In Vitro Fertilization (IVF)
1) In Vitro fertilization (IVF)
The Assisted Reproductive Technologies (ART) is 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 might be expensive. For all of those reasons, advanced treatment options of infertility can be stressful, but worthful. This natural stress can be minimized if you understand the nuances of the various procedures. I encourage you to learn more, to watch and read additional educational sources listed in the web site and to freely ask any question. Understanding the purpose of each procedure will help you obtain the appropriate treatment and maximize your chance of success. The unknown is always stressful. Knowing what is awaiting you, will minimize the stress.
There are a number of different types of treatments belonging to the ART methods. The main treatment of infertility is In Vitro Fertilization or IVF.
IVF indications or when to use IVF?
In case of problems of the Fallopian tubes, especially if they are blocked, IVF is the 1st line of treatment to bypass the tubes. IVF is also the 1st line of treatment to avoid hereditary and genetic problems or in case of family planning for sex selection by using PGD + IVF or in case of female age factor (advanced age) or in case of egg donation. In other cases, IVF is recommended if simpler treatments fail.
List of Indications for IVF treatment.
1) Fallopian Tube Damage/Tubal Factor:
The fallopian tubes might get damaged or blocked after some pelvic infections or after previous abdominal surgeries such as C - sections for example. The only option for treating significant tubal damage, especially if both tubes are blocked is by bypassing the tubes with IVF. This decision must be carefully individualized in each situation.
The Fallopian tubes might be damaged and filled by a liquid. This is called a hydrosalpinx. In case of hydrosalpinx of the tubes, it is advised to remove or close the damaged tubes by Laparoscopy before doing an IVF procedure to increase the success rate.
2) Male Factor Infertility:
IVF is used in case of a decreased sperm count or sperm motility or sperm morphology using Intra Cytoplasmic Sperm Injection (ICSI). 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 IVF + ICSI (Intra Cytoplasmic Sperm Injection). ICSI is recommended if there is any suggestion of a sperm problem. If sperm are obtained surgically in case of obstructive Azoospermia, or if there has been a prior failure of fertilization, ICSI is used.
Endometriosis may be treated by a combination of surgical and medical therapy. But it’s better to stay away from surgery or to postpone the surgery to treat endometriosis as it damages the ovarian reserve and leads to a decrease in the ovarian reserve, which makes the chances of pregnancy more difficult. It is advised to use surgery to treat endometriosis only after having had children, then the reserve will not matter anymore if damaged. IVF is considered a very effective and successful treatment of infertility caused by the endometriosis.
4) Female age related Infertility:
In normal reproductive life, a woman's ovarian function is decreased with age. As a woman grows older, especially after the age of 35, her ovarian reserve and egg quality decreases, making the chances of a successful pregnancy more difficult and increases the number of miscarriages. Age is the biggest factor affecting a woman's chance to conceive and have a healthy baby. A Woman's fertility starts to decline in her early 30s, with the decline speed increasing after the age of 35. In many cases, this reduced function of the eggs can be overcome through the use of IVF alone or in conjunction with techniques such as Assisted Hatching and ICSI.
Fertility preservation by freezing their own eggs until later use is also a perfect solution for women to keep the conceiving abilities as the woman gets older. After freezing her eggs, a woman can use them later using IVF. The quality of the frozen eggs depends on the age of the woman at the time when it was done.
IVF + Egg donation might also be a solution for women above 40 years old or for those who have premature ovarian failure before the age of 40.
5) Anovulation / Irregular menstrual cycle:
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, because they usually have good ovarian reserve especially those suffering from polycystic ovaries (PCO).
6) Unexplained Infertility:
Approximately 20% of couples will have no known cause of infertility after completing a fertility evaluation. IVF is often successful even if more conservative treatments have failed, especially that some of those couples have some block to fertilization.
7) Pre-implantation Genetic Diagnosis (PGD) or Pre-implantation Genetic Testing (PGT) or PGS:
PGT or PGD technology reduces the potential for adverse pregnancy outcomes for couples ‘at risk’ by testing the embryos for certain genetic abnormalities before they are chosen for transfer.
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. PGD can only be performed during an IVF cycle where eggs and sperm, united in the laboratory, then develop into embryos. On the 3rd day or 5th day a biopsy is done on each embryo to make a chromosomal study 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.
We can also use PGD for gender selection. We choose the required embryos upon their sex, boys or girls before doing the embryo transfer for family planning. We can freeze the healthy embryos that were not chosen for the transfer.
8) Gender or sex selection / Family planning:
IVF + Pre-implantation genetic diagnosis (PGD) is an excellent tool to choose the sex of the embryo before uterine embryo transfer. 3 or 5 days after fertilization in the IVF lab a cell biopsy is done from each embryo using laser and under a special microscope. It is 99% precise in detecting the gender of the embryo. After the embryo biopsy, a chromosome study will be done on the Y and X chromosomes to determine the exact sex, a boy or a girl.
The women will start on the 2nd or 3rd day of the period injections for about 8 - 12 days before making the egg retrieval and fertilization. The embryo transfer of the desired embryos depending on their sex will be done on day 5 after the fertilization. The embryos that were not transferred could be frozen for later use or if not frozen they will stop growing on day 5 - 7 because the embryos cannot live in the culture media of the IVF Lab more than that.
9) Cancer patients and IVF:
All young cancer patients willing to have children in the future have to freeze their eggs in case of women or their sperm in case of men before starting any cancer treatment.
Frozen eggs or frozen sperm procedures are done before starting cancer treatments to preserve female and male fertility after recovery from cancer. The frozen eggs and frozen sperm are used later by their owners to have children using IVF.
10) Egg donation:
Egg donation is the best solution for women after the age of 40 or in case of premature ovarian failure before 40 years.
We use donated eggs from young and healthy donors instead of using a woman's old eggs. In the IVF laboratory, healthy and young donated eggs (donors 18-27 years old) are fertilized with the husband's sperm. Then, on day 3 or day 5 after fertilization the embryos are transferred into his wife's uterus. Pregnancy success rate of egg donation is at least 70%. Once the woman gets pregnant from donor eggs, her pregnancy continues normal development as any other normal pregnancy.
IN Vitro Fertilization (IVF) steps:
It is very important to understand the five basic steps and components of an IVF cycle to decrease the stress of the unknown.
Step One – Controlled Ovarian stimulation:
Hormone injections are given for 8 - 12 days to stimulate multiple egg production rather than the single egg normally produced by the female body each month. This ovary stimulation process needs daily gonadotropin injections to stimulate the development of the eggs and requires injections to suppress the ovaries to prevent ovulation before the desired time. 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 egg maturation and development by measuring their size using a vaginal ultrasound and by measuring blood estrogen levels over several days.
Step Two - Egg Retrieval
Egg retrieval is done under light sedation, by fixing a special long needle on the probe of a vaginal ultrasound. The needle is directed alongside the vaginal probe into the ovarian follicle through the vaginal wall to aspirate the fluid inside the follicles one by one. Not every follicle contains one egg. The follicles might be empty or containing not mature eggs. Only the mature eggs are injected by the sperm to be fertilized. This is a relatively minor procedure and is performed by visualizing the follicles with a vaginal ultrasound. To avoid any discomfort, strong, short acting intravenous sedation is provided.
You have to stop eating or drinking anything 7 - 8 hours before the egg retrieval procedure. Even smoking and chewing gums are not allowed during this period of fasting. This means that you have to make an overnight fasting before coming to the IVF center for 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). Sometimes when the sperm has a very low normal morphology, Intra-cytoplasmic morphologically selected sperm injection (IMSI) might be used.
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, the best looking one and injects it directly into the cytoplasm of the egg using a small glass needle.
ICSI allows even 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 (TESA, TESE, PESA, and MESA) are available for the 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 to evaluate early cell division. They are now called embryos and are placed in a solution called media to promote growth. The embryos are then placed in incubators in the IVF Lab. 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 to six days until they reach the blastocyst stage. On day two or three after fertilization, the embryos will be evaluated for the possibility of a 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 to reach the blastocyst stage.
Step Four - Embryo Transfer
Embryos may be transferred on day 2, 3, 5, or 6 after egg retrieval and fertilization. Transfers on day 5 or 6 are called Blastocyst Transfers. The procedure of intra-uterine embryo transfer is usually done without anesthesia. A speculum is inserted in the vagina to visualize the cervix. The doctor cleans the cervix from mucus and remaining suppositories then prepares the path through the cervix by using a small, soft catheter which is inserted inside the cervix into the cavity of the uterus. The embryologist gives the embryos to the doctor in a special long thin and soft catheter that will be inserted inside the path previously prepared to reach the uterine cavity. Then the doctor softly and with high precision injects the embryos inside the cavity. Through the catheter, the doctor will transfer the embryos, along with a small amount of fluid. This procedure is not painful at all. You may experience very light cramping but nothing more. The number of embryos transferred will depend on the quality and quantity of the embryos and on the age of the woman and on the previous discussion with the doctor.
After the embryo transfer, you'll stay lying down for a couple hours at the clinic and then go home.
If there are "extra" high-quality embryos left over, you may be able to freeze them. This is called "embryo cryopreservation." They can be used later if this cycle isn't successful.
You’ll need bed rest at home for 3 days after the embryo transfer.
Blastocyst culture and transfer is an important technique developed for in vitro fertilization (IVF) that maximizes pregnancy success 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 inside an incubator in the IVF Lab.
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 eggs 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 to return only 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 be 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 embryo 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 test for pregnancy. If you are pregnant, we will follow your progress with blood work and ultrasounds. And you will be advised to continue most of the treatment for 55 more days. The vitamins and anticoagulants have to be taken at least until delivery.
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.
In case of a positive Beta Hcg pregnancy test, you have to visit a gynecologist to make a vaginal ultrasound 7 - 10 days later to be sure that the pregnancy is inside the uterus and to see how many intra gestational sacs are found to exclude multiple pregnancy in cases where more than 1 embryo were transferred.