Advanced Procedures
- Invitro Maturation
- Fertility Preservation
- Egg Freezing and ovarian tissue freezing
- Vitrification
- Cytoplasmic transfer
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ASSISTED REPRODUCTION - TREATMENTS
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IN-VITRO FERTILIZATION & EMBRYO TRANSFER This treatment consists of five steps:
This procedure is done for couples with tubal problem and / or slight sperm problem. OVARIAN STIMULATION Various hormonal preparations are used for ovarian stimulation so that several follicles ( optimal number is 10 ) develop in the treatment cycle. The follicular growth is monitored by ultrasound scans and blood tests for hormone levels. All the ultrasound scans are done vaginally so there is no need to drink water to fill up the urinary bladder. The first scan is done normally on day two and the day five of stimulation and the second scan two days later. Appointments are given for the scan when the treatment is started. At the scan, the ovary is imaged using high frequency ultrasound waves which when directed into the pelvis, reflect the sound waves back at different intensity from the structures on its pathway to produce an image. From the image we can measure each of the ovarian follicles daily to assess the follicular growth. The endometrial (lining of the uterus) thickness is also measured at the same time. It is important to drink at least 3 litres of water per day during ovarian stimulation. Blood sample taken on the day of the scan is analyzed for oestrogen, progesterone and LH hormone. From these tests it is possible to ensure optimal egg production and maturation. The optimal number of eggs to get is 6-10 depending on the treatment that is planned. Once the optimal follicular growth is achieved, injection of human chorionic gonadotrophin (hCG) is arranged. This is a timed injection and once it is administered, the egg collection operation is performed at a fixed time. If the egg collection is delayed then it is possible that the ovulation may occur spontaneously. The response to the hormone stimulation of ovaries to produce follicles vary from person to person depending on age, amount and type of hormones used also from cycle to cycle in the same person. If the scan and the blood tests show poor ovarian response with very few follicles, then the treatment cycle may be abandoned. COLLECTION OF EGGS Collection of eggs from the ovarian follicles is performed under general anaesthesia. Very rarely in selected patients this operation could be performed under sedation. If you want your operation under sedation please discuss this with your doctor. You are admitted to the hospital in the morning or the previous evening of the operation. You will not take anything to eat or drink from the midnight before the operation. Under ultrasound a long needle is guided through the vagina into the pelvis, and the eggs are collected from the follicles by aspiration of the fluid from the follicles. After the general anaesthetic the ultrasound probe is placed in the vagina and the aspiration needle is passed through a special guide into the follicles. The eggs are aspirated along with the fluid which is contained in the follicles. If an egg is not obtained then it may be necessary to wash the follicles with special culture media to detach the egg from the follicle. The eggs are identified under the microscope by the reproductive scientist. OOCYTE CULTURE AND FERTILIZATION The eggs that are collected at the operation are put in a special culture media for two to six hours before the husband's washed sperm are added in precise numbers. The semen specimen is collected after cleaning the genitals with soap and water in a sterile container given by the IVF laboratory by masturbation. The semen is "washed" and the motile sperm are separated by various special techniques, incubated at 37oC and then added to the eggs in precise numbers. The eggs and the sperm are then kept in a special incubator for 48 hours. However they are observed after 18 hours to see the first signs of fertilization. If no fertilization is detected then a second sample of sperm may be added. Often we perform sperm micro-injection for these unfertilized eggs but most of these eggs may not fertilize as these eggs may have abnormal chromosomes. If the sperm sample showed poor motility or poor sperm survival then a single sperm is injected into the egg by a technique called sperm micro-injection (ICSI), which is described later in the website. If the fertilization is normal the embryos will start dividing within 36 hours. We normally transfer embryos at 48 hours or 72 hours. Preparations are made for embryo transfer. EMBRYO TRANSFER The embryo transfer procedure is very simple but very critical. The doctor and the scientist might have already discussed with you the fertilization rate and the number of embryos to be transferred. The number may vary between one to three depending on circumstances of each couple. A speculum is introduced into the vagina and the cervix is cleaned with a special culture media. The embryos are loaded into a very thin soft catheter, which is gently passed into the uterine cavity and the embryos are carefully injected into the cavity of the uterus. You have to rest for about fifteen minutes and then go home. It is advisable to stay at home and rest for the next three days. We advice you should avoid house work and shopping. You can walk around the house. This will give better chance for the embryos to implant and achieve a pregnancy. Complete bed rest is not advised. The doctor will give you a new schedule for hormone support after the egg collection. These may be vaginal suppositories, or daily injections or tablets. Blood test may be advised to check the level of progesterone hormone. Twelve days after the embryo transfer (fourteen days after the egg collection) a blood test for human chorionic gonadotrophin( ßhCG) will determine whether the treatment has been successful. This is a pregnancy specific hormone. The doctor will discuss the results with you. If a pregnancy is diagnosed as indicated by the "day 14" blood test, please do not stop the hormone support unless advised by the doctor. If the level of hCG is low then repeat blood tests may be required two days later. It is possible that the pregnancy is inside the fallopian tube (ectopic pregnancy) and not inside the uterus. This requires careful evaluation and treatment. The doctor will discuss this with you. The first scan to confirm the pregnancy by visualizing the gestation sac within the uterine cavity, foetal echo and heart beat is done on "day 35". The doctor will also advice you how and when to stop the hormone support. You need very careful monitoring of the pregnancy after this by your own OB GYN as nearly 30% of the pregnancies are lost if there is not proper supervision. Normally there are no side effects from the hormone support, as all the hormone preparations that are used in your treatment are natural hormones. However if you have any problems in using the hormones prescribed or you have concerns using the hormones please consult the doctor in the centre. Do not stop the hormones under any circumstances. You should take sensible well balanced diet, good amount of fluids (water) and rest at home. Rest does not mean you should stay in bed but adequately move around the house. You should remember that a spontaneous abortion, ectopic pregnancy or a multiple pregnancy could occur after IVF treatment just as they can after natural conception, though the rate is slightly higher. CRYOPRESERVATION With good quality eggs and good sperm 85% of the eggs are usually fertilized. Normally with IVF only 1-2 embryos are replaced. Any surplus embryos after the transfer depending on the quality are frozen (cryopreserved) in liquid nitrogen for future use. If you are successful with the initial treatment and have a pregnancy then you could use the cryopreserved embryos after the birth of the first baby. If you want to wait for two or more years until the baby has grown up we will keep the embryos safe till that time. Normally the embryos are kept frozen for no more than five years. A small charge is made for the safe keeping of your embryos. You should constantly keep in touch with the centre and pay your dues promptly; otherwise the embryos may not be kept any longer. If however you were not successful after the initial treatment, you could have the cryopreserved embryos transferred after giving you a new schedule of hormones to develop the endometrium (lining of the uterus) or in a natural cycle after the ovulation is monitored. Only when the endometrial lining is sufficiently and satisfactorily developed, the embryos are replaced. Cryopreservation is a very reliable method of utilizing the surplus embryos. The freeze / thaw success rate is 70-75%. Some embryos are naturally lost during freezing and thawing process. The results from our own previous experience in United Kingdom, Saudi Arabia and various other centres round the world suggest that freezing does not in any way damage the baby that is ultimately born. The pregnancy rate from frozen embryos is slightly lower than the fresh embryos at 25% if these are transferred. Very rarely all the embryos are lost during thawing process. We use a rapid freezing technique called vitrification of eggs and embryos. we have been using slow freezing technique for over 21 years with very good results. With vitrification we can get similar results. INTRAUTERINE INSEMINATION ( IUI) This procedure is normally performed when the fallopian tubes and the husband's sperm are normal, the wife is very young and the period of infertility is short. The ovulation induction is normally done with much simpler drug regimen (tablets and / or few injections). If clomiphene citrate or Letrozole is given, it is taken from day 2 to day 6 of the menstrual cycle. A few injections may also be added. Follicular monitoring is started from day 9 by ultrasound scans. The aim is to produce one or two follicles only. Normally ultrasound scans are done but sometimes blood tests are requested to ascertain the hormone status. Once the follicles have reached the optimal maturity then the timed injection of human chorionic gonadotrophin (hCG) is given to trigger ovulation. Ovulation normally takes place 36-40 hours after the injection. You are asked to come to the centre on the day of ovulation in the morning. If there is any doubt a repeat scan may be done to confirm follicular rupture and ovulation. The husband will provide the semen specimen to the IVF laboratory in the morning which is then processed (washing and swim-up) which takes about three hours. The prepared sperm specimen is injected into the uterine cavity using a special catheter. After the IUI you could go home after 10 minutes and carry on with normal activity. Hormonal support is given to maintain the uterine lining (endometrium) in the optimal state to increase the chances of a pregnancy. OVARIAN HYPERSTIMULATION SYNDROME (OHSS) The drugs used in super ovulation (production of multiple follicle and eggs in one cycle) are not without side effects. Great care is taken to monitor the cycle and the drug regimen is tailored to each individual case. But the ovarian response in the same woman, from the same drug, in the same dosage is variable in different cycles. The ovarian response is hence unpredictable. The need for careful monitoring of the cycles with hormone tests and ultrasound scans cannot be overstressed. In about 8-10% of cases the ovaries respond unpredictably excessively with the growth of large number of follicles to gonadotrophin stimulation. In certain condition like polycystic ovaries the incidence could be as high as 60-80% in spite of careful monitoring. This results in Ovarian Hyper Stimulation Syndrome (OHSS) with enlarged painful ovaries, fluid in the abdomen (ascitis), fluid in the chest (hydrothorax), nausea, vomiting, severe electrolyte imbalance in the blood and reduced urine output resulting in kidney failure. If it is not diagnosed immediately and actively treated this could result in death. You are advised to drink about 3 litres of water per day and take a high protein diet. If there is a possibility of OHSS then you are warned to report to the doctor daily by telephone regarding pain, abdominal swelling, vomiting and urine output. You will be asked to come to the centre for check up as necessary. You should follow these instructions without fail. Admission to the centre for several days may be necessary in some cases. Unfortunately this will result in additional expenditure, which may be unavoidable under the circumstances and has to be borne by the patient. The incidence of polycystic ovaries (PCO) in the western world is around 12%. But in India the incidence is around 20%. In Saudi Arabia it is around 60%. The higher incidence is most likely due to genetic factor. The diagnosis of PCO is made by clinical history, clinical appearance of the patient, hormone tests and / or ultrasound scan of the ovaries. Sometimes all the factors may be negative but on ovarian stimulation, the ovaries respond typically in polycystic manner. In some cases of PCO even if the fallopian tubes are normal and patent it may be necessary to resort to IVF treatment as there may be excessive follicular development hence any other treatment may lead to multiple pregnancy. The doctor will discuss these factors with you at the time of consultation. In some cases the treatment cycle may have to be cancelled because of the risk of OHSS. In some cases IVF treatment may be necessary to collect all the eggs, fertilize and freeze them when there is risk of OHSS. No embryos will be replaced as a pregnancy may exaggerate the risk of OHSS. Special treatment to suppress the ovaries and reduce the risk of hyper stimulation is continued. The most important of these is to consume a high protein diet, and drink as much as 4 litres of water apart from the other fluids like coffee and tea. The most effective treatment to minimize the risk of OHSS is called IVM. Here the eggs are collected after 5-8 days stimulation while the ovarian follicles are only 2-5mm in diameter and these immature eggs are cultured in the laboratory to reach maturity. They are then subjected to ICSI and fertilized. The resulting embryos are transferred on day 3, 4 or 5. By this method the risk of OHSS is completely eliminated. This treatment is available at Miracle but NOT in other centres in India. SPERM FREEZING Sperm freezing is done if there is a very low sperm count and motility and there is a risk that sperms may disappear altogether in a short time. Sperm freezing is also offered if the husband is having radiation or chemotherapy for malignancy which often results in complete stoppage of sperm production. If the husband has work commitment and cannot spend lot of time during the treatment, then husband's sperm could be frozen and we could concentrate on the wife's treatment. This is mostly applicable when the couple come from abroad or from anther state. The doctor will discuss this with you at consultation. EMBRYO FREEZING The number of oocytes recovered from each woman in different cycles is variable. There could be as little as one or as many as 88 ( we have collected this number in our unit) this may result in large number of embryos. These extra embryos are kept frozen for future use. Before the cryopreservation procedure was widely available, all these embryos were allowed to grow in the laboratory by repeated division for up to five to six days. These embryos ultimately died. This was a terrible waste. Despite such advances in science it is still not possible to identify the embryos that are most likely to result in a successful pregnancy. Replacement of more than two or more embryos greatly increases the chances of multiple pregnancies with its associated risk. Multiple pregnancies is associated with increased risk of early miscarriage, high blood pressure, bleeding in mid and late pregnancy due to the placenta being in the lower part of the uterus, pre-term labour and foetal abnormality etc. So the risk to the mother and the baby are both increased in multiple pregnancies. Another important use of cryopreservation is in cases of ovarian hyper stimulation syndrome (OHHS) when none of the resulting embryos are replaced but are cryopreserved and used in a subsequent cycle. During cryopreservation, the embryos are placed in a special plastic tube in pairs. The tube is sealed at both the ends. These are identified by the woman's name, patient number and colour coded. All the tubes containing the woman's embryos are gradually cooled in liquid nitrogen to minus 196oC in a special machine. These tubes are then placed in metal "canes" and then lowered into large flask containing liquid nitrogen. The level of liquid nitrogen is periodically checked and topped up. The embryos are thus kept in storage in liquid nitrogen until required. The embryos could be stored indefinitely. But from the practical point we intend to store the embryos for a maximum of five years unless the couple make a special request for extension of the storage. A small charge is made for the storage of embryos per year. When a woman returns to have the frozen embryos transferred, there is no need for the ovarian stimulation or the operation to recover the eggs, as we have stored the frozen embryos. However it is necessary to control the pituitary hormones by a single injection. Two weeks later a scan and a blood test are done to confirm the hormonal control. Oestrogen tablets are now given for ten to fifteen days to develop the endometrium before the embryos are returned. The endometrial thickness and quality are assessed by ultrasound scan. Now hormonal suppositories are given (progesterone) along with the oestrogen tablets. The embryos are thawed either on the day before or on the day of embryo transfer depending on what stage the embryos were frozen. Only about 85% of the frozen embryos are successfully thawed. Some embryos are lost during freezing and thawing process. It is not possible to see the quality or the viability of the embryos until they are thawed. In some cases we might replace the embryos in a natural cycle after confirmation of ovulation. The result of animal studies and the result of frozen thawed embryo replacement in humans suggest that freezing and successful thawing in no way damages the embryos or babies born from this method. The pregnancy rates by frozen embryos in our centre are comparable to pregnancy rates by fresh embryo transfer. INTRACYTOPLASMIC SPERM MICRO INJECTION (ICSI) With the advent of in vitro fertilization, a whole new area of infertility treatment was thrown open. But this was still not the answer for a lot of infertile couple for whom IVF was not possible due to poor sperm. About 35-40% of men have very low sperm count and / or very low motility or presence of antisperm antibodies, which prevent fertilization of the egg even with IVF. In 3-5% cases the eggs fail to fertilize even though the sperm count and motility are satisfactory. All these couple benefit from sperm micro-injection. As the name suggests, Micromanipulation / ICSI means, assisting the union of the sperm and the egg (fertilization) outside the human body at microscopic level. This is a very complicated and precise technique requiring a highly skilled reproductive scientist to perform the procedure under the microscope. The egg and the sperm are minute cells visible only under the microscope. In simple terms, sperm microinjection involves holding the egg with a fine glass tube (called the holding pipette) with gentle suction under the microscope and inject a single sperm into the egg with another fine glass needle (called the injecting needle). The sperm is injected directly into the cytoplasm of the egg (ooplasm) to fertilize the egg. So sperm motility is not essential for fertilization. The sperm should be completely non motile for this procedure. Once the sperm is deposited inside the egg the fertilization process is same as with normal sperm entry into the egg. Some of the eggs are not suitable for ICSI procedure and some the eggs may not fertilize even after ICSI procedure as these eggs may have abnormal chromosomes. The fertilization rate after ICSI is around 80%. TESTICULAR SPERM ASPIRATION (TESA) Some men may not produce any sperm in their semen. These men are called azoospermic. There may be an obstruction as a result of previous infection or absence of the tube conducting the sperm (vas) from the testes to the storage area (seminal vesicle). These cases are called obstructive azoospermia. Or there may be testicular damage due to infection or chemical exposure resulting in impairment of sperm production. These cases are called non-obstructive azoospermia. There may be inherent sperm production and maturation defect in the testes called maturation arrest. Even in these cases there may be very small islands within the testes where there is some sperm production. The number of sperms produced is so small none of them come out with the ejaculate. In all the above conditions it may be necessary to aspirate the sperm directly from the testes. This procedure is called testicular sperm aspiration, which is done under general anaesthesia or sometimes under local anaesthesia. By TESA only a small number of sperm are aspirated hence sperm microinjection ( ICSI ) is a must. ASSISTED EMBRYO HATCHING Normally when the embryo reaches the uterine cavity at blastocyst stage, it will break through the outer layer, hatch and then implant. After the eggs are fertilized (embryo) and before they are transferred into the uterine cavity, a small portion of the outer layer of the embryo is sliced off. This procedure is known as assisted hatching of the embryo by zona thinning. In the early years of IVF they used to use an acid to do this. Later we used to use a sharp glass needle to thin the zona. But now we use a laser to thin the zona. Some centres do zona drilling by using a laser. Whichever method is used we believe that this may help in the implantation of the embryo on to the endometrium. It is usually offered in cases where repeated IVF treatments have failed to achieve a pregnancy. Assisted hatching can also be done if you make a special request at the start of the treatment cycle. A small additional charge is made for this procedure. Assisted hatching cannot be done if the outer layer of the embryo is thin. If the outer layer of the embryo is thick or in cases of frozen thawed embryos are to be replaced then zona thinning may help. Please discuss this with your doctor. IN VITRO MATURATION OF OOCYTES ( IVM ) In certain conditions like polycystic ovaries or poor responders, in spite of ovarian stimulation follicular response from the ovaries might be poor. It may be necessary to abandon the cycle and try a different stimulation protocol in another cycle. It is never certain that we will get a good response in the second cycle. In polycystic ovaries the risk of ovarian hyper stimulation syndrome (OHSS) could be virtually avoided. Now, we have the technology to aspirate the ovarian follicles at 5-10mm or smaller, instead of waiting for the follicles to grow to 18mm in size. After collecting these immature eggs (germinal vesicles) we can grow them in the laboratory under special culture conditions. However, at present not more than 70% of the immature eggs reach maturity in our laboratory. The eggs which have reached maturity are subjected to sperm microinjection by ICSI. The fertilization of the eggs is around 70%. The eggs that are fertilized (embryos) are transferred in the same way as embryos from routine IVF. If there are any surplus embryos that are good quality they are cryopreserved for future use. This is a big advance in our laboratory technology, thanks to our scientists. The first baby that is born by this method is now 10 years old from an Indian couple in our centre abroad. The first baby from IVM at Miracle is now just over two years old. This technology is also used when the ovarian response is very slow even after ten days stimulation. We think a day will come when we may not have to give ovarian stimulation at all and aspirated immature eggs from the ovarian follicles, mature them in the laboratory, fertilize them and transfer the embryos. This will reduce the cost of infertility treatment and also shorten the number of days the couple have to attend the centre. We feel this treatment can also be used in women who respond poorly to high dose stimulation and produce one of two follicles. Please discuss this with your doctor. CYTOPLASMIC TRANSFER (CT) Some women produce very poor quality eggs in spite of using different stimulation protocols. The situation does not change even in a long protocol or by using recombinant FSH. In such cases the only possible way to use her own eggs in the ART treatment is by cytoplasmic transfer (CT). These women may produce all poor quality eggs all but one good quality egg. In such cases our scientists can by very delicate and precise manoeuvre aspirate about 5-8% of the cytoplasm from the good quality egg and transfer very precise amount into the poor quality sibling eggs thereby improving the quality of these poor quality eggs. This transfer signals the pathway of mRNA of the good eggs into poor eggs. This technique improves the fertilization and cleavage of these sibbling eggs thus the pregnancy rates. The resulting baby will have the same genetic material as the parent. Thus we do not have to use a donor egg. In the event of all the eggs produced by the woman are of very poor quality and we do not have a sibbling good quality egg to get the cytoplasm from then after due counselling and consent we can use a suitable single good quality donor egg to get the cytoplasm. Thus we can produce an offspring for the couple with thier own chromosomes. Hence the resulting baby is genetically thiers but for the mitochondrial DNA We have been doing this technique for the last 9 years and the first baby born by cytoplasmic transfer is now 8 years old. Miracle is the only centre doing this innovative technique except two other centres in the United States. We at the Miracle Advanced Reproductive Centre are very pleased to bring this technology to India and offer it to women who produces poor quality eggs. OOCYTE FREEZING This treatment is relatively new and offered for women who are not married but want to preserve their fertility. Women want to be professionals, get settled in their career, become financially secure before they contemplate marriage and family. Such women can undergo one of two cycles of IVF and have their eggs collected and freeze them until they are ready to have a baby. However there is no guarantee that they will achieve a pregnancy with the finite number of oocytes cryopreserved as pregnancy rates with assisted conception are around 40%. This can also be used for young women who unfortunately having radiation therapy or chemotherapy to combat cancer. Oocyte freezing and ovarian tissue cryopreservation will be available in our centre. FERTILITY PRESERVATION With our egg freezing and sperm freezing programme we can preserve the fertility in the female or the male if in the unfortunate event of them needing either radiotheraphy or chemotheraphy. They can freeze thier eggs or sperm and have a baby with thier own gametes after they have finished thier treatment. So there is no need to use donor eggs or donor sperm. Fertility treatment never guarantees a pregnancy and a baby by any means. But be assured that we will bring you in Chennai the latest innovations in fertility treatment so you do not have to go elsewhere for treatment. |
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