Fertility Journal

Elective single embryo transfer (eSET)

To find that you have succeeded and become pregnant following IVF is a wonderful experience. You have waited for so long and been through so much to get to this stage. Then comes that magical scan at 6 weeks, ….. 2 sacs!…. 2 heartbeats!….. twins! Something you had hardly dared to even dream of. The perfect solution to your problems! One each! A family in one go! Fantastic!

Yet the biggest single risk of fertility treatment is a multiple pregnancy. The majority of twin pregnancies will have a happy outcome in that two live healthy babies are born. However, there is not a shadow of doubt that it is far safer for you to have one baby at a time and for your baby to be born as a single baby than to have been a twin. And if you have a triplet pregnancy the risks are even greater. Sometimes the risks are life-threatening.

What are the risks of having a multiple pregnancy?

Problems can of course arise in a single pregnancy, but in a multiple pregnancy the risks increase both for you and for your babies.

The risks to you:

  • all the general problems of being pregnant, such as morning sickness, varicose veins, constipation and backache are increased;
  • because of the increased iron demands, you are at greater risk of becoming anaemic;
  • the risk of both early and late miscarriage is significantly higher;
  • medical complications such as increased blood pressure, pregnancy induced hypertension, pre-eclampsia and diabetes are more common;
  • there is an increased likelihood of you being delivered by a planned elective Caesarean Section, as an IVF pregnancy plus a problem (the problem being the twins or triplets) will incline your obstetrician towards an operative delivery;
  • post-partum haemorrhage; the double or triple placentae cover a much larger surface area than the placenta of a single pregnancy. There is therefore a larger potential raw area to bleed from. In addition the overstretched uterus in a multiple pregnancy may not contract efficiently after delivery and this reduced muscle tone can in itself lead to torrential bleeding.

The risks to the babies:

  • premature labour is the major hazard of multiple pregnancy because multiple occupancy means that the uterus reaches full term size much earlier. Premature babies will have low birth weights making them more susceptible to medical problems. Three times as many twins require intensive neonatal care for the first weeks of their lives than do singleton babies. Tragically some of these babies will die.Although the majority of twin and triplet pregnancies eventually have a happy outcome, at the worst, you could go into very premature labour, say at 25 weeks (15 weeks early), and then risk losing them all. The majority of those babies that survive such extreme prematurity have a higher incidence of learning and development difficulties and even conditions such as cerebral palsy.
  • To lose any baby is devastating and heartbreaking. To lose a baby after years of infertility can cause life-long grief. The stillbirth and neonatal death rates (deaths in the first 28 days after birth) for a triplet pregnancy with one or more of the babies dying is 6 times higher than for a pregnancy with a single baby.

If you are fortunate and all goes well, you will eventually take your babies home. With two or three babies to look after you will need help! While it may be charming to see three smiling babies being wheeled through the streets to everybody’s “Ooos” and “Aaahs!” of delight, those babies have meant near exhaustion for the mother and it does not go away for many years. The financial implications of a triplet pregnancy may also cause you a major headache.

The aim of fertility treatment must be a singleton pregnancy and the birth of a healthy single child.

Why do fertility treatments result in multiple pregnancies?

The normal incidence of twins is 1 in 80 pregnancies and of triplets 1 in 800.

Not all the multiple pregnancies resulting from fertility treatments are due to IVF and ICSI. Ovulation induction with fertility drugs such as clomifene has a twin pregnancy rate of 1 in 16 and a triplet rate of 1 in 100. When gonadotrophin drugs are to stimulate ovulation the twin rate is 1 in 4 and the triplet rate 1 in 20. Accurate scanning and assessment is important if more than one mature egg follicle is developing (see Ovulation Induction & Intrauterine Insemination information).

Just over 1% of all UK births are due to IVF and ICSI treatments. Yet more than 20% of the UK’s multiple births are due to these treatments. The twin pregnancy rate from IVF and ICSI are 1 in 4 (25%) which is 20 times higher than the natural incidence of twins.

The multiple pregnancy rates from IVF and ICSI are linked to the number of embryos that are transferred. In the UK there are limits to the number of embryos that can be transferred.

If you are under the age of 40:

  • a maximum of two embryos can be transferred.

If you are over the age of :40:

  • exceptionally up to three embryos can be transferred if you are using your own eggs.


  • up to two embryos if donor eggs are used (as the egg donor will be under the age of 36).

See IVF and ICSI information.

If two embryos are transferred there is, a chance of one, two and rarely even more babies.

For blastocyst (day 5 – 6) transfers, there is a very high twin rate when two blastocysts are transferred. The transfer of a single blastocyst on day 5 has a higher birth rate than the transfer of an equivalent quality single embryo on day 3.

The downside of developing embryos to blastocyst is that there are generally fewer embryos available for freezing.

How can the multiple pregnancy rates be reduced?

This cannot simply be achieved by edict. The Department of Health and HFEA have decided that there must be a “National Strategy on minimising multiple pregnancy following fertility treatment”.

A “Multiple Pregnancy Stakeholder Group” has been set up with representatives from HFEA, British Fertility Society (BFS), Association of Clinical Embryologists (ACE), Infertility Network UK (INUK) on behalf of patients, Multiple Births Foundation (MBF), Royal College of Obstetricians & Gynaecologists (RCOG), Royal College of Nursing (RCN), British Infertility Counselling Association (BICA), NHS Specialised Services Commissioning Team, and Paediatricians.

Currently the national multiple pregnancy rates from IVF and ICSI are 25% (1in 4). This means that there will be some clinics that have a higher rate and others with a lower rate.

Following widespread consultations with the clinics and the general public, an initial programme has been set up with the eventual aim of reducing the multiple pregnancy rates to 10%. This is to be staged over a period of several years.

For IVF and ICSI treatments the key to success is to implement an elective single embryo transfer (eSET) protocol for suitable patients. Since January 2009, all UK assisted conception units have had to have their own protocols in place. By 2010 all assisted conception units are required to bring their multiple birth rates down to a modest 24%. Some clinics will not need to change their practice as they are already below this figure, while others will need to do much to achieve this initial goal. The HFEA will need to develop robust methods of evaluating a clinic’s performance.

There has been understandable concern from patients who are worried that a reduction in the number of transferred embryos from 2 to 1 will reduce their chance of conception particularly if they only have a single opportunity to have IVF treatment.

Significant reductions in the multiple birth rates will be dependant upon the implementation of the recommendations made by NICE (National Institute for Health and Clinical Excellence) in 2004.

NICE recommended that couples should be eligible to receive state-funded infertility treatment if the woman was between the ages of 23 and 39, and if there was either a diagnosed cause of infertility or at least three years of “unexplained” infertility. The recommendations included three IVF cycles and the additional use of frozen embryos.

In response to this, John Reid, the Secretary of State for Health announced that after April 2005, couples that met the NICE criteria would be offered just one cycle of IVF although he expected the NHS to make progress towards full implementation of the NICE guidance. Priority would be given to couples who did not already have a child living with them. At a local level, the PCTs (Primary Care Trusts) would be expected to fund the costs of implementation.

There have been startling variations in the provisions made by the different PCTs. These range from no funded treatment to full implementation of the NICE recommendations. Few of the PCTs accept that a treatment cycle includes the fresh embryo transfer plus the subsequent transfer of all frozen embryos that resulted from that same egg collection. The majority of PCTs make no provision for the use of frozen embryos.

How can acceptance of eSET be achieved?

There needs to be adequate NHS funding to fully implement the NICE guidelines.

Patient education is essential. Many patients will find twins acceptable in spite of the risks, particularly if they feel that their chances of success are even minimally reduced.

It is also essential to educate clinicians. Clinicians need to believe the value of eSET and the benefits of reducing multiple pregnancy rates.

How can eSET be carried out without reducing success rates?

It is essential that the need to reduce multiple pregnancy rates is not at the expense of IVF success rates.

Women who have the best chance of getting pregnant also have the highest chance of having a multiple pregnancy.

  • eSET is carried out for those women most at risk of having twins:
    – under the age of 35
    – no more than one previous failed IVF attempt
    – there is more than 1 top quality embryo available for transfer
  • Set up effective embryo freezing programmes so that good quality embryos are available for transfer if the fresh transfer should fail;
  • If there is more than 1 good quality blastocyst available for transfer, only 1 blastocyst should be transferred.
  • 2 embryos are transferred for women aged 35 –39
  • 2 – 3 embryos are transferred for women aged 40 →

eSET need not be reserved for the younger patient with a good prognosis for a successful outcome. There will be a number of older women who have a good yield of top quality embryos for whom sET will be appropriate.

Further information can be found on www.hfea.gov.uk | www.oneatatime.org.uk