Tuesday, June 15, 2010

Egg Retrieval and Conception

As described below, the stimulation phase of our IVF cycle came to an end on Monday night, when Sarah got a nice big shot of hCG.  Now, the next step is to get the mature eggs out of her ovaries into the Petri dishes where they will be fertilized.  The process of getting the eggs is called "egg retrieval" and it happens bright and early tomorrow morning.

The procedure is relatively simple; the doctor uses an ultrasound machine to guide a long needle to Sarah's ovaries, then punches it into each ovarian follicle. Once he's "stuck" a follicle, he sucks out the entire contents of the follicle, which should include a mature secondary oocyte (egg). Hopefully, due to the stimulation process, there will be a large number of these mature eggs: say, a dozen or more. (In 2006 they recovered 14 eggs.)

Sarah is under general anesthesia for the whole process, which is conducted in an outpatient surgery center and takes less than an hour. We'll leave home at 5:30; I expect we'll be back around lunch. There is no recovery to speak of, though it does take a while to fully shake off the effects of the anesthesia; I expect her to be sleepy all day Wednesday but fully back to normal on Thursday.

Meanwhile, tomorrow is also the day I make my genetic contribution. I do this while Sarah's in recovery. Once they have my fluid, it works like this: an embryologist put a drop of it in a Petri dish filled with a nutrient-rich growth medium. Then an egg is added to the drop, and the dish is covered and put in an incubator.

24 hours later, the embryologist check in and sees how many of the eggs successfully fertilized. As a rule, it will not be all of them; in 2006 11 of the 14 recovered eggs were fertilized. We'll get a phone call from the embryologist Thursday afternoon; at that time she'll tell us how many zygotes we've conceived.

Relax; This Is Not What It Appears To Be


Well, it sort of is. It appears to be a positive pregnancy test. And it is. But it doesn't mean Sarah is pregnant. Allow me to explain.

The predictions made on Sunday held up. On Monday we went in for a blood draw (no ultrasound). The results of this E2 test told our doc that Sarah's eggs were mature and ready to harvest. So, yesterday afternoon they called and scheduled retrieval.

Put in the broadest terms, woman's cycle looks like this:

1. End menstruation.
2. Begin building up a new uterine lining while egg matures.
3. Ovulate.
4. Wait to see if egg is fertilized.
6. Begin menstruation.

Now, imagine that during step 4, the egg is in fact fertilized and embeds in the uterine lining. The last thing you want is for the uterine lining to be shed; it would take the developing embryo with it. So you need some signal from the developing embryo to the rest of the body --- something that says:

HOLD EVERYTHING, I AM HERE!

That signal comes in the form of human chorionic gonadotropin, or hCG. This is a hormone that is only produced in the event of pregnancy, and when present it brings the woman's menstrual cycle to a screeching halt. In other words, hCG is a kind of switch that works to shift a woman's hormonal system from "normal" to "pregnant".

(It's also been in the news lately, as the compound that got linebacker Brian Cushing suspended from the Texans and nearly cost him his Defensive Rookie of the Year award. Its presence in a man indicates one of two things: he either has testicular cancer, or has injected the hormone as part of a program of steroid use. Cushing maintains that he is a medical marvel whose body must somehow be producing hCG in the absence of any cancer. He is lying.)

Produced in a laboratory and packed into a kit, it looks like this:


It's one of those binary jobs like the Menopur: the big vial on the left is sterile water; the smaller vial on the right contains crystalline hCG. To prepare the injection, you take the syringe, stick it in the vial of water, and draw 1mL. Then you pull the syringe out of the water vial, stick it in the vial of powdered hCG, and inject the water into the medicine. In this case, the amount of medicine to be dissolved (look closely: it's 10,000 units) is large enough that dissolution is slower and takes a little more agitation. Once dissolved, the solution is drawn back up into the syringe, and the broad needle swapped out for a 27 guage, 1.5in needle. The prepared shot looks like this:


So this looks a lot like the prepared Menopur shot --- except that in this case, that long needle is going to go all the way in.  The shot is meant for intra-muscular (IM) delivery, meaning the needle goes all the way through the skin and underlying fat and into the muscle.  We do this in Sarah's upper hip, where the muscle is big and thick. 

The technique is simple: wipe the injection site with a sterile alcohol pad, press it flat, stick the needle all the way in, pull back slightly (to check for blood, and thereby ensure you haven't inadvertently stuck the needle into a vein; you don't want to accidentally deliver the shot intravenously), and then press the plunger and deliver the med.  It's over lickety-split.

The pregnancy test is a check to make sure the injection worked.  Over-the-counter pregnancy tests are yes-or-no checks for the presence of hCG; the positive test indicates that she's got a good dose of hCG in her blood.  In other words, that means I correctly administered the shot and her cycle is safely halted for egg retrieval, embryo transfer and early pregnancy.

Sunday, June 13, 2010

Sunday SITREP

We went in for blood test & ultrasound this morning (yes, on Sunday). The follicles on the left and right ovaries have diverged somewhat: those on the right now range from 17-20mm in size; those on the left range from  14-17mm.  The doctor looked at this and today's E2 level and decided to let stimulation go on one more day.  So we have Follistim and Lupron tonight, and Menopur in the morning.  As I understand it, the expectation (subject to change after the blood test tomorrow morning) is that we'll then do the hCG injection tomorrow evening and have retrieval on Wednesday.

Friday, June 11, 2010

Progress Report

As I mentioned below, we've had a number of blood tests and ultrasounds this week.  The way this works is, we arrive at the clinic at 7:30 AM. (This, incidentally, means we leave home at 6:00AM; again, the clinic is in Memphis.)  Sarah has blood drawn and (since Wednesday) an ultrasound; we're on the road home by 8:00.  We typically get back to town by 9:15 or so (traffic differences), and go straight to work.

Meanwhile, the lab is doing an E2 test and the ultrasound tech is preparing a report for Dr. Ke.  Sometime around midday, the doctor and nurse meet and discuss our progress, and make two decisions: what (if any) changes to make in the injection regimen; and when we need to come back in.

Friday night we started stimulation.  The original injection regimen was: 75 units (ie, 1 vial) of Menopur in the morning, plus 0.05 mL of Lupron and 125 units of Follistim in the evening.  The precise timings were up to us, but the morning and evening injections need to be 12 hours apart.  We chose 7:30, AM and PM.  Every twelve hours at 7:25, Sarah's phone starts playing the ABBA song "Honey Honey" (I think the version sung by whats-her-name in the Mama Mia movie, technically speaking).  When that happens we stop everything we're doing and prep the relevant shots, then give them right at 7:30.  We do this religiously, and very rarely miss an injection time by more than about 30 seconds.

At this point the astute reader will have noted a conflict: we're giving injections at 7:30AM, but we're also arriving at the clinic for tests at 7:30 AM.  The resolution is simple: on test days, we mix and inject the Menopur in the car right before we walk in the doctor's office.  Yes, this means I shoot Sarah up right there in the parking lot. It's class all over, I tell you.

Anyway, Monday morning Sarah had blood drawn.  Her E2 must have looked a shade low, because the nurse called on Monday afternoon and told us to up the Follistim dosage sightly, from 125 units to 150 units. 

Wednesday we went in for both E2 and ultrasound.  In the ultrasound, things looked good: all of Sarah's follicles were between 9 and 12 mm in diameter.  And the E2 must have been good too, because the drug doses were unchanged.  We were told to come in on Friday morning, as expected.

Friday (ie, today) was another E2 and ultrasound day.  Interestingly, I think we got the broke-ass ultrasound machine today, because it was hard to see anything.  (Sarah's right ovary, which is usually crisply defined and easy to see, was hard to make out; her left, which is hazy under the best of circumstances, was nearly invisible.)  What the tech could see was good news; Sarah's follicles had grown, from the previous 9-12mm bracket to 12-15mm.

That said, when we left Sarah was feeling discouraged, about two things: first, that the tech couldn't see nearly as many follicles as the other tech did with the other machine on Wednesday; and second, that we were told that her follicles are growing more slowly in this cycle than they did during the 06 cycle.  Interestingly, what I heard the tech say was "you're progressing a little slower, and that is perfectly OK", while Sarah apparently heard something like "you're progressing a little slower, and that is THE END OF THE WORLD."  Later, in the car, I would insist that what I heard was much closer to reality, but she would have none of it.  The ride home was very quiet.

Well, guess who was right.  Much as I hate to admit it, the party closer to reality was .... well, actually, it was me, and I don't "hate to admit it" at all.  The nurse called about 3, and it turns out that we're in perfectly good shape.  There are no changes in the medications, and we go back in on Sunday --- at the practically civilized time of 8:00AM.

So that's where we're at: the follicles are 12-15mm.  They grew 3mm in two days (from 9-12 on Wed to 12-15 today), and we're looking for them to be 18-20 mm for retrieval.  Assuming linear growth (an assumption that I base on absolutely nothing --- just so's you know), we'd be talking about retrieval on Tuesday or so.  Backing up this theory, we ran low on Menopur late this weekend were told by the nurse to order more -- but only enough to take us through Monday.  So it looks like we're at least tentatively planning on wrapping up stimulation Monday or Tuesday, and doing retrieval Tuesday or Wdensday of next week. 

Hopefully we'll know more concretely on Sunday.

Follistim: A Photo Essay

In the evenings we do Lupron, which we already covered, and Follistim.  Follistim comes in a handy-dandy pen gizmo and is way more convenient than any of the other drugs.  It's also wildly expensive.  Here's the kit:


The blue case holds the injection pen; the cardboard box holds a cartridge of drug and some disposable needles for the pen.  When we open the case, the pen kit looks like this:


So you've got the pen, you've got some needles (in the little pink things), you've got a place to carry some sterile wipes --- all in a nice zip-up case.  How convenient!  Er, except that once the pen is loaded with drug, the whole shooting match has to be stored in a refrigerator.  Which makes it significantly less convenient, and sort of defies the whole point of the snazzy carrying-case.  Well, whatever. 

The pen itself is a lot like an ink pen with a reloadable cartridge:


So the piece at left is just a cap, liek the cap on any pen.  At top is the bottom of the pen; you stick the catridge in from right to left, then screw on the bit with the plunger.  The cartridge itself is the glass thing at bottom.  Close-up, it looks like this:


It's small.  Here it is loaded in the pen and held in my hand.  The cartridge is about the length of the last two digits of my pinky finger, and much, much narrower; it's maybe 5mm in diameter.  The list price for this 600 unit cartridge is more than $500.  The good news is, they do usually have some extra medicine in them; we got >700 units out of the first "600 unit" cartridge.


Once the cartridge is loaded in the pen, you need to put a needle on it.  The needles come in these little containers that look like miniature versions of the creamer containers at Denny's:



You take the paper top off (again, it's like a creamer container) and just screw the whole thing on the end of the pen:



Then pull off the creamer-container and an internal needle cover to expose the needle.  It's very small; this is not only a sub-q shot, it's one I haven't kludged together from old IM needles.



With the needle on, it's dial-a-dose: you turn the know on the end of the pen until the desired dose appears in the window.  We started out with a 125 unit dose; now we're up to 150.



Ready to go, the pen looks like this:



To use it, I stick it in Sarah's belly and push the plunger down with my thumb.  The dose injected is determined in advance by the dial-a-dose thingy, so it's stress-free (for me).  In the event that the cartridge runs out in the middle of an injection, it's no big deal; you just note on the dial how much drug was left to be injected, reload a new cartridge and needle, and finish the injection.  Of course, this means another stick, which Sarah doesn't care for.  But them's the breaks; given the expense of this stuff, you really really want to use every bit of it.

Menopur: A Photo Essay

So this is the "kit" for our morning Menopur injection:


It's actually very ad hoc, being an amalgam of new drugs and old (from the Ainsleigh cycle) paraphernalia. Clockwise from top left, we have: sterile alcohol pads to clean the vials and injection sites; the syringe, prepackages with a needle that's much too big and so never used; a Q-Cap (see below); the vials of medicine and diluant (ditto); and the actual needle we'll use (in the center).

This particular medicine comes as a powder.  I'm not totally sure why.  It seems likely that the drug is not stable in solution; both the Follistim and Lupron have to be refrigerated to keep from decaying, so perhaps the crystalline form can be stored longer and cheaper, saving the manufacturer and distributors money.  Also, this packaging makes the concentration of the injected solution adjustable.  When you buy solutions like Follistim, the only way to get a bigger dose of the drug is to inject a larger volume of the solution.  With the Menopur, you can get a larger dose by dissolving multiple vials of crystalling drug in a single dose of the saline diluant.  Of course, the flip side is that the volumes we're dealing with here are much greater; 1 mL of Menopur solution vs. 0.05mL of Lupron or some similarly small volume of Follistim.  So it seems like the stability thing is the most likely explanation.

In any case, the technique here is to use this little doodad called a Q-Cap to mix the saline solution (brown label) with the powdered drug (white label).  First, the needle that came with the syringe is removed and the Q-Cap screwed on in its place:


It's hard to see, but the Q-Cap has an outer shell that clips over the lip of the drug/diluant vial, and an inner spike that punches through the rubber top of the sterile vial.  So, the syringe clips over the vial like so:



One draws 1mL or so of the saline back into the syringe, then unclips the Q-Cap from the diluant vial:



and clips it to the drug vial:



Even the tiniest amount of diluant dissolves the drug powder completely:



the resulting mixture is then drawn back up into the syringe, and the Q-Cap unscrewed and discarded:



The injection needle is attached, and we're ready to go.



For scale, here's what the shot looks like in my hand:



Note that this needle is actally much too big.  The shot is subcutaneous, which is a fancy way to say it goes into the fat just under your skin.  For this the needle really only neds to be a half inch long.  However, we had these 1.5 inch needles laying around, and we're trying to cut costs wherever we can.  So we decided to just go with it.  My brilliant plan?  Only stick the 1.5in needle a third of the way in.  Presto, a half-inch needle.  How do you like them apples.

Anyway the shot goes lickety-split, but because of the volume it hurts Sarah more and causes more bruising.  The poor girl has quite the pattern of bruises across her belly, but she's hanging in there.

Stimulus

So, as of last Friday (June 11th) we've entered the stimulation phase of the IVF process.  The basic idea is: hyper-stimulate Sarah's ovaries so that a large number of eggs begin maturing.  Over a span of 10 days or so, the eggs develop rapidly; then, when they're just about to be released, the doc goes in and "retrieves" them for fertilization in the Petri dish.  More on that later.

During the stimulation phase, Sarah takes a combination of hormone injections.  In the morning, she takes Menopur, a so-called "menotropin", meaning a mixture of follicle stimulating hormone (FSH) and luteinizing hormone (LH).  Together, these hormones stimulate the development of follicles, the structures that house eggs as they develop and prepare for fertilization.  In the evening she takes a larger dose of FSH in the form of Follistim, and a smaller dose of Lupron, which as we discussed before is an LH agonist.

The process is monitored in two ways.  The first is easy to understand: Sarah has ultrasounds exams, in which a technician uses the ultrasound machine to look at her ovaries and count the number of follicles.  As the follicles get larger, the tech will not only count them but measure their size.  The ideal result from one of these exams is a finding that:

1.  there are lots of follicles;
2.  they're bigger than they were in the previous exam; and
3.  they're all about the same size.

This is all very intuitive, right?  You want lots of eggs to fertilize; you want them to be growing and maturing; you want them all to be ready at the same time. So, what's ready?  Well, we're looking for the follicles to grow to somewhere right around 2.0cm in diameter.  If you're big like me, that's about the size of your thumbnail.  If you're small like Sarah, it's more like the size of you big toenail.

In addition to the ultrasounds, Sarah has blood drawn regularly.  The draw is for an estradiol (E2) assay.  The idea is, we want to see E2 levels going up and up and up.  The slope of this curve tells the medical team that the eggs are developing on schedule.

So what do the words "frequent" and "regular" mean in this context?  Well, we went for a "baseline" ultrasound and E2 test on June 1st.  This was the low point in Sarah's cycle; it tells the docs what her ovaries and hormone levels look like sans stimulation.  On Friday the 4th, we started the stimulation phase: Menopur in the morning, Lupron and Follistim in the evening.  We went for the first blood draw on Monday the 7th.  Then we went for blood tests on Wednesday and Friday, and we go again on Sunday.  The first ultrasound was on Wednesday the 9th; we had another Friday and will have a third on Sunday. All told, then, "frequent" means: at least every other day.  As retrieval gets closer, it may become every day; it won't surprise me if after Sundays tests we're scheduled to go for more tests on Monday.

More on the results of these tests momentarily.