Understanding In Vitro Fertilization (IVF)

IVF consists of the following stages:

  1. OVARIAN STIMULATION and MONITORING: The process of ripening multiple follicles/eggs to mature within the ovaries. This may require prior and/or concurrent suppression of the pituitary gland. This requires hormonal treatment, multiple office visits, ultrasound examinations, and blood tests;
  2. EGG RETRIEVAL: The removal of eggs by ultrasound-guided follicle aspiration from the ovaries;
  3. EGG FERTILIZATION and EMBRYO DEVELOPMENT: This process occurs within the IVF laboratory. In some cases, assisted hatching (AH) and intracytoplasmic sperm injection (ICSI) may be utilized;
  4. EMBRYO TRANSFER: With IVF, embryo(s) are transferred into the uterine cavity. Some of these embryos will have undergone assisted hatching. Embryos are usually transferred on day 2, 3, or 5 after retrieval;
  5. LUTEAL SUPPORT: The use of the hormone progesterone to help prepare the uterus for implantation and the early pregnancy;
  6. CRYOPRESERVATION (THE FREEZING OF) EXTRA EMBRYOS. This is to allow for the future use of extra embryos.

1. OVARIAN STIMULATION and MONITORING:

MONITORING - While patients are undergoing treatment, they will be monitored in our offices with ultrasound examinations, blood tests and physical examinations. Ultrasound is a safe procedure that is utilized to monitor the uterus and the ovaries. The blood tests are to monitor the woman's hormonal response to the medications.

OVARIAN STIMULATION (may include any or all of the following medications):

  1. ORAL CONTRACEPTIVE PILLS (OCPs) - The possible benefits include shortened use of ovarian suppressive drugs such as GnRH-agonists, decreased chance of developing ovarian cysts prior to starting gonadotropins and an improved ovarian response during ovarian stimulation resulting in better egg recovery.
  2. GnRH-AGONISTS (e.g.: LupronTM [leuprolide acetate]) - The desired effect is to prevent premature release/ovulation of the ripening eggs. Possible side effects of short-term use of GnRH-agonists include irregular vaginal bleeding and symptoms similar to menopause. The effects of GnRH-agonists are very short-lived and symptoms will cease after stopping the medication or after starting on gonadotropins. Another possible benefit of GnRH-agonists usage is an improved ovarian response resulting in better egg recovery.
  3. GnRH ANTAGONISTS (e.g.: AntagonTM [ganirelix acetate], CetrotideTM [cetrorelix acetate]) - The desired effect is to prevent premature release/ovulation of the ripening eggs. Possible side effects of short-term use of GnRH-antagonists include headache, nausea, pain at the injection site and an allergic reaction. Another possible benefit of GnRH-antagonists usage is an improved ovarian response resulting in better egg recovery.
  4. GONADOTROPINS (e.g.: FollistimTM, Gonal-FTM, MenopurTM, RepronexTM, BravelleTM) - The desired effect is to increase the number of eggs that mature resulting in better egg recovery. Possible side effects include ovarian cysts, ovarian enlargement, ovarian hyperstimulation syndrome, and pulmonary and vascular complications. Ovarian enlargement, which may be accompanied by abdominal distention, occurs in approximately 20% of those treated with gonadotropins. This usually regresses without treatment within two or eight weeks. A possible major side effect of gonadotropin stimulation is severe ovarian hyperstimulation syndrome. This occurs in less than 1% of patients receiving these drugs. The long-term risk of ovarian stimulation is unknown. A possible association between ovarian cancer and ovulation inducing drugs in infertile patients had been suggested in a few studies, but most do not show an association. Gonadotropins are administered by means of a subcutaneous injection.

2. EGG RETRIEVAL

This is performed transvaginally. Using ultrasound guidance, a needle is placed through the vaginal wall into each follicle in the ovaries. This is a surgical procedure that is performed under deep sedation, general or regional anesthesia. Complications are rare but may include bleeding, infection or injury to an adjacent organ such as bowel or bladder.

3. EGG FERTILIZATION AND EMBRYO DEVELOPMENT

On average, about 70% of mature eggs will be fertilized by "normal" sperm.

  1. Intracytoplasmic Sperm Injection (ICSI) is a procedure in which sperm are directly injected into the egg. This procedure is used primarily for men with poor semen characteristics. This is a substitute procedure when fertilization is thought to be less likely or unlikely to occur with routine IVF. Under a microscope, the eggs are studied because only mature eggs can undergo ICSI. Using the microscope, the mature eggs are injected with a single living sperm using a very fine glass needle. The risks of ICSI include damage to either the egg or sperm resulting in either lack of fertilization or death of the egg or sperm. On the average, the fertilization rate with ICSI is less than routine IVF so ICSI is not routinely performed on all couples undergoing IVF. ICSI is sometimes performed the day after egg retrieval, i.e., when fertilization with routine IVF does not occur. This is called "rescue ICSI" and both the fertilization rate and pregnancy rate are significantly less than when fertilization occurs within the first 16-18 hours after egg retrieval. It is possible with ICSI to pass some forms of male-factor infertility from the subfertile male partner to male offspring. It is not presently clear whether this procedure further increases the risk of birth defects. ICSI is sometimes performed when PGD (Preimplantation Genetic Diagnosis) is planned.
  2. Assisted Hatching - This process involves making a hole in the zona pellucida, the shell-like encasement that surrounds the cleaving embryo. Assisted hatching (AH) is performed on embryos just prior to day 3 transfers and in some anticipated blastocyst transfers and is thought to improve implantation and pregnancy rates. Complications of AH are rare and can include damage to the embryos that would decrease the embryos ability to implant and survive in the uterus. There is also information that assisted hatching is one of the causes of the increased risk for identical twins with IVF.
  3. Embryo Co-Culture - Studies have shown that embryo quality might be improved by culturing embryos along with various types of body cells. Reproductive Partners Medical Group, Inc. (RPMG, Inc.) uses the patient's own granulosa cells, the cells that normally surround a mature egg, as the co-culture cells. There is a very small risk of losing an embryo or embryos because the embryos can stick to or become hidden within the cells used in the co-culture. The benefit is a potential improvement in embryo quality and thus the chance of pregnancy.

4. EMBRYO TRANSFER

This is the process in IVF or with frozen/thawed embryos when the embryo(s) are replaced into the uterus. The number of embryos transferred varies and is determined by the chronologic age of the woman whose eggs are being fertilized, the quality and stage of embryo development and the woman's past treatment history. At times, however, there are no viable embryos so an embryo transfer is not possible. The transfer of multiple embryos can result in multiple pregnancies. Multiple pregnancies, e.g., twins, triplets or more are associated with an increased risk of birth defects and prematurity when compared to singleton pregnancies. Possible side effects of embryo transfer include uterine/tubal infection, cervical bleeding, cramps, backache, miscarriage and tubal pregnancy. The incidence of tubal pregnancy in women without infertility is approximately 1%. The incidence of tubal pregnancies in IVF is very similar. A tubal pregnancy will result in the loss of the pregnancy and the possible loss of the fallopian tube.

  1. Blastocyst Transfer - Typically, embryos have been transferred into the woman's uterus on the second or third day after egg retrieval. With blastocyst transfer, embryos are implanted that have matured for a total of five or six days in the laboratory. These embryos are called blastocysts. Blastocysts have an increased implantation rate per embryo so fewer embryos need to be transferred. Data indicate that women who have two blastocysts are at least as likely to achieve a pregnancy as are women who have three or more less-developed embryos transferred. Transferring fewer embryos has the marked advantage of reducing the chance of triplets and more. There is also information that blastocyst transfer is one of the causes of the increased risk for identical twins with IVF so the risk of triplets still exists, but it is in the range of 1%. Identical twins, especially when they are in the same gestational sac, have an increased risk for having complications during pregnancy, including but not limited to twin-to twin transfusion, poor growth of one of the twins, an increased risk for birth defects and stillbirth. A very rare complication of identical twining is conjoined ("Siamese") twins. Blastocyst transfers are recommended for most couples in order to maximize the chance of pregnancy with both fresh and frozen embryo transfers because it decreases the risk of triplet pregnancies without jeopardizing the pregnancy rate. There is a risk, however, that none of the embryos will develop/grow to this stage and, therefore, there would be no live embryos to transfer. In the instance that the personnel at Reproductive Partners Medical Group feels that there are an insufficient number of embryos on the second, third or fourth day after egg retrieval, then embryos will be transferred before they reach the blastocyst stage of development. Blastocyst transfer is also used when preimplantation genetic diagnosis (PGD) is performed, in order to allow enough time for the biopsied cell to be analyzed.
  2. Elective Single Embryo Transfer- Blastocyst transfer also allows the option of Elective Single Embryo Transfer. This is particularly helpful to reduce the chance of twins when twins would be more risky than usual, such as with a misshapen uterus due to DES exposure or other congenital uterine abnormalities, and in younger patients or patients using donor eggs where the risk of twins is higher. Any couple wishing to avoid the risks of twins may choose elective Single Embryo Transfer. If there is a high quality blastocyst, and particularly if there are two high quality blastocysts, the success rate with transfer of a single embryo is probably only about 10-20% lower than with two embryos. Single embryo transfer is very highly recommended for women undergoing egg donation who are 45 years old or greater and for one-parent families.

5. LUTEAL SUPPORT

Progesterone and estradiol are made by the ovaries after ovulation to both prepare the uterus for embryo implantation and then to allow the embryos the ability to continue to grow. The placenta of the growing embryo then makes both of these hormones. Egg retrieval may decrease both progesterone and estradiol production by the ovaries so these hormones are administered after the egg retrieval to make sure that sufficient amounts are present to allow for the embryo(s) to implant.

6. CRYOPRESERVATION (FREEZING) OF EXTRA EMBRYOS

A significant number of women will have more embryos than the physicians of Reproductive Partners Medical Group, Inc. recommend to be transferred in their IVF cycle. These extra embryos can be stored in a frozen state so that they can be thawed for later use. There is no guarantee that these embryos will survive the freezing process nor that pregnancy will occur after their thaw but on the average about 60% of embryos will survive the freeze/thaw process. At this time, there is no data that indicates that the risk of birth defects from frozen embryos is any greater than "fresh"/non-frozen embryos.

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