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In-vitro Fertilization (IVF)

IVF treatment is generally suggested only if the doctor feels that the other infertility treatment options are not applicable or have been exhausted. Typically, IVF is suggested n the following cases.

  • After multiple IUI attempts have failed
  • If the woman has bilateral tubal blocks
  • If the male infertility is so severe that IUI and other options are not applicable.
  • Any other clinical situation where the doctor feels that IVF is the only option – low ovarian reserves, egg donor cycles, surrogacy etc.

 

The complete treatment program can be split into the following steps.

  1. The Cycle before the Treatment: Prior to the start of the actual IVF treatment, the patient may be put on medication. It can be thyroid related medicine to get the thyroid levels under control or other drugs to address various other issues. It can even be birth control pills because it has shown to decrease the risk of the ovarian hyperstimulation syndrome and ovarian cysts and may even improve the odds of success.If the cycles do not happen naturally, the doctor may prescribe progesterone to bring on the period. Please follow the doctor’s instructions.
  2. When the Period Starts: The actual treatment starts from the 2nd day after the period. On this day, the doctor will start with some blood investigations and an ultrasound. This is referred to as baseline blood work and the baseline ultrasound. The doctor will be looking at the estrogen levels, specifically E2 or estradiol. This is to make sure the ovaries are not active yet.The ultrasound is to check the size of the ovaries and look for ovarian cysts. If there are cysts, the doctor may decide to just delay treatment for a week, as most cysts will resolve on their own. In some cases, the doctor may aspirate, or suck, the cyst with a needle. This is a procedure done under anesthesia and is not part of the IVF package costs.
  3. Ovarian Stimulation and Monitoring: If the blood investigations and ultrasound scans are normal, the next step is to start with the ovarian stimulation with fertility drugs. Depending on the protocol chosen by the doctor, there may be injections to be taken at different periodicity. Usually, there will be injections for 8 to 12 days. The doctor will monitor the growth and development of the follicles. This may include regular blood investigations to monitor hormone levels, and ultrasounds to monitor the oocyte growth. Monitoring the cycle helps the doctor decide whether medications need to be increased or decreased in dosage. Once the largest follicle is 16 to 18mm in size, consultations and scans will happen daily.
  4. Final Oocyte Maturation: The next step in the IVF treatment is triggering the oocytes to go through the last stage of maturation before they can be retrieved. This last growth is triggered with human chorionic gonadotropin (hCG). Timing this shot is vital. If it’s given too early, the eggs will not have matured enough. If too late, the eggs may be “too old” and won’t fertilize properly.The daily ultrasounds at the end of the last step are meant to time this trigger correctly. Usually, the hCG injection is given when four or more follicles have grown to be 18 to 20mm in size. This is typically a one-time injection. The timing of the shot will be based both on the ultrasounds and blood work.If not enough follicles grow or if there is a risk for severe ovarian hyperstimulation syndrome, the treatment cycle may be canceled and the hCG injection will not be given. It may also be canceled if the ovaries don’t respond well. In such a case, the doctor may recommend different medications for the next cycle. While not common, a cycle may also be canceled if ovulation occurs before retrieval can take place. Once the eggs ovulate on their own, they can’t be retrieved.Cancellation happens in 10 to 20% of IVF treatment cycles. The chance of cancellation rises with age, with those older than age 35 more likely to experience treatment cancellation.
  5. Egg Retrieval: About 34 to 36 hours after the hCG injection is given, the egg retrieval will take place. It’s normal to be nervous about the procedure, but most women go through it without much trouble or pain.Before the retrieval, an anesthesiologist will give you some medication intravenously to help you feel relaxed and pain-free. Usually, a light sedative is used, which will make you “sleep” through the procedure. Side effects and complications are rare and even when they exist, it is very mild.Once the medications take their effect, the doctor will use a trans-vaginal ultrasound to guide a needle through the back wall of the vagina, up to the ovaries. She will then use the needle to aspirate the follicle, or gently suck the fluid and oocyte from the follicle into the needle. There is one oocyte per follicle. These oocytes will be transferred to the embryology lab for fertilization.The number of oocytes retrieved varies but can usually be estimated before retrieval via ultrasound. The average number of oocytes is 8 to 15.After the retrieval procedure, you’ll be kept for a few hours to make sure all is well. Light spotting is common, as well as lower abdominal cramping, but most feel better in a day or so after the procedure. You’ll also be told to watch for signs of ovarian hyperstimulation syndrome, a side effect from fertility drug use during IVF treatment in 10% of patients.
  6. IVF Treatment: After the egg retrieval, the follicles that were aspirated will be searched for oocytes or eggs. Not every follicle will contain an oocyte. Once the oocytes are found, they’ll be evaluated by the embryologist. If the eggs are overly mature, fertilization may not occur. If they are not mature enough, the embryology lab may be able to push them to maturity.Fertilization of the oocytes must happen within 12 hours. The husband will be asked to provide a semen sample on the morning of retrieval. The stress of the day can make it difficult for some, and so just in case, the husband is also asked to provide a semen sample for backup earlier in the cycle, which can be frozen until the day of the retrieval.
  7. Embryology Lab Procedures: After eggs are retrieved, they are transferred to the embryology laboratory where they are kept in conditions that support their needs and growth. The embryos are placed in small dishes or tubes containing “culture medium,” which is a special fluid developed to support the development of the embryos made to resemble that found in the fallopian tube or uterus. The dishes containing the embryos are then placed into incubators, which control the temperature and atmospheric gasses the embryos experience.A few hours after eggs are retrieved, sperms are placed in the culture medium with the eggs (regular IVF), or individual sperm is injected into each mature egg in a technique called intracytoplasmic sperm injection (ICSI).The ICSI technique attempts to achieve fertilization by the injection of a single sperm into the cytoplasm (interior) of the egg. Mature eggs are freed of surrounding cells by a combination of enzyme treatment and micro-dissection. Using special micromanipulation equipment, the eggs are individually injected with a single sperm.Injected eggs are returned to the laboratory incubator and maintained in an environment ideal for embryo growth. The eggs are returned to the incubator, where they continue to develop. Over the next few days, the dishes are inspected so the development of the embryos can be assessed.The following day after eggs have been inseminated or injected with a single sperm (ICSI), they are examined for signs that the process of fertilization is underway. At this stage, normal development is evident by the still single cell having two nuclei; this stage is called a zygote.Two days after insemination or ICSI, normal embryos have divided into about four cells. Three days after insemination or ICSI, normally developing embryos contain about eight cells. Five days after insemination or ICSI, normally developing embryos have developed to the blastocyst stage, which is typified by an embryo that now has 80 or more cells, an inner fluid-filled cavity, and a small cluster of cells called the inner cell mass.Some eggs and embryos are abnormal and so it is expected that not all eggs will fertilize and not all embryos will divide at a normal rate. The chance that a developing embryo will produce a pregnancy is related to whether its development in the lab is normal, but this correlation is not perfect. This means that not all embryos developing at the normal rate are in fact also genetically normal, and not all poorly developing embryos are genetically abnormal. Nonetheless, their visual appearance is the most common and useful guide in the selection of the best embryo(s) for transfer.In spite of reasonable precautions, any of the following may occur in the lab that would prevent the establishment of a pregnancy:
    • Fertilization of the egg(s) may fail to occur.
    • One or more eggs may be fertilized abnormally, resulting in an abnormal number of chromosomes in the embryo; these abnormal embryos will not be transferred.
    • The fertilized eggs may degenerate before dividing into embryos, or adequate embryonic development may fail to occur.

    Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS) are two techniques that can be used during in vitro fertilization (IVF) procedures to test embryos for genetic disorders prior to their transfer to the uterus. PGD and PGS make it possible for couples or individuals with serious inherited disorders to decrease the risk of having a child who is affected by the same problem. Both of these techniques involve the use of the micromanipulator to remove a cell from an embryo. This cell is then sent to a diagnostic lab to determine the embryo’s normalcy. Acceptable embryos can then be transferred into the patient, decreasing her odds of having an affected child. PGS has also been reported to increase the pregnancy rates of some women with chromosomal disorders that result in either lower implantation rates of embryos or higher miscarriage rates.

  8. Embryo Transfer: About three to five days after the retrieval, the fertilized eggs will be transferred. The procedure for embryo transfer is just like IUI treatment. The patient won’t need anesthesia.During the embryo transfer, a thin tube, or catheter, will be passed through the cervix. There may be very light cramping but nothing more than that. Through the catheter, they will transfer the embryos, along with a small amount of fluid. The number of embryos transferred will depend on the quality of the embryos and previous discussion with the doctor. Depending on the age, anywhere from two to four embryos may be transferred. Recent studies have shown success with just one embryo transferred.After the transfer, the patient has to stay lying down for some time and then head home. If there are high-quality embryos left over, you may be able to freeze them. This is called embryo cryopreservation. They can be used later if this cycle isn’t successful, or they can be donated.
  9. Cryopreservation of Embryos Embryo freezing is an important part of the IVF process. Patients who have additional good quality embryos can freeze them for future use. These embryos provide a second or even third opportunity for pregnancy without undergoing another ovarian stimulation and retrieval.Embryos that meet developmental criteria for appearance and rate of growth can be frozen at any of several stages of development. The technique used for freezing embryos is called vitrification. In this ultra-rapid freezing method, embryos are placed into special solutions and then placed immediately into liquid nitrogen (at -196°C or approximately -400°F). Embryos are stored as for slow cooling. The method used to freeze embryos dictates how the embryos must be warmed or thawed. Not all embryos survive the freezing/thawing procedureEmbryos can be transferred into patients whose cycle has been synchronized with that of the stage of the frozen embryo. Alternatively, embryos can be transferred during a “natural” cycle. Embryos can be stored indefinitely without a compromise in their quality.
  10. The Two Week Wait: There really isn’t much going on for the next two weeks after the embryo transfer. The two weeks after the transfer may be more difficult emotionally than the two weeks of treatment. During the previous steps, the couple is busy visiting the doctor. Now, after transfer, there will be a sudden lull in activity.There may be lots of questions about the two-week wait. The doctor is the number one source for any of the concerns.The couple will have to wait the two weeks and see if pregnancy takes place. It can help to keep busy with the life during this wait time and avoid sitting and thinking about whether or not treatment will be successful. There is no need for absolute bed rest. It is suggested that the couple gets on with their normal life. It may be advisable for the woman to refrain from extreme physical exertion, traveling long distances or riding 2-wheelers for longer distances.
  11. Pregnancy Test and Follow-Up: About twelve to fifteen days after the embryo transfer, a pregnancy test is ordered. This is usually a serum pregnancy test and also will include progesterone levels testing. The test may be repeated.If the test is positive, you may need to keep taking the medication supplements for several weeks. The doctor will also follow up with occasional blood work and ultrasounds to monitor the pregnancy and watch for miscarriages or ectopic pregnancies.During IVF treatment, miscarriage occurs up to 15% of the time in women under age 35, 25% of women age 40 and up and 35% of the time after age 42.The doctor will also monitor whether or not the treatment led to multiple pregnancies. If it’s a high-order pregnancy (3 or more), the doctor may discuss the option of reducing the number of fetuses in a procedure called a “multifetal pregnancy reduction.” This is sometimes done to increase the chances of having a healthy and successful pregnancy.
  12. When IVF Treatment Fails:If the pregnancy test is still negative 12 to 14 days post-transfer, however, the doctor will ask you to wait for the period to start. The next step will be decided by the couple and the doctor.Having a treatment cycle fail is never easy. It’s heartbreaking. It’s important, however, to keep in mind that having one cycle fail doesn’t mean you won’t be successful if you try again.There are also other options to try if there have been multiple failures. Please discuss with the doctor to know more about donor cycles, donor embryo transfers, surrogacy etc.