IN VITRO FERTILIZATION (IVF)

IVF, commonly referred to as "test tube baby" treatment, stands for “In Vitro Fertilization”. The procedure involves removing a number of mature eggs from the ovary, fertilizing them outside the body with the husband's sperm in the laboratory and transferring the resultant embryos (fertilized eggs) back into the patient's uterus.

1. Blocked Fallopian tubes
   
2. Unexplained-infertility - where routine tests do not indicate any abnormality in the couple
   
3. Male factor infertility  - severe abnormalities in the sperm parameters like very low sperm count/ motility
   
4. Endometriosis – moderate/severe
   
5. Advanced age of the female

Procedure for IVF
IVF involves several steps which include:

1. Down regulation (switching off the natural cycle)

This step involves “switching off” the production of hormones that normally control the menstrual cycle. This is achieved by administering a drug called Gonadotrophin Releasing Hormone Agonist (GnRHa). The drug is usually given as a daily subcutaneous injection, the duration of which may vary between 7-15 days depending on the individual’s response.

The most common side effects seen while taking this medication include headaches, hot flushes and mood swings.

An ultrasound scan is performed to assess the effect of these injections and if this scan shows as thin uterine lining and small follicles, it is an indication that down regulation is achieved and the body is ready to proceed to the next step of treatment.

In a normal menstrual cycle, usually only one follicle (sac containing egg) reaches maturity and releases an egg each month. However, in an IVF cycle, the aim is to stimulate growth of several follicles so that many eggs are available for fertilization and the chances of success are increased.

Injections called gonadotrophins are the most commonly used injections to develop a good number of follicles in the ovary. They are given daily till the follicles reach a diameter of 18 mm or more and are usually given for 10 to 14 days. Some injections are given subcutaneously (under the skin) while others are given intramuscularly (into the muscle).

The most common side effects noted include mild inflammation at the injection site, transient fever and joint pains.

On an average, 3-4 scans are carried out while taking the stimulation injections to monitor the growth and number of follicles in the ovaries. When at least 3 follicles reach 18mm in size, the egg collection procedure can be planned.

Monitoring the follicle growth is very important to adjust the dose of medication and also to identify excessive stimulation of ovaries which may result in a potentially serious side effect known as Ovarian Hyper Stimulation Syndrome (OHSS). Hormonal assays in the blood might be performed if there is evidence of excessive response to the guided management.

A drug called Human Chorionic Gonadotropin or HCG is given once the follicles reach their desired size and is necessary for the final maturation of eggs prior to ovulation. Once the process of ovulation is triggered, the next step i.e. oocyte retrieval is scheduled at 36 hours after administration of HCG. This injection is given late in the evening 2 days before the day of egg collection.

This procedure is usually done under intravenous sedation or general anesthetic. Since the procedure is performed under sedation, overnight fasting is advised. The procedure is performed in a dedicated theatre adjacent to the embryology laboratory. A fine needle is inserted through the wall of the vagina and into the ovaries using ultrasound guidance. Through the needle, fluids from the follicles are drained and collected in a test tube which is checked under a microscope by the embryologist for the presence of eggs.

The collected eggs are kept in special culture media in an incubator in the laboratory. The incubator mirrors as closely as possible the body environment in terms of temperature and pH.

Most women find the process of egg collection uncomfortable rather than painful.

There may be mild cramp like pain or slight bleeding from the vagina which usually subsides in a few hours. Oral antibiotics are given to the woman as prophylaxis against infection. The woman can go home 2-3 hours after the procedure.

6. Fertilization of the eggs in the laboratory

Sperm preparation
On the day of egg collection, the husband is required to produce a semen sample by masturbation in a clean wide mouthed container supplied by the lab. For an optimum semen sample, there should be a period of abstinence of 2- 3 days. Though a fresh sample of semen is ideal, if the husband cannot be present at the scheduled time, a semen sample can be collected in advance and frozen for use during the IVF treatment.
The semen sample is processed to obtain clean, concentrated and highly motile sperm which are used to inseminate the eggs.

Insemination
The sperm is added to the eggs a few hours after egg collection. It is only necessary to add a relatively small number of sperm to inseminate the eggs. Fertilization of the eggs by the sperm will normally occur during the evening of the collection day.

Fertilization check
 The following day, the dish is checked for fertilized eggs. The embryologist looks for 2 pronuclei within the egg (the genetic material from the egg and sperm). It is not usual for all eggs to fertilize and on an average, 60-70% of collected eggs show signs of fertilization. The embryo (fertilized egg) is then placed in a fresh dish of culture medium and replaced in the incubator.

ET is carried out on any one day, between the 2nd and 5th day after oocyte retrieval.

On the 2nd day after egg collection, the embryo cleaves to form a 2-4 cell stage embryo and if further cultured in the lab, forms an 8 cell embryo on day 3. Around 50% of embryos with further culture become blastocysts. The stages at which the embryos are transferred are based on the number and quality of embryos. The embryos are graded according to their appearance.

The embryo transfer is a simple procedure and does not require an anesthetic. The embryos are deposited in the upper part of the uterine cavity (womb) by means of a soft plastic catheter traumatically.

Risks of fertility treatment
As with all medical treatments, there might be some complications which occur after IVF.

• Ovarian Hyper stimulation Syndrome (OHSS): This is a medical condition that arises when the ovaries overreact to the stimulation injections.
  
• Pelvic Infection: The risk of pelvic infection following egg collection is extremely low. A short course of antibiotics is prescribed following the egg collection procedure to minimize the chances of infection.
  
• Multiple pregnancies: This is a potential risk in all forms of fertility treatment. The overall chances of multiple pregnancies occurring after IVF are 25% when 2 or 3 embryos are transferred. The main complication with multiple pregnancies is the high risk of preterm delivery and subsequent morbidity to the babies. If a triplet or higher order pregnancy results, selective reduction is discussed.
  
  
• Miscarriage: On an average, one in four of all pregnancies (through natural conception or infertility treatment) results in a miscarriage.
  
  
• Ectopic Pregnancy: An ectopic pregnancy is one where the pregnancy develops outside the womb, mostly in the fallopian tubes. For this reason, it is always important to perform an ultrasound scan on all pregnant women at about 6 weeks of gestation to confirm that the pregnancy is developing inside the womb.
  
  

Success of IVF treatment
With IVF, each cycle gives a take-home baby rate of around 30-35%.

Counseling
IVF treatment can be very stressful and hence, it is important to avail the support mechanisms both at home and at the counseling services at the clinic.