Sunday, March 2, 2008

What Is In Vitro Fertilization?

In Vitro Fertilization is a high technology infertility treatment. Couples who have trouble conceiving, having failed to conceive for more than two years, often need to turn to a reproductive specialist who can evaluate and prepare them for this delicate procedure. With this procedure, most of the steps required to become pregnant are basically done outside the body in a specialized laboratory. The basic steps are as follows:

1. The ovary is stimulated to mature many egss. In a normal natural cycle, only one egg is matured an ovulated. With IVF, the goal is to have many, though not too many, eggs because the quality of eggs varies and we want to make sure we have at least one or two good quality eggs. The goal is not to have to repeat the IVF cycle again.

2. The ovary is evaluated by sequential ultrasound examinations to evaluate the response and measure the follicles. Follicles are what contain the eggs. They look like a black circle on ultrasound. The eggs are too small to be seen so we indirectly evaluate the egg by looking at the size of the follicle.

3. Once the follicles, that contain the eggs, are of appropriate size, indicating that the egg within is mature, the aspiration of the follicles is performed. This is a minor procedure whereby a needle is inserted through the vagina into the ovary under ultrasound guidance and the entire contest of the follicle, which includes the egg, is suctioned. Most clinics use some form of sedation for this because it can be painful. The eggs are aspirated into test tubes that the embryologist evaluates and isolates the eggs. These are then placed individually into petri dishes.

4. Sperm is either added to each egg (natural fertilization) or injected into each egg (ICSI) so that fertilization may occur. This will take 24 hours.

5. The eggs that fertilize are now placed into their individual petri dishes to allow for incubation. Incubation is done over a 3-5 day period. During this time, the fertilized egg will divide many times to evolve into a 6-8 cell embryo at 3 days or a blastocyst at 5 days. It's progress is monitored daily.

6. At 3 days from the retrieval or 5 days from the retrieval, the transfer is performed. The patient, with recommendations from the Physician, chooses which embryos to transfer and how many to transfer. These specific embryos are then isolated and placed into a very small and very flexible catheter in the embryology laboratory. The patient is placed into a transfer room, placed into the standard position for doing pap smears, and the cervix is prepared. The embryologist brings the embryo(s) into the transfer room and the Physician very gently slides the catheter into the uterus to a specific place. This location is verified by abdominal ultrasound examination. The embryo(s) is then deposited and the catheter gently and carefully removed. The embryologist will then take the catheter to the lab to verify that the embryo has not been re-aspirated.

7. The patient then takes medications to help support implantation of the embryo.

8. 8-12 days after the transfer, the pregnancy test is performed. If positive, we do pregnancy tests every-other day for four consecutive pregnancy tests. Since these tests measure the pregnancy hormone, BHCG, levels, we can see if the pregnany is progressing well by these four values.

9. If all goes well with the pregnancy tests, then the first ultrasound is scheduled in two weeks to confirm an intrauterine pregnancy and the number. This will be about 6 weeks gestational age based on the transfer date.

10. We then do a second ultrasound at 8 weeks gestation to verify a viable pregnancy.

At this point, the patient is then transferred to her Obstetrician to begin her prenatal care. For all infertility specialists this is a joyous occasion tempered by some sadness at not being able to follow the patient all the way through to delivery. When I began doing IVF, I was still practicing obstetrics and has the rare opportunity to deliver the babies that were conceived with our help. At this point in my practice career, I still do gynecology and I have much more time to focus on the infertility side of my practice as well. My patients benefit from still being able to receive gynecological advice as well as infertility advice.


I thought I would share my approach to the infertility evaluation. I have seen many patients referred to me, who have not undergone a complete infertility evaluation. Many physicians approach this haphazardly, checking some things but not others. Like other disease states, in order to find the diagnosis, all the different possiblities must be ruled out. In 30% of cases, there is more than one problem, and in 30% of cases it involves both the man and women. Therefore all these systems must be checked. There are basically 9 steps that are required to become pregnant. These steps are a sequence of events, such that, if there is a disturbance in any part of the sequence, then the entire process fails. These steps are 1. Brain sends signals (FSH hormone) to the ovary to begin the ovulation process, and the Ovary begins the maturation of the egg > 2. Ovulation occurs where the egg is expelled from the ovary into the culdesac > 3. The egg has to find the fimbria of the tube. > 4. The egg enters the tube where the sperm needs to be waiting, such that, the sperm needs to have proceeded from the vagina into the cervix, into the uterus then into the tube. > 5. The sperm has to fertilize the egg. > 6. The egg begins developing and dividing and passes through the tube (7-days). > 7. The formed embryo now enters into the uterus. > 8. The embryo has to hatch. > 9. the embryo has to implant into the lining of the uterus. The infertility evaluation that is recommended, checks each one of these steps and I've listed them with the respective step in the sequence:

1. Hormone levels on cycle day # 2 or 3. This is to test to see if the hormone levels, that the brain is producing, are normal at the start of the cycle. This can also give an indication of how the ovary is functioning and able to be stimulated. If the FSH level is elevated, it could indicate that the ovary is already beginning to slow down and/or approaching menopause. If the FSH is elevated, some physicians will proceed with a Clomid challenge test to see if the ovary is past the point where it can be stimulated by fertility medications. The only way to see if the ovary is maturing an egg is to do an ultrasound, in sequence, and see if a growing ovarian follicle is present. This is not usually done as part of the basic infertility evaluation.

2. Mid-luteal progesterone test on cycle day # 20-22. The progesterone level is increased when ovulation occurs, so this in an indirect test of ovulation.

3. Laparoscopy. Any abnormalities in the culdesac, the part of the female pelvis where the egg passes through and where the fimbriated end of the fallopian tubes sit, such as endometriosis or adhesions or tubal abnormalities, can affect the eggs ability to be picked up by the tube. The only test for this is laparoscopy, where a scope is inserted through the belly button to look inside.

4. Hysterosalpingogram. Sperm and egg get together in the fallopian tube. A hysterosalpingogram (HSG) is done to test if the tube is open. This is an x-ray test where a dye is injected into the uterus and passes through the tubes. X-rays are taken in various intervals to confirm that the dye passes into the pelvis.

5. Semen Analysis. We do not have a test to see if fertilization can occur. Therefore, we test the sperm as an indirect method to assess its potential. This is done with a semen analysis. In this analysis we test for the number of sperm, the number of sperm that are swimming (motility)-which is also a measure of the number of live sperm, and the number of normally formed sperm (morphology). This is not just a test of numbers. It is an indirect indication of sperm function. If there is an abnormality then this may indicate that the sperm may not be able to fertilize an egg. The only way to assess if your husband's sperm can fertilize your egg is to remove your eggs and put them together with his sperm, then see what happens. That cannot be done without in vitro fertilization.

6. There is no test for this step, but the HSG indirectly gives evidence that the tube is open and the egg has the potential to pass through.

7. Hysteroscopy. The uterine cavity is tested by a procedure called a hysteroscopy. In this test, a scope is passed through the cervix and the uterine cavity is visualized directly to make sure it is normal. I do this test in my office but most gynecologists do this test in a surgery center.

8. There is no test for this step.

9. An endometrial biopsy is done at the end of the cycle, just before onset of menses, usually cycle day # 26-28. The biopsy tells us if the uterine lining is developed adequately for implantation.

10. Pelvic ultrasound. I do one additional test, which is a pelvic ultrasound. This allows me to assess the uterus, especially the muscle layer and anatomy, the ovaries to rule out cysts and tumors, and if there are any adnexal abnormalities (the areas around the ovaries). Sometimes a dilated tube can be seen.


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