ASRM 2013 Update: ART Safety: The twin effect

October 20, 2013Carole 11 Comments »

It’s that time of year again, when the American Society for Reproductive Medicine  (ASRM) holds it’s annual professional meeting. This year it was in Boston (Oct 12-17) and was held jointly with the International Federation of Fertility Societies (IFFS) in Boston. The international participation  brings insights into the regional differences in how IVF is practiced around the world. For instance, some of the first advances in clinical egg freezing came from Italian clinics because embryo freezing is illegal and only three eggs may be inseminated so as not to create excess eggs. Given these legal limitations, clinics were pushed to develop better freezing techniques so that extra non-inseminated eggs could be frozen for future attempts at pregnancy if the first fresh cycle didn’t work.

I attended post-graduate course on the topic of Safety in ART. Is ART a safe method for having a baby? Are there any concerns regarding health effects on the baby, or even later emerging effects as the child grows into an adult and senior? The international perspective is useful for answering these questions because unlike the US, several European countries maintain a registry of IVF patients which allows them to track the health of IVF-conceived kids going forward. The results so far have been reassuring overall with a few areas of concern. Dr. Anja Pinborg, MD,DMSci, Professor of the Fertility Clinic, Hvidovre Hospital, Copenhagen University of Denmark shared outcome data from ART cycles completed in Denmark where single embryo transfer is used in 27% of the cycles, compared to 8% of cycles in the US. In many of the European countries, including Denmark, they have national health registries to track outcome data from medical interventions like ART. I will summarize some of the take home messages from the course here.

With so much attention being paid to lab factors in terms of ART safety, it may shock you to learn that the biggest safety risk from ART is having TWINS!! Yes, the obstetrical risks to the baby from sharing space in the uterus with a sibling are far greater than the obstetrical risks from any other ART related intervention.  In the US, there is a strong preference on the part of patients to have twins for understandable reasons (out of pocket costs for IVF, stress of IVF etc) but also on the part of providers (transferring two embryos increases the chances of pregnancy occurring at all).  So is this a bad thing? Well, it can be.

The most important health risk of ART children is twin pregnancy. That’s an astounding fact when you think about it. If you compare ART twins to spontaneous conception twins, they have similar rates of abnormally low birth weight and premature birth, both features that make it difficult to have a healthy start for a child. In contrast, a singleton baby has  a much reduced risk for severe obstetrical complications. Twin pregnancies can be managed and I am not suggesting that twin pregnancies should be reduced to singleton pregnancies if they come about spontaneously. But if you are using ART, you can elect to have a single embryo transfer and almost entirely eliminate the biggest risk to having a healthy child before the pregnancy gets started. Of course, sometimes (not often) that single ART embryo divides into two and makes identical twins. Finding a good obstetrician with experience with multiple gestation pregnancies can help you out in that instance. But if you can avoid the risk of twin pregnancies up front – why wouldn’t you? Yes, I know the “two for the  price of one” thinking is applied to ART decisions because IVF cycles are so expensive and if you don’t have insurance coverage, it’s easier to be talked into taking extra risks. Just know that you are in fact taking some extra risks with the health of your child.

Take home fact: Obstetrical prenatal risks of ART twins are 5-11 fold greater (depending on the study and the risk) than the risks for ART singletons.

Vanishing twin effect. Sometimes, when two embryos are transferred and implant, one of the two twins dies early in the pregnancy and is termed a “vanishing twin”. In this case, when the pregnancy becomes a singleton pregnancy later in the pregnancy, there is still some persistent increased risk from having been a twin pregnancy at the early stages when the pregnancy was first established.
Some facts about vanishing twins:

  • After two-embryo transfers, one in ten singleton births are due to a persisting “vanishing twin ” survivor.
  • A vanishing twin survivor has increased perinatal risks.
  • The farther along in pregnancy at which one twin is lost, the greater perinatal  risk for the remaining twin who is more likely to have a low birth weight.

I often hear patients – and doctors- say they want to do two embryo transfers because the chance of pregnancy is greater in that single attempt. That is true. Buying two lottery tickets gives you another chance at winning.  But here are the counterarguments to consider.

  • If you transfer one embryo at a time, you are more likely to have at least one left over- often more- to freeze for additional attempts. If you factor in the pregnancy chances from the future frozen embryo transfer (FET),  your cumulative pregnancy rate is nearly as high as a double embryo transfer without the risk of twin complications. Of course, your program must be good at freezing and thawing embryos for this to be true.
  • There is increasing evidence that the uterine lining is negatively effected by the high estrogen environment caused by ovarian stim meds so that implantation may be less likely in the fresh cycle – no matter the quality of the embryo- compared to later FET cycles where the uterus is purposefully primed for implantation. So it may make sense to save some of your embryos for a later FET attempt.
  • With the advent of better embryo selection methods (routine aneuploidy testing and/or time lapse imaging), the odds of picking a “likely to implant”embryo the first time increases, so you aren’t putting back low probability embryos so the first time pregnancy rates with single embryos should be improved when more informative embryo selection techniques are used.

One thing that would make it easier for patients in the US to choose elective single embryo transfer (eSET) would be if IVF package price might be rejiggered so that the cost of an IVF cycle is spread out among not only the fresh IVF but several FETs.  Another thing that would help is if IVF were an essential  insurance benefit that all patients who needed it could access. If you don’t have to mortgage your house to get one IVF try, then having a fresh cycle followed by several single embryo transfer attempts to get pregnant isn’t so scarey, because multiple attempts are expected as part of the package. In states were infertility coverage is mandated, there are fewer ART twin births–because if you take the financial incentives away- more patients would likely choose eSET to improve their chances of having a healthy pregnancy and baby.

Next time, I’ll share what I learned about persistent ART risks even with singleton ART  births.

© 2013, Carole. All rights reserved.

11 Responses to this entry

  • Fertility Lab Insider - Lessons learned from over fifteen years of working inside fertility labs. » Blog Archive » ASRM 2013 Update: ART Safety: Singleton pregnancy Says:

    […] ASRM 2013 Update: ART Safety: The twin effect […]

  • NLK Says:

    Thanks for this safety update! I’ve been caught in this eSET conundrum myself. The only reason I have begun doing multiple embryo transfers (after 5 eSET’s) is cost. I wish the FDA would step in to require clinics to eliminate cost structures that dis-incentivise eSET. It’s odd that it’s been seen as ok that clinics turn out a 40% twin rate, when adjustments to their pay structures could minimize massive health risks.

  • Carole Says:

    I agree with you on all counts. Affordability of IVF yields better outcomes for patients and babies! If you want to move the FDA or more easily, your local clinic, let them know how you feel. If enough patients want this and let providers know, it will happen. Good Luck on your next transfer! Carole

  • Clara Says:

    Carole, will it really happen? The providers, FDA and congress must know almost every patient, especially those of us paying OOP, want coverage or some other relief. As part of this has been a continued effort with little change. I’ve written many letters to all parties involved but they don’t listen, maybe because there’s no incentive to. Your information above about twins being the largest risk was eye-opening. I’d never thought of it that way. I would switch to eSET immediately if it meant an increase chance of me having a healthy baby, but money doesn’t warrant that option seeing as my State is not mandated to cover ART. My question is, why don’t the clinics want national coverage if it means fewer costly complications with the pregnancies and healthier babies?

  • Carole Says:

    Hi Clara,
    I don’t know if widespread incentives for eSET will really happen here in the US. We love mixing capitalism with healthcare. The idea of national coverage for IVF is not supported by all IVF providers because just as with national coverage of healthcare in general- there are a lot of opinions about whether this is a good thing- for either patients or doctors. There is the patient specific argument against eSET that some doctors put forth- “we need to transfer more embryos in poor prognosis patients” which is true in the present context when patients can only afford 1-2 out-of-pocket tries, then you have to stack your deck each try. (Of course, if each try were made more affordable- that argument largely goes away because even if it takes more “tries” to hit, hitting with a singleton is a better obstetrical result- especially for a poor prognosis patient who may be older or have other issues, so it may be worth going through some negative singleton attempts.)

    When I worked in clinics that were privately owned by the doctors- as opposed to hospital based centers- they didn’t want widespread insurance coverage because they’d have to see more patients to make the same money. In hospital centers , they accepted the idea that some service lines might lose money, others would make money so they played the financial game on hospital wide board.

    Based on what the insurance provider wanted to reimburse us for IVF for patients who did have coverage- it WAS NOT sufficient to cover the costs of the cycle- so the self-pay patients actually subsidized the insurance covered patients. So the clinic-owner docs I knew looked at this and said, if we had only insurance covered patients, we couldn’t cover the costs and make money. This problem of what health care actually costs is at the root of the problem. Both providers and insurance companies have been gaming these prices for so long that there is little correlation to what things actually cost. I talked about my frustration with calculating IVF costs in an earlier post.

    Clinics should care deeply about long term outcomes but in reality, their official work on your case ends when you are referred to the OB- although of course they want a live birth for the stats and- I think most providers do care about the patient’s welfare but they don’t spend much of their professional life thinking about how twins may be affecting you. Many REs have a lot of faith that the Maternal-Fetal-Medicine (MFMs) will take care of any complications so it won’t be a problem. It used to make me sick when we heard about a patient of ours who lost twins mid-pregnancy. It happened several times a year. The docs weren’t happy about it – but patients wanted twins is what they told me- like they really had little say in the matter. So I think education is the key. Know the risks so you can make the best decision. Many times outcomes are fine. But when they are not, the results can be hell for the unprepared family. Here’s another article about the twin issue

    Fertility Within Reach ( is one organization (Full disclosure- I work on the board) that is trying to advocate for patients who want to have insurance coverage in their state or from their employer. They will be rolling out a new tool kit for advocacy shortly on the website with practical information to help patients advocate for themselves. Can we have more healthier babies from IVF? I think so, but it might be by educating one patient at a time. Good Luck!!!

  • Fertility Lab Insider - Lessons learned from over fifteen years of working inside fertility labs. » Blog Archive » ASRM 2013 Update: Safety: Effect of the ART lab environment Says:

    […] ASRM 2013 Update: ART Safety: The twin effect […]

  • ART Safety | veryverycurious Says:

    […] Source: Carole Wegner (PHD), Fertility Lab Insider […]

  • laura Says:

    you also forget that a twin pregnancy has health implications on the mother. it’s exceedingly difficult and rough on your body in every way imaginable, and since so many women pregnant with twins are put on bed rest, those consequences can be deadly. i developed blood clots in my legs and lungs! what’s the point of having twins if you won’t be around to mother them?

  • Carole Says:

    Not forgotten, just another post. Here is a overview of the topic with maternal dangers of multiple pregnancies from the American Society of Reproductive Medicine. You can download a free booklet from this link if you want more info. I am sorry that you had such severe complications with your pregnancy. Thanks very much for sharing your experience!

  • laura Says:

    You’ve really nailed the problem. For us, a diagnosis of “unexplained,” followed by 3 IUIs, 2 fresh and 2 frozen transfers, and $60,000 spent…well, we transferred 2 on our third and final fresh IVF, never thinking we’d get twins out of it — we put in 2, hoping for 1, thinking we’d get none. After all, all our previous tries had failed. We were never those people who *wanted* twins. Of course, now that they are here, they are wonderful and well worth everything we went through…but it sure was close there for a while.

  • laura Says:

    You’ve really nailed the problem. For us, a diagnosis of “unexplained,” followed by 3 IUIs, 2 fresh and 2 frozen transfers, and $60,000 spent…well, we transferred 2 on our third and final fresh IVF, never thinking we’d get twins out of it — we put in 2, hoping for 1, thinking we’d get none. After all, all our previous tries had failed. We were never those people who *wanted* twins. Of course, now that they are here, they are wonderful and well worth everything we went through…but it sure was close (scary) there for a while.

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