In Vitro Fertilization (IVF)
1) In Vitro fertilization (IVF)
The Assisted Reproductive Technologies (ART's) are a group of treatment options used for couples with infertility that cannot be treated using simpler methods. These procedures have excellent success rates but require significant effort and can be expensive. For all of these reasons, advanced treatment options can be stressful. These natural stresses can be minimized if you understand the nuances of the various procedures. I encourage you to learn more, freely ask questions, and to watch or read additional educational resources listed in the web site. Understanding the applications for each procedure will help you obtain the appropriate treatment and maximize your chance for success.
There are a number of different types of treatments belonging to the ART methods. The main treatment is IVF, it is important to understand the four basic components of an IVF cycle.
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a) IVF indications or when to use IVF?
In case of tubal factor, IVF may be the first-line treatment to bypass the tubes. In other cases, IVF is recommended only if simpler treatment fails or in case of female age factor. Below is a list of common indications for IVF treatment.
Fallopian Tube Damage/Tubal Factor
The only options for treating significant tubal damage are surgical repair or bypassing the tubes with IVF. This decision must be carefully individualized in each situation.
Male Factor Infertility
One of the most advances in the treatment of infertility has been to obtain fertilization and pregnancy in the IVF lab with severely abnormal sperm samples by using ICSI (Intra Cytoplasmic Sperm Injection). ICSI is often recommended if there is any suggestion of a sperm problem, if sperm are obtained surgically, or if there has been a prior failure of fertilization.
Endometriosis may be treated by a combination of surgical and medical therapy. IVF is very effective as a second line of treatment if the initial treatment is proven unsuccessful.
Age Related Infertility
In normal reproductive life, a woman's ovarian function is decreased with age. In many cases, this reduced function can be overcome through the use of IVF alone or in conjunction with techniques such as Assisted Hatching and ICSI.
The majority of patients with anovulation will get pregnant using simpler treatments. However, those patients requiring IVF are typically "high responders" to gonadotropin therapy and have a good prognosis.
Approximately 20% of couples will have no known cause of infertility after completing an evaluation. IVF is often successful even if more conservative treatments have failed, especially that some of those couples have some block to fertilization.
Pre-implantation Genetic Testing (PGT) or Pre-implantation Genetic Diagnosis (PGD)
Genetic testing or diagnosis on pre-implantation embryos may be indicated for patients who are at risk for genetic disorders such as Thalassemia and for patients with infertility related to chromosomal abnormalities such as recurrent pregnancy loss or repeated unsuccessful IVF or for gender (sex) selection (to choose boys or girls).
Pre-implantation genetic testing (PGT) or PGD is a procedure used in conjunction with in vitro fertilization (IVF) to select embryos free of chromosomal abnormalities and specific genetic disorders before transfer to the uterus. PGT improves the likelihood of a successful pregnancy and birth for two distinctly different groups of patients; couples with infertility related to recurrent miscarriage or unsuccessful IVF cycles and couples who are at risk for passing on an inherited genetic disease to their offspring.
Pre-implantation genetic testing may be recommended by your physician when there is a possibility, indicated by your medical history or advanced maternal age, which could affect your embryos by a genetic disease. PGT can only be performed during an IVF cycle where eggs and sperm, united in the laboratory, then develop into embryos on the 3rd day and after the testing results on day 5, only the normal embryos would be selected for embryo transfer, reducing the possibility of miscarriage or birth defects.
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a) IN Vitro Fertilization (IVF) steps:
Step One –Controlled Ovarian stimulation:
Hormone injections are given to stimulate multiple egg production rather than the single egg normally produced by the body each month. This stimulation process usually requires injections to suppress the ovary to prevent ovulation until the desired time and daily gonadotropin injections are added to stimulate the development of the eggs. These are usually given subcutaneously (under the skin) or intramuscular (IM) and are much less uncomfortable than the previous generations of medications. We then monitor the progress of ovulation induction with vaginal ultrasounds and blood estrogen levels over several days.
Step Two - Egg Retrieval
Egg retrieval is done under light sedation, by placing a special needle into the ovarian follicle through the vagina and directed by an ultrasound probe to aspirate the fluid inside the egg. This is a relatively minor procedure and is performed by visualizing the follicles with a vaginal ultrasound probe. A needle is directed alongside the probe, through the vaginal wall, and into the ovary. To avoid any discomfort, strong, short acting intravenous sedation is provided.
You must not eat any solid food or drink any opaque liquids for seven hours before your procedure. You may drink in moderation transparent liquids, such as water, bullion, or apple juice up to four hours before your procedure. You may also drink tea or coffee without cream or milk also 4 hours to the procedure.
Step Three - Fertilization and Embryo Culture
Once the follicular fluid is removed from the follicle, the eggs are identified by the embryologist and placed into an incubator. The eggs are fertilized with sperm later that day by conventional insemination or by Intra-cytoplasmic Sperm Injection (ICSI).
During conventional insemination approximately 50,000 sperm are placed with each egg in a culture dish and left together overnight to undergo the fertilization process. The ICSI technique is used to fertilize mature eggs with the best looking sperm. Under the microscope, the embryologist picks up a single sperm and injects it directly into the cytoplasm of the egg using a small glass needle.
ICSI allows couples with very low sperm counts or poor quality sperm to achieve fertilization and pregnancy rates equal to traditional IVF. It is also recommended for couples who have not achieved fertilization in prior IVF attempts. Special urological procedures are available to you for cases where it is difficult to obtain sperm or for men with no sperm in the ejaculate.
The eggs will be checked the following day to document fertilization and again the next day to evaluate for early cell division. They are now called embryos and are placed in a solution called media to promote growth. Until recently, embryos were cultured for three days and then transferred to the uterus and/or cryopreserved (frozen). We now have the ability to grow the embryos for five or six days until they reach the blastocyst stage. On day two or three after fertilization, the embryos will be evaluated for blastocyst culture. If there is a sufficient number of dividing embryos they will be placed in special blastocyst media and grown for two or three additional days.
Step Four - Embryo Transfer
Embryos may be transferred on day 3, 5, or 6 after egg retrieval (pickup). Transfers on day 5 or 6 are called Blastocyst Transfers. They are placed through the cervix into the uterine cavity using a small, soft catheter. This procedure usually requires no anesthesia.
Blastocyst culture and transfer is an important technique developed for in vitro fertilization (IVF) that maximizes pregnancy rates while minimizing the risk of multiple pregnancies. The ability to grow embryos for five or six days to the blastocyst stage of development in the laboratory, rather than the traditional three days, allows to determine, with greater certainty, which embryos are really the "best" for implantation.
Blastocyst culture and transfer
Culture media now are designed to take into account the myriad and changing needs of the developing embryo in vitro.
After five days of growth, the cells of the embryo should have divided many times over, and have begun to differentiate by function. The embryos that survive to this stage of development are more likely to be strong, healthy, and robust. They are now called blastocysts.
Are there benefits of blastocyst transfer with IVF?
Let's use an example. Historically, if a woman has 15 eggs retrieved, an average of 10 will fertilize by day one of observation. It is impossible to determine at this point which of these 10 are most likely to implant and develop into a baby. Perhaps all will, but perhaps not. On the traditional day of embryo transfer (day three), 5 of the 10 embryos may be developing into vibrant, growing embryos. The others may have slowed or stopped their development altogether as naturally many eggs and embryos are abnormal.
In this example, we are left with several embryos that still look like they may have excellent potential. Which ones to transfer? Which ones are really the "best"? Two additional days in the blastocyst culture medium allows the natural winnowing process to continue. Thus, after 5 or 6 days of growth in the laboratory, only 2 or 3 of the original ten embryos may remain viable, showing their inherent potential. We now know the best embryo(s) to transfer.
Embryos transferred at the blastocyst stage have made it through key growth processes and typically offer a greater chance of implanting. Without compromising pregnancy rates, we need only return 1 or 2 blastocysts to the mother instead of the typical 2 or 3 early embryos. In addition, the fewer embryos transferred the more may available for cryopreservation for future use.
A significant benefit of blastocyst culture and transfer is the reduction of multiple births that can result from in vitro fertilization. This means that the many obstetrical complications that may arise from multiple pregnancies can be minimized. It is especially important in helping patients avoid having to make the difficult personal and ethical decisions regarding selective reduction.
Is IVF with blastocyst transfer right for everyone?
No, blastocyst transfer is not good for everyone. Patients having few oocytes retrieved, fewer fertilized or fewer dividing embryos by day three in culture have no advantage using blastocyst culture, since little is to be gained in further embryo "self-selection".
Unfortunately the new blastocyst culture media does not improve the health or viability of an individual embryo which is not otherwise able to sustain five days of growth and then implant; rather it allows embryos capable of sustained growth to continue in culture and reach their maximum inherent capability.
However, a large proportion of patients with fewer eggs and/or fewer embryos do very well with a transfer day 3 when we can recommend to them which embryos for transfer earlier. Many patients undergoing Day 3 embryo transfer still have very good pregnancy success rates.
Be sure that whether day 3 or day 5 or 6 transfer is recommended for you, it is a decision made by the experienced and expert clinical and laboratory teams aligned to give you the best individualized advice for a safe and successful outcome.
Step 5 - Testing for Pregnancy
Two weeks after the embryo transfer you have to do a blood pregnancy test. If you are pregnant, we will follow your progress with blood work and ultrasounds.
It takes about two weeks from the time an embryo implants in the uterine wall to start emitting enough of the hormone hCG (human chorionic gonadotropin) to be detected by a blood test. This period of time is referred to as the two week wait. The blood test - officially called a beta hCG blood test– detecting the hCG is the most accurate indication of pregnancy.