized trial. In other words, an investigator takes, for example, 100 patients and prospectively divides them at random into two treatment groups. In this example, 50 randomized IVF patients would have an embryo transfer on Day 3 and 50 would have a transfer on Day 5. Pregnancy and delivery rates would then be compared to see if there is a statistical difference in outcome between the two treatments. In fact, this research has been done, and several prospective, randomized studies have been published in both the American and European literature. The overwhelming majority of these studies show that there is no difference in either pregnancy or delivery rates between Day 3 and Day 5 transfers when patients are appropriately randomized. In addition to well designed clinical trials, there is also a large review of the literature – published by the Cochrane Collaboration – that shows no difference between these two treatments.
In summary, it appears from the medical literature that delaying embryo transfer to Day 5 offers no advantage to the typical patient undergoing IVF. The numerically higher pregnancy rates observed in most programs with Day 5 transfers can most likely be explained by the fact that physicians advise patients with many high quality Day 3 embryos to delay their transfer.