Two American fertilityclinics reported freezers failing last month, and had thawed to an undisclosed degree. This rare event shocked hundreds of patients who were storing embryos, eggs and ovarian tissue. Maybe it was the equipment that failed or a human error, but responsibility rests on the shoulders of clinics except for major fires or criminal intent out of their control. These freezers have electronic alarms. When Lucinda was managing Cornell’s IVF laboratory she could be called automatically on her cell phone if liquid nitrogen levels fell to critical levels. It never happened. She knew the danger because there can be no recovery for cells that thaw improperly.
A tank may contain over a thousand frozen eggs and embryos. To patients, they are prospective children waiting for the day when they will be called by their parents. Some women can repeat IVF treatment to replace their loss, but not everyone because fleeting years of female fertility soon rob them of the chance to be new mothers of their genetic children. I chose another hard case for my example, who came through a tunnel called cancer to renewed health, but she lost her next best hope from a plunge in temperature. Money from a lawsuit is no compensation to warm this kind of chilled heart.
Predicting the future is fickle, as Stephen Hawking once observed: “it exists only as a spectrum of possibilities.” And, yet, divining the future is irresistible and physicists strive to forecast the future of stars, black holes and climate. Biologists are more chary, although even they venture to predict extinctions. I recently indulged my curiosity, not by straining at tea-leaves or astrological charts but using math with the help of my son and a statistically-sophisticated friend. We are interested in an aspect of world population that hasn’t stirred much attention. Yet.
The United Nations projects world population growth to the year 2100, but no one has previously estimated the contribution of infertile people. “Eh?” I hear you say. That sounds absurd.
Infertility is an original scourge. Didn’t Jacob’s wife cry, “Give me children or I die!” It was always a private grief with few options, and even fewer effective remedies. I remember a generation or two ago hearing whispers, like, “Why didn’t Uncle Joe and Auntie Jane have children?” No one dared ask them. It was less embarrassing to ask some poor soul if they had cancer. Thankfully, infertility has ‘come out,’ mainly due to attention on revolutionary in vitro fertilization or IVF. The revolution started a few minutes to midnight on July 25, 1978, when Louise Brown was born as the world’s first test-tube baby.
Male infertility, premature menopause and some other relatively common problems were resistant to standard treatment with pills and surgery, but starting with the hub of basic IVF for bypassing blocked Fallopian tubes, a bevy of new technologies has sprouted. Almost no one is now denied a chance to become a parent if they want, provided they can afford to pay in countries where no subsidy is offered. There is now egg, sperm and embryo donation with freezing for longer-term preservation, sperm microinjection, IVF surrogacy for women without wombs, and genetic testing to avoid a blighted conception (PGD).
Since Louise Brown, about seven million babies have been conceived who would not otherwise exist. The children grow up to be as healthy as the rest of the population, and they become fertile adults. The first ones are now having babies of their own.
How will this industry making babies grow in future? We wanted to know how many will be added by technology to the world in decades to come up to 2100. We were even more interested in the broader question of how many people will owe their existence to IVF either directly as test-tube babies OR as their children and grandchildren as IVF services rapidly expand across the globe. We chose conservative data for our calculations, and expect our predictions will underestimate growth, unless there is a global catastrophe. But our estimates still surprised us.
The paper came out today. It is short, readable and currently offered free until May 15 by the publishers. Click Science Direct. I will send a pdf if you have problems connecting.
We called the ambitious program, ‘Egg Farming,’ over 30 years ago when I worked at Edinburgh University. That goal drew a step closer today as my graduate student from so many years ago published results of growing human eggs in vitro, to a blaze of publicity.
We started by growing mouse and rat eggs in Petri dishes. They were tiny cells nested in follicles that nurse their development, and some reached full size in a week and even ovulated a fertile egg into the culture medium. Our sole competitor in this new science was in the USA where John Eppig developed a more efficient method, and he called the first pup conceived from an egg grown in vitro, ‘Egbert.’ He was a strange and obese animal, and we worried if egg farming was too risky to apply in veterinary or human medicine, but many healthy mice were born later.
It seemed a huge leap from mouse to clinic. Human eggs grow more slowly in the ovary, and we expected the cultures would take weeks or even months and be risky. Progress was agonizingly slow because human ovarian tissue is rarely available for research, especially at the premenopausal ages required. Instead of relying on rodents, we needed intermediate species to forge better methods, and turned to sheep and cow ovaries. Visits to the local slaughterhouse for discarded tissue from butchered carcasses were some of the most unpleasant experiences ever, and almost turned me vegetarian from hearing the crack of the bolt-gun followed by a heavy slump. But they helped us to gain new knowledge when human tissue was unavailable.
Professor Telfer’s team in Edinburgh has succeeded with human eggs through careful work with clinical colleagues who asked consent from women to donate tiny slivers of ovarian tissue during C-section. The biopsy doesn’t harm them.
They watched eggs growing in dishes from the earliest stages to full size when a nuclear division occurred and signaled they were ready for fertilization. It is puzzling why the growth is much faster in vitro than in the body, though it is welcome if the eggs are no less competent for making babies. They look normal, but we know from experience how deceptive appearances can be. The only sure test is to fertilize eggs to see if they create healthy embryos, and that will require a special license under UK law.
Why is farming eggs worth the trouble and long struggle?
Progress will continue at a dawdling pace because a mature egg is the rarest cell in the body. For every egg ovulated each month, a man makes 3 billion sperm cells which offer researchers enough material for galloping discoveries in testes. Animals that fertilize eggs outside the body, like frogs and most other species, release as many eggs as they can make because the cost to them is small while superovulation maximizes the chance of making babies. But ovulation in mammals with internal fertilization and pregnancy is restrained by the limited accommodation of the uterus. Nature has arranged a bottle-neck in the egg production line to ensure that few eggs, or only one or at most two in humans, ripen at a time. The rest are consigned to the trash, which egg farming aims to rescue.
If more eggs can be ripened in vitro there will be benefits for animal breeding technology and young patients will have a better chance of preserving their fertility after freezing ovarian tissue during sterilizing treatment for cancer and other diseases. Egg farming will work better for child patients with their larger stores of eggs than in adults. Nearly a quarter-century ago, our first patient at an infant age had ovarian tissue stored while she was treated for Wilm’s tumor. The news from Edinburgh today was welcome for her and others with investments in the frozen ovary bank.