Single vs double embryo transfer in IVF

Double embryo transfer (DET) in IVF was traditionally done to improve the odds of implantation. However, DET can be the reason for various neonatal complications and also cause serious problems for the mother. It is important to assess the risks and benefits of double embryo transfer in IVF vs. single embryo transfer (SET) before you go through with the final procedure.

According to a CDC report, the NICU admission for babies born from single embryo transfer is significantly lower as compared to those born from DET. One out of every 10 women with twin babies are more likely to have preeclampsia, high blood pressure, and other health complications (1).

Risks of double embryo transfer in IVF

Having a safe pregnancy is the ultimate goal of any fertility treatment. Both ASRM and SART revised their guidelines in 2023 and recommended the transfer of a single euploid blastocyst in women less than 35 years of age, for the best outcome in their first IVF cycle (2). 

What happens when two embryos are transferred?

During a typical IVF cycle, multiple mature eggs are retrieved from the ovaries and fertilized by sperm in the lab. If everything goes well, you should have several good-quality embryos from this.

On day 3 (cleavage stage) or day 5 (blastocyst stage) of fertilization, one or more high-quality embryos are then delicately placed inside your endometrial cavity.

According to a CDC report, the chances of having a healthy baby with different embryo transfer options are explained through this chart (3):

Embryo stage/ Day of transferSingle embryo transfer(fresh)SET (fresh) followed by 1 SET (frozen)Double embryo transfer (fresh)
Cleavage stage (2-3 days)At least one baby – 38%
Twins – <1%
At least one baby – 55%
Twins – <1%
One baby – 49%
Twins – 16%
Blastocyst stage (5-7 days)At least one baby – 51%
Twins – <1%
At least one baby – 66%
Twins – 1%
One baby – 60%
Twins – 27%

The women candidates for this assessment were younger than 38 years and were using IVF for the first time.

The above data indicates that transferring one fresh embryo followed by one frozen embryo has the best embryo outcomes without raising the risk of twins.

A different analysis also found that the transfer of two good-quality blastocysts provided a higher clinical pregnancy and live birth rates as compared to the transfer of a single embryo, but the multiple pregnancy rate was also higher (4).

Pros and cons of transferring Two Embryos in IVF

Many couples prefer double embryo transfer, especially when they don’t want any of the potential embryos to get wasted. The number of embryos to transfer in an IVF cycle depends on the quality of gametes and embryos, your age, previous failures, etc. Normally, your doctor would advise considering all these factors but if you have the freedom to decide, you should consider these pros and cons of transferring two embryos:

Pros

  • Raises your chances of pregnancy
  • Saves both time and money
  • Can have twins, if you want

Cons

  • Risk of labor complications (such as labor and delivery bleeding and less than 29 weeks of gestation period)
  • Risk of gestational diabetes and pre-eclampsia (high blood pressure, high levels of proteins in urine, or other signs of organ damage)
  • Higher infant mortality rate
  • Possibility of cerebral palsy in babies
  • Children born with low birth weight or those born prematurely can suffer from both cognitive and emotional issues later in life

Chances of twins with IVF (2 embryos)

Many couples facing infertility issues are often tempted by the idea of having twins. By 2011, about 36% of twin births and 77% of triplet births in the US resulted from assisted fertility treatments (5) but given the risks, many doctors are now advocating for single transfer in IVF.

Sometimes the concept of ‘vanishing twins’ may be applied to increase the chances of a successful pregnancy. In a study of 4,640 IVF cycles, it was shown that transferring a good-quality blastocyst with a poor one confers no advantage (6). On the other hand, if any of the embryos you choose to transfer are chromosomally abnormal, it may also have an effect on the other healthy embryo.

Vanishing twin survivors have an elevated risk of preterm birth and low birth weight compared to singletons from a single gestation as seen in an analysis of 709 multiple and 5962 singleton pregnancies (7). In comparison, if both embryos are of poor quality, you may have a higher chance of positive pregnancy.

Single vs double embryo transfer in IVF

In an approach called the Mixed Double Embryo Transfer (MDET), two embryos at different developmental stages – Day 3 (cleavage stage) and Day 5 (one blastocyst) stage are transferred together in a single unstimulated cycle. The technique is usually applied to patients with repeated implantation failure or those who wish to have twins. Frozen embryos are used for this purpose.

While any pregnancy has risks, the chances of healthy twins or triplets with IVF are relatively lower in a single transfer. So, if you wish to avoid dizygotic twins, opt for a single embryo transfer at a time.

Double embryo transfer success stories

Over the past decade, more fertility specialists have recommended SETs for safer outcomes. However, not all stories are equal. Celine Dion’s second pregnancy story is one of the most inspiring double embryo transfer success stories that we know.  After having her first child René-Charles in 2001 through IVF, she planned for a second pregnancy. With 6 failed IVF attempts and a rollercoaster of emotional tolls, she was finally pregnant with fraternal twins at the age of 42 in 2010.

The similar IVF story of Nita and Mukesh Ambani (one of the top ten of the world’s richest) resulted in the birth of their twins Isha and Akash Ambani after 8 years of marriage. Neeta also conceived her third son Anant Ambani naturally after 3 years of her first pregnancy.

Transferring two untested embryos

It is estimated that about 20% of all human eggs are aneuploid, which means they have an abnormal number of chromosomes. The proportion of defective eggs increases with age, along with deteriorated egg quality. A single gene disorder may be inherited by the embryo which can be the cause behind implantation failure or miscarriage.

It is also important to note that cleavage-stage embryos have a significantly higher aneuploidy (chromosomal abnormality) rate compared to blastocyst-stage embryos.

One of the top reasons for IVF failure is often due to aneuploidy and the transfer of untested multiple embryos. Twin babies born without prior testing are 6X times more likely to be born preterm than single babies (1).

By using Preimplantation genetic testing for aneuploidies (PGT-A), the number of euploid chromosomes (or healthy chromosomes) can be detected before the transfer. When two PGT-approved embryos are transferred, the likelihood of live birth per transfer is more promising than two non-tested transfers. Therefore, genetic screening is recommended to improve IVF success and minimize the risk of miscarriage or having a chromosomally abnormal child before transferring into the womb.

If you have a favorable prognosis at an advanced age, it is best to opt for single embryo transfer, regardless of the stage of the embryo or the results of screening with PGT-A.

Single vs. Double embryo transfer success rate

The success rate of an embryo transfer has much to do with embryo quality rather than quantity. In a comparison of SET vs DET in IVF-PGT cycles of 611 patients between January 2017 to February 2021, the following observations were noted (8):

Double embryo transferSingle embryo transfer
Live birth64.2% (with 35.3% twin gestations)81.9% (with a 98.5% singleton rate)
Reasons for no live birth27.5% biochemical loss, 18.5% clinical loss, and 53.9% not pregnant21.5% biochemical loss, 23.7% clinical loss, and 54.8% not pregnant

In general, younger women or those who haven’t faced failed IVF earlier may opt for either single or multiple embryo transfers, but women their late 30s or 40s are advised for single embryo transfer to reduce strain on the uterus and the placenta and improve their chances of having a healthy baby. 

According to recent trends, if you have more than one good-quality embryo, it is now considered best to implant one embryo at a time and freeze the others. In a 2020 study in the British Medical Journal, it was found that 2 frozen embryo transfer success rates (or the freeze-all strategy) were similar to a fresh transfer strategy (9).

It is a fact that twin pregnancy is risky for the baby as well as the mother, whether you choose IVF or not. The transfer of a single euploid embryo can lower the risk of adverse neonatal outcomes and it is certainly a better option if you are also diagnosed with obstetric risk factors. Consult with your fertility doctor who can optimize the chances of a safer pregnancy, even when you have a poor prognosis.

If you have more questions on the risk and benefits of double embryo transfer in IVF, consult with a fertility expert before making any firm decision. To plan your affordable IVF, get in touch via the form on this page.

References:

  1. CDC: Having healthy babies one at a time (Handout 2). https://www.cdc.gov/art/pdf/patient-resources/Having-Healthy-Babies-handout-2_508tagged.pdf
  2. American Society for Reproductive Medicine guidelines for a number of embryos (fresh or frozen) to transfer. https://www.uptodate.com/contents/image?imageKey=OBGYN%2F56555
  3. CDC: Having healthy babies one at a time (Handout 1). https://www.cdc.gov/art/pdf/patient-resources/Having-Healthy-Babies-handout-1_508tagged.pdf
  4. Park D.S, Kim J.W, Chang E.M, Lee W.S, Yoon T.K, Lyu S.W. Strategies in the transfer of varying grades of vitrified-warmed blastocysts in women aged over 35 years: A propensity-matched analysis. J Obstet Gynaecol Res. 2019; 45: 849-857. DOI: 10.1111/jog.13897.
  5. Aniket D Kulkarni, Denise J Jamieson, Howard W Jones Jr, Dmitry M Kissin, Maria F Gallo, Maurizio Macaluso, Eli Y Adashi. Fertility treatments and multiple births in the United States. DOI: 10.1056/NEJMoa1301467
  6. Micah J Hill, Allison E Eubanks, John M Csokmay, Alicia Y Christy, Samad Jahandideh, Alan H DeCherney, Kate Devine, Eric D Levens, Matthew T Connell. Is transferring a lower-quality embryo with a good-quality blastocyst detrimental to the likelihood of live birth? 2020 Aug;114(2):338-345. DOI: 10.1016/j.fertnstert.2020.03.027
  7. Dickey RP, Taylor SN, Lu PY, Sartor BM, Storment JM, Rye PH, Pelletier WD, Zender JL and Matulich EM (2002) Spontaneous reduction of multiple pregnancy: incidence and effect on outcome. Am J Obstet Gynecol 186,77–83. DOI: 10.1067/mob.2002.118915
  8. J Rodriguez-Purata, M Roque, R Colabianchi, M Colabianchi, E Cervantes-Bravo. -779 Single (SET) versus double embryo transfer (DET) in PGT-A cycles: cumulative live birth rates (CLBR) and multiple pregnancy rates using a Markov decision-analytic model. Human Reproduction, Volume 37, Issue Supplement 1, July 2022, deac107.719. 30th June 2022. DOI:  https://doi.org/10.1093/humrep/deac107.719
  9. Sacha Stormlund, Negjyp Sopa, Anne Zedeler, Jeanette Bogstad, Lisbeth Prætorius, Henriette Svarre Nielsen, Margaretha Laczna Kitlinski, Sven O Skouby, et al. Freeze-all versus fresh blastocyst transfer strategy during in vitro fertilization in women with regular menstrual cycles: multicentre randomized controlled trial. 5th August 2020. BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2519

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