By Rebeca Reus BSc, MSc (embryologist), Gorka Barrenetxea Ziarrusta MD, PhD (gynecologist), Laura García de Miguel MD, MSc (gynecologist), Manuel Fernández MD, PhD (gynecologist), Mark P. Trolice MD, FACOG, FACS, FACE (reproductive endocrinologist) and Aitziber Domingo Bilbao BSc, MSc (embryologist).
Last Update: 09/13/2018

One of the most controversial issues of In Vitro Fertilization (IVF) procedures is the one concerning the number of embryos to transfer. This decision should be made considering the chances of success, but at the same time aiming to reduce the risk of multiple birth. Currently, there seems to be a consensus between experts in the field: the general recommendation is one embryo per transfer, both in fresh and frozen cycles, irrespective of whether own or donated eggs are used.

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

How to decide how many embryos to transfer

Multiple embryo transfers are directly linked to higher chances of getting pregnant, but also of multiple pregnancy (twins or triplets), with the subsequent risks of this type of pregnancy for both the mother and the babies.

Embryologist Aitziber Domingo explains that they never transfer more than one or two embryos per patient. She agrees with this topic being one of the most controversial ones in the field of Assisted Reproduction. However, determining if 1 or 2 embryos should be transferred depends on the peculiarities of each couple.

Depending on the patient, particularly factors like age and embryo quality, we can make the right decision. Nowadays, the trend is to transfer a single embryo, something favored by the embryo vitrification technique to a large extent. Almost 90% of embryos survive this technique. By doing this, we reduce the chance of multiple pregnancy, as the embryos are transferred one by one.

Advances in reproductive technologies

A few years ago, the most common practice was to transfer two or even three embryos per cycle. But presently, the outcomes of fertility treatments have increased so much that specialists never transfer three embryos in a single cycle. Instead, transferring a single embryo is increasingly becoming the most common practice.

This change is due to the improvements achieved in this field, including:

  • Optimization of embryo culture systems
  • Time-lapse monitoring systems
  • Optimization of embryo vitrification technique (embryo freezing)
  • Endometrial Receptivity Array (ERA) Test

These advancements have enable the availability of a higher amount of good quality embryos to choose from, which allows the embryologist to select the best ones with more accuracy. Also, it allows us to predict the moment of optimal endometrial receptivity, and to schedule the embryo transfer for that day in order to maximize the chances of success.

Criteria used to make a decision

When making the decision of how many embryos to transfer, the following aspects should be taken into consideration:

  • Embryo quality
  • Stage of embryo development (day 2, day 3 or blastocyst)
  • Maternal age
  • Previous cycle failure (implantation failure, recurrent miscarriage, etc.)
  • Cause of infertility
  • Endometrial receptivity
  • Uterine anomalies
  • Own or donated eggs
  • Egg quality

The number of embryos to transfer will be determined considering all the factors listed above, especially embryo quality to determine the implantation potential. The decision should be made on a case-by-case basis, always with the ultimate goal of achieving a singleton pregnancy.

For example, imagine a young patient with three class A embryos (optimal quality) available, without previous IVF failure. The embryologist will recommend that she opts for a single embryo transfer, as she has a good prognosis, that is, the chances for embryo implantation to occur are high.

Conversely, if we consider the case of a patient who is over the age of 35, with embryos of class B and C quality (medium to poor quality) and previous failed IVF cycles, she may require a two-embryo transfer, as the chances for both embryos to attach to the uterus are lower.

Read more: Embryo Classification According to Their Quality.

Guidelines by the Spanish Fertility Society

In this area, the Spanish Fertility Society (hereinafter SEF, due to its initials in Spanish) has established some guidelines, although each case requires an individual approach:

Women under 30
Ideally, a single embryo transfer; 3-embryo transfers should be avoided.
Women aged between 30 and 37
Single or two embryo transfer depending on embryo quality; three embryo transfers are only indicated after 3 failed IVF cycles.
Women over 37
Preferably, a two embryo transfer; only in cases of poor quality will be a three embryo transfer recommended.
Egg donation
When donor eggs are used, they are more likely to be high quality eggs; therefore, one can only expect a better embryo quality, and subsequently greater odds for implantation. That is why there is a preference for single or double embryo transfers, by no means is a three embryo transfer advisable.

Risk of multiple pregnancy

For couples who have been trying to conceive for a long time, the desire to have a baby is so strong that sometimes they find shelter in the fact that chances of getting pregnant increase if more than a single embryo is transferred. The problem is, most of them do not take into account the risk of multiple births it entails.

When it comes to determining how many embryos to transfer, the risks associated with multiple births should be taken into account.

The likelihood of preterm birth (before week 37) is higher in this type of pregnancies and, sometimes, they can even lead to extreme preterm birth (before week 26 of pregnancy).

Moreover, multiple pregnancies are associated with a higher chance of premature rupture of membranes (PROM), gestational diabetes, hypertension, and other problems associated with pregnancy, such as anemia.

Finally, the likelihood of requiring a C-section is higher, as well as the risk of miscarriage.

Find more information about this topic in the following article: What Are the Risks of Multiple Births?

Single Embryo Transfer (SET)

For all the reasons explained above, assisted reproduction specialists have reached a consensus whereby a SET is the option of choice as long as it is possible.

By doing this, we increase the chances of success per transfer, due to elevated embryo quality, thereby preventing the risk of multiple birth.

In the words of Dr. Gorka Barrenetxea, MD, PhD, the secret to success with SETs is to perform a thorough process of embryo selection, culturing all embryos to blastocyst stage, and trying to select them genetically if possible.

FAQs from users

Do you follow the same procedure with fresh and frozen embryos?

By Laura García de Miguel MD, MSc (gynecologist).

The treatment to follow varies depending on whether it is a fresh embryo transfer (after an IVF cycle) or a frozen embryo transfer.

With fresh embryos, patients follow a hormonal treatment based on applying injections to stimulate the ovaries during 10 days approximately. After retrieving the eggs, the patient starts taking progesterone vaginally or subcutaneosly.

With frozen embryos, patients have to prepare during 2 weeks with estrogens (in patches or tablets). Depending on the day of the embryo transfer, progesterone may be prescribed as well. In some cases, the patient follows a natural cycle, without using estrogens.

A large number of multiple births have occurred throughout the history of reproductive medicine. How can multiple pregnancy be prevented?

By Manuel Fernández MD, PhD (gynecologist).

There are lots of actions to be taken, most of them being implemented with increasing success. As for in vitro fertilisation, a three-embryo transfer should be avoided: cases with a good prognosis should bet on a single embryo transfer instead. This requires a process of raising awareness not only by the couple undergoing the treatment but also by the professional team. The “success” of an assisted reproductive treatment does not consist only on achieving pregnancy. More and more, we need to be aware that the ultimate aim should be having a healthy baby, that is to say, that the child is not born too early. Despite changing this mindset may be difficult, we insist on the need to prevent multiple births.

Some patients think that transferring multiple embryos increases the chances for success. Are they right?

By Manuel Fernández MD, PhD (gynecologist).

Yes, technically they are right. By transferring two embryos instead of a single embryo, the chances for pregnancy are greater. The importance of a good embryo freezing programme is that it allows the chances to be the same if we compare performing a two-embryo transfer at the same time with performing a two-embryo transfer in two different cycles, one of them after being frozen. The concept is “1 + 1 = 2″.

In the United States, for instance, there is no limit regarding the number of embryos to transfer. Where do you stand on this?

By Manuel Fernández MD, PhD (gynecologist).

I think that the European policy is much healthier at aiming to encourage a single embryo transfer in order to avoid multiple births.

Does the number of embryos transferred have an influence on the endometrial preparation process?

By Mark P. Trolice MD, FACOG, FACS, FACE (reproductive endocrinologist).

The endometrium can be stimulated either naturally, by the woman’s ovarian estradiol, or artificially, by applying estradiol usually in the form of tablets or transdermal patches to obtain adequate endometrial lining thickness by ultrasound measurement. Unless a woman ovulates, the hormone progesterone is administered by the woman vaginally or by intramuscular injection to achieve optimal endometrial preparation for embryo implantation. Alternatively, following natural ovulation, the woman’s ovaries produce progesterone to accomplish this same purpose toward embryo transfer. Either natural or artificial method occurs without regard to the number of embryos planned for transfer.

Does the day of embryo transfer influence how many embryos to transfer?

By Rebeca Reus BSc, MSc (embryologist).

Yes, since blastocysts (day 5-6 after fertilization) are more likely to attach to the uterine lining, as they are synchronized with the uterine lining and allows for a more accurate selection process. Thus, if we transfer two class A blastocysts, they will have higher chances of implanting than two class A embryos on day 3.

Read more: Day 5 vs. Day 3 Embryo Transfer – What Are the Pros & Cons?

How many embryos should be transferred with donor eggs?

By Rebeca Reus BSc, MSc (embryologist).

Specialists do recommend everyone undergoing IVF, whether it is done using own or donated eggs, to transfer one embryo in order for a multiple pregnancy to be prevented. There exist certain cases where transferring two embryos would be justified, including poor embryo quality and previous failed IVF attempts with a single embryo.

Also, given that the final decision is in the hands of the patient, sometimes younger patients who wish to have twins request a 2-embryo transfer from the beginning. The older the woman is, the higher the number of risks associated with a multiple pregnancy.

Is it possible to predict which embryos will implant and which don’t?

By Rebeca Reus BSc, MSc (embryologist).

In spite of the progress made in reproductive technologies already explained, we still cannot predict with 100% accuracy which embryo will be able to implant.

However, it is possible to predict which one will have higher chances of implanting. Implantation is a complex process where the endometrial lining plays a major role. In this sense, the relationship between endometrial thickness and embryo implantation is crucial.

Check out this for information: What Is Embryo Implantation? – Process & Stages.

Suggested for you

Throughout this post, we have made several process to the technique of embryo vitrification, in which embryos are stored in liquid nitrogen storage tanks for later use. Get more info by clicking the following link: What Is Embryo Vitrification?

Also, blastocyst culture refers to transferring an embryo that is on the fifth or seventh day of development. Learn more about this type of embryo culture by clicking here: What Is IVF Blastocyst Culture? – Success Rates & Timeline.

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References

Cattoli, M. and Borini, A. (1996) The ideal number of transferred embryos: a retrospective analysis. [Abstr. no. 187] Hum. Reprod., 11 (Abstr. Book 1), 88.

Englert, Y., Devreker, F., Bertrand, E. et al. (1993) Double instead triple embryo transfer as a prevention of multiple pregnancy. [Abstr. no. 18] Hum. Reprod., 8 (Abstr. Book 1), 13.

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.

McLernon DJ, Harrild K, Bergh C, Davies MJ, de Neubourg D, Dumoulin JC, Gerris J, Kremer JA, Martikainen H, Mol BW, Norman RJ, Thurin-Kjellberg A, Tiitinen A, van Montfoort AP, van Peperstraten AM, Van Royen E, Bhattacharya S: Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomized trials. BMJ 2010, 341:6945.

Montag M, Toth B, Strowitzki T. (2013). New approaches to embryo selection. Reprod Biomed Online;27:539–46.

Pandian Z, Marjoribanks J, Ozturk O, Serour G, Bhattacharya S: Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection. Cochrane Database Syst Rev 2013, 7:CD003416.

Practice Committee of American Society for Reproductive Medicine; Practice Committee of Society for Assisted Reproductive Technology: Criteria for number of embryos to transfer: a committee opinion. Fertil Steril 2013, 99:44–46

Practice Committee of the Society for Assisted Reproductive Technology and Practice Committee of the American Society for Reproductive Medicine: Elective single-embryo transfer. Fertil Steril 2012, 97:835–842.

Reproducción Asistida ORG. Video: ¿Si la pareja tiene un hijo previo se recomienda hacer transferencia de un solo embrión? (If the couple already has one child, do you recommend a single embryo transfer?), by Gorka Barrenetxea, MD, PhD, Sep 28, 2017. [See original video in Spanish].

Reproducción Asistida ORG. Video: ¿Cuántos embriones se recomienda transferir? (How many embryos should be transferred?), by Aitziber Domingo, 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.

Tomás C, Tikkinen K, Tuomivaara L, Tapanainen JS, Martikainen H. (2002). The degree of difficulty of embryo transfer is an independent factor for predicting pregnancy. Hum Reprod; 17:2632–5.

Vilska S, Tiitinen A, Hyden-Granskog C, Hovatta O. Elective transfer of one embryo results in an acceptable pregnancy rate and eliminates the risk of multiple births. Hum Reprod 1999;14:2392– 2395

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

 Rebeca Reus
BSc, MSc
Embryologist
Degree in Human Biology (Biochemistry) from the Pompeu Fabra University (UPF). Official Master's Degree in Clinical Analysis Laboratory from the UPF and Master’s Degree about the Theoretical Basis and Laboratory Procedures in Assisted Reproduction from the University of Valencia (UV). More information
 Gorka Barrenetxea Ziarrusta
Bachelor's Degree in Medicine & Surgery from the Public University of Navarra, with specialty in Obstetrics and Gynecology from the University of the Basque Country. He has over 30 years of experience in the field and works as a Titular Professor of Obstetrics & Gynecology at the University of the Basque Country and the Master's Degree in Human Reproduction of the Complutense University of Madrid. Vice-president of the SEF. More information
License: 484806591
 Laura García de Miguel
MD, MSc
Gynecologist
Bachelor of Medicine and Surgery from the Autonomous University of Barcelona, with specialization in Obstetrics & Gynecology at Sant Joan de Déu University Hospital. Master's Degree in Human Reproduction from the Complutense University of Madrid. Currently, she is the Medical Director of Clínica Tambre in Madrid, Spain. More information
License: 280843059
 Manuel Fernández
MD, PhD
Gynecologist
Graduate in Medicine and Surgery from the University of Seville. Specialist in Obstetrics and Gynecology from the University Hospital Virgen Macarena de Seville. Master's Degree in Assisted Reproduction from the Rey Juan Carlos University of Madrid. Gynecologist at IVI Seville since 2003 and Director since 2005. More information
License: 4114231
 Mark P. Trolice
MD, FACOG, FACS, FACE
Reproductive Endocrinologist
Mark P. Trolice is the Director of Fertility CARE – The IVF Center and Clinical Associate Professor in the Department of Obstetrics & Gynecology (OB/GYN) at the University of Central Florida College of Medicine. He is Board-certified in REI and OB/GYN, and maintains annual recertification. His colleagues select him as Top Doctor in America® annually, one among the top 5% of doctors in the U.S. More information
License: ME 78893
 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
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3 comments

  1. Featured
    Binny parekh

    Hi, I had two embryos transferred on the 23rd. I have been getting pain in the stomach on and off since then. But suddenly after two days the pain stopped completely. I am really worried, is everything ok inside???

    • Sandra FernándezBA, MA

      Hello Binny,

      the pain you felt in the stomach is a common symptom post embryo transfer. Given that you had it transferred on March, 23rd, it is likely to be due to ovulation induction drugs. Don’t panic, because it is a common symptom and does not indicate the transfer has been unsuccessful at all. Be patient during the 2WW. Hoping for the best!

      Regards

  1. Aria Terrell

    It is so true what you explain here! Making the right decision is complicated… because at first you’re totally unaware of how risky can a multiple pregnancy turn out to be… Until you get pregnant with twins. That’s my case, but I got triplet, so you can imagine how complicated it was… I encourage every woman reading this to be more sensible and give more importance to the risks a multiple pregnancy involves rather than paying only attention to their desire to be mothers, no matter how strong it is. Just make the right choice, girls! Otherwise you may put your own life in danger, what if you have your babies but you cannot live to see them grown? Is it really worth it?