Synopsis: More than five million children have been born as a result of in-vitro fertilization, but many are born as twins, triplets and even quadruplets. Experts discuss the challenges that result in multiple births and new technology that promises to reduce the number of multiples in IVF.

Host: Reed Pence. Guests: Dr. Arthur Wisot, Professor of Obstetrics & Gynecology, UCLA School of Medicine & Reproductive Partners Medical Group; Dr. Barry Behr, Professor of Obstetrics & Gynecology and Lab Director, Fertility and Reproductive Health Program, Stanford University; Courtnay Kinney, IVF

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Multiples In IVF

Reed Pence: Having a family is part of the natural order of things that many people imagine for their future. Many couples assume they’ll have kids. Many men figure that one day, they’ll get cards for Father’s Day, but a surprising number have trouble achieving that dream. Infertility is remarkably common.

Arthur Wisot: Infertility affects about one in eight couples. In the last year that we have information, seven and a half million people have used infertility services.

Reed Pence: That’s Dr. Arthur Wisot, Professor of Obstetrics and Gynecology at the UCLA School of Medicine and the reproductive partners medical group.

Wisot: We really don’t know how many people are really suffering from infertility because it’s not something people usually go and talk about, and many people don’t go for treatment because they’re ashamed, or they don’t want to have to deal with the medical issues, or they’re afraid of the costs. And they don’t realize that most of the people that walk in our office with an infertility problem can have it solved fairly simply. We see many patients in their second and third, fourth, fifth, sometimes tenth year of trying before they come and see a reproductive specialist.

Pence: And the odds of infertility are increasing, according to Dr. Barry Behr, professor of Obstetrics and Gynecology and lab director of the Fertility and Reproductive Health program at Stanford University.

Barry Behr: Due to social pressures and just changes in our culture, the age at which women embark on childbearing or procreation has been protracted or moved later on in years, which has really resulted in the likelihood of infertility becoming a factor for a couple increasing.

Pence: Wisot says a couple is considered infertile if they’ve been unsuccessfully trying to conceive for a year.

Wisot: We’ve modified that over the years, because we realize that people in the older age group, maybe above 35 to 37, probably should come in sooner, because if they keep trying and trying they will be wasting time. And we really need to do an evaluation to see if there are any issues which can be corrected to get them sooner rather than later. If you ask any specific couple when they would consider themselves infertile they probably would tell you the first month they tried and didn’t succeed they would be worrying about this.

Pence: When the problem causing infertility isn’t so simple, doctors often turn to in vitro fertilization. IVF is far from rare anymore. Since Louise Brown, the first test tube baby, was born in 1978, she’s been joined by about five million more. But only around a third of IVF attempts result in a live birth. Younger women are much more likely to succeed.

Wisot: Most important factor that affects the success rate is the age of the woman. If you look at the average success rate in the United States, looking at 2013, a total of 175,000 cycles of IVF were performed in the U.S. in 2013 resulting in about 65,000 live births. And if you look at the difference in live birth rate on average, if a woman was under 35 she would have the chance of a live birth in 42.5% of retrievals or 47.7% in transfers of embryos. When she gets into the age group of 35-37, the live birth rates per transfer goes down to 39.2%.

Pence: And in women older than that, the numbers go down quickly. But with the clock ticking, and an average cost of $12,400 per cycle, there’s a lot of incentive to make IVF work the first time, and make sure an embryo sticks.

Wisot: When we first started with IVF, we didn’t have very sophisticated ways of knowing which embryos were really the best, and so we had to place back into the uterus larger numbers of embryos. It was not unusual to be putting four embryos into a woman’s uterus, even at young ages, and we ended up with a high incidence of multiple pregnancies, twins and even triplets and quadruplets.

Behr: The problem of multiple births from IVF is a black eye that our field has, unfortunately, and the reason we replace more than one embryo at a time is to attempt to increase the odds of a single embryo implanting. There is never an intention when we transfer more than one embryo to create more than one baby at that particular cycle. Humans were not designed to carry litters. We were designed to have one baby at a time, and any time there is a condition that would result in a pregnancy being shorter than the ideal 39 weeks or so, as would be the case with multiples, it generates a sub-optimal condition for the babies born as well as the mother potentially.

Pence: Triplets and quadruplets are 36 times more likely to die within about a month

of birth compared to single infants, according to a study in the journal JAMA Pediatrics. So, medical guidelines in the United States were changed in 1998 to discourage transferring three or more embryos, and since then, Wisot says, the average number transferred per IVF cycle has dropped to 1.8. But even that is higher than Wisot and Behr would like it. IVF still results in twins 30 percent of the time.

Wisot: The problem with twins is everybody says “well I really like twins, and I can get all my childbearing done at once.” Well, that’s when pregnancy is a more dangerous pregnancy, more prone to premature labor, which will leave either an immature or premature baby that will have to spend time in the NICU and can have breathing problems and feeding problems. And really what we want to give a couple is a healthy, single baby. The incidence of triplets, though dropped to less than 1% in women under 35 in 2013. So, we are doing a better job of eliminating the higher order multiple pregnancies, triplets, and quadruplets. Still getting too many twins, and so what we really want to do is make almost every embryo transfer a single embryo transfer, especially in young women.

Behr: Despite trying to convince patients that we would prefer to transfer one embryo at a time, many couples want twins. It’s a novelty; it’s having your family two for the price of one, if you will, when you’re going through IVF. So, we have to do a lot of education and sort of leg work, if you will, to many times convince patients that one at a time is the way to go, even though we can provide data to show the benefits of having a full-term, healthy singleton versus a pre-term twin delivery. Many people, I think like most things, don’t think anything is going to happen to them, this wouldn’t happen to them–this happens to somebody else.

Pence: The challenge for IVF doctors, then, is how to transfer just one embryo and still guarantee a good chance that it will implant and result in a pregnancy. The key is the quality of the embryo. Some are more viable than others and more likely to implant. And now doctors have a better chance of figuring out which ones those are, thanks to a test just approved by the FDA called EEVA.

Behr: So the EEVA test is a time-lapsed microscopy system that provides an embryo diagnostic through an algorithm that was developed with myself and two colleagues at Stanford, which allows embryos’ morphokinetics to be quantified. And the quantification I am referring to really is the actual measurement of the cell divisions: the first few cell divisions of the embryo during its first two or three days in culture in the IVF lab. And there are inferences that can be made about the embryo’s potential based on how they divide, how fast they divide, how synchronously they divide.

Wisot: EEVA is the first test of its kind which uses time-lapsed video along with time-lapsed evaluation by the computer to observe the exact moment of division of the first cell to get from one cell after fertilization to two cells, then to four cells, then to eight cells. And studies have shown that it is in a very narrow range of time to be able to say this embryo is a viable embryo, and this time-lapse image analysis software is really what makes EEVA so special.

Pence: Behr says EEVA can reliably separate embryos with good potential from those with less.

Behr: Now remember the potential is not absolute. It doesn’t mean that if you have a low potential that it’s zero or that if you have a high potential you’re absolutely going to make a baby, but it really is an additional tool that I believe already has, but definitely will in the greater capacity, change the confidence and the comfort level that practitioners have to be more commonly transferring single embryos.

Wisot: When they took the embryos that were examined by EEVA, and they gave a panel of five embryologists the embryos to look at the shape and the number of cells, the standard way we evaluate embryos, and then did the standard number of embryos but added the factor of which EEVA said had the highest chance of implantation, the ones that were selected by EEVA were 58% more successful than the ones just selected by the embryologists in the standard way. So, I can tell a patient who is in her thirties, and has been trying for four years, and comes in, and does an IVF cycle has quite a few embryos and says to me “well I’d like to put two back because I’d really want this to work,” I can say, with the reassurance I have from EEVA, I can put one embryo back and give you a really good chance of success.

Pence: For some couples, that reassurance is enough to finally go ahead with IVF after years of infertility. For example, Courtnay Kinney of Walnut Creek, California and her husband Michael wanted to be aggressive with treatment after two years of infertility. But they had medical reasons to avoid a multiple pregnancy. They’re now proud parents of an eight-month-old boy.

Courtnay Kinney: It was actually going to be very dangerous if I were to get pregnant with twins. We found out that I have a short cervix. So the likelihood of having complications with twins was very high, so with EEVA technology it was very comforting knowing that we were expecting the right embryo for transfer since we only ever be able to transfer one embryo.

Pence: Even though EEVA adds cost to the IVF procedure, Behr says it ultimately should save couples money, because the necessity of a second or third IVF cycle will often be eliminated. And while older women still typically have multiple embryos implanted today, he hopes that practice will end soon, too.

Behr: The guidelines are to transfer a single embryo if you’re under 35. But I’m just going to report to you because I have these in front of me; only 22.5% of cycles under 35 for women under 35 had single embryo transfer. So, what you’re quoting is what the guideline is, but what is actually practiced is far from that. So, what we are hoping for is to allow people to follow the guideline with a greater degree of comfort and less impact on the outcome. So that’s the power of the technology.

Pence: so while the proportion of twins has doubled over the last 40 years, mostly due to IVF, that could start to decline. Triplets have already declined by about 30 percent in the last 15 years. Families with IVF kids should start to look a little more like every other family, but with parents who can thank technology for being parents at all.

You can find out more about EEVA at That’s e-e-v-a-test-dot-com. You can find out more about all our guests and find archives of our programs on our website, You can also find archives on iTunes and Stitcher.

I’m Reed Pence.


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