IVF's Future And IVF's Past: Lessons From The Cutting Edge In The Year 2000

(A speech I gave to the American Fertility Association in 2000.)
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In planning to speak about advances in the field of assisted reproduction I have two conflicting images in my mind: the first is filled with impressive slides and graphs, detailing what is new in ART and, more importantly, what is coming. The second, and more real, is the disturing and disquieting image of a detached doctor, close in proximity but miles apart from the hearts and minds of his patients.

I spend many nights staring at the ceiling, thinking about the two challenged that face RE's. The first and obvious challenge is pushing closer and closer to the holy grail of our field, that of a reliable, predictable procedure with low risk and consistent outcome, one that is easy enough to place on an actuarial table so that insurance coverage becomes not only an easy ethical choice but an easy business choice as well. We have taken many steps in that direction over the past few years, and we can be justifiably proud of the development of ICSI, blastocyst transfer, single sperm freezing, preimplantation genetic diagnosis, assisted hatching with fragment removal and cytoplasm transfer.

But to inch closer to where we need to be, to the only truly acceptable set of goals for our science, we need to find some huge pieces of the puzzle. In the short term, we need a better means of assessing whom we can help and whom we cannot help. Two years ago I wrote an internet piece on FSH testing and our means of assessing eggs, in which I lamented the limited means we have to counsel many of our patients on what we can do for them. Every RE who will speak to you today knows that it is far easier to counsel an auditorium full of 500 couples on their chances of a good outcome than the one couple who sits across your desk.

In the longer term we need to better understand what makes some eggs, and some sperm, "good" and others "not good" and find ways to either rejuvenate those with lesser potential or make new eggs de novo. Now there are people, none of whom probably need this type of technology, who get uncomfortable with this type of talk. Some of these bold steps might need to use "cloning" technology. And we all know that anything that needs cloning technology, or even brings us to the possibility of speaking about the need for cloning technology, or even makes us think about the need for cloning technology should be banned and outlawed and never spoken or thought of again. Or should it?

A thirty one year old woman sits in my office, a survivor of leukemia or lymphoma or some other disease whose treatment left her not only infertile but menopausal. She and I discuss the very real and wonderful possibilities of her onceiving through egg donation, and we both silently say thanks that we live in the year 2000 and can offer this possiility to her. But what of the undeveloped option of using her "own" eggs? But did we not just say she has no eggs? And since women are born with all the eggs that they will ever have, how can we even think about or talk about using her own? Well, why don't we make new ones? Now, thankfully I have already passed my reproductive endocrine boards so if any board examiners are in the audience I cannot be blackballed, (at least I hope I cannot.) But let's for a moment propose for one of our long term goals the development of techonology that allows us to not only swap the nucleaus (and therefore the genetic material from my patients' eggs to donor eggs) and therefore make new "good" eggs but to swap a brand new nucleus from a stomach cell (yes, I know it has twice the needed number of chromosomes and is **gasp** technically a clone cell) and then zap it with electricity or an enzyme or two so that it DIVIDES and becomes.... a new egg. And my lovely thirty one year old patient can now have her own babies.

But we have used cloning technology! We have stepped onto the slippery slope that will lead to an Orwellian nightmare of genetic engineering and online ordering of blue eyes and perfect skin and high SAT scores. Or maybe we have just refined a technique enough to allow my 31 year old to have her own babies. And if, in so doing, we have allowed 41 year olds to have their own babies more rapidly and with higher percentages, than I am all in favor of that too. And if it allows us to say to our patients with really high FSH levels who cannot respond to stimulation regimens or to women whose endpometriosis has aged their ovaries by an extra two decades to have their own babies then that's a good thing too. But but but... if you can take the cell from a woman's stomach and make an egg with her chromosomes and she can get pregnant and have a baby when before she could not, could you not take the nucleus from a man's stomach and make an egg for him too? uhhh,, yeah. So we're perfecting a (**gasp**) cloning technology and we're allowing men to have eggs and we're supposed to let this just happen, knowing full well that we have stepped onto the slippery slope that will lead to an Orwellian nightmare of genetic engineering and amazon.offspring.com etc etc etc....

No, we are finding ways to help couples to have babies where before we could not. In 1995 we started larger scale use of preimplantation genetic diagnosis for the detection of abnormal numbers of chromosomes. If I can manage to deliver some reasonably well matured eggs to Dr. Cohen's lab, and he can grow the resulting embryos for three days and deliver one good cell from that embryo to Dr. Santiago Munne, then Dr. Munne can tell me and my patient and her partner the likelihood that that embryo will have an extra number 21 chromosome, or only one X and no Y chromosome, or pass on Muscular Dystrophy. We can also do, with pretty much 100% accuracy, sex selection.

With the enormous amount of information that we will soon have from the human genome project we may be able to greatly reduce the risk for breast cancer within a family, or the risk for diabetes. But this uses a technology that allows accurate sex selection, which as you all know, is a step onto a slippery slope that will lead to Orwellian nightmares of.... oh forget it.

The point I am trying to make is that there are enormous opportunities to help people and locked inside some of our more "dangerous" technologies. The challenge is not to suppress the technology, or to outlaw it; the challenge is to use it well. Just as we can choose to use a sharp object to remove a diseased appendix we can use a fluorescent in situ hyridization probe to prevent the passage of disease. And we can use intracellular manipulation to help families have babies.

That's the future-- now what about the present? A long time ago I wrote an article called "Reflections of an RE." It probably should have been called observations of an RE because that's all it really was, but a lot of my patients read it and commented on it. I had noticed certain periods during infertility treatment that tended to recur one patient to the next-- I called them emotional crisis points. They are pretty obvious: a first failed treatment cycle with injectable medications, a painful diagnostic test, that sort of thing. In discussions with my patients after that, we looked at another side: strategies for infertility treatment survival. To finish my talk today, I would like to share some of the lessons I have learned from my patients.

Ten tips for surviving your IVF cycle
1. Take yourself off the hook. Recognize that there is nothing you can do the will screw the process up. Entry fee to the "I screwed up my own IVF cycle" club:
2. Don't sweat the small stuff. Realize that there is no one right way and that a minor deviation from what happened last time can still be ok. There are a hundred valid ways to overlap lupron and the birth control pill. 10,000 units of HCG is probably 5000 more than you really need, so if a tiny drop dribbled down the side of your rear end it will not make a difference.
3. Lower the bar. Remember when you thought that your Algebra II final exam was like your final grade in Life? Your IVF cycle and its outcome are extremely important and you have invested tremendously of yourself in doing it. It is not everything though.
4. Repeat after me: the limitations are in the technology. If my IVF cycle cannot use your eggs, the problem is my IVF procedure, not your eggs.
5. Be as stressed as you want to be. Recognize that a major dose of stress is unavoidable during your treatment cycle. Don't try to deny it away and don't let its presence become a further source of stress for you. Look stress in the eye and keep it in its place.
6. Speak your mind but keep your composure. Remember "please" and "thank you" and if you page your doctor in the middle of the night, preface your question with, "I am really sorry to disturb you." Don't do this for the doctor. Do it to show him or her, and the rest of the world that even though you are going through IVF, you are dealing from strength.
7. Win both ends of the IVF cycle doubleheader. The greater goal is pregnancy and children, but a short term goal is to beat the evil treatment itself. Infertility treatment can chip away at self-image, can rob of us our positive self-image and cause us to question some of the more important decisions we have made as to how we run our lives. Let your actions show the world that you will not let the uncertainty turn you around. (h/t to Jackson Browne)
8. Let yourself be amazed at how well your spouse is putting up with everything. Be over the top in the way you support your spouse. Say nice things to your friends about him or her within his or her earshot.
9. Don't save up the love and attention. It is not going anywhere.
10. Take a crayon and draw a picture of yourself getting a progesterone injection. Make yourself look really silly. Take another crayon and draw a picture of whatever sperm collection technique you employ. Make everyone look really silly. Next take another crayon and a piece of paper and draw the head nurse talking on the phone. Give her really big hair and a cartoon balloon coming from her mouth and make her say, "blah blah blah blah blah blood and ultrasound" and make her look really silly. Next take another crayon and draw a picture of your doctor doing an ultrasound while you, the patient lie on the table with a thought balloon in which you hit him or her over the head with the probe. Make yourself look really powerful and make him or her look really silly. Then hang the pictures on the refrigerator with magnets.

The most impressive part of the advances in reproductive technology is the way IVF patients channel their strength and determination into grace, humility and humor. The rest of us can learn a lot from you.