IVF - In Vitro Fertilization

IVF was originally introduced for women with irreparably damaged tubes. Today, it is a first line therapy for a variety of problems such as endometriosis, tubo-peritoneal disturbances, pelvic adhesions, PCOD and cases of unexplained infertility. Also, patients who have had repeated failures of IUI or simple treatment methods in the past qualify for IVF.

In vitro fertilization (IVF) literally means "fertilization outside the human body" or, in broader terms, in the laboratory. This term applies to any form of assisted conception where fertilization takes place outside the body, such as ICSI or ZIFT.

You would require an initial screening and evaluation for sexually transmitted disease and a semen analysis with a trial wash to categorize you for either IVF or ICSI. Next, we would decide upon a suitable protocol for stimulating your wife's ovaries in order to get a good harvest of eggs.

Controlled ovarian stimulation

This involves a series of hormone injections to encourage your ovaries to produce more eggs than usual. You can have these injections either at our clinic if you stay in the vicinity or from your general practitioner or you could have a nurse or clinic assistant to come and inject you at home or we could teach your husband how to give the injections OR YOU COULD SELF INJECT.

The common drugs which would be prescribed to you are as follows

• GnRH-agonist (gonadotropin releasing hormone agonist) or a GnRH-antagonist (e.g. Antagon) to suppress the LH surge and ovulation until the follicles are mature.
• FSH product (follicle stimulating hormone) or hMG to stimulate development of multiple follicles.
• HCG (human chorionic gonadotropin) to cause final maturation of the eggs in the follicles.

The purpose of the GnRH-agonist (or antagonist) is to suppress release of LH (luteinizing hormone) from the woman's pituitary gland during the ovarian stimulation process. LH surges would cause premature ovulation (release) of the eggs.

The purpose of the FSH product is to stimulate development of multiple follicles (structures that contain eggs) in the ovaries.

Every month, as you approach ovulation, a number of follicles begin to mature (exactly how many varies, and depends on your age). Usually, the follicle that is mature first is ovulated, and all the other developing follicles shrink away and are lost in a process call Artesia. When you are on the hormone treatment, most or all these developing eggs are allowed to continue growing until a number of them have reached maturity. In this way, we can make use of eggs that would have otherwise been wasted, without using up your egg total any faster. Throughout the stimulation period, you will need to visit either one of our clinics or suburban centers for ultrasound monitoring and sometimes blood hormone levels. This will help us know when there are enough follicles that are mature enough for us to go ahead with the "egg pick-up".

Collecting the eggs

Usually, the egg pick-up is performed through the wall of the vagina, guided by ultrasound. We prefer a short acting propofol anesthesia to help you recover immediately after the procedure. The ovaries are scanned through the vagina, in the same way that they were during your monitoring. A needle is placed through the wall of the vagina and into the ovary, where the follicles are emptied of their fluids and their eggs. You will feel some pressure on the ovaries during the procedure and there is often a small amount of bleeding from the wall of the vagina.

Simultaneously, an embryologist is present at the time of the procedure, looking through the follicular fluid, finding the eggs, and scoring them according to their maturity and quality. All this is done in a special controlled environment in what is called the culture room.

Collecting the sperm

To ensure that we have an adequate quantity of sperm for IVF, 2 days abstinence is required before giving the semen sample. However, the sperm also need to be quite fresh, so you should not abstain for more than 4 days beforehand. (We recommend that you ejaculate on the day of the trigger injection.) Sperm collection can be done in one of our special, very private collection rooms . You may do this alone or together with your wife, whichever you prefer. If you anticipate that you will have any trouble providing a sample on the day of the egg pick-up procedure, we can arrange for you to collect ahead of time and have the sperm frozen. We can also provide special non-sperm-toxic condoms if you wish to collect at home instead. If you choose this option though, you do need to get the sample to us as quickly as possible afterwards. In the laboratory, the sperm will be washed and specially prepared for IVF.

Fertilization

Your eggs and sperm will be taken to our embryology lab, which is on the same floor as the day surgery where you will have had the procedure. Once in the lab, the eggs are isolated from the fluid and other cells, and prepared for IVF. The prepared sperm and eggs are combined in a glass dish filled with a nutritive medium. The eggs are then left in an incubator overnight. The next day, the eggs are checked for signs of fertilization. You can tell the difference between a fertilized egg and an unfertilized egg by two faint spheres visible in an egg after fertilization.

These two spheres (pronuclei) hold the DNA of the sperm and the egg, and will fuse to form the nucleus of the embryo (called syngamy). The fertilized eggs will be left to grow for several days in the laboratory. The embryos grow in the special mini-incubators that hold only 4 culture dishes, so that your embryos are not disturbed every time someone else's embryos are checked on, as they would be in the traditional bigger incubators. The embryologist will record how many eggs are successfully developing, and two or three of the embryos will be chosen for the embryo transfer. Any remaining good quality embryos can be 'frozen' for future use if you wish.

By the time the embryo is transferred, it consists of at least 2 to 8 cells, surrounded by a soft "shell" (the zona pellucida). After the transfer, the growing embryo will need to hatch out of the zona pellucida to implant in the lining of the uterus. On the day after the egg pick-up procedure, please call us to find out if the eggs have been fertilized. If at least one embryo is available for transfer back to your uterus an appointment will be made for the embryo transfer procedure.

Embryo transfer

The embryo transfer itself is a very simple procedure, usually taking just a few minutes, and requiring no anaesthesia or sedation. The embryos are kept in the laboratory until you are ready for the procedure. A scientist brings them to the day surgery in the special controlled-environment chamber, so that they are kept in optimum conditions right up until they are transferred to your uterus. The embryos are picked up with special two-part catheter (a bit like a very thin syringe ). This is carefully guided through the cervix, and a thin soft tube that will not damage the lining of the uterus is advanced out to reach the middle of the uterus, and the embryos are deposited there. The front and back of the uterus are normally touching, and this holds the embryo in place - so you can get up straight away.

After the transfer

To make sure the lining of your uterus (the endometrium) is ready for the embryo to implant, you will need to have two injections of hCG (human chorionic gonadotropin) or better still, daily injections of progesterone in oil (Inj Gestone / Puregest / Susten). This helps the endometrium swell up and envelop the embryo so it has the best chance to implant. If your hormone levels are high, we many recommend progesterone pessaries instead of further Profasi or Pregnyl.

From this point, it is a matter of waiting to see if an embryo implants successfully and begins to develop. A pregnancy test can be performed about 16 days after the egg pick-up and the nurse co-ordinators will have the results for you.

Blastocyst Transfer

A Blastocyst transfer is the transfer of an embryo from the laboratory to the uterus at Day 5 of development, instead of Day 3. it is one way of selecting the embryo or embryos most likely to survive and implant, giving a better chance of pregnancy. To appreciate the difference two extra days can make to an embryo, first you need to understand a little about early embryo development.

The first week.

After the sperm enters the ovum, the sperm head enlarges to form the male pronucleus. Within 24 hours, two small spheres, called the pronuclei, can be seen in the cytoplasm of the egg. These contain the genetic material from the mother and the father. When the two pronuclei fuse, joining the DNA from both parents together, fertilization is complete. As the pre-embryo grows, it undergoes cleavage, where the cell divides into smaller cells call blastomeres. After 2 days, the embryo will consist of 4-8 blastomeres. At this point it is impossible to tell which embryos are most likely to survive and develop normally. After about 3 days, when the embryo consists of 12-16 blastomeres, the cells begin to compact, forming a morula. This is the stage at which the embryo would normally enter the uterus, where it floats for a day or two before attaching to the lining of the uterus.

During those two days, huge changes in the embryo's appearance can be seen, as the cells begin to differentiate into those that will become the fetus, and those forming the amniotic sac and placenta. These changes are characterized by the formation of a cavity in the morula, to create a blastocyst.

After 4 or 5 days the embryo "hatches" out of the outer shell of the egg, the zona pellucida, and the blastocyst is able to attach to the endometrium. By Day 7, the embryo has completely implanted in the lining of the uterus.

Why have a blastocyst transfer?

By watching the embryo develop to the blastocyst stage, the embryologists can have a better idea of which embryos are most likely to be healthy and continue to develop. One of the factors that decides an embryo's fate is whether or not it has enough energy for the first week of development, hatching and implantation. Of course, there are still many stages of development that the embryo must pass through to create a successful pregnancy, but choosing the healthiest 5-day-old embryos and transferring them just before they would normally implant has given us the best success rates yet. Ultimately, our goal is to have such high success rates that only one blastocyst will need to be transferred in each cycle for a good chance at pregnancy.

We often recommend blastocyst transfers for couples who have had a number of unsuccessful attempts at routine IVF. Whether you have your embryos transferred at Day 2-3 or Day 5 is your decision. Some patients prefer to have the embryos put back earlier rather than risk there not being any still developing on Day 5, while others would prefer not to have the transfer if the embryos do not survive to Day 5.

Freezing Blastocysts

Normally "spare" embryos are frozen at the 4-8 cell stage, and provide good results when transferred after thawing. We are now able to successfully freeze and thaw blastocysts. The limited number of cases so far mean that we don't yet have reliable data on success rates for transfer after blastocyst freezing.

What does a blastocyst transfer mean for you?

Essentially, a blastocyst transfer means that your transfer will be one or two days later than it would have been otherwise. There are no different medications or extra procedures, although it does incur an additional charge. Having a blastocyst transfer can also mean that by Day 5 you might have fewer embryos than at Day 3, but that those embryos lost along the way would not have created a pregnancy anyway.

How is assisted hatching performed?

The embryo is held with a specialized holding pipette.
A very delicate, hollow needle is used to expel an acidic solution against the outer "shell" (zona pellucida) of the embryo.
A small hole is made in the shell by digesting it with the acidic solution.
The embryo is then washed and put back in culture in the incubator.

The embryo transfer procedure is done shortly after the hatching procedure. Embryo transfer places the embryos in the woman's uterus where they will hopefully implant and develop to result in a live birth.