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BEGINNINGS OF LIFE: High-resolution 3-D rendering of a blastocyst (early developmental stage of the fetus).
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Most children conceived via assisted reproductive technology (ART), such as superovulation are fine, although some recent studies are raising doubts about whether these fertility fixes are as safe as promised. The extensive handling of these crucial cells is a concern, and there are mixed reports on the long-term health of these hard-won children, with several studies suggesting increased risks of low birth weight, rare disorders down the line, and even death.
For starters, one study published in July 2009 links ART embryos with poor health outcomes along a few dimensions. Another paper, from January 2010, shows that the genes in ART embryos bear different epigenetic marks than non-ART embryos. And the laboratory procedure of ART itself, during which eggs, sperm and embryos are typically sucked in and out of pipettes and left to sit in culture dishes, concerns some researchers and potential parents alike. Scientists such as Mellissa Mann, a researcher at Children's Health Research Institute in Canada and the University of Western Ontario, speculate that these manipulations could affect the health of ART babies.
"More attention should be paid to the safety of ART offspring as they now account for the large proportion of the population," says He-Feng Huang, an obstetrician and gynecologist at Affiliated Women's Hospital and Zhejiang University School of Medicine in China. Indeed, according to a 2009 study published in Human Reproduction, the number of ART procedures is on the rise and so-called test-tube babies account for an estimated 250,000 births every year worldwide.
ART encompasses several techniques: With superovulation, women receive high doses of hormones to stimulate egg production. Eggs and sperm are brought together in a dish so that in vitro fertilization (IVF) will take place. If a man's fertility is low a single sperm cell can be chosen and injected into an egg, forcing fertilization. Another procedure, called pre-implantation genetic diagnosis (PGD), involves removing one or two cells from an early-stage IVF embryo for genetic testing to screen for various diseases.
Molecular changes
The 2009 health outcomes work, by biologists Ran Huo, Qi Zhou and colleagues at the Chinese Academy of Sciences and Nanjing Medical University, involved comparing mice that had undergone IVF and PGD with those that had undergone IVF alone. The team reported in Molecular and Cellular Proteomics that, compared with controls, PGD mice were more forgetful, heavier and had less myelin (a fatty coating on nerves that allows electrical signals to move quickly across nerve cells). They also expressed abnormal levels of proteins involved in neurodegenerative conditions.
Although mouse outcomes do not always parallel those in humans, the lab animal studies are helpful because "when we're studying humans, we can't separate out the effect of the procedure versus fertility issues," Mann says. For example, it is hard to say whether an ART baby has died because of the ART technology or because one of its parents had a mutation that mutually contributed to subpar fertility and infant death.
Mann's group, for the 2010 work on ART and epigenetics, used mice to examine changes on four genes following a superovulation procedure. The team looked at methylation, in which a methyl group is placed onto cytosine in DNA sequences. Methylation typically silences genes so that they are not expressed. Mann's team reported in Human Molecular Genetics that superovulation affected the establishment and possibly the maintenance of methylation in mice. Messed-up methylation early in development can cause disorders, such as Beckwith-Wiedemann syndrome (an overgrowth disorder), in humans. Another study by a different group in the same journal in October 2009 looked at ART effects on epigenetics (non-DNA changes in genes) in humans. They found methylation defects on several human genes in the cord blood and placentas of ART embryos, suggesting that a similar effect might be occurring in humans as well.
Cause and effect
Molecular studies paint a potentially bleak picture, but researchers warn that the effects and causes of these differences are unknown. "I think it's hard to make any firm conclusions so far," says Liv Bente Romundstad, a fertility doctor and researcher at Saint Olav's University Hospital in Norway.
To tease out the effects of ART from the impact of underlying fertility issues in humans, Romundstad's team studied mothers who had one pregnancy with ART and one naturally. Because the women had children on their own either before or after ART, the researchers assumed that fertility was not a problem. Multiple births were excluded because even naturally conceived multiples have a high risk of complications, Romundstad says.
When ART babies were compared with the entire population they had a lower birth weight and increased risk of death around the time of birth, but that risk disappeared when compared with their siblings. The analysis, published in August 2008 in The Lancet, suggests, "the infertility treatment per se for the outcomes we have studied does not seem to give any additional risk," Romundstad says.
But there's still reason for concern. In a talk at the European Society of Human Genetics conference this month, Géraldine Viot, a clinical geneticist at the Maternity Hospital, Port Royal in Paris described her team's large study of French ART centers. Although ART children had a slightly higher than normal rate of birth defects, their risk of developing epigenetic disorders, such as Beckwith-Wiedemann syndrome, was 4.5 to six times higher.
So, is ART safe? "For some of these children, we still don't know what the long-term results of the ART will be, in that a lot of these children are not yet reproductive age," Mann points out. Romundstad says that although it's possible that health effects could surface later on, she will continue to offer fertility treatment in her practice. "I don't think the timing is right to start to scare the population, but I think it's important to focus on this and continue with studies," she says.
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25 Comments
Add CommentPeople who have trouble conceiving should adopt. There are literally MILLIONS of unwanted children in the world. Why take drastic measures to make new ones just so they can share the parent's genes - it's selfish.
Reply | Report Abuse | Link to thisLet's just list them all on ebay and bid on them. Those millions of unwanted children all over the world are NOT available to those who want them. People who don't want kids shouldn't have them. Have you heard of birth control?
Reply | Report Abuse | Link to thisElizabetta, I suppose you've adopted some of those MILLIONS? Adoption is a serious decision that should be made by each couple, not a fallback for those who happen to be medically diagnosed with infertility. Children are not "consolation prizes" but human beings who deserve to be adopted by those who make a conscious decision to bring that child into their life and care for that child. As for those with infertitlity, each individual couple should be allowed to decide how to handle their MEDICAL CONDITION. If you can do that, maybe they will stay out of your business when you have a personal decision to make about your life, body and family.
Reply | Report Abuse | Link to thisIMO it's not easy to be uncompassionate, but I strongly suspect that if I adopted all of those millions and brought them all home, in a short time there'd be another bunch of suffering millions. I think those seemingly unwanted millions are the product more of regional social/economic/environmental failures that are most likely beyond anyone's control. Unfortunately, babies will be born into all but the most intolerable conditions.
Reply | Report Abuse | Link to thisFeeding starving millions in an unproductive environment will not produce a functioning society to support them. It hurts to be cruel...
I personally have never understood the intense need to breed that some people apparently feel, so excuse me if my previous post seemed insensitive to the MEDICAL CONDITION of infertility. Fact is, we are multiplying at rates that will cause mass extinctions and starvation within a few decades, but hey, I guess everyone has the right to do that. After all, it's our planet and if we want to cause all the other species, and then ourselves, to become extinct, then that's our prerogative. I agree with a previous poster - if I adopted all the MILLIONS of starving children in the world, they would just be replaced by new ones. Could that be because certain religious leaders go to places like Africa and actually tell them they'll burn in hell if they practice birth control? With that sort of irresponsible behavior, and the belief that we are all entitled to breed out of control, our species and the entire planet is probably doomed already.
Reply | Report Abuse | Link to thisUgh. Breeders. I can find two reasons to keep creating new people in the face of the millions going without parents in this world. One is a gigantic ego trip, the other is an inability to elevate oneself even over the low hurdle of ones most base primal instincts.
Reply | Report Abuse | Link to thisOh hey, just keep making more. We'll just keep paying for them so everyone else can starve to death. Selfish pigs.
Our planet is vast and natural resources well managed with improved technology will provide for the increasing population. Another problem is the global warming that is causing sea level to rise, which will displace millions of people from their coast lands to higher lands. Humans are so fragile, a natural cathastrophe can kill many. On the other hand, violence and nuclear wars could lead to mass extinction, the product of human selfishness and pride, and the human "instinct" for power control. In contrast, following the desires of our hearth to fullfill life with love will allow spiritual growth and progress.
Reply | Report Abuse | Link to thisFamily is the pillar of society, the driver of the human species. Try all means to have your family, is that's what you feel deep inside.
Adoption is a wonderful personal option.
Hotblack, I feel for you. Non-"breeders" are, evolutionarily speaking, the walking dead.
Reply | Report Abuse | Link to thisMaybe we don't understand the part about out of millions of sperm cells one is selected to fertilize the egg. How is that sperm chosen? This step is omitted with ART
Reply | Report Abuse | Link to thisIn IVF.....one egg is placed in a petri dish with a couple million sperm. The best swimmer or whichever one gets inside the egg first wins and fertilizes it. The rest are left to die in the dish. Some people doing IVF (and I mean some, not all) need a special procedure called ICSI where a single sperm is selected and injected into the egg to force fertilize it. Not everyone doing IVF does this though. Would that sperm have been the "fertilizer" otherwise in the dish? Who knows. The embryologist selects the one that looks the best at the time.
Reply | Report Abuse | Link to thisGo with adoption or work with children if you cannot do the job properly. I do not understand why having a child is a "right".
Reply | Report Abuse | Link to thisIt is a shame that so many have a hard time conceiving. From what I have read in the past few years about the interference of the birth-control pill confusing the natural selection process may be a link to infertility, this does not surprise me. I am glad to see that some have started to think outside the box. Science is a wonderful thing but we are far more complex then science gives us credit for. I think in the bigger picture we need to know why so many women are having fertility problems instead of skirting around.
Reply | Report Abuse | Link to thisTo many posting, we are here for one reason and like it or not that purpose is to breed to insure survival. Have we gone beyond survival of the fittest? Maybe, but it is human to want a family to love. This is what drives us and to refuse that would take away our humanity.
Different sorts of ART are not discussed. IVF is at the more interveionist end. As a doctor and a donor I initially donated to a clinic, but was persuaded by a donee mother to help her use 'turkey baster' methods without anything being frozen and stored.
Reply | Report Abuse | Link to thisSince then I have helped several others this way. There is an increased disease risk for the donee, (which can be mitigated by screening), and it may not always be suitable where the problem is a female fertility issue, but for the majority of would be parents, it is suitable, and this sort of demedicalised approach is both more natural and much cheaper.
Another advantage for me is meeting and getting to know the parents you are helping. As a donor, from the outset, I insisted on meeting and vetting the potential parents, and on them agreeing to give their children details of genetic siblings. In practise this has translated into Christmas cards with photos and meeting and talking to a couple of these children as they grow up, which reinforced how normal both these wanted children and there families are, and how privilged I was to have been able to help them.
Ahhhhh.... Adoption is a SERIOUS situation that should be undertaken seriously by qualified people only... I see.
Reply | Report Abuse | Link to thisAssisted Reproduction, then (to your "mind") is the same as the normal unassisted kind, and any MORON can and should do it.
Your kind of "thinking" is what has gotten us into this Frankensteinian healthcare nightmare in the U.S.
I feel your sarcasm bro. If a child cannot be born naturally, most likely it's better for the parents as well as the prospective child, if you will, regarding long-term health. Health is, after all, one of the most important assets of life. Therefore it should not be messed around with.
Reply | Report Abuse | Link to this1.
Reply | Report Abuse | Link to thisOne would hope readers of Sci Am are able to distinguish between fact and fiction:
Reply | Report Abuse | Link to this1.Adoption forms families and offers children secure, loving futures as productive members of society. It does not contribute to overpopulation or lessen the importance of birth control.
2.High rates of sickness in the population is a significant part of the economic downturn (see
http://armchairactivist.us/2010/03/08/a-nation-of-patients/ ) . Many choose in vitro fertilization due to fears of health problems in adoptees of unknown parentage. If this presumed advantage is actually not a reality, it should be known so rates of adoption and foster parenting can increase.
3.Many women world-wide (including some in the US) have no choice as to whether they will produce children in an overpopulated world. It is a requirement for their inclusion in society and carries severe penalties if the woman is unable to perform that 'duty'. As a former educator, I saw women denied birth control in abusive relationships, producing unplanned babies. If you are worried about overpopulation, try intervening as a advocate for education and free reproductive health services for women world- wide.
Every child placed in an adoptive home increases quality of life for society as a whole. Automatic provision of free health care for adopted children might also weigh heavily in favor of such options.
Item 1 - If, like me, you think the world is overpopulated, then don't have more than 1 daughter if you can help it. Sons don't count because women control baby production.
Reply | Report Abuse | Link to thisItem 2 - If you want more children but already have a daughter, then adopt. It does not matter what gender. The girl has already been born after all.
Item 3 - Feeding the poor is stupid. Improve the area infrastructure and education system. Areas aflicted with greedy dictators or religious zealots can be firebombed with the actual vermin targeted. This frees the survivors to take advantage of the improved infrastructure.
Item 4 - Everyone has the right to choose to starve. Welfare should be limited to labor opportunities where private employment isn't viable.
Item 5 - Getting back on topic, If invitro is more risky then the prospective parents need to know to make an informed descision. That said, I'd rather an at risk life than to be dead.
Life is a constitutional right after all.
Suggest you look up Robert Malthus. Your ideas sound just like his. As a theist (RC), I believe that each of us is here because we're part of God's plan. He'll figure where each of us will be able to stand when the time comes that we need a place. HOWEVER, having said that, I tend to agree with you that adoption sounds fairly reasonable to me. ALL kids need homes, so why not?
Reply | Report Abuse | Link to thisIVFMom, you put your finger right on a serious problem.
Reply | Report Abuse | Link to thisGiven that some three out of four fertilized eggs result in spontaneous abortions, it seems crucial to me, that artificial fertilization mimics the natural "fertilization race", where one of the best sperms can be expected wins.
A few years ago, I met the mothers of two children who were conceived via Invitro Fertilization (IVF). These women were told by their own doctors that children conceived by IVF have poor immune systems and that they need to be really careful with them for at least the first 3 or 4 years. We were told that if our kids had so much as the sniffles, we were to contact them and they would keep their kids home from the kids activities for the day.
Reply | Report Abuse | Link to thisAside from natural selection due to the many sperm, what sort of selection is done in regards to the eggs, and what care is taken for the removal process?
Reply | Report Abuse | Link to thisIt is selfish. However, based on an evolutionary perspective, it is acceptable. Reproduction for an individual in a particular species is a way of passing on the organism's genes to future generations and thus the future gene pool. This is why many of the males in many organisms mate with multiple females; multiple matings ensures reproductive success. It is partly instinct that explains why people want to choose IVF (if they are having trouble conceiving) rather than adopting a child that does not contain the similar genetic makeup as the adopter(s).
Reply | Report Abuse | Link to thisBirth control is not available in many places. Sadly, some of those places are in the US.
Reply | Report Abuse | Link to thisAdoption from anywhere is difficult, expensive and risky. I don't mean to discourage anyone but my wife and I have two children adopted from abroad and had we knew of the challenges we would face I don't know if we would have done it. I don't think we realized how traumatic the experience of parental abandonment and life in an orphanage could be and we've experienced a lot of problems with the kids because of that. We are not, unfortunately, alone in that respect. For US adoption, the average age of an available child is 8 years old and they may bring with them a considerable amount of psychological baggage and trauma. If you wish to adopt, go into it with your eyes open and educate yourself as much as possible to the potential problems. In my wholly unscientific estimation, about a third will do well, a third will have problems and a third will have significant and potentially dangerous problems. Educate yourselves.
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