IVF Conundrum: Too Many Twins. But Caution: ART Procedures Can Cause Twinning; and, "Blastocyst Culture" Not a Moral Solution

Dianne N. Irving
Copyright November 30, 2005
Reproduced with Permission

Australia, like most other countries awash in IVF, are coming up against the serious familial and social strain and damage caused by mothers undergoing multiple pregnancies and giving birth to too many children at once [Caroline Overington, "[IVF] Mums having too many twins, doctors warn" (Nov. 28, 2005), News.com.au, at: http://www.news.com.au/story/0,10117,17383604-421,00.html; see full article copied at end.] International conferences are about to begin in Australia to address this persistent and growing problem.

Aside from the obvious concerns about the immoral practice of IVF itself, one hopes that such an international assembly of IVF practioners will also address the well-known fact that many of these artificial reproductive technologies (ARTs) themselves cause such phenomena as monozygotic twinning (where a single implanted human embryo splits in utero to form twins, triplets, etc.), conjoined twins, and "vanishing twins". This source of twinning results from a single human embryo that has been implanted - not from multiples (i.e., dizygotic twins) being implanted. Thus simply reducing the number of individual embryos implanted will not automatically solve the problem of the increased rate of formation of human monozygotic twins in utero caused by the use of many ART procedures themselves.

One "solution" to "multiple pregnancies" that has been used for several years might also now be endorsed by the conferees to solve the problem: "blastocyst culture and transfer". However, women should understand precisely what is involved in this technique. Essentially, in "blastocyst culture" several IVF-produced human embryos from a single patient are allowed to remain in culture longer than the traditional time in order to allow the "best" of the lot to survive the rest  the "survival of the fittest" -- and then be implanted as a single human embryo. True, this might possibly assure a better pregnancy rate (for the clinic), and thus tend to reduce the problem of multiple pregnancies (for the woman). But given that all of these IVF human embryos are innocent living human beings, shouldn't all of them be given the best chance of survival that is possible?

Apparently not  at least that is the position of some of the major IVF clinicians. I have copied here one such "advertisement" from the Shady Grove Fertility Center in Maryland (staffed by several Georgetown University physicians). Read for yourself their cold description of this "survival" technique, and consider if "blastocyst culture" is a morally acceptable solution to the problem of multiple pregnancies in the IVF industry. - Dianne N Irving, Ph.D.


by Robert J. Stillman, MD and Michael J. Tucker, PhD

The IVF Program - Additional Advanced Technologies

Blastocyst Culture And Transfer At Shady Grove Fertility

IVF Technique Promises to Maximize Safety and Success Rates

Blastocyst culture and transfer is a new important technique developed for in vitro fertilization (IVF) that maximizes pregnancy rates while minimizing the risk of multiple pregnancy. The ability to grow embryos for five days to the blastocyst stage of development in the laboratory, rather than the traditional three days, allows clinicians to determine with greater certainty which embryos are really the "best" in terms of their potential for implantation. Consequently, blastocyst culture makes it possible to select the best one or two blastocysts vs. three or four early embryos to transfer back to the mother. This reduces the occurrence of potentially risky multiple births. "Fertility centers like Shady Grove constantly strive to improve IVF success rates through the steady refinements of clinical and laboratory techniques. Clinical blastocyst culture and transfer is the next important step in that evolution," explains Robert Stillman, MD.

What is Blastocyst Culture and Transfer?

Traditionally, embryos have been transferred to the uterus on the second or third day of development after in vitro fertilization and initial embryonic cell division. This day of embryo transfer has been a compromise between maximizing the degree of embryo selection available through longer culture in the IVF Lab versus minimizing the exposure of the embryos to culture media which, in the past, could only sustain growth for 2-3 days.

Michael Tucker, PhD explains, "the dynamic processes of embryo development were not taken into account by the static nature of the "one size fits all" culture media that has been used prior to this point. Because of this, blastocyst growth in vitro had always been suboptimal." New culture media now are designed to take into account the myriad and changing needs of the developing embryo in vitro.

After five days of growth, the cells of the embryo should have divided many times over, and have begun to differentiate by function. The embryos that survive to this stage of development are usually strong, healthy, and robust. They are now called blastocysts. Two important factors had limited the number of embryos that will survive to this stage. First, the inherent "health" of any embryo will dictate its ability to continue to grow and divide. Several eggs may have initially fertilized, but only a few will progress to the four-cell stage, fewer still to the eight-cell stage, and even fewer will develop into blastocysts. Simply put, this self selection can be viewed as "survival of the fittest". The second limiting factor in preventing continued growth of embryos in culture had been the culture media itself. Recently, researchers have identified shortcomings of the in vitro culture environment and have developed new culture solutions called Blastocyst Media. These are rich in life sustaining nutrients that give the embryos every chance to reach there full potential. "From egg collection onward, the embryo will now be exposed to specific media that are designed to meet the nutritional requirements of each stage of development," says Dr. Tucker.

What Are the Benefits of Blastocyst Transfer?

Let's use an example. Historically, if a woman has 15 eggs retrieved , an average of 10 will fertilize by day one of observation. It is impossible to determine at this point which of these 10 are most likely to implant and develop into a baby. Perhaps all will, but perhaps not. On the traditional day of embryo transfer (day three), 5 of the 10 embryos may be developing into vibrant, growing embryos. The others may have slowed or stopped their development altogether.

In this example, we are left with several embryos that still look like they may have excellent potential. Which ones to transfer? Which ones are really the "best"? Two additional days in the blastocyst culture medium allows the natural winnowing process to continue. Thus, after 5 days of growth in the laboratory, only 2 or 3 of the original ten embryos may remain viable. We now know the best embryos to transfer. Embryos transferred at the blastocyst stage have made it through key growth processes and typically offer a greater chance of implanting. Without compromising pregnancy rates, we need only return 1 or 2 blastocysts to the mother instead of the typical 3 to 4 early embryos. In fact, pregnancy rates in the group using blastocyst transfer may even be higher because the uterine lining is more receptive to the advanced embryos. In addition, if there are more than two available at the time of transfer, the remaining blastocysts may be cryopreserved for future use.

A significant benefit of blastocyst culture and transfer is the reduction of high order multiple births that can result from in vitro fertilization. This means that various obstetrical complications that may arise from multiple pregnancies can be minimized. It is especially important in helping patients avoid having to make the difficult personal and ethical decisions regarding selective reduction.

Is Blastocyst Culture and Transfer for Everyone?

In thinking of the example above, patients who have fewer oocytes retrieved, fewer fertilized or fewer dividing embryos by day three in culture have no advantage using blastocyst culture, since little is to be gained in further embryo "self selection". Dr. Stillman emphasizes, "Unfortunately the new blastocyst culture media does not improve the health or viability of an individual embryo which is not otherwise able to sustain 5 days of growth and then implant; rather it allows embryos capable of sustained growth to continue in culture and reach their maximum inherent capability."

Helping Patients

In this field of medicine, continued refinements and change offer greater opportunity for infertile couples. Blastocyst culture is the latest important step. "It is exciting for us to be able to offer our patients this promising state-of-the-art technique, as it provides us the ability to further tip the balance of success versus risk in favor of couples when we assist them in their pursuit of parenthood," explains Dr. Stillman.

November 28, 2005
By Caroline Overington

[IVF] Mums having too many twins, doctors warn

IVF specialists have launched a push to limit the number of twins being born in Australia, saying multiple pregnancies are too dangerous for mothers and babies.

"The rate of twins is unacceptably high," said Robert Norman, of the Research Centre for Reproductive Health in Adelaide.

Professor Norman will today address a national conference designed to get a consensus from IVF doctors to limit the number of twins being born.

"We have to reduce the number of embryos we are transferring," he said.

According to recent figures from the Australian Bureau of Statistics, there were 4200 multiple births in 2004 - 75 per cent more than the number recorded just 20 years earlier.

Of these, 4105 were twins; the rest were triplets or higher multiples, such as quadruplets and quintuplets. While twins are often born healthy, many are born premature, with a range of health problems.

The perinatal mortality rate for twins is three to six times higher than for singletons, and the risk of cerebral palsy is six times higher for twins and 20 times higher, for triplets.

There is increased risk of miscarriage and of premature birth and twins are most often delivered by caesarean section.

"It's just ideal if women have one baby at a time," said Michael Chapman of IVF Australia, who is chairman of a national body representing the directors of IVF clinics. "We want to prevent twins and triplets and other multiple births, and we can save the community a lot of money on the health budget by doing it."

IVF has been responsible for most of the rise in twin births, because it involves fertilising more than one embryo at a time.

Robert Jansen of Sydney IVF said the rate of twin births had increased as doctors sought to maximise the chance of pregnancy "by transferring several embryos at a time".

There is also great pressure from patients, who want to limit the number of IVF cycles they have to have and complete their families quickly.

But Victor Yu of the Ritchie Centre for Baby Health Research at the Monash Institute of Medical Health said multiple births accounted for about 11 per cent of perinatal deaths in Australia.

Professor Yu will tell the Monash Institute's conference on multiple births today that the stillbirth rate for twins is three times higher than for singletons.

The move to limit the number of twins comes after IVF clinics successfully halved the number of triplet pregnancies in the past 10 years.

Mark Umstad, who runs the multiple birth clinic at Melbourne's Royal Women's Hospital, said "the incredibly responsible attitude, and the maturity of infertility specialists, has bought about this fantastic result".

"It takes some incredible restraint, and a responsible attitude (for IVF doctors) to put back fewer embryos because their patients are desperate for a baby," Dr Umstad said.

Melbourne's Kellie Boyce, mother of IVF twins Morgan and Olivia, says they are delightful, but the pregnancy was stressful.

"A multiple pregnancy is difficult on your body. I love them to bits, but the last 10 months have been very difficult," she said.

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