Infertility treatments at Bangkok IVF Clinics

Treatment options range from the most simple to the most high-tech , according to the causes of infertility and the decision making will be made together by the patients and the doctor. The successful of treatment needs a shared concern , co-operation and understanding of both partners.

Assistance may first be given to couples trying to achieve a pregnancy by monitoring cycles and timing natural intercourse. If ovulation is not regular then drugs may be used in the early part of the cycle to help ovulation more reliable. The chance of conception are higher if more eggs are produced , therefore an ovarian stimulation protocol may be used. Each patient’s prescription is carefully designed and the dosage varies depending on age and the cause of infertility.

Ovulation induction & Cycle Monitoring

If a woman has an irregular menstrual cycle, monitoring with ultrasound scans and hormone assessments may help to identify the fertile time of the month and so improve the chances of natural conception. If ovulation is not occurring, then drugs may be administered after the onset of menstruation to stimulate egg production.

A number of drugs are now available to aid the female partner to achieve multiple follicular growth and to bring about ovulation ( the release of the egg from the follicle into fallopian tube ). Some drugs may be taken by oral , by injection or by intranasal spray. There are several methods of ovulation induction depending on each patient. The combination of GnRH-a and FSH is currently the most frequently used methods for stimulating the ovaries. The new and effective drug , GnRH-antagonist , is now also introduced into this kind of treatment.

Careful monitoring will prevent the development of too many eggs and will thus reduce the chance of multiple pregnancies and the development of the ” ovarian hyperstimulation syndrome “.

Monitoring can be performed in two ways :

• by endocrine assay of the blood levels of estrogen , LH and progesterone
• by ultrasound scanning using the modern technique of vaginal ultrasound which does not require the full bladder. Using ultrasound , a picture of the ovaries , the follicles and the endometrial lining of the uterus can be obtained

When the follicular development has reached the stage of the optimum sizes, hCG will be administered to trigger ovulation. Egg retrieval will be scheduled within 34 – 36 hours after hCG administration.

Intrauterine insemination (IUI)

Intrauterine insemination by husband’s sperm is a procedure by which specially prepared sperm is placed directly in the uterus ( womb ) near ovulation time. This process usually involves ovulation induction which the process of follicle development is monitored by blood hormone and ultrasound scanning. When ovulation has occurred , the male partner is asked to produce a semen sample by masturbation. This specimen is prepared in our sperm laboratory to select only active motile sperm. The prepared sperm is placed right into the uterine cavity by mean of a fine catheter.

The development of the ovarian follicles is monitored with ultrasound and the insemination is timed to take place 36-40 hours after administration of the hormone injection hCG, which triggers ovulation. When ovulation has occurred, the male partner is asked to produce a semen sample. This sample is prepared in the laboratory, and is then placed in the uterine cavity by means of a fine catheter.

IUI should be performed in cases where the woman has healthy fallopian tubes and the sperm preparation is satisfactory. IUI with husband’s sperm is used to treat patients with at least one healthy fallopian tube. Because the cost per pregnancy is significantly less with IUI than with assisted reproductive technologies , many experts recommend patient trying at least 3 IUI cycles before moving to the more advances and expensive ART.

In-vitro Fertilization (IVF)

IVF is a process by which eggs are recovered from the ovary , fertilized in the laboratory and transferred into the uterus 3 – 5 days later as cleaving embryos or blastocysts.

Ovulation induction was performed to stimulate the ovaries to produce several eggs for IVF in order to increase the chance of conception. Once more than three follicles have ripened , the female partner will be given an injection of hCG which will trigger the final maturation process of the eggs. The egg recovery will be performed 36 hours after hCG administration and on that day the husband will be required to produce semen samples. The eggs are recovered from the follicles using ultrasound- guided technique. The oocytes are carefully identified and washed before being placed in incubator. After a period of time , usually 3 – 4 hours, they are inseminated with the specially prepared sperm. The oocytes and sperm are cultured together and inspected on the following day to see if fertilization has occurred. The first signs of fertilization , are shown by the presence of two small dots within the egg , the pronuclei. If this has occurred , the zygote ( a fertilized egg ) may then divided into two , four or more – cell embryo.

When the eggs have fertilized and cleaved , no more than three embryos will be transferred into the women on day 3 or day 5 after egg collection. Husbands are encouraged to accompany their wives during this special time , but only they wish to do so. The couple will be shown the embryos before the transfer takes place and the embryos’ picture will also be given. If there are more than three good quality embryos , the extra embryos can be frozen for future attempts.

In reality, there are a number of factors that have to be taken into consideration to analyze the success or the failure of any IVF treatment. Possible reasons why a particular cycle treatment may fail include:

• Patient’s age
• Sperm and egg quality
• Failure to collect eggs
• Failure of implantation of the embryos

On an average, there is a 20% to 30% success rate associated with IVF.

In general women above 40 find it a little more difficult to conceive using IVF as the ovulation rate as well as quality of eggs decreases with age. Those who have had a normal delivery before or successful IVF births earlier have a greater chance of getting pregnant the second time over.

The IVF centre where the treatment is done also influences the success rate. Factors like size of the clinic, technical expertise of the team, type of equipments used, protocols for ovary stimulation, and transferring of embryos play an important role in inferring the overall success rate.

ICSI (Intra Cytoplasmic Sperm Injection)

If there is a question of the sperm’s ability to fertilize the egg, due to either a low sperm count or poor quality of the sperm, that poses no problem whatsoever. Intra-Cytoplasmic Sperm Injection (ICSI) would be performed instead of regular In Vitro Fertilization (IVF). With ICSI, the eggs are retrieved the same as if you were doing conventional IVF. However, the eggs and the sperm are then fertilized in the laboratory, by direct injection of a single sperm into each egg. Three days later the resulting embryos are simply placed into your uterus with no surgery, just as with IVF. Extra embryos are frozen for later attempts at pregnancy.

The availability of this Intra-Cytoplasmic Sperm Injection, “ICSI” technique (which was developed and perfected by the Brussels University and our institution in St. Louis) means that men whose sperm previously were too weak or too few to fertilize in vitro (IVF), now have no problem fertilizing their wife’s eggs. The fertilization rate per egg using ICSI is about 70% despite the sperm being terrible, the fertilization rate per infertile couple is over 99% if the wife has adequate eggs, and the pregnancy rate per treatment cycle is over 50%. This is not significantly different from regular IVF with normal sperm. This technique is very cost-effective, and will give you the same high chance for getting pregnant as any couple with normal sperm.

ICSI can only be carried out on a mature egg. Unfortunately egg maturity can only be truly identified under the microscope and it is, therefore, possible that following egg collection, none of the eggs are suitable for ICSI. This situation is normally rare, but it is still a possibility.

PGD (Preimplantation Genetic Diagnosis)

PGD (Preimplantation Genetic Diagnosis) technology 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 inherited genetic disease to their offspring.

Following ovarian stimulation , egg collection and fertilization, embryos are cultured for another 2 days which they usually consist of 6-8 cells. Each of these cells has complete genetic information and also each cell has the potential to continue growth to establish pregnancy. Therefore, one or two cells can be removed from an 8-cells embryo by using an embryo biopsy procedure and the embryo will continue to develop normally. The removed cells will then be analyzed by using a technique called Fluorescent in situ Hybridization ( FISH ) or Polymerase Chain Reachion ( PCR ). The FISH technique can tell us whether an embryo cell has two X chromosomes ( female ) or one X and one Y chromosome ( male ) and FISH can also be used to detect specific chromosome problems such as Down syndrome. FISH analysis can give us the results within one day and the resulting normal embryos will be transferred back into the uterus.

This technique is now suitable for specific couples such as advanced maternal age who have a very high risk to have a child with Down syndrome , carriers of genetic disease , recurrent abortion and couples who carry X-linked diseases. Haemophilia and Muscular dystrophy are examples of X-linked diseases.

In the future it is likely that genetic testing of embryos will be used more routinely to improve IVF success rates as well as to prevent transmission of genetic disease. With the transfer of genetically normal embryos, a higher percentage of implantation and reduced miscarriage rates can be expected. This sophisticated and technologically advanced testing identifies which embryos are free of abnormalities and more able to achieve the patient’s goal of a healthy baby.

PGD is recommended for families with a history of a specific genetic disease. Using polymerase chain reaction, fluorescent PCR and DNA sequencing, the scientists in our PGD laboratory can examine each developing embryo to identify the absence or presence of these specific genetic disorders. As a result, only those embryos free of genetic disease will be transferred to the patient’s uterus so as to increase the chance of conception and ultimately a healthy baby.

Single gene disorders are categorized depending upon whether the gene is located on the X chromosome, an autosome or whether the gene is dominant or recessive. These classifications include autosomal recessive, autosomal dominant and X-linked.

For a dominant disorder, one only needs to have the abnormal DNA sequence on one chromosome. If that mutation is passed on to the embryo, the embryo will be affected with that genetic disease. One example of an autosomal dominant disorder is Myotonic dystrophy.

Recessive disorders require that the mutation be present on both chromosomes of the chromosome pair. If one only has the mutation on one chromosome, the individual is normal but carries the mutation in his cells and is called a carrier. The fertilization of an egg from carrier parents may result in an embryo having the mutation on both chromosomes of the chromosome pair and the embryo therefore being affected with that genetic disease. For example, Cystic fibrosis (CF) is a common autosomal recessive genetic disorder that primarily affects the lungs of CF patients. The CF mutation affects a protein within the cell that reduces the cell’s ability to function properly. This results in a build up of mucous within the lungs, lung dysfunction and possible death.

X-linked disorders are due to mutations of genes on the X chromosome and have different patterns of inheritance due to their transmission on a sex chromosome and whether the embryo is male or female. Examples of X-linked diseases are the Fragile X syndrome and Duchenne muscular dystrophy.

Pre-implantation genetic aneuploidy screening (PGS)

Preimplantation genetic aneuploidy screening (PGS) has been performed as a way of enhancing embryo selection in patients with an increased incidence of embryonic numerical chromosome abnormalities (advanced maternal age, recurrent miscarriage and recurrent implantation failure). It has been proposed that the replacement of euploid embryos in these patients would result in a higher implantation and pregnancy rate and a reduced miscarriage rate. Additionally, the transfer of fewer embryos could reduce the chances for multiple pregnancies in all IVF patients. Although, to date, multiple studies have addressed this issue, contradictory results have been encountered. As a result, the effectiveness of aneuploidy screening remains to be established. Moreover, child outcome studies documenting the safety of this procedure are needed.

For couples aware of genetic disorders through family history or based on carrier testing, PGD testing can be performed to help avoid a pregnancy or child born with the specified genetic condition. In genetic disorders where the gene structure is known, such as Cystic Fibrosis or Tay-Sachs, the actual genes of the embryo are examined for presence of the condition. Other genetic disorders, such as Duchenne muscular dystrophy or hemophilia, only affect males and, therefore, the DNA of the embryo is examined to determine the sex and only the female embryos are transferred.

PGD can currently be used to detect the following single gene disorders.

Surgical sperm retrieval

Surgical sperm retrieval is a treatment option for men with an absence or blockage of the tube (vas deferens) or non- obstructive azoospermia.

Sperm can be collected directly from the epididymis situated inside the scrotum (the pouch holding the testicles) where sperm are stored and mature using a fine needle and syringe. This is known as ‘percutaneous epidydimal sperm aspiration’ or PESA. Sperm can also be retrieved from the testicles, a process known as ‘testicular sperm extraction’.

Surgical sperm retrieval is carried out by a Consultant Uroandrologist who works in close association with the fertility unit and the procedure is timed to coincide with the female partner’s egg collection. If enough sperm is retrieved it may be possible to freeze small amounts for use at a later stage. The sperm collected is then used to inject the eggs using ICSI.

Oocyte Retrieval

Fertility drugs, taken through injections, are used to stimulate a woman’s ovaries to develop multiple mature eggs. This improves chances for fertilization and ultimately pregnancy.

When the eggs are mature, they are retrieved by an ultrasound guided procedure. Here a needle is placed through the vaginal opening and into the ovaries. There are no abdominal incisions or suturing. The eggs are then evaluated in our on-site embryology lab. Once there, they are fertilized with sperm from your partner or a donor. Retrieval is performed under light anesthesia as an outpatient procedure. Risks are minimal and recovery takes an hour or two, although post-operative cramping is common.

Oocyte are at present recovered by two main techniques:

• Ultrasound Oocyte Retrieval
  
  This is a technique of choice in the majority of cases since it is a less invasive procedure , the post operative period is less uncomfortable and excellent results are achieved with it. A vaginal ultrasound probe with an attached needle guide is passed into the vagina under sterile conditions and a needle passed through the top of the vagina into the ovary, The follicles are then aspirated until oocytes are obtained.
   
• Laparoscopic Oocyte Retrieval
  
  Originally , oocytes were always collected laparoscopic ally , at present on occasions , patients are recommended to have a laparoscopic Oocyte Retrieval only when GIFT was performed.

Assisted hatching

Under normal circumstances the protective layer that surrounds the embryo known as the zona pellucida undergoes gradual thinning due to the expansion of the growing embryo and the increased pressure causes the zona to break and the embryo hatches and then implants in the uterus around day 5 or day 6.

In some specific couples , the embryos have very thick zona which may be the cause of implantation failure. Assisted Hatching is the method using micromanipulation techniques such as mechanical , chemical or laser to create a small hole at the zona which may help the embryo escaping from its shell.

The most commonly used indications for assisted hatching with an in vitro fertilization case are:

• Age factor – Couples having IVF with the female partner’s age over 37
• Egg quantity and quality factor – Couples in which the female’s day 3 follicle stimulating hormone (FSH) level is elevated
• Embryo quality factor – Couples having IVF with poor quality embryos (excessive fragmentation or slow rates of cell division)
• Zona factor – Couples having IVF with embryos that have a thick outer shell (zona pellucida)
• Previous failures – Couples having IVF that have had one or more previous IVF cycles that failed

Pregnancy rates for in vitro fertilization procedures with assisted hatching have been shown in some published studies to be higher than for IVF without hatching. There is an improvement in implantation and pregnancy rates in our IVF clinic with the use of assisted hatching. This is not seen in all IVF programs.

It is possible to damage embryos with hatching and lower the pregnancy rate in a program. Therefore, it is essential that if assisted hatching is done, it must be expertly performed by properly trained embryologists.

The actual pregnancy and live birth rates seen in an individual IVF center will vary according to the hatching technique used, the overall quality of the laboratory, the skill of the individual performing the hatching, the embryo transfer skills of the physician, and other factors.

Blastocyst transfer

Recently , there is a remarkable development of stage specific sequential culture media which allows the embryos to develop further in vitro for up to 5-6 days after egg recovery and that embryo stage so called “Blastocyst”. The advantages of blastocyst culture are to eliminate those embryos with little developmental competence and to facilitate the synchronization of embryonic stage with uterine endometrial development. This means that we can expect the higher pregnancy and implantation rate from the blastocyst transfer. However , there is considerable patient variation , which means that on the same day using the same media , one patient may get 90% blastocyst development while another patient get only 10%. Additional research data found that about 5 % of patients having blastocyst culture have not at least one embryo develop to blastocyst so they end up with no transfer.

Now the sequential culture media we used at Bangkok IVF Center can produce around 50-60 % of blastocyst development from the fertilized oocytes. Our treatment protocols still depend on each individual patient , considering from the number of oocytes retrieved and developmental potential of embryos in day 3. We believe to do the very best procedure treatment for each of our patients.

Embryo Freezing

Embryos not transferred to the uterus may be suitable for freezing according to the wishes of the couple. We recommend freezing when there are good quality embryos left after the embryo transfer is completed. Poor quality embryos, or embryos which are slow to develop, are unlikely to survive freezing and thawing to give a reasonable chance of pregnancy.

These embryos can be replaced in a future cycle without the woman having to undergo the same drug treatment and surgery. Embryos can be frozen for up to five years, although this can be extended to ten years in exceptional circumstances.

The results following the transfer of frozen-thawed embryos depend on the number and quality of embryos available as well as the age of the woman. Pregnancy rates following frozen embryo transfer are generally lower than after transfer of fresh embryos, but it is much simpler to undertake a frozen embryo cycle. Frozen embryo transfer has been practised since 1983 and there appears to be no increased incidence of fetal abnormality in babies born following this procedure.

Whether to freeze embryos or not is an important decision for a couple. The couple must give written consent to storage and their future use. It is very important that these are completed accurately as any inconsistencies in the couples’ consent forms may make the storage of the embryos invalid. Patients are also responsible for keeping in touch with the unit and notifying us of any change of address. The storage period is governed by law and we do not need your consent to remove these embryos from storage at the completion of the statutory period.

About 70% of all frozen embryos survive the thawing process. Although some couples may have all of their embryos survive in good condition, others may not have any that survive.

Replacement of frozen embryos is relatively simple. The woman’s natural cycle is monitored to time ovulation using an ultrasound scan and ovulation predictor kits. Following ovulation, the embryos are thawed and transferred back to the uterus. If the woman’s cycle is irregular we may recommend hormone replacement therapy (HRT), which will allow us to prepare the lining of the uterus for embryo transfer.