In order for a pregnancy to occur, an egg has to be released from the ovary and unite with a sperm. Normally this union, called fertilization, occurs within the fallopian tube, an organ which joins the uterus (womb) to the ovary. However, during the process of IVF this union occurs in a laboratory after both eggs and sperm have been collected. The fertilized eggs are then transferred to the uterus to continue growth.

There are six major steps in the in vitro fertilization process. All of these are done on an out-patient basis:



1. Stimulation and monitoring of the development of ripening egg(s) in the woman's ovaries.
   
   
2. Collection of the eggs.
   
   
3. Collection and preparation of the sperm sample (ejaculate).
   
   
4. Incubation of the egg(s) and sperm together in the laboratory, to allow for fertilization and early embryo growth. If the sperm are of poor quality, fertilization is facilitated by injection of sperm into egg using micro manipulation techniques (ICSI).

5. Transfer of the embryo(s) into the uterus.

6. A two-week wait for a pregnancy or menstruation.

  IVF STAGES IN DETAIL:

Stimulation of Egg Development:

Fertility drugs are given to control the timing of egg ripening and to increase the chance of collecting more than one egg. At the GOAL Program, we will generally employ a combination of drugs to induce the growth of multiple egg follicles. This process is called "super-ovulation".

The drugs most commonly used, GnRH agonists and menotropins are taken by daily injection. GnRH agonists are a medication used to "switch off" the patient's own hormone signals in order to prevent them from interfering with the super-ovulation process. Menotropins are a medication which consists of the natural follicle stimulation hormone (FSH) that stimulate the ovary to produce egg containing follicles. IVF nurses will teach you to administer some of the medication yourself by injection or nasally spray.

Soon after menotropins treatment has started, the growth of these follicles must be monitored carefully by daily blood hormone levels and ultrasound testing. The daily blood tests will be used to monitor Estrogen levels (a hormone produced by the follicle) and commence at menotropins Day 4 or 5. Ultrasound (a diagnostic procedure which uses sound waves to produce pictures of the ovaries) will be used to assess the growth of follicles by observing their increase in size. The ultrasound technique used for this process at the GOAL Program will involve the gentle placement of a round probe into the vagina for a short ultrasound scan. (see fig. 1.) Results of these tests will allow the physicians to make the necessary medication adjustments in order to get the best follicle development.

Occasionally treatment may have to be cancelled during this process if the ovary does not respond. If this occurs, a different protocol and/or starting dose of menotropins will be employed for the next IVF attempt.



Egg Retrieval:

After at least 3 follicles have reached a diameter of 17 mm size on ultrasound, another hormone called HCG (Human Chorionic Gonadotropin) will be administered. This hormone initiates the final maturation of the eggs. HCG is given late in the evening with the egg retrieval (OPU) scheduled about 34 hours later.
Example: April 14, HCG at 11:00 pm,
April 16, OPU at 9:00 am.

Patients are asked to come to the GOAL Program one hour prior to the scheduled egg retrieval. The woman is asked to change into as hospital gown and an intravenous line will be started by one of the IVF nurses. A tranquillizer will be given into the intravenous line prior to the procedure. This will make you relaxed and drowsy but will not put you to sleep. An intravenous antibiotic is also given to prevent infection. The cervix is frozen with a local anesthetic and you will be given medications to reduce the pain of the procedure.

The procedure used for egg retrieval at the GOAL Program employs the same vaginal ultrasound probe that was used for follicle monitoring. An aspiration needle attached to the ultrasound probe will be advanced through the vagina and into the follicles of the ovary. The follicle fluid and eggs will be aspirated into a test tube (figure 2). The fluids are then handed off to laboratory personnel who will look at the fluid and search for an egg. After egg retrieval, the woman goes to a recovery area and may leave 2 hours later after the effects of the sedatives have worn off.

As eggs are found they will be examined under a microscope. Each egg is then cultured for another 4 to 6 hours, until fully mature in its own plastic dish containing a special growth fluid (media).



Sperm Collection:

When applicable the male partner will be asked to produce a semen sample by masturbation shortly after the egg retrieval. In men who do not produce sperm in their ejaculate, sperm will have to be retrieved from them (MESA or TESA) which can be arranged at the Goal Program. Men who have poor sperm quality or low numbers of sperm may have their sperm injected into the eggs using micro manipulation techniques (ICSI). Donor sperm may be used as an option to be discussed and arranged by one of the IVF physicians prior to starting the IVF treatment.



In Vitro Fertilization:

After a process, in which the sperm are separated from the semen, each mature egg is mixed with a proper number of sperm (usually about 50,000). If the sperm are of poor quality, fertilization is facilitated by injection of sperm into egg using micro manipulation techniques (ICSI).

On the following morning, eggs are examined under the microscope. Fertilization will be evident by the entry of sperm whose genetic material will be seen as a small area in the egg, termed the male pronucleus. Similarly, the egg's genetic material forms a female pronucleus. These two pronuclei fuse and the fertilized egg then begins to divide becoming what is now called a preimplantation embryo (pre-embryo).



Embryo Transfer:

If fertilization is successful the pre-embryos will then be transferred into the woman's uterine cavity. A maximum of three embryos will be transferred for women less than 35 years of age and four embryos for women 35 years or older.

This transfer technique is accomplished by placing the pre-embryos (in a small droplet of culture medium) inside a fine plastic tube (transfer catheter) which is then inserted into the uterus through the cervix during a vaginal examination (figure 3). The process lasts only a few minutes. Afterwards we will ask the patient to rest for two hours following which she can return home and is requested to take it easy for 1 or 2 days.



Embryo freezing and Cryopreservation:

Couples who have more good embryos than they can use may have the "extras" or "surplus" frozen for their future use, provided they have signed appropriate consents PRIOR to starting their IVF therapy and have paid the necessary fees for the procedure.



Follow-up:

If there is no menstrual bleeding 17 days after the embryo transfer, a blood test for pregnancy will be arranged. If the test is positive, an ultrasound examination will be arranged within the next two weeks. Once ultrasound confirms the presence of a healthy pregnancy, the IVF physician will discuss plans for pregnancy care with you.

For those who live at a distance from Ottawa, telephone follow-up visits may be arranged.

  SUCCESS RATES:

Normal Human Reproduction:

Many people are surprised to realize that normal human reproduction is a relatively inefficient process. In a healthy couple, the probability of fertilization for any particular exposure of egg to sperm may be as high as 80%, but by the time of the first expected menstrual period after ovulation approximately one-half have miscarried. The menstrual period may not even be delayed and the couple not even realize that an early pregnancy has been lost. If a menstrual period is actually missed, as many as one-fourth of these pregnancies end in miscarriage. Thus, the probability of a live birth after properly timed intercourse through one menstrual cycle in a normally fertile couple is thought to be no higher than 20%.



IVF Cycle:

It must be acknowledged that problems can and do arise at any point during the In Vitro Fertilization process. To date the rate of live births (per treatment started) following IVF in well established and reputable clinics are about 20% per treatment cycle. Success rates at the Goal Program have been better than reported by the average IVF clinic.

With these data, it must be emphasized that successful conception and childbirth cannot be guaranteed by an IVF Program, even if the couple undergoes multiple attempts. The probability of success depends on many factors including: the woman's age (success rates are much lower when over 38 years old), addictions (alcohol, smoking) and ovarian response to the stimulating medications.



Problems during IVF:

Problems which may arise during IVF treatment include:


A poor hormone response to the medication. If this happens treatment will be terminated before follicular aspirationcan take place. This causes IVF to be delayed to a later cycle (up to 3-6 months).



The inability to obtain eggs due to the poor quality of the follicles or difficulties in egg retrieval.



The retrieval of poor-quality eggs, which are not suitable for fertilization.



Poor quality sperm the day it was collected, even if the samples taken previously were satisfactory. In order for the sperm to be of optimal quality, the man should not ejaculate in the 2 days prior to the retrieval. Collection of sperm must be as clean as possible, hand and penis must be carefully washed and rinsed with water before collection.



Fertilization may not result in the development of an embryo, in which case no transfer will take place.

Implantation may not occur. In such a case, you will have your period 12-15 days after embryo transfer.



Miscarriage may occur after pregnancy has been confirmed.

A tubal pregnancy may occur which may require medical and/or surgical treatment.

Injections:

Medication injections can cause some local irritation and repeated blood testing can be associated with mild discomfort and bruising of the arm.



Medications:

The "fertility drugs" may over stimulate the ovary and cause some pelvic discomfort due to the formation of ovarian cysts. Rarely, (in 2 - 3% of women) these drugs can cause so much ovarian over-stimulation that hospitalization and medical therapy is needed.



Egg Retrieval:

The ultrasound egg retrieval procedure presents a rare possibility of infection or injury to abdominal organs or blood vessels. Although pain medicine (intravenous narcotics and local anesthetic) is given, some discomfort will be experienced during the egg retrieval process.



Embryo Transfer:

The transfer of 3-4 embryos not only increases the chances of a pregnancy but also increases the chance of multiple pregnancy (e.g., twins, or triplets). For this reason not all your embryos will be returned to you if there are more than 3 or 4 of them.



Fetal and Newborn Malformations:

IVF-ET does not increase the chance of an abnormal child being born. Hundreds of thousands of normal healthy children have been born worldwide form this treatment. Similar to normal conception, two to three percent of infants born from IVF have some malformation or abnormality.

  PSYCHOSOCIAL COMPONENT OF
  OUR PROGRAM:

  APPLICATION PROCEDURE AND
  PRACTICALINFORMATION:

A.) Preparation and Enrollment:

You must be referred to this program by a family doctor or gynaecologist. A simple letter of referral is requested.

The pre-IVF tests and information needed through your doctor are as follows:

Consent form

On the man:

Blood screening tests for hepatitis and AIDs (HIV) as well as a sperm test less than one year old.

On the woman:

Blood tests (to be done on the third or fourth day after the start of her menstrual flow) for: FSH, LH, estradiol, rubella, CBC and screening tests for hepatitis and AIDs (HIV).

Transvaginal ultrasound examination of the ovaries and uterus.

Cervical screening for Chlamydia trachomatis and recent pap smear.

Copies of reports of previous operations on the tubes, ovaries or uterus and/or laparoscopy reports. Copies of HSG xray or hysteroscopy reports.

Relevant history of medical problems and prior infertility tests/treatments.

Copies of the stimulation record sheets from prior IVF or superovulation treatments from other centres.

Once we have received all your documents, and accepted you into the program, an initial orientation visit with the IVF nurse will be scheduled. Both partners should attend. For patients who live at a distance from Ottawa, a telephone visit with our nursing staff can be arranged. During this visit any questions you might have will be answered. Interviews with the physicians, counselor and any necessary laboratory tests will be arranged if necessary (especially for out-of-Ottawa patients). Your first visit may vary in length (but usually lasts for 1 - 1.5 hours).




Ontario residents will not be billed for most medical, laboratory or counseling services as long as these services are paid for by the Ministry of Health (i.e.. if the cause of infertility is obstruction of the Fallopian tubes).
Out-of-province residents are charged for each IVF attempt.
In addition to fees paid to the Goal Program, all patients will be responsible for their drug costs. Patients are encouraged to obtain coverage for these drugs from an insurance company. For non-Ontario residents payment in full by a certified cheque is required before the initial interview with the nurse.




The Ottawa Civic Hospital is conveniently located in the west end of the city about 2 minutes from the Parkdale exit of the Queensway (Hwy 417). Parking is available at the Hospital. The GOAL Program is located in the 5th floor of the Civic Parkdale Clinic, 737 Parkdale Avenue, in the out-patient department of Obstetrics and Gynaecology. Affordable accomodations with or without kitchen facilities are available within walking distance of the Goal Program.