In Vitro Fertilization
IVF (In Vitro Fertilization) Overview
With IVF, oocytes (eggs) are retrieved from the ovary and placed in a Petri dish with active, motile sperm. Because fertilization occurs in the Petri dish rather than in the woman’s body, this process has been called “in vitro.” The eggs and sperm are maintained in a special culture media (nutrient fluid) within a controlled environment (incubator). If a fertilized egg is developing properly, it will consist of 6-8 cells at 3 days after egg retrieval. If an embryo is continuing develop appropriately, it will form a blastocyst by 5-6 days after egg retrieval. After embryos have developed in the laboratory for several days, one or more are selected for transfer into your uterus and if additional embryos are developing, they may be frozen to be transferred at a future time.
Step by step guide to IVF
Although the details of individual cycles will vary, all of the assisted reproductive technologies have similar steps.
- Pretreatment preparation
- Ovulation induction
- Oocyte retrieval
- Fertilization of eggs in the laboratory
- Embryo transfer
- Luteal phase
- Pregnancy test and pregnancy follow-up
1. Pretreatment preparation
After the decision is made to proceed with IVF, you will meet with a Registered Nurse and will receive a medication log and a calendar outlining the treatment. In many cases, oral contraceptive pills (OCPs) will be prescribed in the cycle, prior to active treatment. The purpose of the OCP is to reduce the chance that an ovarian cyst will be present at the time when we plan to start treatment and to allow flexibility in the timing of the cycle (the number of days on OCP can be varied).
Ultrasound. While you are on the OCP, you will have a Transvaginal ultrasound to assess whether there are any cysts present in the ovaries. In one commonly used protocol, you will begin a medication called Lupron (a GnRH agonist) while you are still taking the OCP. Your individual protocol may vary, and you may be prescribed a medicine other than Lupron (such as a GnRH antagonist called Ganirelix or Cetrotide) to prevent premature release of the eggs.
Uterine screening. If you have not had an evaluation of your uterus within the last year, your MD may recommend a screening test as a hysteroscopy or a saline infusion sonography to be done while you are taking the OCP. You will be given more information about any procedure that will be recommended.
Backup semen sample. In some cases a semen sample is obtained, frozen, and stored as a “back-up” specimen available on the day of egg retrieval. Please inform your MD or RN if you anticipate any difficulty in collecting a sample on the day of the retrieval so that you can arrange to have a back-sample frozen ahead of time.
2. Ovulation induction
Success rates with reproductive technologies (ART) are improved if multiple mature oocytes are available for retrieval. In order to mature a group of eggs, medications are administered by subcutaneous injection on a daily basis. The medications are in a class called gonadotropins. Some of the commercial names are Follistim, Gonal-F, Menopur and Repronex.
Baseline Ultrasound. Your baseline ultrasound will be performed before starting the gonadotropin. Occasionally you may have an ovarian cyst at this time. If you have a cyst, it often disappears with continued Lupron treatment, or less commonly your MD might recommend aspiration of the cyst. If the baseline ultrasound is normal, you will begin gonadrotropin injections. This medication will promote a group of several follicles (the sacs of fluid which contain the microscopic eggs) to develop together. Ideally about 10-12 follicles develop, but the response is quite variable and you may produce only 2-3 follicles, or as many as 20-30. The dose of medication you will receive is based on a prediction of how your ovaries will respond based on your age, your baseline FSH and estradiol levels, and any previous ovulation induction experience.
When you begin the gonadotropin medication, it is important to not pursue intense physical exercise (kick boxing, jumping, etc.) because such activity could cause discomfort and twisting of the ovaries. The gonadotropin injections have some risks and side effects which are discussed in detail in the medication information and in consent forms that you will be given. Most women taking gonadotropin injections for IVF will feel a sense of fullness in their ovaries. Risks include ovarian hyperstimulation syndrome (OHSS) and multiple birth (particularly if multiple embryos are transferred). There has been some concern regarding the possibility of increased risk of ovarian cancer with the use of fertility medications. However, more recent studies have overall been reassuring.
Timing of hCG. When ultrasound examination suggest that the eggs are mature (usually when the lead follicle size is about 18 mm in diameter), you will be asked to take an injection of human chorionic gonadotropin (hCG). The timing of the hCG is critical, so you need to take it precisely at the time given to you on the schedule. Once you take hCG, your gonadotropin and GnRH agonist or GnRH antagonist will stop.
3. Oocyte retrieval
Approximately 35 hours after the hCG injection, the egg retrieval will be performed under sedation. Intravenous medications will be given to prevent discomfort during the procedure. You will be asked not to have anything to eat or drink after midnight the night before the egg retrieval. If you are taking medications for any other reason, talk to your MD or RN about taking medication prior to retrieval. Once you receive the intravenous medication, the vagina will be cleansed with sterile water. A needle will be placed through your vagina and into the ovary, under ultrasound guidance. Most women will not feel this procedure at all due to the effects of the intravenous medications. The follicular fluid (which contains the eggs) from the follicles in your ovaries is collected in test tubes and passed to the embryologists in the IVF laboratory. The egg retrieval takes approximately 20-30 minutes.
After the procedure is completed, you will be transferred to the recovery room to rest for about an hour. Risks from the egg retrieval include pain, infection in the pelvis and ovaries, injury to the bowel, bladder, uterus, ovaries or major blood vessels. Since the procedure is done under ultrasound guidance and the needle can be seen on the ultrasound, the chance of serious problems is extremely small.
On the day of egg retrieval, you will need to have someone available to drive you home (you cannot drive on the day of egg retrieval due to the intravenous medications that you will be receiving). You should not plan to do any work on the day of egg retrieval. Many women do return to work the next day, while others also rest the day following the retrieval. You may feel some pelvic heaviness or soreness and cramping. It is okay to take Tylenol, but you should avoid ibuprofen (i.e. Advil, Motrin). Often there is a small amount of spotting. Your bleeding should be less than a normal period. We recommend that you avoid immersing yourself in water (avoid swimming, take showers rather than baths, avoid vaginal intercourse) from the day of the retrieval for several days to allow the vagina to heal.
After the procedure, you will be given complete written instructions and phone numbers. It is important to know that your ovaries are still enlarged immediately after the egg retrieval and that they remain enlarged for the next several weeks. For this reason, avoid heavy lifting or vigorous exertion such as running or aerobics until they return to normal size (which occurs either at 6-10 weeks into the pregnancy or with menses if pregnancy does not occur). It is okay to take stairs slowly, and walk short distances, less than a mile. Avoid any vaginal creams, lubricants, or spermicides other than the progesterone that is prescribed. Avoid hot tubs and Jacuzzis. Avoid intercourse until advised by your physician. If you travel, give yourself twice as much time as usual and minimize stress.
Semen sample. Your partner will give a sperm sample the day of the egg retrieval. It is recommended that he abstain from ejaculation for 2 days (48 hours) to 5 days before giving the sample.
4. Fertilization of eggs
Once the eggs are retrieved and placed in the incubator, they rest for several hours before the sperm is added, usually in the afternoon of the egg retrieval. Addition of sperm to the culture media is called insemination, and is followed by fertilization, when the sperm enters the egg. Fertilization can also be accomplished by ICSI (intracytoplasmatic sperm injection). ICSI will be recommended if your physician suspects that there will be a significant chance of no fertilization or a low rate of fertilization with conventional insemination of the oocytes in the laboratory.
We will call you the day after retrieval to let you know how many eggs have fertilized. It is important to understand that all the embryos may not be able to be observed on that day and that of those that are seen, they may not continue to grow. The embryo can begin cleaving, or dividing, first into two cells, then into four. Cleavage to four cells generally takes 36-48 hours or more after the egg retrieval. After 3 days, an embryo which is growing properly will have 6-8 cells. An embryo should reach a blastocyst stage at 5-6 days after retrieval.
5. Embryo transfer
Three to five days after the oocyte retrieval you will be scheduled for your embryo transfer. Your physician will recommend which day is most appropriate for you. In general, blastocyst transfer is recommended when there are a large number of embryos of good quality, or for couples desiring only a single embryo to be transferred. Your physician will give you a recommendation regarding the number of embryos to be transferred based on your age, your history if you have had IVF performed in the past, and the quality of the embryos.
Abdominal ultrasound is used to guide the transfer. To perform the transfer, your physician will place a speculum in the vagina and the cervix will be rinsed with a sterile solution. The embryologist in the laboratory will load the embryos into a small catheter and your physician will ease the tip of the catheter through the cervix into the uterus. You may have a sensation or twinge as the catheter passes through your cervix or you may not feel anything. For this reason, anesthesia is not used for the transfer.
On the day of your transfer wear comfortable clothing and socks to keep your feet warm. Your bladder should feel full, but not very uncomfortable. A partially full bladder often will allow the transfer to be completed more easily and will allow a better picture on the abdominal ultrasound.
We suggest that you rest the day after the transfer, to allow yourself time to relax as much as possible. Also, your ovaries will still be enlarged and activity should be minimized as described above to prevent ovarian discomfort. However, it is important to know that nothing you will do, such as walking or going to the bathroom will cause the embryos to dislodge from the uterine wall. The main factors that determine whether an embryo will implant are the viability (“health”) of the embryo and the quality of the uterine lining. Healthy embryos will be much more likely to implant and develop than embryos which are not viable.
6. Luteal phase
You will take progesterone by injection and/or vaginal suppository gel because it has been shown that progesterone supplementation increases the chance of success with IVF. Progesterone is the natural hormone that your body produces to support the uterine lining and maintain an early pregnancy. Although the FDA requires the drug manufacturer to include warnings about using progesterone in early pregnancy, this is due to the fact that progestins (a synthetic progesterone-like substance) or high doses of progesterone in animal experienced have raised concerns. However, you will only receive progesterone, the same natural hormone your ovaries produce, in a dose that is not excessive. After the egg retrieval, you will receive your first dose of progesterone. You will continue this daily for the next two weeks according to a schedule you will receive. This schedule will include the dose you should take.
As noted above, it is common to have a sensation of heaviness or cramping in your pelvis 4-10 days after egg retrieval. Your ovaries frequently enlarge at this time. If you are gaining weight rapidly (more than a pound a day) which can occur due to fluid retention, or if you are not urinating the normal amount for you, or if you have any other concerns, please call. Light bleeding sometimes occurs in the weeks following egg retrieval, even if there is a normally developing pregnancy.
A pregnancy test will be performed approximately two weeks after your egg retrieval. Waiting for your pregnancy test is a difficult time. It is not unusual to have symptoms of pregnancy that come and go due to the hormonal changes with IVF. The only way to know whether or not you are pregnant is by the pregnancy test done two weeks after egg retrieval. Bleeding may occur even if a pregnancy is developing normally. Please continue to take the progesterone that is prescribed until your pregnancy test, even if you think you may not be pregnant. Because the hormones that you are taking may confuse the symptoms that you have come to recognize as signs that you may or may not be pregnant, try not to guess or do home pregnancy tests before the blood test. They may not be accurate.
If the first test is positive, you will be asked to return for a follow-up test 2-3 days later to see that the level of the hormone hCG is rising appropriately. Hopefully you will receive good news and find out that the pregnancy test is positive and have follow-up as described below. If unfortunately you are not pregnant, you will be instructed to stop the progesterone and expect a period within 2-5 days (you should call us if a menses does not occur within about 5 days of stopping progesterone). If you do not conceive, you may find it helpful to schedule a follow-up visit with the MD to occur about 2 weeks after your pregnancy test results. This visit is important so we can counsel you regarding your next steps. Another cycle of treatment can begin as soon as one month after a failed cycle.
Pregnancy
Hopefully, you will be pregnant, and an ultrasound will be scheduled 4-5 weeks after your egg retrieval. The ultrasound will be done again 2 weeks later (6-7 weeks from retrieval). We will then refer you to your obstetrician for the remainder of the pregnancy. You will remain on progesterone until 8-10 weeks from your retrieval. We truly look forward to hearing from you when you deliver your child.