IVF / ICSI
What is IVF/ICSI?
IVF (In Vitro Fertilisation) is a procedure, used to overcome a range of fertility issues, by which an egg and sperm are joined together outside the body, in a specialized laboratory. The fertilized egg (embryo) is allowed to grow in a protected environment for some days before being transferred into the woman's uterus increasing the chance that a pregnancy will occur.
Intracytoplasmic Sperm Injection (ICSI) is performed as an additional part of an IVF treatment cycle where a single sperm is injected into each egg to assist fertilization using very fine micro-manipulation equipment. In most cases, ICSI can be used to overcome severe male infertility.
Step 1 : Ovarian stimulation
Stimulation drugs or Hormones are given to the woman to boost her egg production. Normally, a woman produces one egg per month. The fertility drugs stimulate the ovaries to produce several eggs. During this step, the woman will have a regular transvaginal ultrasound to examine the ovaries about 3-4 times and blood tests to check hormone levels. Most women will take fertility drugs (FSH) for ovarian stimulation for 8-14 days; the average is 10-11 days. Ovarian stimulation is used to mature multiple eggs. An average of 10 – 20 eggs is usually retrieved for IVF. However, not all of them are viable to use as on average only about two-thirds have the appropriate maturity. Once an ultrasound determines you have a sufficient number of large enough follicles and your estrogen level is at the right level, you’ll receive a trigger shot of hCG or other medication. The egg retrieval will be done approximately 36 hours later.
Step 2 : Egg retrieval
A minor surgery, called follicular aspiration, is done to remove the eggs from the woman’s body. The surgery is normally done as an outpatient procedure in our clinic. The woman will be given medicines so she does not feel pain during the procedure. Using ultrasound as a guide, the health care provider inserts a thin needle through the vagina and into the ovary and sacs (follicles) containing the eggs. The needle is connected to an aspiration device, which pulls the eggs and fluid out of each follicle, one at a time. The procedure is repeated for the other ovary. The woman may have some cramping after the surgery, but it usually goes away within a day.
Step 3 : Sperm collection
The semen sample is collected through ejaculation into a sterile collection cup that we provide in our clinic. The specimen is usually collected in the office in a specially designated private room. The man’s partner may be in the room to help him collect. Occasionally, a man will for several reasons, be unable to collect a sperm specimen in the clinic, even in the special room. In those situations, we will let him collect at home or hotel and bring the specimen within a half hour or so and it should be kept warm.
We will schedule the male for collection approximately 2-3 hour before we schedule the woman for the IVF/ICSI. This allows time for the sperm to liquefy in our incubator and time for preparation for the IVF/ICSI.
Step 4 : Insemination and Fertilization IVF/ICSI
In Vitro Fertilization (IVF)
The sperm is placed together with the eggs and stored in an environmentally controlled incubator. The mixing of the sperm and egg is called insemination. The egg cells are placed in a nutrient solution in the laboratory and coated with approximately 50,000 to 100,000 sperm with good motility. The dishes are incubated (cultured) in an incubation cabinet overnight. The fertilization rate in case of normal sperm quality is 70-90%.
After it has been determined 19 – 21 hours later how many cells have reached what is known as the pronucleus (PN) stage, a normal condition of 2PN-stage embryos must be selected to complete the fertilization process. The pronuclei each contain the chromosomes of the egg cell and the sperm cell.
Intracytoplasmic Sperm Injection (ICSI)
Intracytoplasmic sperm injection, or ICSI, is a technique developed to help achieve fertilization for couples with severe male factor infertility or couples who have had failure to fertilize in a previous in vitro fertilization attempt. The procedure overcomes many of the barriers of fertilization and allows couples with little hope of achieving successful pregnancy to obtain fertilized embryos.
How ICSI Works？
The technique involves very precise procedure to pick up a single live sperm and inject it directly into the center of a human egg. After pick up the eggs, they will be incubated under precise conditions in our embryology laboratory. The semen sample is prepared by centrifuging (spinning the sperm cells through a special medium). This solution separates live sperm from debris and most of the dead sperm. The embryologist picks up the single live sperm in a glass needle and injects it directly into the egg.
Who is indicated for ICSI？
ICSI is considered absolutely necessary in the case of male factor infertility with an abnormal semen analysis. Sometimes, Patients are selecting to undergo ICSI for reasons other than male factor infertility including previous poor fertilization with IVF, variable sperm counts, and unexplained infertility. Therefore, many patients choose to undergo the ICSI procedure to maximize their success even when the procedure may not be clearly indicated. Through the ICSI procedure, many couples with difficult male factor infertility problems have achieved pregnancy. Fertilization rates of 70-90% (of all eggs injected) equivalent to that of fertilization with normal sperm are currently being achieved, and pregnancy rates are comparable to those seen with IVF in couples with no male factor infertility.
Step 5 : Embryo culture/Blastocyst culture
When the fertilized egg divides, it becomes an embryo. The embryos will be placed in a highly effective controlled incubators. Laboratory staff will regularly check the embryo to make sure it is growing properly. Within about 3-5 days, a normal embryo has several cells that are actively dividing. In general, there are 2 stages of embryo culture is referred that are day3 embryo (6-10 cell embryo) and day5-6 embryo (Blastocyst embryo).
Blastocyst culture is becoming extremely popular amongst reproductive physicians and infertile couples. A blastocyst transfer is associated with a number of advantages over the Day 3 transfer procedure.
A blastocyst is referred to an embryo reaches the five to six day development stage. At this point in development, the embryo has between 200 and 300 cells distributed in two areas: an outer embryo lining (which will later form the placenta), and an inner mass (which will later become the fetus). During a natural cycle, the embryo develops into the blastocyst stage as it is leaving the fallopian tubes and entering the uterus. An embryo needs to have entered into the blastocyst stage once it arrives in the uterus to ensure proper implantation.
Blastocyst transfer is considered a more “natural” type of transfer than the Day 3 transfer procedure. This is because the blastocyst embryo is implanted into the uterus at almost the same time that it would have entered the uterus should the pregnancy have been a natural one. Alternatively, during Day 3 transfers, embryos are placed inside the uterus at a time when they should normally still be in the fallopian tubes. By allowing embryos to culture for a longer period of time, embryologists are better able to choose healthy embryos to transfer into your uterus, so it is more likely to achieve a successful pregnancy and better success rate.
Step 6 : Biopsy & PGT
Step 7 : Embryo freezing
A cell is made up mostly of water. The main concern when freezing embryos is ice forming in and between the cells. Ice crystals can hurt the cell wall, and can harm the small structures inside the cell.
The embryo must be protected during the freezing process. This is done using special fluids called cryoprotective agents (CPAs). CPAs are like “anti-freeze” for cells.
Doctors use two different methods to freeze and preserve embryos: slow programmable freezing and vitrification.
In the slow freezing method, the embryos are frozen slowly, in stages. The CPAs are added to the embryos in increasing strengths over 10 to 20 minutes. Then the embryos are slowly cooled over two hours in a machine that lowers the temperature minute by minute. Once frozen, the embryos are stored in liquid nitrogen at -321° Fahrenheit (-196.1° Celsius).
Vitrification is a rapid freezing technique that uses much higher strengths of CPAs. With this method, the doctor first mixes the CPAs with the embryos. CPAs that are very strong can also hurt the cell. To prevent this, the embryos are quickly placed into the liquid nitrogen. This process changes them into an almost-solid state, like glass. In this state, ice is unable to form.
When needed, the embryos are slowly thawed. They are soaked in special fluids to remove the CPAs. This also restores the cell’s normal water balance.
About 95% of all frozen embryos survive the freezing thaw process.
Step 8 : Embryo transfer (FET)
On the embryo transfer day, embryos will be thawed. Then, embryos are placed into the woman’s womb/uterus. The stage of transferred embryo must relate to the day of endometrial preparation controlled by external hormone. The procedure is done in our clinic while the woman is awake. The doctor inserts a thin tube (catheter) containing the embryos into the woman’s vagina, through the cervix, and up into the womb. If an embryo implants in the lining of the uterus and you will get a good pregnancy result.
Normally, one to two embryos may be transferred into the uterus at the same time. The exact number of embryos transferred is a complex issue that depends on many factors, especially the woman’s age.
Before embryo transfer, the woman will take 12-14 days estrogen hormonal supplementation starting from day3 of menstrual period. Then three to five days before the embryo transfer, you'll start giving yourself progesterone supplements. Usually, the progesterone supplementation can be taken as a pill and/or vaginal suppository. Sometimes, the progesterone during IVF treatment is given as a daily intramuscular self-injection as progesterone in oil.
Step 9 : Pregnancy test
About 7 to 10 days after the embryo transfer, a pregnancy test is ordered. This is usually a serum pregnancy test and also will include progesterone levels testing. If the test is positive, the test may be repeated every few days -hCG levels double about every two days.
You may need to keep taking the progesterone and estrogen supplementation for another several weeks until 12th weeks of pregnancy. Your doctor will also follow up with occasional blood work and ultrasounds to monitor the pregnancy and watch for miscarriages or ectopic pregnancies.