The first picture of a baby is usually in the mother’s arms soon after delivery, and becomes pasted into an album for posterity. My mother missed out on that snapshot since I was born in austere post-war London when a box Brownie camera was a luxury my parents couldn’t afford. But nowadays the picture is taken earlier and with a much more expensive camera. My granddaughter, Pippa, was snapped by an ultrasound scanner when she was barely past the fishy stage in her mother’s womb. The next picture taken a few weeks later showed her looking like a real child, and the obstetrician could confirm everything was fine, including beating heart and nuchal transparency. Pictures reassure us all is well, even if we can’t put absolute trust in them.
The first picture can be taken even earlier nowadays – in fact, as early as can be. For most of her thirty years as an embryology lab director, Lucinda gave prospective parents of IVF children a picture of their embryos which she had taken immediately before medical staff transferred them to their Mom’s body. These were embryos that had been fertilized in a Petri dish and grown to a ball of about 8 cells in three days, or had formed a blastocyst with about a hundred cells after a slightly longer incubation. Giving these photos to patients is now a common courtesy in fertility clinics, and more and more couples are having this extraordinary preview. Last year there were over 60,000 babies born after IVF procedures in the USA alone, or 1% of all births.
For such couples (and single mothers undergoing the same treatment) pictures of their embryos probably find a temporary place of honor on a kitchen bulletin-board until the next picture at the six week ultrasound scan – or taken down if the pregnancy test proves negative. But for embryologists and physicians, pictures of embryos are records of the best-looking in the bunch which they hope stand the best chance of getting Mom pregnant. Generally one or two are chosen (sometimes three) for transfer from the half-a-dozen eggs (more or less) that were fertilized, but these pictures say so much less about the embryos’ prospects than my first picture or Pippa’s, and even ours hardly say anything about things that most matter to us – future health, vigor, brains, and beauty.
Upwards of 50% of all human embryos conceived in the IVF lab (and probably the same in the body) have abnormal sets of chromosomes, and therefore no chance of making a healthy child. It is possible to genetically screen embryos so that only the healthy ones are placed in the uterus, but although this can be helpful it is far from foolproof. Some embryos are mixtures of normal and abnormal cells, meaning that a test produces misleading results if only one cell is removed, which is all that most embryologists dare take. And then there is the unanswered question of whether certain kinds of abnormalities can correct themselves spontaneously, implying that embryos could be discarded unnecessarily.
The upshot of this uncertainty is that deciding which one to transfer is still mainly based on how they look at the time when the photo is taken. It’s a beauty contest which Machiavelli would have derided because “men in general judge more from appearances than from reality.” Unfortunately, “reality” is much too deep to plumb, and so, despite the best efforts, the embryos with the best chances of success are not always chosen.
A single snapshot at the end of a growth process that had been going on for days mostly unseen inside the lab incubator is not much to go on. We wondered if a picture is worth a thousand words, perhaps a thousand pictures would better convey the whole story.
Back in the 1990s Lucinda had already started making movies of embryos in Petri dishes, but had to build her own equipment and record them on magnetic tapes. When I joined the project some years later, digital time-lapse recorders, more advanced microscopes, and miniature incubators were available for the job. We could take a snapshot of individual embryos every few minutes, which over five days added up to over two thousand frames. Imagine how eager we were to compile them for a motion picture of the first days of human embryo development! But we didn’t anticipate surprises, accustomed as we were only to static images, but the embryos educated us.
On the first day nothing seemed to be happening, although appearances are deceptive because there was a lot of activity at the sub-microscopic level. But the next day the fertilized eggs made an almighty heave and in a strange contortion never to be repeated divided into two equal halves within their shells. They tolerate only so much fragmentation of cells at this stage, which you can see in the movie. The next division to make four cells started later in the day, and more divisions created a ball of tiny cells without any net increase in overall size. Clinics are now using customized equipment to monitor the rate of embryo development to help to choose which to transfer.
On the fifth day, healthy embryos became blastocysts, hollow balls of cells with a tiny knot at one side that make up the embryo proper. The movies revealed that blastocysts undergo cycles of swelling and collapse rather like a beating heart, although far more slowly and not from muscles contracting because no such cells exist yet. Just as a heart sound or pulse is a sign of life, the blastocyst’s beat is a sign, and probably a better token of vitality than a static picture ever gave.
We had another surprise after pressing the PAUSE button at a random frame if the embryo looked sick, its cells more opaque and less plump. Sometimes it really was unhealthy and had reached the end of the road to development, but in other cases when we pressed RESUME the embryo would shrug off its frumpy appearance to continue growing, often even turning out to be a beauty. So Plato was right for embryos too – beauty really is in the eye of the beholder. A sad-looking embryo might have been discarded or, at the very least, frozen in reserve if its fate had hung on only one picture. Besides, we already knew that, like judges scrutinizing models on a catwalk, embryologists don’t always agree on their scores for embryos. They can tell you stories about patients who produced only a very few scrawny-looking embryos which were transferred to wombs “just in case”, only to find that at least one was successful and made a bonnie baby.
What about the rest, the ones that never survived long enough to be photographed? We seldom mourn things that pass beyond the focus of our eye or camera lens, nor give a moment’s thought to the far, far greater slaughter going on day-in and day-out in the wombs of the world where most embryos never thrive. Embryos may have started out looking hopeful after fertilization and even grow some, only to perish in the dish unnamed and unknown in a Greek tragedy of their own.
Sometimes I am moved to wonder about wasteful nature. I wonder why I can watch in deep sympathy a bee writhing after it has strayed into an insecticide spray or an earthworm wriggling its last as it dries out on the pavement, while we never spare a thought for the anonymous multitudes ending their lives prematurely by being trampled physically or chemically.
I suppose it is the connection with individuals, especially at tender ages, that makes the difference. No matter how alien to the subject we feel there is a biological link and by witnessing the life and death struggle of another creature we are jolted into thinking about our own. Patrick Steptoe (1913-88), who was Bob Edwards’ clinical partner in pioneering IVF, pondered the same thoughts as I do in idle moments. I remember him playing at a conference his musical elegy, For a Dying Embryo. Steptoe_PCS Before striking a key he told us he was sad for the couple who would never have that proud picture of their offspring, but he also had some sort of feeling for the embryo in his care, wondering what it might have become and achieved. Thank goodness Pippa and have pictures so we can muse in the future how we got here.
Next Post: Stem Cell Stuff
Lisa and I cherish our “one, two, four and eight” cell pictures of Caroline, Catie and Carter courtesy of Lucinda. Great post!
Hi Mike and family
Thanks for the message. We often think of you when driving west to our other home in WV, as we will tomorrow (like refugees from heat and humidity!)
fond regards to all