Tuesday, March 9, 2010

Caution: Science Ahead...

We get asked a lot about the process of IVF/ICSI and other fertility treatments and I guess I am not surprised that most people have no clue how involved, how expensive, and how emotionally draining it all can be.  I had no clue two years ago either, I was like everyone else.  Most people just say, "great...so when do you start that?"  No, no.  It's not that simple, at all.

First, you need the money.  I have mentioned this before but I will write another post about politics and insurance later.  Once you figure out how to pay for it, the other half of the battle is the actual process...

To understand the nuts and bolts of IVF, it helps to have a quick refresher of the ideal menstrual cycle. Cycle day one (CD 1) is always considered the first day of full flow. This is followed by several more days of bleeding as the lining of the womb (endometrium) is shed in the presence of low estrogen and progesterone levels.
The brain is able to sense the level of estrogen is low, and in response a hormone called FSH (follicle stimulating hormone) is secreted, causing several egg follicles in the ovaries to begin to grow and make estrogen. As the estrogen rises, the FSH falls and the follicles compete for the decreasing amount of FSH until only the strongest follicle is left.

This dominant follicle is ovulated at midcycle when it produces so much estrogen that it triggers the brain to send a large surge of LH (lutenising hormone). Once the egg has been released, the follicle becomes a corpus luteum and secretes progesterone (a hormone important in preparing the endometrium for a baby and supporting pregnancy, hence pro-gesterone).

The brain continues to send LH signals to keep the corpus luteum functioning until around 14 days post ovulation. If there is no pregnancy, then at this point the LH is withdrawn, the corpus luteum breaks down, estrogen and progesterone fall and the endometrium begins to shed. If pregnancy DOES occur, the HCG from the early embryo acts to keep the corpus luteum producing progesterone until the placenta is able to take over.
  • Down-regulation
Down-regulation is the first phase of a standard IVF cycle. It involves, usually, several weeks on the oral contraceptive pill to both prevent ovulation and control timing of the cycle. In the last week to two weeks of the time on the pill a drug of a type known as GNRH agonists will also be taken. Common examples of these drugs are Lucrin/Lupron and Synarel. Lupron is an injectible medication whereas Synarel is sniffed and they have different dosing frequencies per day, but the net effect is the same. They both cause the brain to release all it's FSH and LH stores and keep them depleted so that premature ovulation does not occur and stimulation can be precisely controlled. Without down-regulation, as you can see from the previous paragraph, there would be a risk of premature LH surge and ovulation (a bad thing in IVF) since IVF creates more egg follicles than the normal number and consequently higher estrogen levels.
  • Stimulation, a.k.a the dreaded needles. They're really not so bad. I have already practiced on myself while in lab for nursing school.  Many are subcutaneous, especially with the more modern drugs and come in fancy injection pens.
In the stimulation phase, the Lupron or Synarel continues to be taken daily, in order to prevent premature ovulation. At the same time, artificial versions of FSH are injected in order to stimulate the ovaries to make more eggs than usual. This dose can be adjusted based upon the results of blood tests and ultrasound scans during this phase of treatment to make sure enough follicles are going to continue with IVF but not so many that the woman is at risk of a problem known as OHSS (ovarian hyperstimulation syndrome). The average duration of this phase is 10-14 days. At the end of the stimulation phase, ovulation is artificially triggered using an injection of HCG (this can substitute for the natural LH surge because HCG and LH have similar structures and the same actions on the ovary). Because the timing of the trigger before retrieval is critical so that A: mature eggs are harvested, but B: are not ovulated and lost, it is important to follow your clinic's instructions precisely. The standard timing is to give the shot around 36 hours before retrieval.
  • Retrieval
This is the part of the process that involves a minor surgery, usually carried out under sedation. Using ultrasound guidance, a needle is passed through the walls of the vagina and into the adjacent ovary. Each follicle is aspirated, and the eggs are sorted out from the fluid by the embryologist. The whole process takes about half an hour. The eggs will then be mixed with the man's sperm, or injected into each egg with ICSI.
  • Transfer
Whether you have a day 2, day 3 or day 5 transfer largely depends on your country of residence, local protocols and is also influenced by the number and quality of embryos you have. As a rough guide, embryos should have about 4 cells on day two, 8 on day three and be a blastocyst by day 5. Pregnancy rates are higher for day 5 embryos than day 2 embryos as they are more likely to be genetically normal.

The transfer process itself is much like a pap smear, with a very fine catheter containing the embryo(s) threaded through the cervix and into the uterus. The embryos cannot fall out after transfer as they are tiny and settle into the endometrium.

  • Luteal support
Since there has been a down-regulation phase, the body will (if left to it's own devices) fail to support any potential pregnancy because there is little or no LH to stimulate the ovaries to make progesterone. Therefore, progesterone is given after transfer in one of several forms (via pessary into the vagina or via injection into the muscles of the buttock) until a blood pregnancy test is carried out around two weeks after transfer.  Most doctors will want to continue progesterone until the end of the first trimester.

  • Blood pregnancy test.
Piece of cake if you've cheated and peed-on-a-stick and got a positive result. Horrid if you know you're not pregnant.  This usually happens one week after transfer.
  • ICSI
ICSI is just like IVF except for some minor details (and a few more bucks of course).  It is a treatment for more serious male factor infertility where either very low sperm count, sperm motility or sperm shape/morphology (and sometimes all three) are present in a man and normal fertilization of an egg unlikely or impossible, even in an IVF setting. It involves the manual selection of a single sperm by micropipette and injection directly into a harvested egg. Before ICSI there was very little treatment that could be offered to couples with severe male factor other than donor sperm or adoption.   Men with very low sperm counts do still occasionally father a spontaneous pregnancy, but the rate is much lower than in couples where the man has a normal sperm count. ICSI greatly increases those odds.

2 comments:

  1. I started out with 36-40 follicles. It didn't take the standard 10-14 days to get mine to mature - it took 18! And the needles themselves don't hurt, but watch out if they prescribe you Follistim because that stuff stung like crazy!

    I also took progesterone suppositories for the first 12 weeks of pregnancy. Fun, fun!

    ReplyDelete
  2. You know, I've heard most of this before, but it is overwhelming to see it all laid out (so succinctly and articulately!) at once. This is quite an undertaking. I feel like my period makes me nuts sometimes, do these hormones do the same thing, or make it worse?

    ReplyDelete