Chapter 5: Focus on IVF
Since the first child was born after successful in vitro fertilization and embryo transfer (IVF-ET) in 1978, more than one million children have been conceived using this technology. IVF is a complex procedure designed to increase the likelihood of conception for couples where other fertility techniques have failed or are not possible. It involves multiple laboratory phases concluding in the insemination and fertilization of oocytes (female eggs). The embryos created by this process are then transferred into the female for implantation. Hopefully these fresh embryos survive and become healthy babies. Each stage of the process has risks that are outlined in the following sections.
Super Ovulation to Stimulate Egg Development
Super ovulation is used to stimulate follicular growth with the aid of hormonal medications. This process increases the number of eggs available for fertilisation and ultimately increases the chance for success during each cycle of IVF. The flipside to this concept is that the greater the number of embryos implanted, the greater the risk of multiple births.
Medications are required to stimulate follicular growth and enhance egg recruitment. Below is a list of medications commonly used for this purpose.
- Lupron (gonadotropin releasing hormone-agonist)
- Antagon or Cetrotide (gonadotropin releasing hormone-antagonist)
- Follistim, Bravelle or Gonal-F (FSH, follicle stimulating hormone)
- Repronex (combination of FSH and LH, luteinizing hormone)
- Pregnyl or Novarel (hCG, human chorionic gonadotropin)
The mode of delivery for these medications is via injection, either intramuscular injection or intravenous injection. As with most injections there are the following risks: tenderness, infection, haematoma, (blood clot underneath the skin), swelling and bruising at the injection site.
The drugs themselves may also cause side effects, such as allergic reactions, hyper stimulation of the ovaries and failure of the ovaries to respond resulting in the cancellation of the treatment cycle. During the stimulation phase it may be necessary to postpone or cancel treatment if the ovaries produce either too many or too few eggs in response to drug stimulation. When ovulation induction medications are used hormone levels of oestrogen and progesterone often reach elevated levels. When the oestrogen level becomes mildly to moderately elevated, side effects that may be experienced include, but are not limited to, fluid retention, nausea, diarrhoea, pelvic discomfort due to enlarged cystic ovaries, breast tenderness, mood swings, headache and fatigue.
Ovarian Hyper-Stimulation Syndrome (OHSS)
Serious health consequences can occur if the oestrogen levels rise excessively in the presence of externally administered ?-HCG. ?-HCG is administered to initiate the final stage in egg maturation. In ovarian hyper-stimulation syndrome there is excessive fluid retention especially in the abdomen and/or chest cavity, which can affect respiration. Thrombosis of arteries and/or veins (blood clots) may lead to stroke, embolus, or other potentially fatal complications. Abnormally enlarged ovaries, which have the possibility of rupturing or twisting (a surgical emergency) is also a potential risk.
These situations are dangerous requiring hospitalisation, and even emergent surgery. They are life-threatening conditions, which need to be taken extremely seriously. Monitoring for such conditions can be done through blood tests to ensure that hormone levels don't rise to dangerous levels.
Risks associated with blood drawing may include, but are not limited to:
- Pain at the site of needle insertion
- Tenderness or infection of the skin
- Bruising or scarring of the site of blood draw
- Development of a blood clot in the vein (thrombosis, thrombophlebitis)
Ultrasound to Monitor Follicular Growth
Intravaginal ultrasound is used to monitor follicular growth. The eggs residing within the follicles also mature in preparation for ovulation. The follicles enlarge as the eggs mature. Ultrasound studies are usually carried out frequently, until oocyte (egg) retrieval and are normally performed using a vaginal probe. There's no notable risk but they may cause discomfort especially closer to ovulation.
Multiple Pregnancies
Ovarian stimulation causes multiple follicles to develop, increasing the number of eggs and hence the chance for success increases. Multiple embryos also increase the risk of multiple pregnancies. Approximately 20-25% of IVF pregnancies are multiple. Most are twins, however triplets, and quadruplets are also encountered. A procedure called "selective pregnancy reduction" is offered in some clinics to reduce the number of pregnancies in such cases. This procedure is highly controversial, both ethically and morally. It involves the elective termination of life by injecting a substance, which causes the beating heart to cease.
Retrieving the Oocytes (Egg Retrieval)
Often called "egg collection", this procedure is usually carried out under transvaginal ultrasound guidance. During this process a needle is inserted through the vaginal wall into the ovaries. The ultrasound helps locate the follicles and the eggs are then "collected" through a special catheter which carefully siphons up the follicular fluid, and is deposited into a test-tube. Some patients may experience some discomfort during and after this procedure. This process takes 20-30 minutes and patients are usually discharged home within hours after the retrieval.
Risks of oocyte (egg) retrieval may include the following:
- Potential reactions from the drugs and procedures used in the administration of anaesthesia.
- Risks associated with the passage of the needle through the vagina(including infection, bleeding, inadvertent damage to adjacent structures including the intestines, bladder, blood vessels, urethra, uterus or ovaries)
- Formation of Adhesions within the fallopian tubes.
Collecting and Preparing the Sperm
The donor normally provides the semen sample via masturbation on the day of the procedure. It is a good idea to avoid ejaculation for a few days before to ensure volume and quality of the sperm donation. Some men find producing a sample difficult due to anxiety and expectation on the day. It is often possible to freeze a sample in advance as well. Testicular biopsy is another option which can also be used to extract sperm if the donor cannot ejaculate.
Insemination of Eggs and Embryo Culture
After extraction, the follicular fluid is processed to identify eggs and to prepare for insemination with the donated sperm. Normally all eggs collected will be inseminated with prepared sperm and incubated over night. The next day the eggs are examined to check for signs of fertilisation. If no eggs have been fertilised the eggs may be re-inseminated or intracytoplasmic sperm injection (ICSI) may be tried. If these additional attempts are not successful the eggs will be disposed off and treatment will have to be redone.
In cases of successful fertilisation the newly formed embryos are transferred to the womb. Progesterone is also administered to maintain "pregnancy like" conditions, within the female.
Side effects of progesterone may include, but are not limited to the following:
- Vaginal dryness
- Bloating, breast tenderness
- Depression, and mood swings
- Delay of menses
Natural progesterone should be used as synthetic components have been linked with birth defects.
Transferring Embryos to the Uterus
Within 3-5 days of successful fertilisation the embryos are transferred to the uterus through a small tube (catheter). This usually painless procedure is similar to a pap smear. The embryos are passed through the cervix in a fluid filled catheter and deposited near the top part (the fundus) of the uterus. The number of embryos transferred is dependant on the individual treatment plan and geographic location however a common amount ranges between 1-4 embryos. The trick is to maximise reproductive potential while minimising the risk for multiple births.
Subsequent to the transfer process there is a risk of the following:
- Mild cramping
- Tubal pregnancy (if the embryo displaces into the fallopian tubes)
- Bleeding
- Infection
A pregnancy test will be carried out 12-14 days after the transfer to confirm pregnancy. The levels of B-HCG will be continuously monitored for the next several days. These serial B-HCG levels provide valuable information with regard to the pregnancy. In normal conditions when pregnancy occurs, the B-HCG doubles every 48hs. In cases of ectopic pregnancy this doubling pattern is not seen.
