About Giant Eggs & Double Yolks

This week’s gift from a neighbor’s chicken coop included one extra-large egg. After hard-boiling and cracking open we found a double yolk, which some say is a good omen on our wedding anniversary. The following conversation over a meal would be unlikely in most homes, but perfectly natural in ours.

“Have you ever seen a giant human egg?” I asked my wife, Lucinda Veeck. I have only had a few hundred eggs under my microscope, but Lucinda has examined tens of thousands over a long career in her IVF lab.

Chicken egg with double yolkShe said it happened once. It was obviously immature because there were two nuclei in a cell enclosed by a membranous ‘box’ (the ‘zona pellucida’). A normal egg contains one nucleus and it vanishes shortly before ripening at ovulation by ejecting a surplus set of chromosomes in a cytoplasmic bleb. This elimination is so a fertilizing sperm can add a matched set to restore the pair.

Now here’s the thing. Her giant egg was not a microscopic version of the cooked egg. If a hen bird ovulates two yolky eggs simultaneously, which happens occasionally, they are quickly bathed in albumen, then enclosed in a common membrane and a shell during their journey down the oviduct, a process that takes about 24 hours to laying. As the nuclei are in separate yolks, the outcome is a normal genetic makeup with two chicks hatching from the same egg, although the cramped space affects their viability . The closest parallel is when non-identical human twins are conceived after a double ovulation.

But the nuclei in Lucinda’s giant shared the same cell, so their DNA would be inherited together. Had it been mature for fertilization the embryo would likely have three sets of chromosomes (two female and one male), called digynic triploidy, and fail to develop.

We explored explanations for its origin. If you have seen densely packed eggs in biopsies of young human ovaries you might wonder how they manage to grow independently instead of being swayed by neighbors, like people jostled in a football crowd. Sometimes they lose autonomy. I have seen two or more eggs combined inside follicles of every species examined, up to 14 in dog ovaries, although some looked unhealthy from the competition.

When boxed inside their own membrane eggs can’t fuse to make giant eggs. They have unique genetic makeups, just like eggs from separate follicles that go forward to make non-identical twins. But what happens when they coexist in a ‘box’ and don’t fuse to form a single cell?

Lucinda saw an example five days after an IVF procedure. It was a double embryo at the blastocyst stage with about 64 cells each. If separated for implanting in the womb, it seemed likely they could make non-identical twins, but if they had originated from a fertilized egg that had split instead of from two separate eggs they would make identical twins. It’s possible that they could unite (or reunite) to make a singleton pregnancy, and, if originating from two fertilized eggs, the baby would inherit mixed genetic lineages, a known condition called chimerism.

In the interests of being (somewhat) intelligible, I avoided more abstruse explanations and outcomes. With so many ways that development can go awry, it is a marvel that we turn out well, or mostly, and I am thankful for my genesis otherwise you wouldn’t be reading this post. I usually avoid writing technical stuff, but correspondence is welcome from readers who like to crack eggs.

Next Post: The Sound of Noise & Silence

Elegy for a Significant Speck (frozen eggs and embryos)

Eggs in an icescape

Two American fertility clinics 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.

Demography of IVF and World Population

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.

Next Post: Calamity in cryopreservation labs