IN VITRO FERTILIZATION

IVF is the treatment method which enables people, who suffer from genetic problems or infertility, to have babies. During IVF the eggs are matured, collected and fertilized in a laboratory with sperm from the male. For IVF your own egg or sperm, or someone else’s egg or sperm can be used. (The latter method is illegal in Turkey.)

The possibility of conception after IVF depends on a number of factors including age, the reason of infertility etc. If more than one embryo is placed in the uterus, the possibility of multiple pregnancies occurs. One cycle of IVF takes about two weeks. It can be time consuming and invasive.

IVF is the most effective method for the treatment of infertility. If one has infertility problem, drug treatment, intrauterine insemination and other treatments for the problem must be applied before beginning the IVF. If the patient is over 40, IVF can be the first choice to be resorted to without losing any time.

WHY IT'S DONE

In vitro fertilization (IVF) is a treatment for infertility or genetic problems. If IVF is performed to treat infertility, you and your partner might be able to try less invasive treatment options before attempting IVF, including fertility drugs to increase production of eggs or intrauterine insemination — a procedure in which sperm are placed directly in your uterus near the time of ovulation.

Sometimes, IVF is offered as a primary treatment for infertility in women over age 40. IVF can also be done if you have certain health conditions. For example, IVF may be an option if you or your partner has:

Fallopian tube damage or blockage. Fallopian tube damage or blockage makes it difficult for an egg to be fertilized or for an embryo to travel to the uterus.

Ovulation disorders. If ovulation is infrequent or absent, fewer eggs are available for fertilization.

Premature ovarian failure. Premature ovarian failure is the loss of normal ovarian function before age 40. If your ovaries fail, they don't produce normal amounts of the hormone estrogen or have eggs to release regularly.

Endometriosis. Endometriosis occurs when the uterine tissue implants and grows outside of the uterus — often affecting the function of the ovaries, uterus and fallopian tubes.

Uterine fibroids. Fibroids are benign tumors in the wall of the uterus and are common in women in their 30s and 40s. Fibroids can interfere with implantation of the fertilized egg.

Previous tubal sterilization or removal. If you've had tubal ligation — a type of sterilization in which your fallopian tubes are cut or blocked to permanently prevent pregnancy — and want to conceive, IVF may be an alternative to tubal ligation reversal.

Impaired sperm production or function. Below-average sperm concentration, weak movement of sperm (poor mobility), or abnormalities in sperm size and shape can make it difficult for sperm to fertilize an egg. If semen abnormalities are found, your partner might need to see a specialist to determine if there are correctable problems or underlying health concerns.

Unexplained infertility. Unexplained infertility means no cause of infertility has been found despite evaluation for common causes.

A genetic disorder. If you or your partner is at risk of passing on a genetic disorder to your child, you may be candidates for preimplantation genetic diagnosis — a procedure that involves IVF. After the eggs are harvested and fertilized, they're screened for certain genetic problems, although not all genetic problems can be found. Embryos that don't contain identified problems can be transferred to the uterus.

Risks

Specific steps of an in vitro fertilization (IVF) cycle carry risks, including:

Multiple births. IVF increases the risk of multiple births if more than one embryo is implanted in your uterus. A pregnancy with multiple fetuses carries a higher risk of early labor and low birth weight than pregnancy with a single fetus does.

Premature delivery and low birth weight. Research suggests that use of IVF slightly increases the risk that a baby will be born early or with a low birth weight.

Ovarian hyperstimulation syndrome. Use of injectable fertility drugs, such as human chorionic gonadotropin (HCG), to induce ovulation can cause ovarian hyperstimulation syndrome, in which your ovaries become swollen and painful.

Signs and symptoms typically last a week and include mild abdominal pain, bloating, nausea, vomiting and diarrhea. If you become pregnant, however, your symptoms might last several weeks. Rarely, it's possible to develop a more-severe form of ovarian hyperstimulation syndrome that can also cause rapid weight gain and shortness of breath.

Miscarriage. The rate of miscarriage for women who conceive using IVF with fresh embryos is similar to that of women who conceive naturally — about 15 to 25 percent — but the rate increases with maternal age. Use of frozen embryos during IVF, however, may slightly increase the risk of miscarriage.

Egg-retrieval procedure complications. Use of an aspirating needle to collect eggs could possibly cause bleeding, infection or damage to the bowel, bladder or a blood vessel. Risks are also associated with general anesthesia, if used.

Ectopic pregnancy. About 2 to 5 percent of women who use IVF will have an ectopic pregnancy — when the fertilized egg implants outside the uterus, usually in a fallopian tube. The fertilized egg can't survive outside the uterus, and there's no way to continue the pregnancy.

Birth defects. The age of the mother is the primary risk factor in the development of birth defects, no matter how the child is conceived. More research is needed to determine whether babies conceived using IVF might be at increased risk of certain birth defects. Some experts believe that the use of IVF does not increase the risk of having a baby with birth defects.

Ovarian cancer. Although some early studies suggested there may be a link between certain medications used to stimulate egg growth and the development of a specific type of ovarian tumor, more recent studies do not support these findings.

Stress. Use of IVF can be financially, physically and emotionally draining. Support from counselors, family and friends can help you and your partner through the ups and downs of infertility treatment.

NEW TECHNIQUES IN IVF TREATMENT

EMBRYO GLUE

Thanks to recent advances in medical science, couples undergoing IVF now have a number of additional options available to increase their chances of a successful outcome. One of these options involves the use of EmbryoGlue, which is a special solution used to transfer embryos during the final stage of IVF.

Despite the name, EmbryoGlue is not actually a glue, however it does contain an adhesive-like substance that helps to protect the embryo during the transfer process and create a 'bridge' between the tissues of the embryo and uterus. The addition of these substances has now been proven to boost the chances of a healthy embryo to implant into the uterus, in several large IVF studies.

There is a natural substance found throughout our bodies called Hyaluronan that increases dramatically in the uterus at the time that embryos are due to implant.  It makes good sense, therefore, that it should be present during the embryo transfer procedure. 

There are several known actions of Hyaluronan that are beneficial to embryo implantation. Firstly, it is a thick (viscous) fluid that minimises movement of the embryo inside the uterus. Secondly, it contains carbohydrate molecules that are known to be involved in the early stages of embryo implantation.

A close analysis of the published trials that compare the success rates of the EmbryoGlue versus no EmbryoGlue has shown an overall improvement in pregnancy rates. This is especially significant in patient groups over the age of 35, with unexplained fertility and those who have experienced a previous failed implantation. Because EmbryoGlue works by closely replicating the conditions of the mother's uterus during implantation, Repromed recommend the use of EmbryoGlue for most IVF patients.

ERA TEST

Recurrent or repeated implantation failure (RIF) can be devastating. Some patients undergo three or more rounds of IVF and everything seems to go well: a good number of eggs at retrieval, a good fertilization rate, the embryos appear to be healthy and high quality, the uterine lining looks good, the transfer goes smoothly, but the pregnancy never “sticks.”

It can also be a tricky and frustrating situation for fertility experts trying to track down a cause. Patients need answers, and doctors want to help. Happily, new tests and technology are constantly under development to help reproductive experts provide some of these answers and help patients find the right path to pregnancy. The ERA test is one of these new developments, which is offering new information and new hope to patients coping with implantation failure.

ERA stands for Endometrial Receptivity Analysis (or Array). It is a genetic test which uses a small sample of a woman’s endometrial tissue to evaluate whether or not the endometrial lining is prepared to accept an implanting embryo.

Each woman has an “implantation window” in her cycle which is a few days long, generally occurring from the 19-23 days of the menstrual cycle. During this time, the luteal or secretory phase, the ovaries are producing progesterone. The progesterone causes many subtle but important changes to the uterine lining in order to create a perfect state for implantation. Proteins are created which make the lining thicker and more receptive. In about 84% of women this small window occurs at the expected time. However, researches at Igenomix labs in Spain discovered that about 16% of women have a unique window which can be earlier or later than expected. For IVF cycles, this could mean that the embryo transfer is happening on the wrong day, when the window hasn’t opened yet or has already closed, thereby causing implantation failure.

When the endometrial lining is receptive, the genetic material of the endometrial cells have a unique “expression,” which means that they may be making more or less of certain types of RNA. The researchers analyzes the expression of 236 genes per sample and built up a database of more than 12,000 samples of endometrial tissue to see the levels of RNA produced at different times of the cycle. They then used advanced computer algorithms to look for patterns until they could reliably classify a sample as "Receptive” or "Non-Receptive” according to its specific expression profiles. This test is highly reproducible, which means that when samples are tested at the same time of the cycle but months apart, the results remain the same. Using ERA, doctors can identify whether a woman’s “implantation window” is happening when expected or whether they need to move the transfer date to ensure the best “sync” between the embryo and the uterine lining.

When the endometrial lining is receptive, the genetic material of the endometrial cells have a unique “expression,” which means that they may be making more or less of certain types of RNA. The researchers analyzes the expression of 236 genes per sample and built up a database of more than 12,000 samples of endometrial tissue to see the levels of RNA produced at different times of the cycle. They then used advanced computer algorithms to look for patterns until they could reliably classify a sample as "Receptive” or "Non-Receptive” according to its specific expression profiles. This test is highly reproducible, which means that when samples are tested at the same time of the cycle but months apart, the results remain the same. Using ERA, doctors can identify whether a woman’s “implantation window” is happening when expected or whether they need to move the transfer date to ensure the best “sync” between the embryo and the uterine lining.

How is the ERA test performed?

Endometrial Receptivity Analysis requires a sample of the uterine lining obtained at a very specific time in the cycle. 

It is also possible to use fertility medications to prepare the uterine lining, using supplemental estrogen and progesterone. The day the progesterone is started is Day Zero, and the test is done five days after that. 

The tissue sample is taken in a procedure known as endometrial biopsy. A thin catheter is inserted through the cervix into the uterine cavity, and a plunger in the catheter is used to create suction and draw a tiny sample of the endometrial lining into the catheter. Many women find this part of the process quite uncomfortable, but it is a very quick procedure. The sample is then sent to the lab for analysis using Next Generation Sequencing technology. Results are available in around three weeks. If the results come back that the tissue was “Non-Receptive” then the test should be repeated earlier or later, until the optimal time is identified.

Once the patient’s receptive window has been identified, personalized embryo transfer (pET) timing can be used.

SPERM CHIP (Micro Chip)

Sperm chip is a method to select and prepare the sperm in IUI (insemination), ICSI (Intracytoplasmic Sperm Injection) and IVF (In Vitro Fertilization) treatments.Considering the natural sperm selection and sperm race are skipped in ICSI procedures, isolating the damaged sperm and selecting the best quality sperm become more important.The DNA damage in sperm cell decreases the implantation rate.

What is the technique of Microfluidic Sperm Sorting Chips (Sperm Chip)?

• Centrifuge is not necessary in Sperm Chip. In this way rising of Reactive oxygen species (ROS) is prevented. Sperm Chip provides to select the undamaged sperm in terms of ROS and DNA fragmentation.

• Sperm chip is the closest way to the natural sperm selection which is based on the sperms pass through the cervical canals. In this way sperm chip provides to select the better DNA quality sperms and physiologically the best ones for ICSI.

Sperm chip cannot be used in cases of low sperm count and/or low motility. Also, it is not appropriate to use within the sperms obtained by TESA/TESE. 

Array CGH

By using microarray technique, it is possible to diagnose all chromosomal abnormalities including aneuploidies and partial imbalances that may occur in embryos in only 12 hours. It has several advantages over FISH method where only limited chromosomes could be screened.Numerical abnormality in chromosomes is called as aneuploidy. Chromosomally normal human embryonic cells contain 46 chromosomes (22 pairs of autosomes and 1 pair of gonosomes) (Figure 1). Aneuploidy can originate from an excess number of chromosomes (e.g, trisomy) or from missing chromosomes (e.g. monosomy). Chromosomal abnormalities are very common in preimplantation embryos. Trisomy 21 (Down Syndrome), trisomy 16, trisomy 13 (Patau Syndrome), trisomy 18 (Edwards Syndrome); and monosomy X (Turner Syndrome) and Trisomy XXY (Klinefelter Syndrome) are the most frequent chromosomal abnormalities among humans.

It is known that 80% of embryos generated from advanced maternal age patients carry at least one chromosomal abnormality and 30-40% of all chromosomal abnormalities cannot be detected by FISH method. However, array comperative genomic hybridization (a-CGH) method can detect abnormalities of all chromosomes, both numerically and structurally, with high resolution. Deletions, duplications and unbalanced chromosomal regions can be easily detected using this method. With this method it is possible to diagnose all chromosomes in embryos in just 12 hours.

Microinjection (ICSI)

What is Microinjection?

In conventional in vitro fertilization (IVF) system, the sperm and egg cell are brought together and the sperm cell is expected to fertilize the egg cell. However, if the number, motility of sperm cells and the number of sperm cell with the normal morphology are not sufficient to fertilize the egg, a single sperm cell taken into a thin glass needle with a special instrument is directly injected into the egg cell under a microscope and thus, fertilization is achieved. This is called as microinjection, i.e., an in vitro fertilization method with a different procedure. Follow-up and monitoring of the patient is the same as the path followed in conventional in vitro fertilization method.

Who Are Eligible for Microinjection?

Very low sperm count, motility or percentage of normal sperm (morphology):

These problems may be present separately or all together. This procedure can also be applied in cases where sperm quality is sufficient for the conventional in vitro fertilization.

Sperm antibodies:

In some cases, release of agents called antibodies and produced against the sperm cells in female body can be observed. Antibodies prevent the sperm cells to fertilize the egg cell. In such cases, according to the antibody quantity, microinjection treatment can be considered as the first choice.

Patients with no fertilization in IVF.

In IVF patients with less than 10% fertilization rate.

Cases that require sperm cells to be obtained operatively:

If the sperm is obtained through the epididymal or testicular tissue.

What is Sperm Magnet? Does it have any effect?

The cell complex around the human egg (cumulus-corona layer) is made of a high molecule weight substance called hyaluronan basically. Scientific research showed that hyaluronan helps selecting the healthy sperm during fertilization. For mature and mobile sperms to hold onto hyaluronan, they must have some receptors on them. It has been understood that sperm maturity and morphology is proportional to the capacity of hyaluronan adherence. In order to test this feature of the sperm, an IVF center in Turkey announced a test called sperm magnet, more scientifically Sperm Hyaluronan Binding Assay, HBA in short. There is an easy and practical, ready to use kit for this procedure.

How is the method Applied?

A drop (10 microliters) of semen sample of father candidates is put onto the glass which comes out of the HBA kit. Sample is kept there 10-20 minutes. At the end of this duration, semen sample is evaluated according to its hyaluronan adherent or non-adherent mobile sperm ratio. The point here is to detect the sperms that can be adherent to hyaluronan molecule and that are more capable of fertilizating the egg. HBA score is defind for the semen sample as a result of the test.

How useful is Sperm magnet?

Recent studies showed that semen samples with high formal anomalies have low HBA score (approximately %40) while semen with normal morphology have this score anround %70. Heavy shape anomalies of semen samples being in high levels is also an indication of anueploidy (chromosomal disorder) in this sample. Therefore, HBA test can be used as a diagnostic test that can provide us with information about the sperm maturity, shape and chromosomal anomaly risks.

This test has only been studied on the sperm in human studies until today, and it can be used with diagnostic purposes. For more effective test, sperm selection during microinjection is important for viability of the to-be transferred embryo and chance of pregnancy. There is no study comparing classical microinjection and HBA-microinjection in humans in the literature yet.

Some animal researches were reported on this subject (on pigs). According to these studies, embryos acquired from HBA+ICSI (Sperm selected by hyaluronan binding test + Intracytoplasmic sperm injection), risk of aneuploidi (chromosome disorder) is found to be significantly lower than the risk in the embryos acquired from the classical ICSI (selection by shape + microinjection).

It has been suggested that the reason for this difference is that through HBA test sperms with lower risk of chromosomal anomaly is used in microinjection and eggs fertilized by the sper

Oocyte activation with Cult-Active

Recommended in cases with low amount of fertilized eggs in previous Artificial Insemination cycles
Cult-Active is a new method which is used in patients who had low amount of fertilized egg cells (oocytes) during previous Artificial Insemination cycles after ICSI (intra-cytoplasmic sperm injection). It indicates that eggs are immature. Oocyte (egg) activation is initiated by protein contained in sperm. During egg activation there is a fast increase of intracellular concentration of calcium.

After ICSI (intra-cytoplasmic sperm injection) fertilized eggs are placed in the Cult-Active medium for 15 minutes, it helps to activate an egg and increasing amount of fertilized eggs having emulated the biochemical process of egg and sperm fertilization. Calcium ionophore contained in Cult-Active medium- connects calcium ions and delivers them to an egg, thus having activated them.

Vitrification

Vitrification is a technology that is used in the embryo and egg freezing process so that they can be stored for later use. It is a technology that has many uses outside of fertility care with egg and embryo freezing as it allows something with a crystalline structure to be converted into something very smooth. The classic example is the creation of glass using sand (which is crystalline) as the main ingredient. Other examples include the manufacture of china plates and cups (also using sand), cotton candy from sugar (also crystalline) or ice cream which is smooth to the taste and contains no ice crystals despite its frozen state.

When we freeze cells in a lab, the main focus of the process is avoiding ice crystal formation as the fluid in the cell cools to subzero temperatures. Ice crystals pose 2 significant and deadly problems for cells. First, despite its beauty, an ice crystal is razor sharp and will readily shred any cell membrane, killing the cell. Second, as water in the cell turns to ice, it expands in volume, rupturing (killing) the cell. As a result, processes must be developed that allow cells to be frozen while avoiding the formation of ice. This science, called cryobiology, has come up with 2 methods that work well with human embryos, slow freezing and vitrification.

WHN offers you successful and trustworthy treatment options. We manage all the procedures for you at the most affordable cost while serving you with highly successful doctors in the world-standard hospitals.