How many embryos should you transfer for IVF?

WHEN I PRODUCED 41 EGGS AT RETRIEVAL – 18 OF WHICH WENT ON TO BECOME EMBRYOS – my husband thought it would be a marvellous idea to put a few of them back in and “kill at least four birds with one stone”.

While he was kidding about FOUR embryos, he was keen on the idea of two.

But then we read the “Multiple Pregnancy Information Sheet” provided by our clinic (a “multiple pregnancy” is any number other than one). It was suitably terrifying, and we opted to put one frostie back in – after I’d been in hospital with severe ovarian hyperstimulation syndrome (OHSS), that is. Forty-one bloody eggs will do that to you.

That one frostie is now the cuddliest, cheekiest kid on earth, so I have no regrets. But after I gave birth, I started to wonder… are the risks of multiple embryo transfer really so bad? Or are the NHS and other clinics scaring us off needlessly?

Also, I was pretty sure I’d heard of some clinics actually recommending double embryo transfers. Why do they do that, when others are so adamant about transferring just one? Are there other incentives at play here? Why else would some places advocate single vs multiple while others recommend the exact opposite?

Below you’ll find what I discovered. You’ll see that some of the studies I looked at compare single embryo transfers to double embryo transfers, while others refer to single vs multiple. In the UK, there are very few occasions where more than two embryos are transferred at once – so when you see “multiple”, you can assume most of those will be double embryo transfers.

One embryo vs two: likelihood of success

Having more than one embryo transferred (in one go) makes it more likely you’ll get pregnant. Here’s one set of stats from a British Medical Journal (BMJ) meta-analysis of 1,367 patients in 2012:

• Of the 1,367 women in the analysis, 683 had a single embryo transfer and 684 had a double embryo transfer.
• Of the 683 who had a single transfer, 27% of them (181) gave birth.
• Of the 684 who had a double transfer, 42% (285) gave birth.

I wanted to know how many of those “double transfer” births resulted in the birth of more than one baby, and the BMJ was able to tell me: 29% (84/285) of “double embryo transfer” births involved more than one baby (most of those likely from the two embryos transferred, rather than one embryo dividing in two).

Did the other 201 (out of 285) women who gave birth start off with two babies but miscarry one? The BMJ study doesn’t tell us, but research from the Human Fertilisation and Embryology Authority (2011) suggests not: it found that the majority of women (81.5%) who had an early multiple pregnancy (as a result of a multiple embryo transfer) went on to have multiple live births. Only a fifth (18.5%) lost one or more foetuses and gave birth to only one baby.

Putting these two studies together suggests that the majority of women who had a double embryo transfer became pregnant with just one baby: the other embryo simply “didn’t stick” from the start.

(If you’re wondering about the relative ages of the women in these studies, the HFEA stats are for women of all ages, and two-thirds of the women were aged 37 and under. The BMJ research compiled data from a number of studies, which had differing age limits ranging from 34 to 37.)

Note: it’s far from ideal to mix together studies as I’ve done above, but the aim is to give you a broad overview of the outlook for single vs double – rather than something uber scientific and accurate.

With data like that, you’d be forgiven for thinking it’s insane to even consider a single embryo transfer. After all…

• A double embryo transfer is more likely to result in success.
• A double embryo transfer is more likely to lead to a single pregnancy (which is far less risky than a multiple pregnancy).

But before you go to your doctor and yell “Shove 'em up me!” bear in mind what the BMJ discovered in its 2010 meta-analysis:

“An additional frozen single embryo transfer [after a failed fresh transfer] resulted in a cumulative live birth rate not significantly lower than the rate after one fresh double embryo transfer.”

That is: “1 embryo fresh transfer” + “1 embryo frozen transfer” = very similar live birth rates to “2 embryos fresh transfer”

(If you’re wondering whether frozen embryo transfers are as effective as fresh ones, I have an entire article on that too. The gist is: yes, they are as effective.)

“Why would I go through the hassle and expense of two separate transfers if I can get the same outcome as a double embryo transfer?” you might be wondering.

Five reasons:

1. There’s a good chance you’ll end up with twins rather than just one baby. The BMJ study mentioned earlier found that 29% of all pregnancies from two embryos resulted in a multiple pregnancy (compared to 2% in the general population). In case that doesn’t seem very high to you, put it this way: if you get pregnant, there’s nearly a one in three chance that you’ll give birth to twins.
   
2. All the women in the BMJ study used two/three-day embryos (that is, embryos that have developed in an incubator for two or three days before being transferred into the uterus). But it's becoming the norm for five-day embryos to be transferred instead. Evidence suggests that embryos that make it to Day 5 have already survived a ton of development hurdles (compared to Day 2/3 embryos) and are therefore more likely to be strong and hardy enough to survive pregnancy too.
   
   What's more, Day 5 embryos have a stronger chance of implanting because it’s a more natural time for an embryo to be in the uterus. (In a “natural” pregnancy, the embryo would still be travelling down the fallopian tube at Day 3 – and would reach the uterus around Day 5.) 
   
   The HFEA has evidence that Day 5 embryo transfers tend to be more successful here: https://www.hfea.gov.uk/media/1783/fertility-treatment-2014-trends-and-figures.pdf
   
   Basically: the odds are better today for embryos (because they're likely to be transferred at Day 5), so why risk a multiple pregnancy if you have a really good chance with one embryo?
   
   There’s SO much more to the “two/three-day vs five-day embryo transfer” debate, which you can read about here.
   
3. Thanks to the HFEA’s aim of reducing the number of multiple births in the UK, many clinics now offer “packages” that include one (or more) fresh cycles plus a certain number (often unlimited) of frozen embryo transfers. And if you’re doing IVF on the NHS, most local clinical commissioning groups (CCGs) will fund a fresh and follow-up frozen transfer. To find out what your local CCG will fund, visit Fertility Network UK. Then choose your country (e.g. England), and you'll be able to download a spreadsheet of all the CCGs there.
   
   This is related to the “1 fresh embryo transfer” + “1 frozen embryo transfer” = very similar live birth rates to “2 embryos fresh transfer” calculation I referred to earlier. Basically, if you end up with more than one good-quality embryo during IVF treatment, you can choose to transfer just one to the uterus and freeze the remaining one(s), to be transferred in follow-up attempts.
   
4. A recent study has concluded that transferring two embryos of differing quality can actually cut the chances of a successful pregnancy, compared to just transferring the best-quality embryo. Experts believe this might be because the body focuses on the poorer-quality embryo and rejects a possible pregnancy for both of them. The body throws the baby out with the bathwater, basically.
   
5. If you really think you’re happy to change twice as many nappies and clean up twice as much puke, there’s also a number of medical risks associated with having twins. Read on…

What are the real risks of a double pregnancy?

Below is a selection of what my “Multiple Pregnancy Information Sheet” says.

• Approximately 50% of twins require admission to a neonatal unit at birth, compared to 20% of singletons.
  
• Twins are nearly six times more likely to have cerebral palsy than a singleton (12.6/1,000 births compared to 2.3/1,000).
  
• At least one twin has a significant disability in 7.4% of cases.
  
• Twins are six times more likely to die in the first year of life than singletons (24.1/1,000 births compared with 4.4/1,000).

All these risks are associated with the fact that at least half of twins are likely to be born prematurely – i.e. before 37 weeks – whereas a singleton baby is usually carried for 40 weeks. The earlier a baby is born, the bigger the risks – and 12% of twins are born before 32 weeks compared to 2% of singletons.

As the info sheet points out, the absolute risk of being born very prematurely is low, but the consequences are extremely serious.

I haven’t even started on risks to the mother:

• 20% of mothers carrying twins suffer from pregnancy-induced hypertension (high blood pressure), compared to only 1–5% of mothers of singletons.
  
• The risk of pre-eclampsia is up to 30% for twin pregnancies, compared to 2–10% in singleton pregnancies. 
  
• You have a 12% risk of developing gestational diabetes when you’re pregnant with twins, compared to only 4% if you’re pregnant with one baby.

And then, of course, there are the risks during and after birth:

• Birth complications (such as one or both babies being in breech position) are “more likely” with twins, which means caesarean sections are more likely.
  
• For the mother, there are higher risks of haemorrhage and anaemia after a twin birth, and double the risk of death. (We’re talking tiny numbers here – 1 in 25,000 for singleton pregnancies and double that for twin pregnancies – but it’s still worth knowing.)
  
• Plus: “Parents of twins (both mothers and fathers) are at a greater risk of all forms of stress (psychological and financial) during the first few years after delivery.”

Can we trust these facts and figures? Yes. I’ve looked at clinic reports and meta-analyses from both the UK and USA, and the findings are always the same: multiple pregnancies are riskier in almost every way possible. It’s why there are so few “naturally conceived” twins and triplets in the world: women’s bodies are designed to grow one baby at a time.

(In case you were wondering, pretty much all the “risks” associated with having a baby by IVF – compared to natural conception – come from carrying twins (or more) as a result of double (or more) embryo transfers. When you compare singleton IVF pregnancies to singleton natural pregnancies, there’s barely any difference in risks.)

Does it EVER make sense to have more than one embryo transferred?

Yes. If you’re older than 37 and/or have a history of failed IVF treatments, you may well be advised to transfer two embryos. That’s because getting pregnant at all is less likely (read more about age, fertility and IVF here), and it’s also less likely both embryos will develop into foetuses. As a result, the benefits of transferring two embryos are considered to outweigh the risks.

Why do some private clinics seem so keen on double embryo transfers?

Three reasons:

• Success rates. When one transfer (of two embryos) leads to pregnancy, the success rates (when calculated “per embryo transfer event”) are better than two separate transfers (one fresh embryo, one frozen). Patient health or baby health aren’t factored into these success rates. Here's lots more information about the (many) cheeky clinics that trick people with their “success rates” in the UK. 
  
• Patient cost-benefit analysis. Patients want to get pregnant ASAP. They know the risks, they’re comfortable with the risks, and they’re the ones spending the money – so clinics give them what they want.
  
  Note: if you’re planning to have IVF on the NHS (which means you meet all their eligibility requirements), you’ll be strongly discouraged (or even prevented) from transferring more than one embryo at a time.
  
• Patient age and/or you have a history of failed IVF treatments. Many people visit private IVF clinics because their age makes them ineligible for NHS treatment – or they may have already used up all their “free” rounds with the NHS. These people would potentially benefit most from a double embryo transfer, so it makes sense for clinics to recommend it.

How many embryos can I legally have transferred at once?

In the UK, women under the age of 40 are legally allowed to have a maximum of two embryos transferred. Women over the age of 40 can have up to three.

Phew! Done!

If there's anything I've missed, or anything I've overcomplicated, please do contact me and let me know!