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Assisted Reproductive Techniques (ART) are treatment designed to assist infertile couples who are unable to conceive by natural way. There are many choices of ART and the option will depend on the cause of infertility and the condition of the patient. Your doctor will give you the best suggestion after completed investigation of your infertility. In ovarian induction, fertility drugs are used to stimulate the ovaries to enhance the growth of multiple follicles and yield more eggs with better quality. There are two types of ovarian induction:
(a) Ovarian stimulation This is a simple treatment whereby the ovaries are stimulated with oral drugs (clomiphene citrate) to produce a number of eggs and allow fertilization to occur at timed intercourse. This is the best choice of treatment for those with uncomplicated hormonal disorder and PCOS (polycystic ovarian syndrome).
(a) Controlled ovarian hyperstimulation (COH) In a COH, GnRH (gonadotropin releasing hormone) agonist or antagonist is used to suppress the hormone in the body, then rFSH (recombinant follicular releasing hormone) is given to stimulate the growth of multiple follicles. When the eggs reach optimum size, ovulation is induced by hCG (human chorionic gonadotropin) injection. There are two protocols for COH, long protocol applied on younger women and good responders while short protocol applied on older women and bad responders.
IUI is useful in women with deficient cervical mucus and antisperm antibodies. It is widely used for unexplained infertility, mild endometriosis and mild oligospermia (low sperm count) before resorting to IVF. However, IUI can only be applied on those who have normal uterus and patent Fallopian tubes. In this treatment, female partner undergoes ovarian stimulation. When the ovarian follicles reach 18 mm in diameter, hCG injection is given to mature the eggs. 36 hours later, washed sperm is inserted into the female partner¡¯s womb with a catheter inserted into her vagina and through the cervical canal.
3. Gamete Intrafallopian Transfer (GIFT) GIFT is only performed when previous investigation has shown that Fallopian tubes are normal. GIFT is used for unexplained infertility and certain mild male infertility cases. However, it is not as popular as IVF because it involves minor surgery, laparoscopy and general anaesthesia. After ovarian stimulation, the eggs are collected using the laparoscopy and are mixed with washed sperm. The mixture of sperm and eggs is then transferred into Fallopian tubes to allow fertilization to occur naturally within the tubes. GIFT is still needed where the laboratory facility is inadequate for IVF and in cases of repeated IVF failure.
4. In Vitro Fertilization (IVF) IVF is also known as ¡°test-tube-baby¡±, as the fertilization takes place outside the body (inside a test tube). This is the best treatment for those who have tubal damage, endometriosis, sperm disorders and unexplained infertility. IVF is also performed when sperm or egg donation is involved. Female partner undergoes controlled ovarian hyperstimulation (COH), either with long protocol or short protocol, depending on her condition. When the leading follicles have reached 18 mm, hCG injection is given to mature the eggs. 34 hours later, oocytes are retrieved. Oocyte retrieval is a process of aspirating the eggs through the vagina. This is performed under sedation or general anaesthesia. On the same day, semen collected from male partner is washed and processed. The washed sperm is then put into culture media containing the eggs to allow fertilization to occur. The mixture will be cultured in an incubator. After two days, the embryos formed are put back into the womb using a catheter and under ultrasound scan guidance. The excess embryos that are not transferred may be kept for freezing. After the embryo transfer, luteal support in the form of oral tablet, vaginal pessary or injection are given to improve implantation.
5. Intracytoplasmic Sperm Injection (ICSI) 20 years ago, when we encountered the male partner with severe poor sperm quality, the options were sperm donation or hope for miracle to occur. Fortunately, now we have ICSI to help those couples with severe low sperm quality to have baby of their own. ICSI is a newly developed technique which has greatly improved the management of male infertility due to severe oligospermia (low sperm count). This technique can treat those men who produce extreme poor quality sperm. In ICSI, we need a few sperm only and one single sperm is injected directly into ne egg using a very fine suction pipette. Whereas in IVF, the sperm is mixed with the eggs to allow fertilization to occur. In ICSI, we ¡°fertilize¡± the eggs with sperm manually and in IVF we let fertilization occurs naturally.
Blastocyst is a embryo that has advanced to the five-day stage which consists of 50-200 cells. While the majority of fertilized eggs will develop into a three-day old embryo, only the strongest and healthiest embryos will develop into a blastocyst. Therefore, blastocysts are considered to be a more "select" group of embryos with a higher chance of implantation. Blastocyst transfer is not an option for all IVF patients. The technique is most successful with patients who are younger and have a large number of eggs available at retrieval.
Normally, the zona pellucida (a protective layer surrounds the embryo) will breaks down at later stages of embryo development to allow the inner cells of the embryo to implant in the womb. In other words, before an embryo can implant into the womb, it must hatch from the zona pellucida. There is some evidence that in some women, the zona becomes toughened and restricts the embryo to hatch. Assisted hatching helps the embryo to hatch by making a small hole in the zona pellucida. Just before the embryos are replaced, whether they are fresh or frozen/thawed, a small hole is made in the zona pellucida using a micromanipulation technique. The process is repeated for each embryo. The process will damage about 1% of embryos.
8. Preimplantation Genetic Diagnosis (PGD) Preimplantation genetic diagnosis (PGD) is a technique used to identify genetic defects in embryos created before transferring them into the uterus. The approach through PGD assists couples at risk of an inherited disorder to avoid the birth of an affected child. When an embryo reaches eight-cell stage, one or two cells are removed from it. Genetic analysis is then done on the cells to see if the embryo from which they were removed contains the abnormal gene. Embryos with normal gene can be transferred back in the hope that they will develop. Those embryos that had a copy of the faulty gene are allowed to perish.
9. Cryopreservation (Embryo/ Sperm Freezing) Cryopreservation is freezing of sperm or embryos and keeping them in nitrogen liquid at -196°C for future use. Survival rate of thawed sperm or embryos depends on their quality before freezing. Normally, survival rate of sperm and embryos will decrease after thawing. (a) Sperm freezing Sperm freezing is done when male partner is not available to produce semen on the day of IUI or IVF. The sperm is frozen and kept in liquid nitrogen. It is thawed and used when needed. However, sperm freezing is not encouraged as the survival rate is much more lower compared to fresh sperm. Fresh sperm is preferred for ART. (b) Embryo freezing Embryo freezing is done whenever there are more than three embryos obtained from IVF or ICSI cycle. The best three embryos are chosen for embryo transfer while the rest will be kept for freezing. Embryo freezing is also performed when the female partner cannot undergo embryo transfer due to conditions such as OHSS (ovarian hyperstimulation syndrome). After freezing, the embryos are stored in liquid nitrogen for as long as required. The frozen embryos are thawed when the female partner is ready for a new cycle.
(a) Egg donation It is designed for women who are unable to produce eggs of their own, have premature menopause or have hereditary diseases. The egg donor will receive COH similar to IVF cycle, while the recipient will be prepared so that the womb is ready to accept the embryo at the right time. These are all done by the usage of hormones. Eggs collected will be fertilized with the sperm of the male partner. (b) Sperm donation Sperm donation is designed for men who are azoospermia (no sperm) or have hereditary diseases. Sperm collected from sperm donor is processed and used for IUI or IVF.
11. Surgical Sperm Retrieval (PESA, MESA, TESA) This is a daycare minor surgery done to collect sperm from the vas deferens, epididymis or testis. Sedation or general anaesthesia is required for the procedure. Surgical sperm retrieval may help those who are able to produce sperm but the sperm cannot enter semen due to blockage of vas deferens or epididymis to retrieve sperm. Sperm that are retrieved surgically will be used for ICSI. There are three types of surgical sperm retrieval, namely percutaneous sperm aspiration (PESA), micro-epididymal sperm aspiration (MESA) and testicular sperm extraction (TESA). Option of the treatment will depend on individual condition. PESA is usually the first option for azoospermia patients. In PESA, a fine needle is inserted into the epididymis through the scrotum and fluid is gently aspirated from the epididymis. This liquid is then analyzed for sperm content and motility. MESA is a microsurgical treatment where a small cut is made through the scrotum and into the epididymis. Fluid collected is then taken for microscopic examination. If no sperm is found in the epididymal fluid, TESA is the option treatment. TESA involves testicular biopsy (small surgical incision in the testis), where a needle is inserted into the testis and removes a small sample of testicular tissue, which is then examined for sperm. This procedure requires general anesthetic and will cause some pain and soreness.
Luteal support in the form of injections (hormone), oral tablet or vagina pessary are given to female partner after IUI, IVF or ICSI. This injection is given in order to help the implantation of embryos in the endometrium.
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