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In Vitro Fertilization (IVF)

WHAT IS IN VITRO FERTILIZATION (IVF)

In vitro fertilization has recently become an accepted clinical procedure for treatment of specific fertility problems not amenable to other forms of therapy. The procedure has been termed "the test tube baby program" by the media but simply stated, IVF refers to a process whereby a number of eggs are stimulated to develop in one particular menstrual cycle; these eggs are then retrieved from the ovary under ultrasound guided needle puncture.

The eggs are then transferred to the laboratory where they are fertilized with the husband's sperm and are allowed to develop in special culture medium. The embryos that result are then replaced in the uterus where they will hopefully attach and develop further.

THE TREATMENT CYCLE FOR IVF

One treatment cycle consists of a number of phases which together take approximately four weeks:

Stimulation of Follicles

Starting early in the treatment cycle a nasal spray (Synarel) will be used to achieve ovarian suppression. Multiple eggs will then be artificially stimulated to develop using hormonal injections. The exact protocol will be discussed with you and selected after your initial consultation session. While the eggs are developing within fluid filled follicles in the ovaries, you will be followed closely with blood tests to check the level of estrogen, and with ultrasound scans to assess the location, size and number of follicles. At a certain critical time, a single injection of Human Chorionic Gonadotropin (HCG) will be given to facilitate the final maturation of the eggs. Approximately 36 hours later the eggs will be retrieved.

Retrieval of Eggs

The retrieval can be performed in one of two ways: the original method required a general anesthetic during which a laparoscopy was performed; the current method uses an ultrasound guided needle puncture in each follicle which is usually performed with only some sedation rather than a general anesthetic. Most IVF retrievals are performed with ultrasound guided puncture.

The fluid that is removed from each follicle is examined in the IVF laboratory which is next to the procedure room. Any eggs that are identified are then set aside in special containers.

We have the ability to freeze extra embryos that result from the fertilization process. If you choose to have extra embryos frozen, as many eggs as possible will be retrieved in order to maximize the number of embryos available for both replacement and storage.

Fertilization in the Laboratory

A semen specimen is required from your husband shortly before the eggs are retrieved. He is therefore required to be in the waiting room of the IVF laboratory prior to starting your egg retrieval procedure. The semen specimen is specially prepared and thereafter approximately 50,000 to 100,000 motile sperm are added to each individual egg.

Fertilization can be confirmed on examination of the eggs one day after they have been retrieved. Once fertilization has taken place and the cells start dividing, they are then referred to as a pre-embryo and are usually ready for replacement in the uterus approximately 48 hours after the retrieval.

Intracytoplasmic Sperm Injection (ICSI)

The standard insemination procedure of in vitro fertilization (IVF) is to place the egg and sperm in a laboratory dish; however historically, this method to treat couples with male factor infertility has had relatively disappointing results. This has led to the application of intracytoplasmic sperm injection (ICSI), a technique allowing the microinjection of a single sperm into the cytoplasm of a mature egg (oocyte).

Male factor infertility is associated with abnormal sperm parameters. These include absence of sperm in the ejaculated semen sample (azoospermia), low sperm count (oligozoospermia), poor motility (asthenozoospermia) and increased abnormal morphology (teratozoospermia). Any on of these abnormalities in the sperm can lead to failure of fertilization or low fertilization rates from a standard IVF procedure.

ICSI can overcome these problems. A single sperm, independent of motility, morphology and developmental stage (sperm can be retrieved from testis and epididymis) can be used to fertilize an egg with high fertilization and pregnancy rates.

ICSI is a major advancement in the treatment of severe male factor infertility. It has increased choices for couples with severe male infertility that in the past may have used donor insemination. So far there is no evidence to suggest that ICSI increases pregnancy loss or birth defects. Like other centres, our centre uses the ICSI technique as the primary method of assisted fertilization.

Cryopreservation

Cryopreservation is a process whereby embryos may be frozen in a step-wise fashion using a computerized freezer. These embryos are then stored in liquid nitrogen at

-196 degrees Celsius for replacement in a subsequent treatment (cryo) cycle.

Embryo Replacement

Compared to what has gone before, the embryo replacement is a relatively simple procedure, ie. similar to a pap smear. With a normal semen analysis, approximately 70% of healthy eggs should fertilize to become embryos. In order to maximize the chances of success and minimize the chances of multiple embryos implanting, a maximum of three embryos will be replaced.

Luteal Phase Follow-up

We will know within two weeks of embryo replacement whether pregnancy has occurred. A blood test will be arranged whether you live in Vancouver or out-of-town. Hormonal support to encourage implantation is usually given in the form of natural progesterone. It is administered as a vaginal insert twice a day for at least two weeks after replacement. If the pregnancy test is positive, these suppositories will be continued for six more weeks.

You will be encouraged to rest at home, or at your hotel, the evening after the embryos have been replaced in the uterus, and to avoid strenuous exercise for fourteen days.

While there is no evidence that bedrest is necessary during this time, you are encouraged to take it easy for fourteen days after replacement.

If less than the expected number of eggs fertilize, you will be notified by telephone the morning after egg retrieval. Sometimes fertilization happens later than expected. A final check is made the following day and you will be notified whether to come in for embryo replacement.

OUTCOME

It should be realized that even in normally fertile couples the expectation of pregnancy occurring in any one menstrual cycle is only in the range of 25-30% at most. In our Program, the chances of a clinical pregnancy, when at least one or more embryos have been replaced, is approximately 25%. Once early pregnancy losses are subtracted, we are left with approximately 21% of cycles resulting in a live birth. Given this, treatment on the IVF Program may be very stressful from an emotional, as well as a physical and psychological point of view. One has to approach the cycle realistically, understanding the chances of failure, while at the same time being optimistic for a positive outcome.

The success rate depends directly upon the number of embryos available for replacement. The chance of getting pregnant is the same in patients with tubal factor, endometriosis, and unexplained infertility. In couples with a male factor problem, the important determinant is whether fertilization happens or not. Once there are embryos available for replacement, the chance of conception is the same as for other indications.

An important aspect in human reproduction that should be recognized by couples qualifying for IVF is that a certain percentage of naturally conceived pregnancies are complicated by genetic or other developmental abnormalities occurring at birth. Even with careful prenatal screening, including amniocentesis and ultrasound, it is not possible to exclude all abnormalities. Two to three percent of all naturally conceived pregnancies are complicated by some form of congenital abnormality such as a cleft lip or a heart abnormality.

There have been many thousands of babies born through IVF in the world. Very careful studies of these babies thus far has not demonstrated an increased incidence of abnormalities. In fact, the risk of an abnormality appears to be slightly less than that which is seen in the general population. Please let us know at the time of your consultation whether there is a family history of birth defects so we can arrange special genetic counselling to assess the risks of this repeating and plan any special testing to make an early diagnosis should pregnancy occur.

Should a pregnancy result, it is the experience of our Program that there is a 20% chance that this pregnancy could be multiple.

The miscarriage rate after in vitro fertilization appears to be the same as in nature, approximately 15-25%. Where the maternal age is 40 or greater, the miscarriage rate appears to be higher.

Even though embryos are replaced in the uterus through the cervix there is still a risk of tubal pregnancy ranging somewhere between 2-12% of those patients who do conceive. Patients at greatest risk are those who have tubes which are damaged and blocked at their distal ends especially when the tube is dilated with fluid. We should be in a position to detect a tubal pregnancy early and thereby deal with this complication as soon as possible.

SIDE EFFECTS

As mentioned previously, a combination of Synarel to achieve ovarian suppression, as well as hormonal injections are used to encourage multiple eggs to develop. You will be monitored very closely with blood tests and ultrasound to prevent the most serious side effects of these medications which is hyperstimulation. This is fortunately a very rare occurrence (less than 1%) with in vitro fertilization. The procedure of aspirating the fluid in each follicle seems to significantly decrease this complication.

Some patients may have mild nausea or occasional hot flashes. Towards the time that the eggs are ready for retrieval there may be some bloating and lower abdominal discomfort similar to menstrual cramps.

Recent research findings have suggested that the use of certain fertility agents may increase the risk of developing ovarian cancer by two to three times that of the general population. Although this risk has not been proven, it remains the subject of on-going research.

Failure to conceive is always disappointing and occasionally professional help may be required to assist with the resolution of the grieving process. Considerable stress can also be placed on marital relationships and as such, mechanisms of resolving this additional pressure should be discussed beforehand. Our Program has a certified Counsellor available should you wish to address any issues.

COSTS

The Program at U.B.C. is university-based and is a non-profit organization. The initial infertility assessment and testing is covered by the Medical Services Plan (MSP), but thereafter all costs are borne by the patient.

Click here to see a detailed breakdown of our Fee Schedule. Should the patient commence ovulation induction and, for whatever reason, the cycle be cancelled prior to retrieval of eggs, only the costs incurred up to that point will be charged.

If egg retrieval is performed, then the full cost of the cycle will apply even in the event of no fertilization and there are no embryos for replacement. The reason for this is that it requires more work on the part of the Gamete Laboratory when there is no fertilization, ie. additional checking and tests that are required to be performed.

The cost of the medications will obviously vary depending on the body's response but the range is somewhere between $2,000.00 and $4,000.00.

Approximately one in ten treatment cycles are cancelled before proceeding to retrieval of eggs because of a poor response in that particular cycle. As mentioned, the unused portion of the fee will then be returned.

PRELIMINARY TESTING

At the time of the consultation and medical screening appointment, certain blood tests will be performed on the wife to check the hormones relating to reproduction and to ensure that all is ready for pregnancy. These tests include haemoglobin, TSH, hormonal screening and a check for immunity to German Measles.

In addition, blood is drawn from both partners and a check is made to exclude antibodies to certain organisms that may pose a hazard to yourselves, your unborn child, or the members of the IVF Team. These include tests for antibodies against Hepatitis B & C and HIV (AIDS).

It is your right to refuse any of the above tests in which case you should contact us before coming in for a consultation as these blood tests results are mandatory before proceeding in the Program.

GENERAL INFORMATION

We would like to have both of you in the peak of health at the time of your treatment cycle. We encourage both partners to be non-smokers and to eliminate any unnecessary medications. It is also in your best interest to be eating a healthy diet and to avoid being either over or under weight. In addition, involvement in some form of exercise regime as discussed with your family doctor would certainly be advantageous.

Where the female partner will be greater than 35 years at the time of delivery, amniocentesis is available through the Department of Medical Genetics so that abnormalities of chromosomes can be detected.

Because of the labour-intensive nature of the IVF treatment cycle, the only way that a significant number of patients can participate in the Program is to utilize a team approach. You will be supervised by a group of IVF nurse clinicians during your ovulation induction period. The technical aspects of the cycle, such as retrieval of eggs and replacement of embryos is performed by a team of gynaecologists who have been specially trained.

Your infertility management so far has probably been supervised by a specialist of your choice and your experience has probably been that of a personal relationship under his or her guidance. Unfortunately, the only way that IVF can be provided to the numbers of couples that require it, is to utilize a team approach and the result is, therefore, a less personal experience as no single physician will be involved in all facets of your care.

The IVF procedure is very arduous with approximately a 21% chance of taking home a baby when at least one embryo is replaced. You should remember, as with all infertility investigations, that it is your right to bail out at any time without feeling obligated to either family or members of the medical team. There are alternatives including donor insemination for severe male factor problems as well as adoption.

There are also advantages to remaining childless and, in fact, a number of couples who would otherwise be fertile elect to do this on a voluntary basis.

In addition to the support provided to you both from all members of the IVF team, there are support groups available with members who have been through IVF treatment. For those couples who are having an especially difficult time, there is a mechanism for referral to colleagues who have more expertise in the area of psychology and psychiatry.

The start-up date for a treatment cycle will be some time within three months following your consultation appointment, or may be sooner depending on the patient volume and the number of patients already booked.

SUMMARY

It is hoped that this information package has been informative in preparing you for your consultation and examination session. We hope also that it explains the limitations of the IVF procedure in that at present our success rate is only one in four per embryo replacement. This should help people to be sure that they have exhausted all other avenues of treatment before attempting IVF. The procedure is traumatic emotionally, physically, and psychologically, not to mention the financial aspects.

During your initial visit to the clinic, both partners should be present. A detailed physical examination will be performed on the female partner only. Blood will be taken from both partners for various tests. A summary letter of your appointment will be forwarded to your referring doctors.

Ovulation induction and superovulation

Stimulation protocols are used to increase the number of eggs available for fertilization.

Medications and protocols

Hormones called gonadotropins (which are secreted by the pituitary gland) are used for ovarian stimulation. Follicle Stimulating Hormone (FSH) is the gonadotropin which stimulates growth and maturation of the follicle, the sac in which the egg matures. Preparations containing FSH commonly employed today are Puregon and Gonal-F which are pure forms of FSH. Other preparations are a mixture containing both follicle stimulating hormone and luteinizing hormone.

Additional medication is usually given with FSH to prevent ovulation from occurring before the egg collection procedure is performed. Preparations used for this purpose are the Gonadotropin Releasing Hormone Agonists (GnRHa); these agents prevent premature ovulation by preventing the natural secretion of luteinizing hormone from the pituitary gland. GnRHa are administered with FSH; they are given as a nasal spray or an injection beneath the skin surface. Recently, agents called GnRH antagonists have become available. These agents like the GnRH agonists, also act by preventing pituitary luteinizing hormone secretion.

Monitoring of the stimulation cycle is by blood tests and ultrasound scanning of the ovaries. The dose of FSH is adjusted daily based on the results of the blood test and the ultrasound. Once the stimulation with FSH is completed, the last injection called Human Chorionic Gonadotropin (HCG) is given to activate the final stage of oocyte maturation; egg retrieval is then scheduled. If the monitoring shows a poor response to the stimulation protocol the cycle may have to be canceled.

With careful monitoring the potentially serious complication called Ovarian Hyperstimulation Syndrome can be prevented to a large extent.

Donor Egg

The donor egg program at the BC Women's Centre for Reproductive Health is a “known” donor program. An egg donor can be either a close relative or friend of the recipient couple who is willing to have in vitro fertilization treatment without receiving any payment.

What are the criteria for an egg donor?

  • under 36 years of age
  • previous pregnancy and delivery
  • no major medical problems

What is required before a donor egg cycle?

  • referral from family doctor or gynecologist*
  • complete medical history and physicial examination*
  • psychological counseling*
  • scheduling

*for both the egg donor and recipient couple

What are the costs?

  • $1,000 for the initial consultation for the egg donor (this is non MSP covered)
  • $5,000 for the treatment cycle (includes services for both egg donor and recipient but not intracytoplasmic sperm injection, assisted hatching or daycare surgery fee)

Donor Sperm

Donor sperm insemination is a service provided at the BC Women's Centre for Reproductive Health

What is required before donor sperm insemination?

  • referral from your family doctor or gynecologist
  • complete medical history and physical exam
  • psychological counseling (for both partners if applicable)
  • selection of sperm donor

Where do the sperm donors come from?

The sperm used for donor insemination is provided by donors screened by commercial sperm banks who meet all the current Health Canada requirements.

 

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