By Zaira Salvador BSc, MSc (embryologist), Antonio Forgiarini MD, MSc (gynecologist), Emilio Gómez Sánchez BSc, PhD (senior embryologist), José Luis de Pablo BSc, MSc, PhD (senior clinical embryologist), Aitziber Domingo Bilbao BSc, MSc (embryologist) and Patricia Recuerda Tomás BSc, MSc (embryologist).
Last Update: 09/20/2018

The Embryo Transfer (ET) is the last step of the In Vitro Fertilization (IVF) process. If the cycle has been a successful one, the patient will get a positive pregnancy test on day 15 post embryo transfer. In other words, she will be able to confirm whether she is pregnant and the treatment has been successful.

Determining the best day for the embryo transfer actually depends on the progression of each patient through the IVF process from the beginning. Keeping this in mind, your IVF coordinator will choose between doing the embryo transfer on day 3 or day 5 of embryo development.

Nowadays, most specialists have a preference for single blastocyst embryo transfers (day 5) in order to prevent multiple pregnancies. The main advantage of blastocyst transfers is that the implantation rates are higher.

The different sections of this article have been assembled into the following table of contents.

Definition of Embryo Transfer

Embryo Transfer (ET) is a fundamental step of IVF procedures whereby the embryo or embryos are placed into the womb of the prospective mother.

In anticipation of the embryo transfer due date, the embryologist has to make two important decisions at the beginning of every transfer cycle:

How many embryos to transfer
Although there is no legal limit as regards the number of embryos to transfer, experts agree that betting on Single Embryo Transfers (SETs) is the best option to prevent multiple births, which increase the number of risks for the woman and the baby.
What’s the best day for the transfer
Embryos can be transferred at any stage, that is, from day 1 up until day 6 or 7. However, embryo transfers are typically performed on day 2-3 or day 5-6 because it is at these stages when their quality can be determined with accuracy.

Determining the best day for the ET has been a controversial issue for a long time, mainly because there are studies proving that high success rates can be reached on both days.

For the reasons explained above, most specialists bet on personalized embryo transfer plans, that is, choosing the best cycle day for the transfer on a case-by-case basis.

Day 3 Embryo Transfer

When conception occurs naturally, fertilization takes place in the Fallopian tubes of the woman. After egg fertilization, the embryo begins a journey toward the uterus. That’s where embryo implantation occurs.

But in cases of assisted conception, the embryos are cultured in the laboratory prior to the transfer. Given that the environment surrounding the embryo(s) is obviously different from the conditions of the female reproductive tract, experts need to reduce the number of days during which the embryo is supported in culture media at the laboratory.

So, firstly, we shall explain the main pros and cons of choosing a day 3 embryo transfer:

Pros

The main benefit of day 3 embryo transfers is that there is a larger number of embryos ready to be transferred.

While embryos develop in the culture media, some may cease their development early and become non-viable. This is the reason why some embryologists prefer day 3 transfers, when the embryos have between 6 and 8 cells.

To sum up, we can say that the risk of cancellation on day 3 is lower than if culture is extended to up to day 5-6, Moreover, the number of embryos available for freezing is higher, should you wish to use them in future cycles.

Cons

The different methods used for morphological scoring of pre-implantation embryos are insufficient to select the embryo with the greatest implantation potential.

Even if the embryo with the best apparent quality were selected, there is no definitive proof that embryonic arrest is not going to occur anyway after the embryo transfer. In other words, with day 3 transfers, the risk for the embryo to be a non-viable one is still there.

Embryos that are able to grow from cell stage (day 3) to blastocyst stage (day 5) go through a critical phase that may compromise their viability.

Given the high likelihood of early embryonic arrest with SETs, transferring two or even three embryos on day 3 is a common practice. This, at the same time, increases the chances for becoming pregnant with twins or more, with the subsequent risks associated for both the mother-to-be and the babies.

Day 5 Embryo Transfer

Embryo culture using sequential media involves keeping the embryos in the culture media for 5 days. On day 5, the embryos become blastocysts. This complicates things a little bit, as the embryologist will have to pay special attention to the metabolic requirements of the embryos, as they change from day 3 onwards.

As in the case of day 3 embryos, day 5 embryo transfers have a series of advantages and disadvantages that we will explain below:

Pros

In cases where egg fertilization results in multiple embryos, extended embryo culture to day 5 may be a good option. The main advantage is that the embryo with the highest implantation potential is selected “naturally”—most embryos with chromosomal abnormalities are unable to make it to day 5-6.

Also, the embryo morphology score is more accurate on day 5 than on day 3, as it is more likely to be in line with embryo quality.

When the evaluation of embryo quality is based on their morphokinetics and morphology, the selection of the embryo with the best implantation potential can be done more accurately.

Blastocyst embryo transfers can be synchronized with the endometrial lining, which is a major advantage as well, keeping in mind that embryos do not attach to the uterus until day 5 when conception occurs naturally. In other words, the endometrium is more receptive on day 5.

Finally, selecting the embryo with the biggest chance of implanting to the uterus increases the success rates of single embryo transfers, thereby preventing multiple pregnancies.

Cons

In spite of all the advantages, it is still possible for genetically normal embryos are unable to make it to blastocyst stage due to inadequate IVF culture media conditions in the lab.

When pregnancy occurs naturally, the embryo travels through the uterine cavity on day 4 and comes into contact with endometrial cells, which produce molecules that nourish it. For this reason, having the adequate culture media and temperature, humidity, and light conditions can promote embryo development.

On the other side of the coin, embryo transfer cancellation rates are significantly higher in the day 5-6 group, especially if the number of eggs retrieved is low.

Customized IVF treatment

Irrespective of the opinion of each professional on the best moment for the embryo transfer, embryologists and specialists agree on the need for customizing each treatment cycle.

As a matter of fact, in the words of embryologist Aitziber Domingo, generalizing about the day of the embryo transfer is not possible. She agrees that each patient should be treated individually, evaluating each case on an individual basis.

Determining the embryo transfer due date based on each patient’s circumstances is the most recommended option. The following are some of the aspects that determine a day 3 or day 5 embryo transfer:

  • Number of embryos obtained
  • Embryo quality
  • Previous IVF cycle information
  • Use of additional techniques: PGD, egg donation, ERA test…
  • Conditions of the laboratory

When Preimplantation Genetic Diagnosis (PGD) is required, the embryo is biopsied on day 3 and the results of the genetic screening is typically available within 25-48 hours. So, in these cases, the embryo transfer is done on day 5, which is to say, when the embryos have reached the blastocyst stage.

Extended embryo culture is used in IVF with donor egg cycles as well, given the higher number of good quality embryos available. Success rates of single embryo transfers in donor-egg cycles are amongst the highest.

Finally, when uterine receptivity problems are detected and an ERA test is needed, the embryo transfer will be scheduled for the most appropriate moment of the implantation window, depending on the results of the test.

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How to make a decision

Dr. Antonio Forgiarini states that there is actually not an “ideal” day for performing the embryo transfer. It depends basically on endometrial receptivity.

The most important thing to do during the process is to pay attention to the endometrial lining while the embryos are developing, that is to say, that there is synchrony between them. Keeping that in mind, deciding the day of the transfer will depend on many other factors.

In any case, such difficult decision is made by the medical staff but also by the patient or patients. At this point, physician and other staff from the clinic should inform patients about the risks and benefits of each option in order to help them to make a well informed choice.

FAQs from users

What are the success rates with blastocyst embryo culture?

By José Luis de Pablo BSc, MSc, PhD (senior clinical embryologist).

By blastocyst culture we refer to keeping the embryos in the incubator until day 5-6 of development, that is, until they reach blastocyst stage. By doing this, we perform a much more thorough embryo selection process. The fact they they are capable of making it to blastocyst means that they have a greater implantation potential, as it was able to stay longer in the lab. Pregnancy success rates depend on age, though.

Embryo transfer on day 3 or on day 5, which is better?

By Patricia Recuerda Tomás BSc, MSc (embryologist).

Existing evidence shows that culturing embryos till stage 5-6 of development, we can increase the pregnancy success rates per fresh and frozen embryo transfer. This is due to the fact that the embryos to transfer or cryopreserve can be selected more properly, since blastocysts have a higher implantation potential. It also improves embryo-endometrial synchrony.

One should keep in mind that about 50 percent of viable embryos will arrest on day 3 of development. In other words, they will not make it to blastocyst stage.

Can the embryo transfer be done on day 3 after PGD?

By Emilio Gómez Sánchez BSc, PhD (senior embryologist).

Today, over 90% of the embryo biopsies that are performed for a PGD procedure are done on day 5, which makes it impossible for embryos to be transferred on day 3. In any case, when the biopsy is carried out on day 3, the result won’t be available until day 5, so the embryos will be transferred on day 5 anyway.

I have a history of recurrent miscarriage, when should the embryo transfer be done in my case?

By José Luis de Pablo BSc, MSc, PhD (senior clinical embryologist).

The fact that a woman has had repeated miscarriages in the past has nothing to do with the day of the embryo transfer. In most of the cases, it is associated with the chromosomes of the embryos. Keeping this in mind, ideally the best treatment option in these cases would be IVF with PGD (Preimplantation Genetic Diagnosis). With PGD, we examine 6-8 cells of each embryo. It allows us to find out which embryos are genetically norma and which don’t.

How many embryos should be transferred on day 5?

By Zaira Salvador BSc, MSc (embryologist).

With day 5 transfers, a major advantage is that we can transfer one embryo without diminishing the success rates, while at the same time the risk for multiple pregnancy is eliminated. The decision depends on the prognosis category for each patient.

How many day 3 embryos make it to blastocyst?

By Zaira Salvador BSc, MSc (embryologist).

It is estimated that only 20 to 50 percent of day 2-3 embryos are actually able to develop in vitro to day 5, irrespective of the quality of the culture system used. So, one of the main risks of extended culture to day 5 is that there may be a loss of some embryos that would have implanted if they had been transferred earlier.

Is a day 3 or day 5 embryo transfer better?

By Zaira Salvador BSc, MSc (embryologist).

It depends on each patient. According to the ASRM and SART guidelines, those with a favorable prognosis should opt for 1 embryo transfer, regardless of embryo stage. From ages 38-40, they recommend 2 blastocyst embryo transfers (day 5), and from age 41, 3 blastocysts (day 5) as well.

Can you perform an embryo transfer on day 6?

By Zaira Salvador BSc, MSc (embryologist).

Yes. Embryo transfers on day 6 are performed when embryo development to blastocyst stage goes slower than usual and it the embryologist determines that doing it on day 6 is the best option.

What percentage of embryos make it to day 5 blastocyst?

By Rebeca Reus BSc, MSc (embryologist).

It is estimated that only 20-50% of day two embryos can continue developing in vitro to day 5, irrespective of how perfect the in vitro culture system is.

Is day 4 a good day to perform the embryo transfer?

By Zaira Salvador BSc, MSc (embryologist).

No, this option is not recommended because on day 4 the embryos are at the morula stage. Determining embryo quality at this stage is considerably complicated and, for this reason, it is not possible to determine what’s the best moment for the transfer.

Suggested for you

Presently, the selection of the embryos to transfer is done based on their morphology and morphokinetics. To learn more about the criteria followed, visit the following post: Embryo Quality & Grading.

Elective single embryo transfers (eSETs) is becoming an increasingly popular option for patients with mild infertility problems amongst clinics from all around the world. In any case, each patient is different and the transfer cycle should fit her individual needs. Click here to read more: How Many Embryos Should You Transfer for IVF?

The next phase after the ET is the so-called two-week wait or 2WW. Surviving this period is complicated for some women. Want to learn more? Read: Post Embryo Transfer Tips & Precautions – What Should You Expect?

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References

Bolton, V.N., Wren, M.E. and Parsons, J.H. (1991) Pregnancies after in vitro fertilization and transfer of human blastocysts. Fertil. Steril., 55, 830–832.

Bruno I, Pérez F, Tur R, Ricciarelli E, De la Fuente A, Monzó A. et al. (2005). Grupo de interés en Salud Embrionaria. Sociedad Española de Fertilidad. Embarazos múltiples derivado de FIV-ICSI en España: Incidencia y criterios sobre la transferencia embrionaria. Rev Iberoam Fertil; 22 (2): 99-110.

Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, et al. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril 2013;100:100–7.e1.

Glujovsky D, Blake D, Farquhar C, Bardach A: Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev 2012, 7:CD002118.

Huisman, G.J., Alberda, A.T., Leerentveld, R.A. et al. (1994) A comparison of in vitro fertilization results after embryo transfer after 2, 3 and 4 days of embryo culture. Fertil. Steril., 61, 970–971.

Källén B, Finnström O, Lindam A, Nilsson E, Nygren KG, Olausson PO: Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome? Fertil Steril 2010, 94:1680–1683

Pope CS, Cook EK, Arny M, Novak A, Grow DR. (2004). Influence of embryo transfer depth on in vitro fertilization and embryo transfer outcomes. Fertil. Steril.;81:51–8.

Reproducción Asistida ORG. Video: ¿Qué día de cultivo embrionario se recomienda hacer la transferencia embrionaria? (What is the recommended day for performing an embryo transfer?), by Aitziber Domingo Bilbao, BSc, MSc, Nov 27, 2017. [See original video in Spanish].

Roseboom, T.J., Vermeden, J.P.W., Schoute, E. et al. (1995) The probability of pregnancy after embryo transfer. Hum. Reprod., 10, 3035-3041.

William B. Schoolcraft, M.D., for the ASRM American Society for Reproductive Medicine (April 2016). Importance of embryo transfer technique in maximizing assisted reproductive outcomes. Vol. 105, No. 4. Colorado Center for Reproductive Medicine, Lone Tree, Colorado

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Authors and contributors

 Zaira Salvador
BSc, MSc
Embryologist
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia (UPV). Embryologist specializing in Assisted Procreation, with a Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI). More information
License: 3185-CV
 Antonio Forgiarini
MD, MSc
Gynecologist
Bachelor's Degree in Medicine from the Università degli Studi di Roma “Tor Vergata”, with specialty in Obstetrics and Gynecology at University Clinical Hospital of Valencia, Spain. Master's Degree in Human Reproduction, and currently works as an OB/GYN specialized in Assisted Procreation at fertility clinics Millet and IMER Valencia. More information
License: 464621719
 Emilio Gómez Sánchez
BSc, PhD
Senior Embryologist
Bachelor's Degree in Biology from the University of Seville. PhD in Biology from the University of Valencia. Large experience as an Embryologist Specialized in Assisted Reproduction. Currently, he is the IVF Lab Director of Tahe Fertilidad. More information
License: 14075-MU
 José Luis de Pablo
BSc, MSc, PhD
Senior Clinical Embryologist
Double Degree in Biology and Biochemistry from the University of Navarra. Master’s Degree about the Theoretical Basis and Laboratory Procedures in Assisted Reproduction from the University of Valencia (UV). Senior Clinical Embryologist from the ESHRE and ASEBIR Certification in Clinical Embryology. More than 15 years of experience as the director of IVF labs. More information
 Aitziber Domingo Bilbao
BSc, MSc
Embryologist
Bachelor's Degree in Biology from the University of the Basque Country. Master's Degree in Human Assisted Reproduction from the Complutense University of Madrid, and Master's Degree in Biomedical Research from the University of the Basque Country. Wide experience as an Embryologist specialized in Assisted Procreation. More information
 Patricia Recuerda Tomás
BSc, MSc
Embryologist
Bachelor's Degree in Biology from the University of Alcalá de Henares. Master’s Degree about the Theoretical Basis and Laboratory Procedures in Assisted Reproduction from the University of Valencia (UV). Extensive experience working at several Assisted Reproduction laboratories. More information
License: 19882M
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