Adventures in making and raising our test-tube babies

Tuesday, March 25, 2008

The Devil is in the Details

"Is Evolution God's Creation?" was the catchy saying that a pastor friend arranged, letter by letter, on her church's front billboard. Within hours, someone took down the letters in a huff and reported the incident. This person was surprised to learn that her very own pastor had been the one to make the blasphemous suggestion.

The nitty gritty of trying to make a baby could lead you to believe in evolution or creation or both. There are so many details involved, that it is absolutely a miracle when they all come together and form a normal baby. An impossible number of evolutionary accidents had to happen to make mammals able to reproduce the way they do. At the same time, with billions of variables at stake every time two people try (or don't try) to conceive, how could anyone expect evolution not to happen?

Whichever way you look at it, as my friend Jeff's mom (a nurse) says from her medical-scientific standpoint, every time a baby is born, it's a miracle.

What we learn about human reproduction in school barely gets us past giggling. But beyond the boy-and-girl-like-each-other part, let me tell you some things you might not know. Hunker down. These are some serious details.

There are only about 36 hours per month that a woman can get pregnant. The sperm can either be there waiting for the egg's debut (they can last 5 days), or they can show up to the party within the next day and still have a shot at the old gal. But if they miss her coming out party entirely, they have missed their chance for the month. The reason women take their temperature when they're trying to conceive is that their bodies run slightly hotter when the party is going on. Maybe that's why they say certain species are "in heat" when they're ovulating. Hot to trot.

The sperm have a deadly gauntlet to run before they can get to the egg. There are between 20 million and 200 million sperm in any given "batch," and every one of them is needed; 11 million seriously isn't enough. They have to swim up the birth canal, using it to slough off all the extra moisture and material in the semen. Only the actual sperm cells themselves are allowed through the cervix into the uterus. If any of the extra stuff comes with them, it could make for a life-threatening infection. To make matters worse, some women have anti-sperm antibodies in their system that kill off any boys that come into their territory. Talk about a hostile environment for conception! A blood test can detect that condition.

In the meantime, ever since her period (where last month's uterus blood is tossed out, sometimes with a baby in that bathwater -- oops), the woman's ovaries have been preparing an egg for her. One or more follicles, bags of fluid that contain fluid and incubate the egg, grow on the ovaries. Or if she's on fertility treatments, medicine might have induced her to make ten, twenty, or even thirty follicles. The woman's pituitary gland or doctor, two entities that control her hormones, pumps the woman's system full of a follicle-stimulating hormone so that follicle(s) get nice and plump, preferably to about 2 or 3 centimeters in diameter. Imagine a grape, or if you're going through fertility treatments, imagine a bunch of grapes. Imagine the woman trying to fit into her normal jeans.

In a normal woman's body, the single egg will be released when it is at the perfect stage of ripeness. A doctor has to anticipate when the stimulated multiple eggs are large and mature enough to fertilize, but not so old as to be post-mature, or so big as to hyperstimulate (could lead to organ failure in a woman's body, and maybe her death). So this period of time involves a TON of "monitoring" during the IVF cycle. I'd go in to the doctor's every other day, and then every day. They would use a transvaginal ultrasound wand to get a good picture of the follicle sacs and what the uterine lining looked like. They'd take a blood test to see how my hormones were doing. Every afternoon the nurse called me to tell me how much of what medicine to take that night. She would adjust the hormone dosages depending on what my body had done overnight. Sometimes I took four injections, in the stomach and/or rear end, in a single night. James administered them like a champ. And he didn't like it.

So back to the biology. When the egg looks good, at about 14 days, a different hormone tells the woman's ovaries to let loose, and the egg goes spinning through the fallopian tubes, a gossamer-like silky hose, where it may or may not meet a viable sperm. If the woman is going through IVF, the doctor will have stuck a needle into her ovaries right before ovulation happens, to suck up the mature eggs while they're still findable. If they've already gone swimming in the fallopian tubes they're lost for ever. If the uterus still has a live sperm in it, and the sperm happens to make it to the right spot, and it has the right shape to be able to nuzzle his way through the microscopic egg shell, well, magic.

If the woman has been going to a bad or unethical fertility doctor, he might have helped grow a carton-full of eggs and then let them loose on a bunch of sperm -- through artificial insemination or through regular means -- while they're all still free in the uterus. That's how you get octuplets or more. A more responsible doctor will insist that either you fertilize the eggs outside the body so you can control how many go back in, or will make sure your uterus takes in no viable sperm that month. They talk about the "risk" of twins. As a twin I am offended. But multiple births pose a huge risk to mother and babies alike. I recently saw a photo of twin boys born at 22 weeks - halfway through a normal gestation. Their heartbroken mom went into early labor. The boys in their tiny stocking caps were right at the border between fetus and recognizable child. Heart breaking. They didn't make it. Their mom did, but boy, does she grieve.

So anyway, if a sperm and egg surmount the zillions of obstacles and actually get together, that's just the beginning. Fertilization is a challenge. The sperm has to have the right shape and get there on a timely basis to get through the egg wall. If a doctor is involved, the sperm will be given the best possible chance by going through a "wash" before they get to do their thing. The semen goes into a chemical bath and gets spun on a centrifuge to separate the live sperm from the dead or malformed sperm, along with all the other juices and germs of the semen mixture. Perhaps this leads to babies with inner ear/balance problems, or just dizzy blondes.

Once they have the sperm, in the laboratory, embryologists often use a technique called ICSI, which means intracytoplasmic sperm injection. That means you pay more for your IVF. It also means the lab technician makes a tiny cut in the microscopic egg wall and shoves the newly-washed sperm in. It just gives the little guy a better chance of getting in. But the better chance isn't all that great. If the egg wasn't a good egg -- and that happens all the time with human cells, where they just aren't going to be viable -- the egg would not have been very receptive to letting the sperm in anyway. So ICSI just helps a sperm get into an inviable egg. Big whoop. Nothing happens. The embryo doesn't survive. But sometimes the embryo does survive. That's what we're always pulling for.

Once you have a live embryo, it has to keep growing. Sometimes it does, sometimes it doesn't. Nothing you can do about this except pray and keep every finger and toe crossed. If it works, the embryo's one cell splits into two, and those split into four cells, and so on. After three days, if they're still alive and growing, there are about 8 or 16 cells and they're big enough to squeeze out of the egg shell and burrow into the lining of the uterus. In the lab, sometimes the technicians do assisted hatching. That means more money. I mean, that means they make teeny holes in the shell of the egg with a laser, so it will be easier for the embryo cells to bust out. Which they may or may not do.

In the meantime, the woman's body hormones have switched to progesterone, pro-gest, to make a nice bloody bed to feed and house the embryo in the uterus. If the woman's hormones aren't doing it on their own, or if they are, just to help them along, the doctors prescribe tons of injectible hormones to make this happen. Progesterone shots are absolute hell. You have to put an ice pack on your butt to freeze the area so you won't feel the huge needle or stinging progesterone in a sesame or olive-oil base (!!!) going into your muscle. Then when it's in, you switch to a heating pad to help disperse the hormone and the oil. Because oil does not naturally disperse from water-based muscle tissue! You have to help it along or it will create pockets of oil. Welts. The bruises that result are phenomenal. The hip hurts all day and all night, and the pain sometimes goes along with areas of numbness. My hip alternately hurts and is numb, and I last did IVF about six months ago. I'm told this goes away in a few months. Still waiting. So the shots happen for two weeks at least, from ovulation to when the woman's period would be expected. If she's pregnant, they last for longer.

Although progesterone makes for a lovely uterine lining, it makes for a terrible, terrible body to be stuck in. I believe that progesterone is responsible for the PMS stereotypes that women get plagued with. Progesterone has made my body very sore and incredibly lethargic, has made me burst out in tears all the time for no reason, and has made me feel the need to take emergency naps - when my body lets me know it has two minutes before it is going to stop. Then I have to race home and hope I make it before I shut down. When I'm awake, it makes me very, well, irritable. I don't know why the progesterone, which is supposed to be so good for family-building, doesn't drive the husbands away. It should, by all rights. The partner has to be the one to give the deadly, scary shot to his love's butt every night (alternating sides night by night); this "hurts him more than it hurts her," but only kind-of. Yes, it's scary when the injection site shoots out a spray of blood. And it's damned tedious to have an emotional, pained spouse. I think giving the shots may be a kind of vetting process. If the couple can't stand each other during this period, they weren't cut out for the very worst aspects of parenting together. If they can get through it, their own chances of survival are a lot higher.

So now the action shifts back to the uterus -- or the lab. In IVF, the embryos were formed outside of the body and get put back into the uterus through a catheter when they are three or five days old. If there are any extra embryos they can be frozen to be used next time. On our last IVF, we had 11 follicles that produced 11 eggs, and 9 of them fertilized. By Day 3 they looked so good that the doctor pushed us two days to be able to transfer them back to me on Day 5. On Day 5, the embryo has turned into a blastocyst and has a better chance of implanting in the uterus. We were thrilled that by Day 5 we still had three blastocysts. We transferred two back in, and hoped to freeze the other blastocyst or maybe any other embryos that hadn't become blastocysts. But nobody else survived to be frozen. That's a shame, because as you can guess, it's a pain in the butt to produce an embryo from scratch.

After the embryo forms on its own or in the petri dish, it has only a few days to squeeze out of its egg shell and burrow down into the uterine blood. It might or it might not do it. Once you have two good embryos in there, there's still only a 50% chance that one or both of the embryos will stick. If you do this process naturally, you go on your merry way and then keep an eye out for your period in two weeks. In the IVF world, this is the dreaded Two Week Wait (2ww). It's awful. You can think of nothing but progesterone shots and wondering whether the little embryos who are in you, which make you technically count as pregnant, are still there and are still alive.

If the uterine lining is okay, and the embryo is okay, and the implantation happens, and the genetic make-up of the egg and sperm are okay, and the embryo can hang on for about a week and a half, you might be pregnant. If you have the luxury of being calm about it, you can wait and see whether you have a menstrual period on time, and if not, you can take a home pregnancy test and watch to see whether in two minutes you make the second pink line show up, or if it's just the first pink line. If you've done IVF, you have an appointment for a blood test at your doctor's office, and you are admonished not to take a home test ahead of time because it is much less accurate than the blood test at the doctor's office. You may or may not put yourself through the hell of trying to find out early, and then wondering whether the test was actually accurate.

Books advise you to have your nurse call you with the results of the pregnancy test, and leave them on an answering machine that you will not be at. In the evening, when you are away from work and can be with your spouse, you can listen to the message together and find out the good or bad news. We chose to have a pitcher of margaritas ready. Somehow the nurse misunderstood my instructions, and at 7:00, when the office was closed and everyone had gone home, James and I shakily listened to our message. It said, "call us back." What!?! How could they play such a nasty trick? We called the nurse's emergency line, and she called us back within a few minutes from a payphone on the side of the road (her cell phone was broken). She told us she was sorry, but it was negative. We thanked her and hung up. And sobbed. And went for the margaritas.

After all that. After ALL THAT. And not a single embryo to freeze. And with all our follicles, eggs, sperm, embryos, uterine lining, blastocysts looking good along the way.

My friend Ashley is going through her third IVF right now. Her eggs were always immature and had a low fertilization rate. This time the doctors manipulated her hormones in such a way that she got to keep the eggs in their follicles, cooking, for a longer period of time. The hope was that they would be better at fertilizing when they came out slightly later. Well, of 18 follicles, they only got 8 eggs. And then only one fertilized. Those are heartbreaking numbers. Yes, they still have a chance that that one embryo will keep growing and then will hatch properly and implant properly... but it would be better if there were more to work with.

And that brings me to another post, for another day, on unfairness in the world.

1 comment:

DAVs said...

I'm exhausted reading this and I've been through it three times!!
Now, I appreciate the "shout out" but I have to say (just to add another element to this agony) we usually had GOOD fertilization rates (just not a lot of mature eggs to fertilize) and this time we had good maturity rates and CRAPPY fertilization rates. See? Patch one hole and something else springs a leak. So confusing. Anyhoo, in the end what does it matter except that our one sad lonely YONO IOTO keeps dividing. :)