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.

Frozen Eggs Perks as Policy

Ashton Carter announced the Pentagon will make a bigger commitment to family-building for people serving in the military. The package includes new benefits for maternity leave and child care, and even a pilot scheme for egg and sperm freezing. The news is less surprising since Facebook and Apple rolled out a policy of offering $20,000 perks to young employees for defraying the costs of egg banking, which amount to >$10,000 per cycle + annual storage fees.

The aim is to retain highly-trained staff from leaving early to start a family. Most women are aware that their biological clock starts to wind down from around age 30, long before the average age of menopause. Egg banking is portrayed as fertility insurance, but is it just a lottery?

egg freezing
Eggs come in from the cold

The first freezing trials with human eggs were far less successful than with embryos. Since they are delicate single cells, their survival is all-or-nothing, whereas embryos afford to lose one or two cells from the bunch. Fewer than half were surviving in the 1980s, and very few of them made babies with IVF. Even more alarming was the evidence that chilling damages apparatus in eggs on which the chromosomes “dance” during cell division, putting babies at risk of birth defects from the wrong number of chromosomes. Many labs besides our own tried to improve results, but the breakthrough came with vitrification, which turns cells into a glassy solid instead of ice. Masashige Kuwayama at the Kato Clinic in Japan perfected the method. It involves ultra-rapid cooling in a highly concentrated solution, similar in some respects and different in other ways to making smooth ice cream. Like home-made ice cream, vitrification is not a technically sophisticated process, but it demands expertise of the technician who, working under a microscope, mounts each egg in a minute droplet for plunging into liquid nitrogen. I wonder if a technique that depends so heavily on operator skill in an unregulated environment can produce consistent results across clinics.

Egg banking emancipates fertility preservation for women, whereas men have had sperm freezing since the 1950s. The original rationale for banking was to help young women preserve their fertility from the sterilizing effects of high-dose chemotherapy and radiation. It also helps women to have genetic children after a hysterectomy, although a surrogate must then be commissioned to carry the baby. Before egg banking there was embryo freezing, but that requires IVF and therefore a male partner, or ovarian tissue freezing, which we developed as an alternative technology and is still used for child patients. One of the great advantages of freezing eggs versus embryos is that there are fewer issues surrounding the disposal of surplus eggs because they carry less moral gravity.

Although egg banking has been a bright hope on the dark road through cancer treatment, it is now embraced by far greater numbers of healthy women. This is being encouraged by perks from employers and lauded by media reports and TV. As if that publicity was not enough, clinical providers are heavily invested in advertising. I am told that business is booming, and more and more fertility clinics want some of the action.

But pause to consider the “customer.” I think that word is more apt than either patient or client, because these women are seeking treatment for a non-medical condition (aging) and from for-profit clinics. More and more fertility clinics that started as private medical practices are becoming absorbed into big business. I suspect these entities are now looking less and less like a familiar medical environment and more and more like normal commercial operations.

And who is the typical customer? She is a professional or businesswoman in her 20s or early 30s who dares not step off the career ladder during her most fertile years, or perhaps she hasn’t found a Mr. Right yet. There are other reasons, but a common conflict is between biological imperatives and social pressures. Employers are slowly recognizing this dilemma, but the answer they provide (if any) is technology instead of a better deal for women’s careers. Consequently, the average age of motherhood is rising, and already passes 30 at the birth of the first child in several countries. Men are luckier, although fresh mutations are more common in older sperm.

What price would you pay for a child of your own? There’s the nub of it. Fertility treatment involving IVF is unaffordable by most couples on low incomes, and those who can afford egg banking to delay family-building are investing in uncertainty. As this is a new technology there are very few centers with enough data to provide a reliable estimate of the chances of pregnancy with banked eggs. A British authority (HFEA) reported that up to 2012 there were only 20 babies born from 160 treatment cycles, and the US registry (SART) announced 162 live births in 2014, a success rate of 1 in 5 cycles. We await updates.

Success can never be assured. Since the chances with one batch of eggs are unlikely to be high, multiple rounds of treatment (i.e., more eggs) are required, and preferably collected at very young adult ages. Can you think of another product costing as much with so little security? Would you buy a new car or boat from a dealer without a guarantee? Would you dare commit thousands of dollars to a lottery? The reason that people will spend so much on fertility services, even taking out large loans or remortgaging their home, is because having a baby is a life event. Nothing compares with it.

This cautious post may seem surprising from someone who spent his whole career in reproductive technology and biology. Egg freezing is, of course, a wonderful breakthrough which I welcome unreservedly for patients needing emergency fertility preservation, but to others I say let the buyer beware.

Posted in New Zealand

 

 

Howard W. Jones Jr., M.D. (1910-2015)

Our dear friend and mentor died today in Norfolk after a short illness. Lucinda and I were able to exchange a few words and smiles with him in the hospital yesterday. He asked how our children are doing—so typical of him.

Howard Jones will be remembered as one of the “Greats” of American medicine because of his pioneering work in reproductive surgery and in vitro fertilization (IVF). He was an inspirational figure for his students and fellows and beloved by everyone who knew him. He had a wonderful blend of humanity, dignity and generosity of heart. Modest and conservative in his own habits, he was indefatigable at work, progressive in outlook and a charismatic speaker. His laugh was infectious.

Some of this character and strength came from his matrimonial and professional partnership with Georgeanna Seegar Jones, a brilliant reproductive endocrinologist. They were a perfect team, sharing an office for most of their careers, co-editing books and journals, and co-supervising junior medical staff and research projects. He said they never had angry words.

Jones Institute
Howard W. Jones Jr., M.D.

Howard was born in Baltimore, Maryland, and graduated cum laude from Amherst College in 1931 and M.D. from Johns Hopkins University in 1935. After military service as a surgeon in France during World War II, he returned to Hopkins where he switched to gynecological surgery and was involved in developing cervical screening services (Pap test) and immortal cancer cells (HeLa cells) from Henrietta Lacks, who was his patient. He remained a surgeon and member of staff at Johns Hopkins until retirement age when they moved to Norfolk and created America’s first successful in vitro program.

When I asked him recently which breakthrough was most important in his career, he replied without hesitation: it was IVF because infertility had been a “great unsolved problem” and the technology has had “a big impact on society.” He became deeply engaged in the ethics of reproductive medicine as an author and committee chairman. Howard and Georgeanna were the sole American doctors invited to Rome in 1984 to advise the Holy See about the new reproductive technologies. I guess that IVF in America was lucky because a controversial technology would surely have drawn greater resistance if it had not been launched by a doctor duo looking like wise and kindly grandparents. Unfortunately, their powers of persuasion did not sway the Vatican, although Howard still hoped for change.

We expected he would lose heart after the death of his beloved Georgeanna in 2005, but he was soon back in his office and flourishing again. New books were published, lecture invitations were accepted when mobility allowed, and young researchers and visitors were welcomed. Work gave meaning and continuity to life, and resonated with memories of his English teacher at Amherst, who wrote:

Robert Frost

The last time I heard him recite the poem was at a conference here in Williamsburg. He was then only 93 years old. We were blessed to have him for more than another decade until he fell ill last week shortly after finishing another book, titled Howard and Georgeanna.

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