Leaders in successful pregnancies

• Intra-cytoplasmic Sperm Injection (ICSI): The embryologist selects a single best looking healthy sperm and injects it directly into the center of each egg. 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 called a micropipette.

 ICSI is used in cases when the quantity or quality of sperm is poor and therefore unable to effectively penetrate the egg on its own. Since fertilization only requires one healthy sperm, ICSI has become one of the most incredible advances in treating severe male factor infertility.

ICSI allows even couples with very low sperm counts or poor quality sperm to achieve high fertilization and pregnancy rates.

It is also recommended for couples who have not achieved fertilization in prior IVF attempts.

Usually in the traditional way, before a man’s sperm can fertilize a woman’s egg, the head of the sperm must attach to the outside of the egg. Once attached, the sperm pushes through the outer layer to the inside of the egg (cytoplasm), where fertilization takes place.

Sometimes the sperm cannot penetrate the outer layer, for a variety of reasons. The egg’s outer layer may be thick or hard to penetrate or the sperm may be unable to swim. In these cases intra-cytoplasmic sperm injection (ICSI) can be done along with in vitro fertilization (IVF) to help fertilize the egg.

Who needs ICSI?

ICSI helps to overcome fertility problems, such as:

• The male partner produces too few sperm to do artificial insemination (intrauterine insemination IUI) or conventional IVF.
• The sperm does not move in a normal way.
• The sperm may have trouble attaching to the egg.
• A blockage in the male reproductive tract that may keep sperm from getting out.
• Eggs were not fertilized by traditional IVF, even if the sperm is in good condition.
• In vitro matured (IVM) eggs are being used.
• Frozen eggs are being used.

Intra-cytoplasmic Morphologically Selected Sperm Injection (IMSI)

IMSI is one of the techniques that increase the success rate of IVF.

The sperm is selected under a high power light microscope (enhanced by digital imaging) to magnify the sperm sample over 6000 times. With this microscope we can see the internal morphology of the sperm and discard those with abnormalities. According to the WHO a mature sperm should ideally have an oval head with a length of between 4 and 5 microns and a width between 2.5 and 3.5 microns. One healthy sperm is injected into each egg

The embryologist selects the best looking sperm using a high-power and accurate optical microscope (equipped with digital imaging) to enlarge the sperm sample more than 6000 times, which allows the detection of abnormal sperm. This technique is used when the number of sperm abnormalities is large, so one normal sperm is injected into each egg.

IMSI is a method to increase the success rate of the IVF procedure, by selecting the sperm without morphological abnormalities using a high-definition microscope that allows a magnification of the sperm up to 6000 times and this exceeds the magnification capacity usually used in laboratories of reproduction whose magnification strength reaches only 400 times. Thus, detailed head imaging allows us to assess the gaps that are likely to exist. In this way pre-selection of sperm before fertilization is done using microscopic injection and only the best sperm is used. Using this microscope, allows us to view and examine the internal morphology of sperms (including the nucleus) and ignore those with abnormalities. This permits us to choose sperms without morphological problems.

The selected sperm is injected into the egg's cytoplasmic membrane. One sperm is inserted into each egg.

The use of this technique improves the chances of success and the opportunities for fertilizing eggs in the laboratory and can be used in cases of repeated failures, i.e. after several failed attempts of IVF or in cases where the sperm has a very high number of abnormalities.

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.

Pre-implantation Genetic Diagnosis (PGD) or Pre-implantation Genetic Testing (PGT) or PGS:

Preimplantation genetic diagnosis (PGD) is a procedure used in conjunction with in vitro fertilization (IVF) to select embryos free of chromosomal abnormalities and specific genetic disorders for transfer to the uterus. PGD or 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.

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 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 3^rd day or 5^th 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.

Egg Freezing (Vitrification)

Egg freezing consists of retrieving a woman’s eggs from the ovaries and then freezing and storing the viable eggs (oocytes) only without fertilizing them by sperm. In the future, when a woman finds a partner and decides to have children, her stored frozen eggs are then thawed and fertilized with the sperm of her partner for the purpose of getting pregnant. In case the woman doesn’t have a partner, she might decide in the future to fertilize her stored frozen eggs by donor sperm.

Woman’s fertility is largely dependent on the quality and quantity of her eggs. As woman ages her fertility potential or egg quality and quantity decreases as does the chances of conception. This is an option to save the fertility of a woman who decides to marry late. Additionally, some medical conditions such cancer for example require treatments such as chemotherapy that often have an adverse effect on fertility, and premature menopause or premature ovarian failure accelerate the aging of eggs. Whatever the cause, diminished egg quantity and quality significantly impacts one's ability to conceive. 

The Egg Freezing Program offers egg freezing technology (also called oocyte vitrification) to protect a woman’s fertility in all of these situations. By making the choice to freeze her eggs today, a woman can lock in her fertility potential for future use when the circumstances and timing are right for her. She can stop the aging of her eggs by freezing them for an indefinite period of time. The ovaries age with time but the uterus doesn't age. This is why by freezing her eggs a woman can use them at an older age to be fertilized by the sperm of her future partner and then transfer the embryos inside her uterus even if she is above the age of 55 as long as her health allows her to get pregnant. The uterus doesn't lose its function with age.

Age and Fertility Preservation:

Egg freezing is intended to extend the biological clock. Female fertility begins declining in the mid-20s but conception rates remain high until the age of 35. By her mid-30s, the decline accelerates to reach minimal pregnancy potential by the time the woman reaches age 42. In addition, women over 35 have an increased risk of miscarriage and/or genetic abnormalities in their children as a result of age-dependent changes in egg quality. Therefore, the best age to preserve eggs is in your early to mid-30s. When a woman uses her frozen eggs in the future, even if a number of years have passed, both the pregnancy rates and the incidence of miscarriage and genetic abnormalities will depend on the age of the woman when the eggs were frozen, not on her age when she will use the eggs.

Egg freezing procedure:

Egg Freezing procedure for virgins:

We have a special technical way for virgins to make egg retrieval while maintaining their virginity. 

We start monitoring the growth and size of the egg follicles by an abdominal ultrasound.

Once the eggs are ready and become mature by reaching the required size, we do egg retrieval under anesthesia through the vagina, even for the virgins, using a long thin needle fixed on a probe of a thin vaginal ultrasound. After the egg retrieval is done, the hymen of the virginity is examined and if it has been scratched or injured during the procedure of egg retrieval, it will be repaired by 1 suture or 2 in a very easy way to keep it as it was before. The girl does not lose her virginity. She can continue her life with reassurance as if nothing had happened until she finds her partner in the future.

The initial steps of Egg freezing are the same as the initial steps of in vitro fertilization (IVF) 

Step 1 - Preparing for the Egg freezing cycle

Prior to the start of your cycle, you will work with your physician to outline a schedule for your egg freezing cycle. 

Preparation will involve a few additional blood tests and a lecture explaining how to make the injections. 

Scheduling your egg freezing cycle can be coordinated with your needs depending on when you would like to complete the egg retrieval. To help time the cycle, you will be placed on birth control pills for approximately three weeks.

Step 2 - Stimulating the Ovaries

To stimulate the ovaries, you will be instructed to take injectable medications, which you will administer at home, for an average of 9–14 days. During this period of time, you will be asked to come to the clinic for “monitoring” appointments. These appointments are done in the morning, in an average of 3 - 4 visits before the egg retrieval, at the clinic and consist of an abdominal ultrasound for the virgins and a Trans-vaginal ultrasound for the others to measure and monitor your follicles, the fluid-filled sacs on the ovaries in which the eggs grow. As well as blood tests to measure and monitor your hormone levels. Both the ultrasound and blood tests allow your physician to monitor your progress and determine when to retrieve the eggs. 

Once the follicles reach a mature size, your egg retrieval will be scheduled at the clinic. 

Step 3 - The Egg Retrieval & Freezing

The actual egg retrieval procedure takes approximately 10 - 15 minutes, during which you are given light sedation Intra Venous. Due to the sedation, you have to come to the clinic early in the morning without eating or drinking anything (fasting) and you’ll be asked to take a day off the next day.

After you sleep, the eggs are retrieved through the vagina, even for the virgins, using a long thin needle attached to a probe of a thin vaginal ultrasound. For the virgins after the egg retrieval, the hymen of virginity is examined. If the hymen is scratched or injured, 1 or 2 sutures will be done to repair it. Thus, the girl does not lose her virginity and as if nothing had happened.

The day of the egg retrieval, specially-trained embryologists will assess the maturity of your eggs and the mature eggs are then frozen in the lab. Following the procedure, you will be told the number of mature eggs frozen. After the egg retrieval, you will be sent home to rest and relax. Most women are able to resume normal activities and return to work the next day.

Step 4 - Post - Egg Freezing

After your egg freezing procedure, your menstrual cycle will come as normal; however, you may wish to continue with another cycle of egg freezing to procure enough eggs for multiple attempts to have pregnancy in the future by thawing the eggs and fertilizing them by the partner's sperm. The optimal number of frozen eggs to have a baby is freezing at least 16 eggs. In this case, you can contact your doctor and tell him when you’ll be ready to prepare for an additional cycle. 

Future Options

Once eggs are frozen, you now have a back-up plan, should you need them in the future. Use of these eggs in the future involves thawing, inseminating the egg with sperm, and transfer of healthy embryo(s) into the uterus. The age of the eggs at the time of freezing is the most important factor impacting success. If we freeze the eggs before the age of 35, women will have a greater chance to obtain a successful pregnancy from the frozen eggs. In Europe, the pregnancy has to be pursued before the age of 51 for legal reasons. At our clinic we don't have any age restrictions for the woman to get pregnant as long as she will be healthy. The woman’s age when the eggs are thawed does not impact success rates. The most important factor is the age when the egg freezing took place.

Note: The optimal number of frozen eggs to ensure childbirth is approximately 15 frozen eggs.

Egg Freezing (Vitrification)

Egg freezing consists of retrieving a woman’s eggs from the ovaries and then freezing and storing the viable eggs (oocytes) only without fertilizing them by sperm. In the future, when a woman finds a partner and decides to have children, her stored frozen eggs are then thawed and fertilized with the sperm of her partner for the purpose of getting pregnant. In case the woman doesn’t have a partner, she might decide in the future to fertilize her stored frozen eggs by donor sperm.

Woman’s fertility is largely dependent on the quality and quantity of her eggs. As woman ages her fertility potential or egg quality and quantity decreases as does the chances of conception. This is an option to save the fertility of a woman who decides to marry late. Additionally, some medical conditions such cancer for example require treatments such as chemotherapy that often have an adverse effect on fertility, and premature menopause or premature ovarian failure accelerate the aging of eggs. Whatever the cause, diminished egg quantity and quality significantly impacts one's ability to conceive. 

The Egg Freezing Program offers egg freezing technology (also called oocyte vitrification) to protect a woman’s fertility in all of these situations. By making the choice to freeze her eggs today, a woman can lock in her fertility potential for future use when the circumstances and timing are right for her. She can stop the aging of her eggs by freezing them for an indefinite period of time. The ovaries age with time but the uterus doesn't age. This is why by freezing her eggs a woman can use them at an older age to be fertilized by the sperm of her future partner and then transfer the embryos inside her uterus even if she is above the age of 55 as long as her health allows her to get pregnant. The uterus doesn't lose its function with age.

Age and Fertility Preservation:

Egg freezing is intended to extend the biological clock. Female fertility begins declining in the mid-20s but conception rates remain high until the age of 35. By her mid-30s, the decline accelerates to reach minimal pregnancy potential by the time the woman reaches age 42. In addition, women over 35 have an increased risk of miscarriage and/or genetic abnormalities in their children as a result of age-dependent changes in egg quality. Therefore, the best age to preserve eggs is in your early to mid-30s. When a woman uses her frozen eggs in the future, even if a number of years have passed, both the pregnancy rates and the incidence of miscarriage and genetic abnormalities will depend on the age of the woman when the eggs were frozen, not on her age when she will use the eggs.

Egg freezing procedure:

Egg Freezing procedure for virgins:

We have a special technical way for virgins to make egg retrieval while maintaining their virginity. 

We start monitoring the growth and size of the egg follicles by an abdominal ultrasound.

Once the eggs are ready and become mature by reaching the required size, we do egg retrieval under anesthesia through the vagina, even for the virgins, using a long thin needle fixed on a probe of a thin vaginal ultrasound. After the egg retrieval is done, the hymen of the virginity is examined and if it has been scratched or injured during the procedure of egg retrieval, it will be repaired by 1 suture or 2 in a very easy way to keep it as it was before. The girl does not lose her virginity. She can continue her life with reassurance as if nothing had happened until she finds her partner in the future.

The initial steps of Egg freezing are the same as the initial steps of in vitro fertilization (IVF) 

Step 1 - Preparing for the Egg freezing cycle

Prior to the start of your cycle, you will work with your physician to outline a schedule for your egg freezing cycle. 

Preparation will involve a few additional blood tests and a lecture explaining how to make the injections. 

Scheduling your egg freezing cycle can be coordinated with your needs depending on when you would like to complete the egg retrieval. To help time the cycle, you will be placed on birth control pills for approximately three weeks.

Step 2 - Stimulating the Ovaries

To stimulate the ovaries, you will be instructed to take injectable medications, which you will administer at home, for an average of 9–14 days. During this period of time, you will be asked to come to the clinic for “monitoring” appointments. These appointments are done in the morning, in an average of 3 - 4 visits before the egg retrieval, at the clinic and consist of an abdominal ultrasound for the virgins and a Trans-vaginal ultrasound for the others to measure and monitor your follicles, the fluid-filled sacs on the ovaries in which the eggs grow. As well as blood tests to measure and monitor your hormone levels. Both the ultrasound and blood tests allow your physician to monitor your progress and determine when to retrieve the eggs. 

Once the follicles reach a mature size, your egg retrieval will be scheduled at the clinic. 

Step 3 - The Egg Retrieval & Freezing

The actual egg retrieval procedure takes approximately 10 - 15 minutes, during which you are given light sedation Intra Venous. Due to the sedation, you have to come to the clinic early in the morning without eating or drinking anything (fasting) and you’ll be asked to take a day off the next day.

After you sleep, the eggs are retrieved through the vagina, even for the virgins, using a long thin needle attached to a probe of a thin vaginal ultrasound. For the virgins after the egg retrieval, the hymen of virginity is examined. If the hymen is scratched or injured, 1 or 2 sutures will be done to repair it. Thus, the girl does not lose her virginity and as if nothing had happened.

The day of the egg retrieval, specially-trained embryologists will assess the maturity of your eggs and the mature eggs are then frozen in the lab. Following the procedure, you will be told the number of mature eggs frozen. After the egg retrieval, you will be sent home to rest and relax. Most women are able to resume normal activities and return to work the next day.

Step 4 - Post - Egg Freezing

After your egg freezing procedure, your menstrual cycle will come as normal; however, you may wish to continue with another cycle of egg freezing to procure enough eggs for multiple attempts to have pregnancy in the future by thawing the eggs and fertilizing them by the partner's sperm. The optimal number of frozen eggs to have a baby is freezing at least 16 eggs. In this case, you can contact your doctor and tell him when you’ll be ready to prepare for an additional cycle. 

Future Options

Once eggs are frozen, you now have a back-up plan, should you need them in the future. Use of these eggs in the future involves thawing, inseminating the egg with sperm, and transfer of healthy embryo(s) into the uterus. The age of the eggs at the time of freezing is the most important factor impacting success. If we freeze the eggs before the age of 35, women will have a greater chance to obtain a successful pregnancy from the frozen eggs. In Europe, the pregnancy has to be pursued before the age of 51 for legal reasons. At our clinic we don't have any age restrictions for the woman to get pregnant as long as she will be healthy. The woman’s age when the eggs are thawed does not impact success rates. The most important factor is the age when the egg freezing took place.

Note: The optimal number of frozen eggs to ensure childbirth is approximately 15 frozen eggs.

Testicular sperm aspiration (TESA)

TESA is a procedure where a sample of sperm cells and tissue are aspirated from the testicle by a small needle attached to a syringe without opening the testicle. The needle is inserted in the testicle and tissue/sperm are aspirated with negative pressure produced by the syringe.  It is done with local anesthesia in the operating room of an IVF center and is usually done after the partner’s female egg retrieval. Under a microscope in the laboratory, the sperm is separated from the tissue. It may then be used right away to fertilize the eggs or frozen for future infertility treatment.

After the procedure the man will be asked to wear a very tight pair of underpants to provide support to the scrotum and to put ice over the underpants on the testicles to prevent inflammation. There is no other special preparation for the patient.

How TESA is performed?

TESA is performed under local anesthesia. This means that an anesthetic is injected into the scrotum by the specialist to make the area numb. When this has been achieved the doctor will swab the scrotum with a warm antiseptic. The doctor will examine the testes by gently feeling the scrotum. A small needle will be inserted into the testes and the doctor will instruct the nurse assisting to draw back the syringe in order to aspirate seminal fluid and tissue. When fluid and testicular tissue is obtained it is passed to the embryologist to be examined for sperm under a microscope. The procedure may need to be attempted again until sperm will been found. The procedure is usually performed just prior to the woman’s oocyte collection (on the same day).

Sperm donation back up will be prepared by the IVF center in case the couple asked for it.

TESA is done for men who are having sperm retrieved for IVF/ICSI in the following cases:

• TESA may be useful for men who have fertility problems caused by a blockage that keeps sperm from being ejaculated. This is called obstructive azoospermia that might be caused by certain genetic conditions, ejaculation problems, infection, or other conditions.
• Previous vasectomy.
• High Sperm DNA Fragmentation.
• After having treatment that may cause infertility, such as certain cancer treatments.

Sometimes TESA doesn’t provide enough tissue/sperm for the IVF + ICSI and an open testis biopsy is needed (TESE).

Testicular sperm extraction (TESE)

TESE involves making a small incision in the testis and examining the tubules for the presence of sperm. TESE is usually done in the operating room with sedation or with local anesthesia alone. It is either done as a scheduled procedure or is coordinated with their female partner’s egg retrieval. During TESE the testis is opened by an incision and a biopsy is done and testicular tissue is removed and examined under a microscope to search for sperm. Then the incision will be sutured. The patient will be asked to put some ice on the testicles after the procedure to reduce the inflammation and he can continue his life as usual without any pain. Patients usually cryopreserve sperm during this procedure for future IVF/ICSI or use the fresh sperm found for the ICSI.

Patients frequently have donor sperm backup in case sperm are not found in the male partner.

You have the following options in case sperm is not found by TESE:

1. Egg retrieval of the IVF might be cancelled if the doctor sees no harm in cancelling it, or the egg retrieval can be done without fertilization, and then the eggs can be destroyed.

2. Eggs retrieved can be frozen for later use.

3. Fertilize the eggs by sperm donation.

Micro TESE has replaced this as the optimal form of retrieval for men with no sperm in their ejaculate (azoospermia) from a problem with production.

Micro - dissection TESE (micro TESE)

Micro TESE is a procedure done for men who have a sperm production problem and are azoospermic. Micro TESE is done in the operating room with general or local anesthesia alone under an operating microscope. The testis is opened by an incision and under the microscope we can spot the places where sperm is found to obtain them. This allows us to remove less testicular tissue with higher possibility to find good sperm. Micro TESE is carefully coordinated with the female partner’s egg retrieval, and can be done the day before egg retrieval. Patients frequently have donor sperm backup in case sperm are not found in the male partner. Micro TESE has significantly improved sperm retrieval rates in azoospermic men, and is a safer procedure since less testicular tissue is removed. Patients can cryopreserve sperm during this procedure for future IVF/ICSI.

Percutaneous Epididymal Sperm Aspiration (PESA)

PESA is a simple technique to obtain sperm for Intra Cytoplasmic Sperm Injection (ICSI) in men who have an obstruction of the vas deferens, either due to vasectomy or other obstruction. PESA involves aspiration of sperm from the epididymis with a fine needle, through the skin without opening the testicle. To minimize scarring and damage, PESA usually is attempted on one side only. It is sometimes necessary to aspirate from both sides. Sufficient sperm for ICSI is obtained in 80% of attempts. In 10% of cases we can also find enough suitable sperm for cryopreservation.

The procedure is performed in the operating room of an IVF Centre. After the procedure the man will be asked to wear a very tight pair of underpants to provide support to the scrotum. There is no other special preparation for the patient.

PESA is performed under local anesthesia. This means that an anesthetic is injected into the scrotum by the specialist to make the area numb. When this has been achieved the doctor will swab the scrotum with a warm antiseptic. The doctor will examine the testes to locate the vas deferens by gently feeling the scrotum. A small needle will be inserted through the skin into the vas deferens and the doctor will instruct the nurse assisting to draw back the syringe in order to aspirate seminal fluid. When fluid is obtained it is passed to the embryologist to be examined for motile (moving) sperm. The procedure may need to be attempted again until motile sperm have been found.

The procedure is usually performed just prior to the woman’s oocyte collection (on the same day). And sperm donation back up will be prepared by the IVF center in case the couple asked for it.

You have the following options in case good sperm is not found by PESA:

1. IVF egg (oocyte) retrieval might be cancelled if the doctor sees no harm in cancelling the egg retrieval, or the egg retrieval will be done without fertilization, then the eggs they will be destroyed.

2. Eggs retrieved can be frozen for later use.

3. Fertilize the eggs by sperm donation.

Microsurgical Epididymal Sperm Aspiration (MESA)

MESA is an open surgical sperm retrieval procedure that uses an operating microscopy to locate the tubules of the epididymis precisely, so that large numbers of sperm can be extracted.

MESA is a procedure performed for men who have vasal or epididymal obstruction (s/p vasectomy, congenital bilateral absence of the vas deferens). It is either done as a scheduled procedure or is coordinated with their female partner’s egg retrieval.

MESA is done in the operating room with general anesthesia under the operating microscope. MESA involves opening the testicle by an incision after locating the epididymis and then aspirating the sperm directly from the epididymis with a fine needle. One aspiration may provide enough sperm for several attempts at IVF using ICSI. MESA can be performed well in advance of any proposed IVF procedure. Patients usually cryopreserve sperm during this procedure for future IVF/ICSI. MESA allows an extensive collection of mature sperm as compared to aspiration techniques, and it is the preferred method of retrieval for men with congenital bilateral absence of the vas deferens as it does not impact steroid production of the testis.

Patients frequently have donor sperm backup in case sperm are not found in the male partner.

You have the following options in case sperm is not found by MESA:

1. Egg retrieval of the IVF might be cancelled if the doctor sees no harm in cancelling it or the egg retrieval can be done without fertilization, and then the eggs can be destroyed.

2. Eggs retrieved can be frozen for later use.

3. Fertilize the eggs by sperm donation.

Assisted Hatching:

What is assisted hatching?

During the first 5 to 7 days of development, the embryo is surrounded and protected by an outer shell called the Zona Pellucida. Normally, when the embryo reaches the uterus, this Zona partially dissolves and the embryo ‘hatches’ and get out, in order to implant in the uterus. In some patients infertility may be caused by a hardening of the Zona, which makes it difficult for the embryo to hatch and implant. Assisted hatching is a laboratory micromanipulation technique carried out just before the embryos are placed in the uterus to help the embryo to hatch from the Zona.
The laser assisted hatching is designed to improve the efficiency and success rates of assisted reproductive technology procedures (ART) such as IVF & ICSI.
The unfertilized egg is surrounded by a shell called Zona Pellucida. The Zona has an important role in fertilization. It allows only one sperm to penetrate the Zona and enter the egg to make fertilization. After fertilization of the egg, and during the cleavage stage of an embryo, the Zona Pellucida hardens. This development is normal in order to keep the cells in the egg together. The embryo has to "hatch" or break out and get out of the Zona in order to embed and implant into the endometrium lining of the uterine cavity. This happens about 2-3 days after embryo transfer when the embryo is at the blastocyst stage. Naturally this happens by expanding/contracting of the Zona until it distorts, allowing the blastocyst to "hatch" and get out. When sperm fertilize the eggs in the IVF laboratory, the Zona Pellucida hardens at much faster rate than natural, making it more difficult for the embryo to implant. Before implantation, the embryo has to escape out of its Zona Pellucida by a process called hatching. If this process is not completed properly, implantation failure occurs and a pregnancy is unable to continue.
Assisted hatching consists of creating a hole in Zona Pellucida, to help the embryo in the hatching process. The Laser technology for Assisted Hatching (LAH), where a precision laser beam is focused over the Zona Pellucida making a small opening, between 10-20 microns to facilitate embryo hatching. LAH is done just before the Embryo Transfer. This helps to increase pregnancy rates by improving implantation rates, since embryo hatching is made easier. It’s a fast, and safe method compared to the old method of hatching which was performed by using acidic medium on the Zona to create a small hole. The accuracy of the laser is determined by its programming. There is high degree accuracy.
It is also recommend that thawed embryos (frozen embryos) should be treated with laser assisted hatching before Embryo Transfer to increase success rates.
 

Who can benefit from Laser Assisted Hatching?
•    Patients with day 3 embryos having a thick Zona noted by embryologist.
•    Patients with failed previous IVF/ICSI cycles.
•    Women older than 35 years of age, have a tendency to produce eggs with a harder Zona Pellucida than younger women.
•    Women with a high Follicle Stimulating Hormone (FSH) level.
•    Patients having IVF/ICSI for the first time, who are considered poor responders, because they needed a high dose of gonadotropins for poor ovarian response.
•    Patients who in previous IVF cycles had low fertilization rate, resulting in three or fewer embryos.
•    Patients who ask for laser assisted hatching and are fully informed of its use and function.
•    Frozen embryo before transfer.

Platelet Rich Plasma (PRP) treatment for thin endometrium:

Intrauterine perfusion of Platelet Rich Plasma  (PRP) has been used for treating thin endometrium. PRP is blood plasma prepared from fresh own whole blood that has been enriched with platelets by centrifuge. Platelets have positive effects on local tissue repair and contain a significant amount of growth factors that stimulate proliferation and growth. It's efficacy in endometrial growth has been fully established.

PRP can expand endometrial thickness by providing growth factor to the endometrium. PRP is a safe procedure, with minimal risks of infectious disease transmission and immunological reactions since it is made from autologous blood samples derived from patient's own blood.

Endometrial thickness <7 mm and thin endometrium decreases pregnancy rates and significantly lower implantation and pregnancy rates and also correlates with a higher risk of miscarriage. The thin endometrium is an extremely bad factor that interferes with an ongoing pregnancy. 

Common causes of the thin endometrium:

• Uterine Infections and inflammations; pelvic infectious diseases lead to unresponsiveness to estrogens.
• Repetitive curettage causing damage to the basal layer of endometrium.
• Intrauterine adhesions; especially Asherman’s syndrome.
• Low estrogen levels due to repetitive use of anti-estrogenic treatment (clomiphene Citrate)
• Cancer treatments, such as radical surgery, chemotherapy and radiotherapy (RT) can permanently affect the uterus lining.

Endometrial treatment by PRP:

PRP contains activating platelets that stimulate the action of cytokines and growth factors. They can regulate cell migration, attachment, proliferation and differentiation, and promote extracellular matrix accumulation. According to this theory, local infusion of PRP (that contains several growth factors and cytokines) into the cavity of the uterus may improve endometrial thickness, receptivity and implantation.

PRP Procedure:

• PRP is prepared from patient’s own blood (autologous), by collection of 1 8 ml blood from the vein of the arm.
• 1^st dosage of PRP is prepared and injected in the cavity of the uterus on the 10th day of the period.
• PRP is infused into the uterine cavity via a catheter (0.5–1 ml).
• Infusion of PRP can be done 1- 3 times before the embryo transfer if the endometrial thickness is not satisfactory.

Contra-Indications of PRP:

1. Platelet count less than 105/μL
2. Hemoglobin less than 10 g/dL
3. Presence of metastatic disease or blood tumor, and other associated infections.

PRP (Platelet Rich Plasma) Injections:

Ovarian rejuvenation therapy (PRP) offers new hopes to women who are unable to conceive due premature ovarian failure, early pre-menopause, and low ovarian reserve but who wish to have their own biological child.

In Ovarian Rejuvenation, a preparation of a woman’s own blood cells, called Platelet Rich Plasma (PRP), is injected into her ovaries to stimulate new cellular growth in an attempt to restore fertility and ovarian hormone production.

This process of ovarian rejuvenation provides a possibility of resurrecting fertility or some degree of ovarian hormonal function in women who have poor quality eggs in their ovaries.

PRP (Platelet Rich Plasma) Injections – PRP Injections is a technique where blood is taken from the forearm and centrifuged so the platelet-rich plasma is isolated and then injected back into the ovary.

PRP (plasma rich in Platelets) is a natural product where a high level of platelets is concentrated, but with growth factors concentration 3 to 5 times greater than plasma.

The theory underlying this method was derived from a natural healing process. The body’s first response to tissue injury is to deliver platelets to the injured area. Platelets promote healing and attract growth factors to the site of injury. In reproductive medicine, PRP therapy is developed in different directions. The first one refers to the ovarian rejuvenation for women with premature ovarian failure and patient with low ovarian reserve. During this procedure, PRP is injected into the ovary under ultrasound guidance, similarly to egg retrieval in IVF cycle.

Ideal Candidates for Ovarian Rejuvenation Therapy (PRP)

• Women with Premature Ovarian Insufficiency, typically younger than 40 years.
• Women with early pre-menopause.
• Women with low ovarian reserve, and low Anti-Mullerian (AMH) hormone levels.

The 2^nd direction is PRP treatment by intrauterine infusions for patients with recurrent implantation failure and women with resistant thin endometrium.