Fertility Treatment - IVF Regimen

For couples experiencing difficulty achieving conception there are a number of assisted reproduction steps that can be taken with the assistance of a fertility doctor/clinic. These steps are commonly referred to collectively as in vitro fertilization although IVF is but one type of assisted reproduction.

A child conceived through IVF is popularly referred to as a "test tube baby" because conception occurs in laboratory glassware. The steps involved are discussed below and give you a solid overview from which you can investigate in futher detail. You must also, of course, discuss in detail the entire procedure with your doctor.

Treatment options:

• Full investigation of the causes of infertility as required. (Couples who have previously been adquately investigated elsewhere will have no more tests than are considered to be necessary.)
• Follicular stimulation and ovulation induction
• Andrology service - semen analysis using a Computer Assisted Sperm Analyzer, sperm preparation, and sex selection
• Artificial insemination with husban's sperm (AIH) or with donor sperm (AID) as required
• In vitro fertilization (IVF)
• Gamete intrafallopian transfer (GIFT)
• Zygote intrafallopian transfer (ZIFT)
• Intracytoplasmic sperm injection (ICSI)
• Testicular sperm extraction and intracytoplasmic sperm injection (TESE/ICSI)
• Pecutaneous epididymal sperm aspiration and intracytoplasmic sperm injection (PESA/ICSI)
• Bastocyst culture
• Assisted hatching (AH)
• Preimplantation genetic diagnosis (PGD)
• Freezing and storage of embryos
• Freezing and storage of sperm
• Ovum donation program

Initial consultation

It is recommended to arrange the initial appointment a few days before the onset of a menstrual period. This will ensure a minimum of waiting before starting treatment and yet will give time for the consultation and any necessary tests to be carried out. Normally you will first complete required paperwork and meet with a counselor who is experienced in all aspects of infertility treatment. It is recommended that you bring any information or X-rays relating to previous treatments.

Consent forms

You will be asked to sign a consent form appropriate to the kind of treatment you are about to received. The consent form allows management of the appropriate method of treatment but does not commit you to complete the treatment; you can change your mind at any time.

Further investigation

The consultation with the doctor usually lasts about half an hour during which time you will be assessed as a couple and your medical history taken. Both partners will be examined by the doctor and the type of treatment discussed in detail. Any necessary drugs will be prescribed and a mutually suitable date to start the treatment wil be arranged. Treatment can usually be started whenever a couple wishes to do so.

A thorough assessment of both partners should be made which includes a physical examination, blood tests and other investigations as appropriate. At the beginning of an assisted conception cycle a hormone profile should be completed if these tests have not already been performed. Typically patients are tested for Follicle Stimulating Hormone (FSH), Luteinising Hormone (LH), Prolactin, Adrogens, Estrogen and Progesterone prior to any drung administration. In addition, vaginal and cervical swabs for pathogens may be requested for some women.

Female investigation

It may be recommended that you complete a monitored assessment cycle. This will give essential information regarding your hormone profile and ultrasound scans allowing confirmation of ovulation. This can be combined with timed intercourse and a test of sperm survival within cervical mucus (post-coital test) performed 6 to 12 hours later.

Other investigations which are commonly required are:

• Laparoscopy to assess pelvic organs
• Hysterosalpingogram (X-ray of the womb and tubes)
• Hysteroscope (to look inside the womb)
• Transvaginal ultrasonography to assess the ovaries, uterus and endometrium
• Doppler ultrasound to measure blood flow to the uterus and ovaries

Male investigation

The husband is usually asked to produce a semen sample for analysis in the laboratory. A detailed analysis of the seminal plasma and sperm function tests are most important for a comprehensive evaluation. The Hamilton-Thorn sperm analyzer is a state-of-the-art computer controlled system that uses real time image analysis for assessing motion characteristics of human sperm. The system is used to perform analysis not only for routine assessment and IVF but also for sperm used in micromanipulation procedures.

If there is any abnormality in sperm quality, additional blood tests for hormone evaluation (FSH, LS, Testosterone, Prolactin) should be performed. In some cases of azoospermia (no sperm found in ejaculated semen), testicular biopsy is recommended.

Patients entering treatment are normally asked to have a blood test for Hepatitis B and HIV (AIDS) screening. This is for the protection of the patients and the potential child.

Infertility Treatment Procedures

1. Follicular Stimulation and Ovulation Induction

The body has four main hormones working in concert to bring about ovulation:

• FSH (Follicle Stimulating Hormone) which initiates growth of follicles at the beginning of each cycle
• LS (Luteinising Hormone) which has two roles
  • to help FSH in the initiation of follicle growth
  • to be produced in large amounts (the LH surge) when follicles are big enough to make the egg ripe and bring about ovulation
• Estrogen is released by the growing follicles and helps to regulate the the release of LH and FSH
• Progesterone is released by the follicles as they are ripening and ready to ovulate. It is of major importance in preparing the endometrial lining of the uterus for the implantation of embryo.

A number of drugs are now availalbe to aid the female partner to achieve multiple follicular growth and to bring about ovulation (the release of the egg from the follicle into the fallopian tube). Some drugs may be taken orally, by injection or by intranasal spray, depending on what is suitable for each patient. The progress of your cycle is checked by means of blood tests for Estrogen, LH, Progesterone, and vaginal ultrasound scans to assess ovarian response.

2. Intra-uterine Insemination using Husband's Sperm

Artificial insemination procedures usually involve ovulation induction which is the process of follicle development that is monitored by blood tests and ultrasound scans. 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. A portion of this is placed high into the uterine cavity by means of a fine catheter.

Intrauterine insemination with prepared sperm is only useful when all other more natural means have failed and if one or both fallopian tubes are known to be patent, and if the husband's sperm count is more or less normal.

3. Intra-uterine Insemination using Donor Sperm

Artificial insemination with the use of donor sperm may be indicated when the husband is azoospermia (no sperm in ejaculated semen). Coupes must be carefully counselled before such a procedure. Donor semen is obtained from a sperm bank. Donors are typically screened for their familial and medical history. Blood tests are carried out for blood group, Rh type, hepatitis and HIV. HIV testing is repeated on the donor after six months and only when this is clear is the sperm released for use. Donors are matched as closely as possible for physical characteristics to the male partner of the woman receiving the donor sperm.

4. In Vitro Fertilization (IVF) and Embryo Transfer (ET)

The IVF procedure cousists of recovering eggs from the ovary, fertilizing them with the husband's semen, and transferring the resulting embryos into the uterus.

Drugs are prescribed to stimulate the ovaries to produce severa eggs for IVF in order to increase the chance of conception. Once the follicles have ripened and are ready to be induced to ovulate, an injection is given of hCG which will trigger the final maturation process of the eggs. The egg recovery wil be performed 36 hours after the hCG administration and on that day the husband will be required to produce one and occasionally two semen samples. The eggs are recovered from the follicles using ultrasound-guided technique. The oocytes are carefully identified and washed before being placed in the incubator. After a period of time, usually three to four hours, they are inseminated with the specially prepared sperm. The oocytes and sperm are cultured together overnight and inspected 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 (fertilized egg) may then divide into two and subsequently four or more-cell embryo.

When the eggs have fertilized and cleaved the wmbryos will be ready for transfer to the woman. This wil normally be two or three days after the egg recovery. Husbands are encouraged to accompany their wives during this special time. The couple will be shown the embryos before the transfer takes place and the embryos' picture will be given later. Normally, a maximum of three embryos are transferred into the uterus, if as many as three are available. If there are more than three, the extra embryos can be frozen for future attempts.

5. Gamete Intrafallopian Transfer (GIFT)

GIFT is suitable for patients who have at least one fully patent and normal fallopian tube. Oocytes are recovered by the laparoscope technique. After collection, the oocytes are mixed with a preparation of the husband's sperm and the mixture is taken directly into a fine catheter and passed down the end of the fallopian tube or tubes. If surplus occytes remain after the GIFT procedure they will be inseminated in vitro and checked the following day for signs of fertilization and can be frozen for future attempts. GIFT can be used to treat couples with unexplained infertility, cervical mucus problems, pelvic endometriosis or disorder of ovulation but it is not suitable for male factor conditions unless donor sperm is used.

6. Zygote Intrafallopian Transfer (ZIFT)

Many believe that the fallopian tube may provide a better natural environment than in vitro culture of the environment in fallopian tube may be more suitable for the zygote than in utero. Therefore, in certain cases, it may be desirable to transfer the zygote or embryo to the fallopian tube rather than culture the zygote in vitro or transfer the embryo to the uterus. ZIFT does have the advantage over GIFT in that fertilization and embryo quality may be first observed.

7. Intracytoplasmic Sperm Injection (ICSI)

In the past, treatment of the male partner to improve sperm quality has largely proved unsuccessful. A number of patients undergoing in vitro fertilization fail to achieve fertilization. Often these cases are due to a small number of sperm or the sperm being unable to penetrate the outer shell of the egg. Novel techniques have been developed to get the sperm into the egg. Intracytoplasmic sperm injection (ICSI) is the new technique which involves directly injecting the sperm into the cytoplasm of the egg so that it bypasses all the natural barriers that the sperm normally has to encounter. ICSI procedure consists of recovering eggs from the ovary and fertilizing them by using a very tiny injection glass micropipette to pick up only one spermatozoon and injecting it into the egg cytoplasm. After that the rest of the process is the same as the IVF procedure.

8. Testicular Sperm Extraction (TESE) or Percutaneous Epididymal Sperm Aspiration (PESA) and Intracytoplasmic Sperm Injection (ICSI)

In some cases sperm are formed in the testes but are not present in the ejaculate due to a blockage or absense of vas deferens, ejaculatory dysfunction or he presence of necrozoospermia. Viable sperm can usually be recovered by testicular biopsy (TESE) or by aspirating from the proximal part of the epididymis (PESA) and can be used to fertilize the egg by ICSI procedure.

9. Egg Donation

Some women are unable to produce their own eggs due to hormonal deficiency or genetic disease. The techniques of IVF and ET enable such couples to achieve pregnancy using donated eggs from volunteer donors. Such donors are screened for genetic disorders and transmittable diseases in a similar fashion to sperm donors. The patient receiving the donated eggs is treated with hormones which help to thicken and prepare the endometrial lining of the uterus to receive the embryos. Eggs are recovered from the donor as for in vitro fertilization. The sperm from the recipient's husband is used to inseminate the eggs. The resulting embryos are transferred two days later to the recipient's uterus.

10. Frozen Embryo Repacement

Following IVF a maximum of three embryos may be transferred in each cycle. Only good quality embryos survive the freezing process so fragmented, abnormal or damaged embryos will be discarded. Depending on the quality of the spare embryos, they may be frozen for embryo transfer at a later date. The replacement of frozen embryos is preferably carried out after hormone replacement therapy (HRT). The artificial cycle has been shown to be beneficial both in terms of results and in keeping monitoring to a minium. The actual day of transfer can also be planned in advance for optimal convenience.

11. Blastocyst Culture

After the couple has been through the steps of IVF treatment, normally embryos in the four to eight cells stage will be transferred into the uterus about two to three days after the egg recovery. Recently there has been a remarkable development of stage-specific sequential culture media which allows the embryos to develop further in vitro for up to five or six days after egg recovery and that embryo stage is called blastocyst. The advantage of blastocyst culture are to eliminate those embryos with little development competence and to faciliate the synchronization of embryonic stage with uterine endometrial development. This means that one can expect higher pregnancy and implantation rates 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 only gets 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 can produce around 50 - 60% of blastocyst development from the fertilized oocytes. The treatment protocols depend on each individual patient, considering the number of oocytes retrieved and the developmental potential of embryos in day three.

12. Assisted Hatching

In some couples the embryos have a very thick zona (the outer shell of the embryo) which may be the cause of implantation failure. Assisted hatching is the method of using micromanipulation techniques such as mechanical, chemical or laser to create a small hole in the zona which may help the embryo escape from its shell and implant in the uterus. Some drawbacks of this method are an increase in monzygotic twins, use of chemicals such as acid to make a hole can be harmful to the embryo, and studies have found that embryo with thin zona do not benefit from this method. The assisted hatching method is recommended only for select groups of patients: embryos with thich or hardened zona, advanced maternal age, elevated FSH, previously repeated failed implantation and cryopreserved embryos. The laser technique has proved to have many advantages over mechanicl and chemical methods.

13. Primplantation Genetic Diagnosis (PGD)

A new high tech method for detection of normal embryo before transfer is now available called PPGD).

Following ovarian stimulation, multiple egg collection and fertilization, embryos are cultured for two days at which time they usually consist of six to eight cells. Each of these cells has complete genetic information and each cell has the potential to continue growth to establish pregnancy. Therefore, one or two cells can be removed from an eight-cell embryo by using an embryo biopsy procedure and the embry will continue to develop normally. The removed cells will then be analyzed by using a technique called Flourescent in situ Hybridization (FISH). The FISH technique can tell whether an embryo cell has two X chromosones (female) or one X and one Y chromosone (male) and can also be used to deted specific chromosone problems such as Down syndrome. FISH analysis can give us results within one day and the resulting normal embryos will be put back into the uterus.

The technique is suitable for specific couples such as advanced maternal age which have a very high risk of having 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 can be expected.