You are unique and thus the decision of when to transfer an embryo into your womb in the course of an IVF procedure is an individual matter. In this post, we will discuss the two most frequently preferred developmental stages when an embryo can be transferred into the womb – the cleavage stage (2-3 days after fertilization) and the blastocyst stage (5-6 days after fertilization).
Blastocyst versus cleavage-stage
With a natural pregnancy, the embryo reaches the womb in the blastocyst stage, which has long been thought to be the more biologically appropriate stage supporting further implantation. This is more likely in the implantation window, which is the receptive womb lining (endometrium) phase, i.e. the time suitable for transferring the embryo. Other stages include the pre-receptive and post-receptive stages, i.e. the times before and after the receptive stage, respectively. The receptive or, to a lesser extent, the pre-receptive stage is required for embryo transfer; therefore, it may be necessary to perform an endometrial receptivity array (ERA) test, a state-of-the-art diagnostic method of evaluating receptivity from the molecular point of view. Experience shows that transferred blastocysts are able to implant only in the receptive stage; otherwise, they die. Prolonged cultivation (to the blastocyst stage) may also have side effects on the embryo’s development due to the stress induced by the artificial conditions, causing the epigenetic information to be altered. Furthermore, blastocysts are highly sensitive to manipulation and transfer. There is also a higher risk of splitting into two embryos, resulting in monozygotic twins (from a single egg) or a failed pregnancy. Conversely, cleavage-stage embryos are transferred directly into the womb 2-3 days earlier than in natural pregnancy. Therefore, transferring an embryo with a cushion of 2-3 days is possible in the longer-term cycle, as the embryo may survive in the pre-receptive stage, with the womb lining possibly developing into the receptive stage.
Until recently, it was thought that blastocyst transfer was superior to cleavage-stage transfer, while advances in cultivation media have made it possible to extend embryo cultivation, allowing a blastocyst’s cells to unite to form outer and inner layers and a fluid-filled cavity in the centre, whereas a younger cleavage-stage embryo contains simpler round cells called blastomeres.
Which stage promises a better chance of successful implantation
With this in mind, it is clear that embryos are developmentally more competent at the blastocyst stage, offering a greater chance of successful implantation. Therefore, transferring a single blastocyst is preferred, as transferring two blastocysts increases the risk of twins. A pregnancy with more than one fetus (multigestational pregnancy), increases the risk of preterm birth and is associated with small for gestational age, which describes babies that are smaller than usual for the given number of weeks of pregnancy.
Because not all embryos are able to reach the later stages, it may happen that no embryos will become available for transfer, especially when cultivating blastocysts. Many studies describe the risk of having a viable embryo available for transfer but fewer embryos for freezing. Blastocyst grading is more accurate than with younger embryos, so there is a greater chance of obtaining higher-quality embryos and thus a higher pregnancy success rate per transfer. Not all embryos reach this stage and thus the number of available embryos is lower. Conversely, there are numerous available cleavage-stage embryos. For this reason, cleavage-stage transfer results in a higher cumulative pregnancy rate. In addition, male embryos are thought to be better at reaching later developmental stages and there is thus a higher prevalence of boys in blastocyst transfers. However, there is a need for more research in this area.
Blastocyst transfer is also the preferred option in patients under the age of 35 who have high-quality embryos. As a blastocyst has a larger number of cells, it is easier to remove some of them by means of a biopsy for pre-implantation genetic diagnosis/pre-implantation genetic screening (PGD/PGS), for which at least six (ideally eight) high-quality blastocysts are needed. If enough blastocysts are not available, there is a very low statistical chance of having a genetically healthy embryo after PGD/PGS. Chromosomal abnormalities could also be caused by the extended stay in artificial conditions, which is why fewer young embryos are damaged and more of them survive.
The choice of embryo transfer stage is determined on a case-by-case basis through consultations with doctors and embryologists. The ideal stage depends on the patient’s anamnesis, IVF history, age, family history and, of course, the number and quality of oocytes/embryos.
Because every patient is different, there is no common rule for which stage is better for transfer. Studies have yet to confirm any correlation between fresh blastocyst transfer and an improved live-birth rate compared to fresh cleavage-stage embryos. No significant difference has been found with respect to the cumulative pregnancy rate following fresh and frozen transfers. Furthermore, a successful pregnancy can arise even from embryos that are of lesser quality, i.e. those that do not develop to the blastocyst stage. In women with very few embryos, there is also a high risk of having no embryos for either fresh transfer or cryopreservation for possible future use.
There are numerous variables that determine whether your IVF procedure will result in a successful pregnancy, including your age, previous reproductive history, overall health and lifestyle factors, as well as the chosen embryo transfer stage. So, before setting out on the path to the joy of motherhood, seek the advice of experienced medical professionals, who will evaluate your specific needs and help you make the right choice. Fertilitypedia is here to help you find the right professional for you. Start today and calculate your Chance to Conceive with our unique tool.