In Vitro Fertilization

IVF is the procedure in which eggs are taken out of the ovaries, fertilized in the lab, and then some of the resulting embryos are placed back into the uterus.  It has the best pregnancy rates of all of the fertility treatments, and it is the most expensive.  It can be done with a woman's own eggs or with an egg donor's eggs.  The partner's sperm or donor sperm can be used.

The first step in an IVF cycle is oftentimes birth control pills.  This seems odd to most women, since birth control pills are used to prevent pregnancy.  They do two key things for us, though.  By shutting down ovulation and letting the ovaries rest for a few weeks, we get a more uniform group of follicles (the sacs with the eggs).  The rest period also allows any Clomid or other fertility medications to get out of your system.  The second thing it helps with is timing.  I know that if I give a patient birth control pills and have her stop them on a Thursday, say, she will get her period on Sunday or Monday.  That is handy for timing cycles and giving everyone a good idea of when the different procedures are likely to be.  The birth control pills are usually taken anywhere from 2.5 to 4 weeks, but it can go even longer than that.  Sometimes estrogen is used instead of birth control pills, and some cycles are done without either.

Next comes the injections.  This usually involves a combination of medications including FSH with or without hCG, and a medication to inhibit ovulation.  The FSH with or without hCG is used to stimulate the ovaries to mature follicles/eggs and get them ready for ovulation.  These days, they are usually given under the skin of the belly once a day.  Common names for these medications include: Follistim, Gonal F, Bravelle, Menopur, Repronex, and low-dose hCG.  For a complete discussion of these medications, see the previous blog entitled "Injectables".  The medication to keep you from ovulating (those eggs are microscopic, if they get out of the ovaries, your doctor will not be able to find them!) can be given two ways.  The traditional way is with a medication called Lupron.  Lupron is an unusual medication.  Before it shuts down your pituitary's ability to trigger ovulation, it actually stimulates the pituitary.  This can be helpful or undesired.  If your doctor thinks you need a little extra boost in the beginning of the stimulation phase, then he or she can use the Lupron to get your pituitary sending out  your own FSH to supplement the FSH you are already taking.  This is called a flare or microflare protocol (depending on the dose of Lupron given).  The Lupron is usually started at the beginning of you cycle, right before the FSH medication is started.  The Lupron is then continued through the stimulation phase.  After a few days, the Lupron will turn from a stimulant to an inhibitor. So by the time your follicles are big enough to be at risk of ovulating, the Lupron is now inhibiting ovulation.  If the stimulation phase of Lupron is not needed, the Lupron is usually started while you are on birth control pills to get it out of the way.  The Lupron is then continued through the stimulation phase.  Another way to inhibit ovulation is with a newer group of medications that don't have the stimulation properties that Lupron does.  They simply shut down the pituitary's ability to trigger ovulation.  The advantage to this is that they can be given just for the last few days of  the stimulation phase.  The two medications used in this manner are called Ganarelix and Cetrotide.

You will be closely monitored with blood tests and ultrasounds every 3-4 days at the beginning and 1-2 days near the end of this stimulation phase to make sure your response is ideal.  The follicles and the lining inside the uterus will be measured to see how well they are growing.  As the follicles grow, they make more and more estrogen, so the estrogen levels in your blood will be monitored too.  Most centers will ask you to come in first thing in the morning, so that they can get the blood test results back the same day.  Hopefully, this will also keep the disruptions to your daily schedule to a minimum too. During this time you may feel full or bloated as the ovaries grow in size.  The mucus from the cervix becomes stretchy, and there is lots of it.  The higher estrogen levels can make you a little naseous, and you may feel like you have more energy.  Near the end of the cycle, a dull-achy sensation is usually felt in the pelvis as room becomes tight down there.   Once your doctor thinks the eggs are ready, he or she will ask you to take an injection of a large dose of  hCG.  This does a final maturing process on the eggs and gets them ready for fertilization.  This injection is often given into the muscle of the buttocks, although it is sometimes given like the others into the belly.  At this point, you are done with the FSH, hCG, and inhibiting medications.

The next thing that happens is the egg retrieval procedure.  This is usually done about a day and a half after the final hCG is given.  Anesthesia is given to make you comfortable and very sleepy.  Most centers use a combination of medications that will put you under enough that you should not feel or be aware of anything.  Once you are comfortable, an ultrasound probe is placed into the vagina.  The ovary is located on the ultrasound screen.  Then a needle is run along the ultrasound probe, through the wall of the vagina, and into the follicles in the ovary.  The fluid is drained out of each follicle that has developed that cycle, and the egg should come along with the fluid.  Once one ovary has been completed, the same procedure is carried out on the other ovary.  This usually takes about a thirty minutes, but definitely depends on how many follicles you have.  You will feel sore afterwards, and perhaps a little crampy too.

Once the fluid has been removed from the follicle, it is handed to the embryologist.  This is the person who will be taking care of your embryos while they are in the lab.  He or she will look at the fluid under the microscope and find the eggs.  The eggs are then placed in petri dishes and the sperm is added.  If there is a  sperm problem, then ICSI (intra-cytoplasmic sperm injection) may be performed.  This is a procedure where a single sperm in injected into each egg to ensure that sperm and egg are getting together.  Later on, the eggs are checked for signs of fertilization.  Not all eggs will act like they are fertilized, even with the ICSI procedure.  The fertilized eggs are then kept in the incubators to grow and divide.  The embryologist will check on the periodically to make sure that they are dividing the way they are supposed to.  In this country, most embryos are allowed to grow 3-6 days before they are put back into the uterus, although there are special circumstances where they may be put back on the 2nd day too.  A procedure called assisted hatching may be performed prior to putting the embryos back.  There is a shell around the embryos called the zona pellucida.  The embryo must break out of this shell (hatch), before it can implant in the uterus.  Sometimes, especially in older women, this shell is too hard and thick for the embryo to break out.  This can keep you from getting pregnant, so we give those embryos a little help.  The embryologist will make a small hole in the zona pellucida.  This acts like a perforation does, it gives the embryo a place to start breaking out of the shell.  This is called assisted hatching.

The procedure to put the embryos back into the uterus does not require anesthesia, usually.  It feels a lot like a PAP smear does.  Your doctor may ask you to come in with a full bladder, which helps straighten out the uterus and makes it easier to see on ultrasound.  A speculum will then be placed into the vagina, and then a small tube called a catheter is passed through the canal in the cervix and into the uterus.  The embryos are then placed in the upper third of the uterus, which is where they like to implant.  This usually takes just a few minutes to do.  The embryologist may be present for this, and he or she will then check the catheter afterwards to make sure that no embryos remain in the catheter.

How many embryos are put back into the uterus at one time will vary.  Your doctor will take your age, medical history, and your embryo quality into consideration.  The American Society of Reproductive Medicine has  the following guidelines:  when transfering embryos on day 3, one to two embryos be transferred for women under 35,  two to three embryos for women 35 to 37, three to four embryos in women 38 to 40, and no more than 5 embryos in women over forty.  For embryos that are 5 or 6 days old (blastocysts),  no more than 2 be transferred in women under 38 and no more than 3 in women 38 and over.  The lower number for each age group should be used for good quality embryos. Extra healthy embryos can be frozen and kept for future use too.  Following these guidelines will help prevent disasters like the octomom from occurring. She was 33 at the time of her IVF cycle, and therefore should have had only one or two embryos transferred. 

During this period, your doctor may ask you to take a few other medications.  Antibiotics are often prescribed to prevent infection during the embryo transfer.  Some clinics use anti-inflammatory steroids, baby aspirin, and extra estrogen too.  Most clinics will also ask you to take progesterone too.  This is a hormone that your ovaries make after ovulation.  It tells the uterus to get ready for embryos to implant and keeps your period from coming until a pregnancy has a chance to declare itself.  When the fluid is taken out of the follicles to get the eggs, a lot of the cells that make progesterone come out too.  To keep you from getting your period too early, extra progesterone is therefore given.  There are several different ways to give progesterone, and more are coming soon.  The traditional way is with an injection that goes into the buttocks. It is reliable, but obviously not the most comfortable option.  There are creams and suppositories that go into vagina.  They are a less painful option, but can sometimes cause some bleeding of the cervix.  This can be distressing, especially if you are hoping to become pregnant.  There will also be a ring that goes into the vagina soon.

I think, and I have done 2 IVF cycles myself, that the hardest part of the IVF cycle is this next part:  the waiting.  You will have to wait about 2 weeks from the day the retrieval is done to find out if you are pregnant or not.  You can't cheat and do a test earlier, because pregnancy tests look for hCG.  Since you took a big shot of hCG right before the egg retrieval, a pregnancy test will come out positive afterwards.  Urine tests are not as accurate as blood tests, so your doctor will want to do a blood test.  Depending on which type of progesterone you are taking, it will probably keep you from getting your period.  So if you do see any bleeding, don't assume that it is your period and stop your medications.  About a third of normal pregnancies will have some bleeding in the beginning, so keep taking that progesterone and call your doctor!

If you are pregnant, your doctor may ask you to continue the progesterone through the first few weeks of prengnancy.  If you have extra embryos frozen, don't worry.  They will wait until you are ready for your next child.  There have been successful pregnancies with embryos that had been frozen for more than 10 years!