Embryos created in a fertility clinic spend their first few days bathing in a special solution. The ingredients matter — they can affect birthweight and more — but nobody has to tell you what they are.
4 minute read
We spend a lot of time telling expectant mothers what they should and should not consume. But for parents whose embryos are conceived in the lab, the first few days are a bit of a mystery.
Their embryos are nurtured in petri dishes that contain special solutions — "culture media" — which can contain things like salts, sugars, amino acids and lipids. But the exact ingredients and concentrations are not public. And unlike with, say, peanut butter, they aren't required to be disclosed.
Does it matter what's in them? Does it make a difference?
Some years ago, a group of Dutch scientists, among them John Dumoulin, head of the IVF laboratory at Maastricht University Medical Centre, decided to take a closer look. They knew that in animals, culture media could affect birthweight. Sheep and cattle could be born at twice the size of the naturally conceived, for instance, and mice cultured in suboptimal media were born small.
As part of the internal quality control process in the Maastricht University Medical Centre fertility clinic, they alternated between two different commercially available culture media, Vitrolife and Cook. Apart from the medium used, all other protocols — ovarian stimulation, fertilization, embryo transfer procedures and so on — were standardized. This provided a great opportunity to compare the outcomes of two randomly-assigned groups.
Out of 826 cycles during the study period, there were 188 children born live and on their own following fresh transfers. The researchers found that the ones who'd spent their first embryonic days in Vitrolife were significantly heavier at birth than the ones who'd bathed in Cook. The pregnancy rate was also significantly higher for Vitrolife.
A subsequent study found that at two years of age, children who'd been in Vitrolife culture medium as embryos remained heavier than those who'd been in Cook.
The same was true at age nine.
And it wasn't only weight — BMI, waist circumference, waist-hip ratio, and fat on the trunk of the body were all greater in nine-year-old Vitrolife kids.
Importantly, there were no cognitive differences between the two groups of nine-year-olds. Nor were there significant differences in blood pressure, heart rate, or blood levels of cholesterol, glucose, insulin and the like.
The finding that there were no cardiovascular differences was reassuring, considering what we know about how early experiences in the womb and around the time of conception can affect metabolic health later in life. Children gestated during the Dutch famine of 1944-45, for instance, were more likely to become overweight adults, with diabetes and high blood pressure. According to the Barker hypothesis, poor nutrition during gestation predisposes a person to these types of illnesses in adulthood.
"The exposure to an adverse environment in utero may induce structural and functional adaptations that have an effect later in life," the authors of the study on nine-year-olds write in their introduction. "Whereas the foetal period is a critically sensitive time, it is most likely that the embryonic period is at least as precarious."
What these studies show is that the embryo is indeed sensitive to its environment. And this was true even though the embryos studied here spent only two or three days in culture. These days, embryos spend twice as long.
What is not yet clear is whether either group — lower weight or higher weight — is more likely to develop cardiovascular disease later in life, or, by extension, whether one culture medium is better than the other.
There are currently more than 20 different embryo culture media available, estimates Sebastiaan Mastenbroek, an embryologist at Amsterdam University Medical Centre for Reproductive Medicine, who was an author on several of the above papers. But despite the fact that we now know culture media can have consequences, and that we should be following and analyzing outcomes, the companies that make them are under no obligation to disclose what's in them. "I am currently not aware of any jurisdiction where things are completely transparent," Mastenbroek told me via email.
In a 2019 paper, he and his colleagues analyzed 15 commercially available media. No two were identical, they found, and components changed over time with storage and usage. What would be better would be full disclosure of the ingredient list, he says.
More than a decade ago, the EU committed to regulating the culture media used in IVF as medical devices. It called for manufacturers to submit information — about why they include what they do, how they make it, how they ensure it's safe, and so on — to so-called "notified bodies." But the European Society of Human Reproduction and Embryology's working group on culture media has said it's not clear the system is working. No one even knows where these "notified bodies" are, they point out, and if manufacturers are carrying out post-marketing surveillance, no one knows how it's being done.
They call on clinics and countries to do the right thing: "In light of the large and emerging body of evidence on the importance of the nutritional environment during early development," they write, "national registries should include the type of culture medium embryos have been exposed to as well as unique identifiers for patients and babies on the register to enable large-scale outcome studies to be performed routinely using data linkage."
That sounds great! I could not agree more. Why am I not hopeful?
Many thanks to the Progress Educational Trust, whose event last week, "The Health of IVF Babies: What Do We Know? What Do We Need to Find Out?" prompted me to follow up on this very important subject.