Monday, May 26, 2014

So how does this whole thing work anyway?

A lot of folks have been asking how this whole IVF things works so I figured I'd give a brief tutorial (as if I'm capable of that!) to let you know the drill.  We've actually done 3 different rounds of IVF with three different clinics.  While every protocol is different the process is typically pretty similar- though we definitely experienced some differences at our last clinic in St. Louis.   This post is going to be kind of science-y so if that's not your thing, feel free to skip it.

In general, when doing an IVF the goal is to retrieve as many quality, mature eggs as possible in the hopes that they will fertilize with your partner's sperm and create a healthy embryo.  The embryo is then transferred into the woman with the hopes that it will implant.  IVF stands for In Vitro Fertilization and refers to fertilizing an embryo by manually combining an egg and a sperm in a Petri dish.  However, there are a lot more steps that go into IVF than just the fertilization.

Step 1Baseline Ultrasound - At the beginning of your cycle (when a woman first gets her period) she goes in for a baseline ultrasound to get an AFC or Antral Follicle Count.  Your Antral Follicle Count is the amount of resting follicles that are present during each cycle.  Usually each follicle contains one egg.  In a woman's cycle at ovulation, typically one egg is released (sometimes two or more if fraternal twins, triplets or quads are conceived). During IVF, the goal is to stimulate the maturation of multiple follicles to increase the odds of success.  That whole ticking biological clock thing has to do with your AFC, because a woman is born with all the eggs she will ever have.  As a woman gets older, her AFC decreases.  Less eggs usually equals less chance of success, especially since not all eggs are normal and as a woman gets older, you guessed it, her chances of having normal eggs decrease.  However, even young women can have what is known as Diminished Ovarian Reserve (DOR) which means they might be 24, but have the egg supply of a 39 year old woman.  Thankfully, I always had the reverse. My AFC was usually quite good and we were often able to retrieve a decent amount of eggs.

Step 2: Stimulation phase-  Before stimulation happens, first you have to suppress your natural cycle to ensure that you don't naturally ovulate. This is done using something called a GnrH antagonist, usually in the form of a tiny shot called Lupron that is taken for about 10 days.
After a few days on the lupron, stimulation with fertility meds called gonadotropins commences. Depending on your protocol, you begin to take anywhere from one to four shots daily (sometimes twice daily) for about six to ten days.  You also begin getting monitored pretty closely, which means sometimes daily bloodwork and ultrasounds to determine if the follicles are growing properly and to make sure your estrogen levels don't get too high.  Medications will be tweaked based on the results of the u/s and bloodwork.  If you are not responding well to the medications (meaning the follicles just aren't growing) the cycle may be cancelled, or converted to an IUI. We actually had that happen to us once and it was really disappointing.  If too many follicles are growing too quickly,  there is always the risk of something called OHSS.(Ovarian Hyper Stimulation Syndrome) Mild forms of this mean bloating and discomfort, severe cases mean hospitalization.  I've had mild OHSS before and it wasn't fun so can only imagine what severe cases feel like.  This is an example of the last protocol I did for my retrieval in St. Louis.  Things were a little different there as the monitoring didn't start until Day 8.  I was a bit nervous about this as I usually went in for monitoring on day 4 with my cycles in Atlanta, but my cycles in St. Louis went surprisingly well so we were pleased.

Step 3: Trigger shot- After about a week on stimulation medication when the follicles reach maturity (about 18-20mm) you are ready for your trigger shot. This shot has to be timed perfectly and needs to be given exactly 36 hours prior to retrieval. When we were in St. Louis we were instructed to take our shot at 3am.  Nothing like getting woken up to get a shot in the ass!

Step 4: Retrieval- The next phase of IVF is the egg or oocyte retrieval.  The actual technique used to collect eggs for in vitro fertilization is known as an ultrasound-guided transvaginal aspiration. During this procedure, an ultrasound probe is used to provide a visual image of the ovary and the surrounding structures. Then, a very fine needle is inserted into the ovary. Through magnification of the ultrasound image, the physician can locate the individual follicles that contain mature eggs and apply gentle suction to remove the contents of each one, which is known as aspiration.  The whole procedure generally takes about  20 minutes and is done under sedation.   The average number of oocyte so retrieved is between 8 and 15.   I remember crying after I came to from my first ivf retrieval when I learned I had retrieved just 9 eggs.   Even though this fell within the average range, I was still disappointed because I had hoped for more.  Still, some woman retrieve far less and as they say, all it takes is one. 

Step 5: Fertilization-  At the end of the day, the number of eggs retrieved isn't as important as how many fertilize properly. Generally, 70% of oocytes will do so. On the day of retrieval, your partner provides a semen sample.  The semen is then put through a special washing process to separate he sperm from the other components of the semen and then the strongest swimmers are put in the Petri dish with the oocyte. In some cases, a process called ICSI (Intra-Cytoplasmic Sperm Injection) happens.  During ICSI, the embryologist will take a single sperm and inject it into an oocyte.  Then the waiting begins. First you wait to see how mature eggs were retrieved and of these how many fertilize normally.  Next, you wait to see how many of these will make it to Day 3.  By day 3, the cells have begun to divide and you will have 6,7, or 8-celled embryos.
Photo of a high quality day 3 human embryo at the 8-cell stage
6 cells are visible in this plane of focus
 During a fresh transfer, embryos may be transferred on Day 3 or Day 5, depending on embryo quality.  I still don't really get how all that works.  They typically say Day 5 transfers are better because they know that the embryo is strong enough to make it to the blastocyst stage, which is the stage right before an embryo implants. However, when you have a 3 day transfer they will tell you that an embryo fares best inside the uterus rather than in a laboratory ( if this is true, then why not always do day 3 transfers?)  I think they may just tell you an embryo does best inside the uterus to make you feel better if you end up needing a 3 day transfer.  Since not all embryos make it to blast (5days) if there aren't enough good looking embryos by day 3 , the lab will suggest transferring then rather than waiting till day 5 and risk losing all of them.   For various reasons, some folks will have a frozen transfer.  When this happens, you wait for the embryos to grow out to the blastocyst stage and then freeze them on either day 5 or 6.  In our case, after our first failed IVF, we did genetic testing on our embryos due to my age and history of miscarriage.  This involves taking a biopsy of one of the cells on either day 3 or 5, freezing the blastocyst, and then sending off the biopsy of the embryo to test for anueploidy (extra chromosomes).  When an embryo is frozen the transfer, known as an FET, (Frozen Embryo Transfer) occurs at a later date.   

This picture shows a high quality blastocyst embryo on day 5

Step 6: Transfer-  During a fresh cycle, the best looking embryos are transferred to the woman's uterus on either day 3 or day 5 depending on the quality.  The transfer is a quick and painless procedure done via catheter.  Depending on a woman's age, often more than one embryo will be transferred in order to increase the chances of success.  This is why so many IVF babies result in fraternal twins.  In these cases, at least two embryos were transferred and both "took".  Many people mistakenly refer to the transfer process as implantation and that is actually a pet peeve of mine.  Not all transfers result in implantation. In fact, only 30% do. We transfer with the hopes of implanting.  

Step 7: The 2WW- (Two week wait). After transfer, a woman takes medications to mimic her body's natural cycle.  In a natural pregnancy, progesterone is produced to help support the development of the fetus.  However, during IVF, your body doesn't initially produce progesterone on its own. Therefore progesterone supplements must be given, either via suppository in a medication called Crinone or via injections (PIO or Progesterone In Oil shots).  Estrogen is also given in various forms (oral, patch or injection).  During an FET, a woman begins priming her uterus with these supplements for weeks  prior to the transfer and continues taking supplements after the transfer occurs.  If you become pregnant, you stay on these supplements until about 10 weeks gestation, when the baby's placenta takes over progesterone production.   Typically, two weeks after the transfer you get bloodwork to give you a quantitative HCG or beta.  HCG is the pregnancy hormone and anything above a 5 indicates pregnancy.  Often, serial betas are given to determine if the pregnancy is viable as the number should  double every 48-72 hours. If the number is slow-rising or falling, this is usually indicative of a chemical pregnancy.  A chemical pregnancy is when implantation occurred but for whatever reason (usually an abnormal embryo) the pregnancy does not sustain. This is also known as a very early miscarriage. It was my chemical pregnancy of a genetically normal embryo that led us to our clinic in st Louis.  

When we were in St Louis, prior to the  2WW we had a 6WW which added another step to our process.  Our RE (Reproductive Endocrinologist) uses a special type of genetic testing that involves biopsying the embryo on day 3, growing it out to day 5 or 6, and then shipping the embryo biopsy off to Turkey for metaphase CGH testing.  The process is extremely laborious and takes 5-6 weeks for the results.  When we went to St. Louis we did what was called staggered IVF and embryo batching.  We did two embryo retrievals in the hopes of getting enough embryos to test.  Each time I retrieved a good amount of eggs (12) most fertilized properly (10) and we're still going strong on day 3 when they were biopsied.  Unfortunately, by day 5 and 6, only 2 embryos remained. This happened both cycles so we ended up with just four embryos that we were awaiting test results.   It was a looooooong six weeks and we were just hoping for one healthy embryo so we could have one more shot at a successful transfer.   We felt like we hit the jackpot when we finally got our results and learned we had three healthy embryos. That meant three shots at a baby and (gasp!) maybe even a sibling.

Unfortunately, while that FET did result in a pregnancy with perfectly rising betas,  we once again miscarried.  That is when we turned to surrogacy and found Ellen.  With our embryos still in St Louis we just had one extra step in our IVF process- ship our embryos to Atlanta.  This involved having one clinic ship a cryopreservation tank to the other for the safe transportation of the embryos.  Believe it or not, they are shipped via FedEx.  It just so happened that our embryo shipment was slated to occur during the Snowpocolypse of 2014.  I made sure to request a delay in shipment as this cargo was just too precious to be lost (I could just picture the plane being re-routed to Mexico due to ice storms in Atlanta and the embies being lost or melting during that process). Thankfully, they made if safe and sound to Atlanta are are just waiting to be transferred into Ellen's uterus!

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