Stage 1: Ovarian stimulation and monitoring
At the beginning of your menstrual cycle the hypothalamus releases a hormone called gonadtrophin-releasing hormone (GnRH). GnRH in turn causes the pituitary gland to release a hormone called follicle stimulating hormone (FSH) to prepare an egg for release. When the egg is mature the pituitary gland produces another hormone called luteinising hormone (LH). This promotes the follicle to release the egg into the fallopian tube in the process known as ovulation. Follicles are fluid filled sacs in which eggs grow to maturity.
With IVF, certain medications are used to prevent an early release of eggs while other medications, which are synthetic versions of FSH, are used to stimulate the ovaries to develop more ovarian follicles. By having several mature eggs available for attempted fertilisation and transfer it is hoped that at least one will result in pregnancy.
In the ovarian stimulation phase, your ovaries are stimulated to produce more eggs than usual. You will take daily injections of luteinizing hormone (LH) and follicle stimulating hormone (FSH) for about 8 to 10 days. These hormone injections will stimulate your ovaries to produce several follicles, each of which may contain an egg. One of our nurses will teach you how to give the injections to yourself.
Two types of medication are used during this stage to suppress ovulation:
- Cetrotide is added in as a subcutaneous injection once the follicles reach about 14mm in size in the most popular protocol. This is known as the antagonist protocol and begins on the third day of menstruation.
- In the Long Course Protocol a medication called Lucrin is commenced subcutaneously from the twenty first day of the menstrual cycle to prevent ovulation of the stimulated follicles. Once the period begins the FSH and LH are commenced to stimulate follicle growth as in the other protocol.
During ovarian stimulation we use ultrasound to monitor your ovaries, and blood tests to measure your estrogen levels. Ultrasound scans are performed after five days of hormone injections to determine the number of follicles and the follicle size. Not all follicles contain eggs and the size of the follicle determines the maturity of the eggs. Usually the follicles are small at the first scan, subsequent scans and hormone injections will continue until the leading follicle reaches 18mm or more in size.
Ovulation Injection (Ovitrelle or Lucrin) – This injection is usually given at a specific time in the evening. Egg retrieval will then take place 36 hours or so after the ovulation injection.
You will have your ultrasounds and blood tests done at Medfem Fertility Clinic between 7:00 am and 9:30 am Monday to Friday, and between 7:30 am and 9:00 am on weekends.
Stage 2: Egg (oocyte) retrieval
Once the ultrasounds and blood tests show that you have a reasonable size and number of follicles, you will take an injection of hCG (human Chorionic Gonadotropin) to trigger final maturation of the eggs. Egg retrieval is arranged just prior to expected ovulation, usually 36 hours after the administration of the ovulation inducing drugs. Your doctor will try to retrieve as many mature eggs as possible.
Egg retrieval is done under local anaesthetic, most commonly by ultrasound guided fine needle. The mature follicles are identified using ultrasound, and then a needle is passed through the vaginal wall into the follicle and the fluid withdrawn from the mature follicle with gentle suction. The fluid is immediately examined under a microscope to see if an egg has been retrieved. The process is repeated for each mature follicle in both ovaries.
Not every follicle contains an egg so don’t be surprised if the number of eggs retrieved is less than the number of follicles you’ve been watching develop on ultrasound. The average number of eggs retrieved is between eight and nice and the retrieval process lasts approximately 20-30 minutes.
Most commonly, men will provide an ejaculated sperm sample for use, just before the egg retrieval procedure. In other situations, previously cryopreserved sperm, donor sperm or surgically retrieved sperm will be used for fertilisation.
How might you feel?
After the procedure some women may feel a little tender in their abdomen – a hot water bottle may help. You may also feel tired because of the anaesthetic. You will be monitored for a couple of hours before being allowed to go home. Following the procedure you may notice some light vaginal spotting. This is normal and nothing to worry about. It is recommended that someone drives you home from the clinic and you may need to take the following day off work because o of minor pain and fatigue.
Stage 3: Fertilisation and Embryo Development
About two hours before egg retrieval, a semen sample is collected from the male partner. Two to three days abstinence from intercourse is preferred prior to the sample collection day. The sperm is then processed to select the strongest and most active sperm. This is called sperm washing.
Extensive infection tests on both male and female are necessary before the IVF procedure to prevent the growth medium being contaminated. The dish with eggs and sperm are placed in an incubator, fertilisation will occur naturally.
The eggs are placed into a dish that has a highly specialised growth medium in place. The medium allows the eggs and later embryos to continue developing as they would in the fallopian tubes. The sperm are then placed with the eggs in an incubator set to the same temperature as a woman’s body.
One of our embryologists examines the eggs the next day for fertilisation. The eggs are examined under a microscope to determine whether fertilisation has occurred and you will be phoned about how many of your eggs have been fertilised. The resulting embryos will be ready to transfer to the uterus two to five days later.
If undergoing ICSI, the eggs are prepared for injection and their maturity confirmed. A single sperm is then placed directly into the cytoplasm of the egg – hence the name intra-cytoplasmic sperm injection. Fertilisation can then be identified in a similar fashion to IVF after about 24 hours.
If the sperm sample looks normal, we expect about 70% to 80% of the eggs to be fertilised. It is important to know that not every follicle will contain an egg, not every egg will be fertilised, and not every egg that is fertilised will go on to form a good-quality embryo.
During IVF, your embryos are cultured for up to six days in a temperature-controlled incubator. Every other day the embryos are evaluated for quality and development. This information is shared with the doctors to help determine the appropriate day for embryo transfer, which is typically day three or day five of embryo culture. Our embryologists will call you after each examination of the embryos to update you on the embryo quality and to answer any questions that you may have.
The Stages of Development
Zygote: A single sperm penetrates the egg and the resulting cell is called a zygote. The zygote contains all of the genetic information (DNA) necessary to become a child. half of the genetic information comes from the mother’s egg and half from the father’s sperm. the zygote spends the next few days dividing to form a ball of cells. The term cleavage is used to describe this cell division.
Morula: When the zygote reaches 16 or more cells it is called a morula. The morula is no larger than the zygote, but keeps producing smaller and smaller cells through cleavage.
Blastocyst: the morula continues to divide, creating an inner group of cells with an outer shell. This stage is called a blastocyst and consists of approximately 100 cells. The inner group of cells will become the embryo, while the outer group of cells will become the membranes that nourish and protect it.
Embryo: The blastocyst reaches the uterus around day five, and implants into the uterine wall on about day six. The cells of the embryo now multiply and begin to take on specific functions resulting in the various cell types that make up a human being e.g. blood cells, kidney cells and nerve cells.
One of the most common reasons for an IVF cycle to fail is because the embryo/s have failed to implant. An embryo must hatch out of its shell in order to implant into the lining of the uterus. This usually occurs five days after fertilisation.
During fertilisation the sperm must penetrate the hard shell surrounding the egg. This hard shell is called the zona pellucida. Once the sperm has penetrated the egg, the zona hardens again to prevent any additional sperm from entering the egg. During the following days the embryo undergoes a series of development stages, from zygote to morula to blastocyst. In nature this development occurs in the fallopian tubes and when the embryos reach the blastocyst stage they leave the fallopian tube and enter the uterine cavity.
In order to implant into the uterine lining, the embryo must hatch out of its shell, the zona pellucida. If hatching does not occur the embryo cannot implant and pregnancy will not occur. A common cause of difficulties with hatching is that the shell is too thick or too hard.
In assisted hatching a small break is made in the zona pellucida to weaken it just prior to blastocyst transfer. In specific cases this results in increased implantation of the blastocyst into the endometrium and increased pregnancy rates.
At Medfem we employ assisted hatching in cases such as advanced reproductive age, elevated FSH, decreased ovarian reserve, thickened zona, and prior implantation failure.
Preimplantation Genetic Diagnosis
PGD is a screening process that enables us to test the embryos of a couple who carry a known genetic marker for a specific inherited disorder so that only healthy embryos are selected to be replaced/transferred to the woman’s uterus in order to attempt to achieve a pregnancy. Read more
Stage 4: Embryo Transfer
The embryo transfer is a very special experience. Three to five days following egg retrieval, the embryo is placed in a catheter and transferred to the uterus via the vagina opening. The number of embryos transferred depends on a woman’s age, cause of infertility, pregnancy history, and other factors. Generally one to two of the healthiest embryos will be transferred to the uterus. It is important to note that the risk of multiple pregnancies increases with the number of good quality embryos transferred. If there are any addition embryos that are of good quality, they may be frozen for later use. You also will receive pictures of your embryos being transferred for your records.
This procedure only takes a few minutes and most women do not find it uncomfortable. Following the procedure you will rest for 30 minutes in our recovery room and will then be released to return home. We suggest that you take it easy for 24 hours after your embryo transfer. You can resume light, non-aerobic activity over the next few days. Many women return to work the next day if their jobs are not that strenuous.
Stage 5: Luteal phase support
The Luteal phase is the two week period between the embryo transfer and the pregnancy test. Starting the day of the egg retrieval process you will be prescribed progesterone in order to support a developing pregnancy. The progesterone will either be in the form of pessaries or injections. A pregnancy test is performed 14 days after embryo transfer. To confirm the positive pregnancy test, we will schedule an ultrasound two weeks following these pregnancy tests. At this visit we will be looking for implantation of embryos and fetal heart motion.
Emotionally this is a very taxing time. Hormone levels are high and there is not much that can be or cannot be done to influence the outcome of the treatment. Whether there is a pregnancy has been determined physiologically soon after the embryo transfer. It is recommended to resume normal activities in this period.
In the event of a pregnancy it is essential that you continue on the medications that were prescribed at the time of embryo transfer. If there is no pregnancy it is important to communicate with your doctor. Even though it will be extremely disappointing – remember your doctor has gained valuable diagnostic information throughout the procedure that will guide him in planning future treatment.
How might you feel?
Some of us find that starting treatment is a positive experience because you have something to focus on. However, others may fear the physical intervention or feel very disappointed that they have to face intervention.
In addition to dealing with feelings of uncertainty and trepidation, as well as hope, you will be dealing with the impact of hormonal changes on your body. Responses to the medications used vary enormously. Some women have no symptoms while others feel emotional and much more prone to tears, anxiety and irritability. Others feel uncomfortable with bloating, headaches, tiredness and other symptoms. While you cannot help the way you feel, with the help of a counsellor, you may be able to find a way to better manage your feelings and reactions during these times.
Initially women may fear the actual process, but waiting for results is often the most difficult part of treatment. Days seem to pass very slowly and it can be a time of acute vulnerability and sensitivity, making it difficult to concentrate on ordinary life.