In vitro fertilization (IVF) is synonymous with the “test tube baby”.

In essence it is the meeting of the sperm and oocyte (egg) outside the woman’s body, in a dish and subsequently getting fertilized. The developing embryo is then placed inside the uterus.

At Bangalore Assisted Conception Centre treatment is individualized without reference to other patients in the clinic as compared to some other centers where patients are grouped together and treatment cycles are planned only at set times during the year. 

IVF is the treatment of choice for couples with the following:

1 Downregulation

• Normally the functions of the ovary i.e. development of follicles is under the influence of the hormones FSH and LH from the pituitary gland (in the brain). In a normal menstrual cycle this results in the development of 1 or 2 follicles, which contain the egg. In the next step of IVF i.e. ovarian stimulation, a large number of follicles (cohort) are made to develop simultaneously by the administration of drugs that contain FSH or FSH+LH. To be able to achieve a good control on this, the influence of the pituitary gland on the ovary needs to be temporarily abolished. This is achieved in what is termed as down regulation.      
• Down regulation is accomplished by administering the drug called gonadotrophin releasing hormone agonist (GnRHa) administered subcutaneously.  The response is monitored by blood tests and ultrasound scans. New drugs such as gonadotrophin releasing hormone antagonist for down regulation is now in use, with equally good results. The treatment duration may vary between 8-21 days depending on the individual response.
• The pituitary recovers completely within 10 days or more following stoppage of GnRHa administration.

2. Ovarian stimulation

• The aim is to develop a cohort of follicles synchronous with the development of the endometrium (uterine lining), so as to increase the chances of a pregnancy. 
• Most commonly used are injections called gonadotrophins. These drugs are akin to the natural hormones FSH and LH. Sources for these hormones are the urine of postmenopausal women. In recent years these are produced using recombinant DNA technology. The dose of gonadotrophins varies from patient to patient. They are given daily till the follicles reach a diameter of 18-22mm. This takes on an average 10-12 days of treatment. On occasions ovarian stimulation may be achieved by tablets such as clomiphene citrate in combination with gonadotrophins.
• The growth of the follicles is monitored by transvaginal ultrasound scans at regular intervals. This route gives the best view of the pelvis. The ultrasound probe is covered with a rubber sheaths, before being gently introduced into the vagina. At the same time the endometrial lining is assessed.  Hormonal assays in the blood are carried out at regular intervals to assess the response to these drugs.

Scan showing Ovarian Stimulation

3. Ovulation trigger

• This is accomplished by administration of another drug called Human Chorionic Gonadotropin or HCG, which is necessary for final maturation of the egg prior to ovulation.
• The next step i.e. oocyte retrieval is scheduled at 34-36 hours after administration of HCG. 

4. Oocyte retrieval

• This is ovum pick-up or egg pick-up.
• This is a short (average 20 minutes), safe outpatient procedure performed under adequate anesthesia.

• The patient should be fasting for at least 5 hours prior to the procedure. Generally she is advised not to have any food or drink from the preceding midnight.
• The procedure is carried out under transvaginal ultrasound with due aseptic precautions, in absolutely sterile surroundings.
• A needle guide fixed alongside the ultrasound probe is introduced into the vagina, though which a fine long hollow needle is inserted. This punctures the vaginal wall only once, and by maneuvering the needle all the follicles are aspirated of their contents that include eggs and fluid. The procedure is repeated for the other ovary.
• The aspirated fluid is examined under the microscope to identify the egg. The eggs are removed and washed in culture medium. They are then placed in small dishes containing the culture medium, which provides them with nutrients.  The dishes are kept in a special incubator.

After-care

5. Sperm preparation

6. Fertilization

• A measured volume of the prepared sperm suspension is added to the dish 3-6 hours after the oocyte collection.
• The following day the dish is checked for fertilized eggs. They are then placed in fresh dishes of culture medium and placed in the incubator.
• Normally 40-70% of the oocytes should fertilize.

• ET is carried out on any one day, from the 2^nd day – 5^th day after oocyte retrieval. 
• The day is determined by the stage of development of the fertilized egg, which is studied under the microscope. When the fertilized egg starts dividing into cells it is termed an embryo. About 90% of the fertilized eggs should become embryos.
• ET is usually simple and straightforward, done with aseptic precautions. No sedation is required.
• Through a fine cannula introduced directly into the uterus via the vagina and cervix, the embryos are gently placed in the uterine cavity. 
• Normally 2 or 3 embryos are placed in the uterine cavity. Increasing the number would involve risk of multiple pregnancies. When 3 embryos are placed there is a 25% of twins and 5-8% of triplets and higher order pregnancy.

• If more than 3 good quality embryos have been produced they can be frozen with the consent of the couple for use in later IVF cycles in case the ongoing one fails. With informed signed consent they can also be donated to others undergoing IVF who are in need of donor embryos. These can be used within 3 - 5 years.
•  In order to support a conception the woman is given progesterone in the form of injections. It is continued till 12 weeks of pregnancy or stopped when the first pregnancy test is negative.
•  Normal menses usually resumes within 2 weeks in cases of a failed outcome. 

Pregnancy Outcome 

• Pregnancies resulting from IVF are considered high-risk because of the mode of conception. The incidence of pregnancy complications like hypertension, diabetes, preterm labour etc is not increased per se due to IVF.
• Abortion as a result of IVF is similar to natural conception i.e. 25%.
• The incidence of congenital malformations is similar to natural conceptions.
• Children born through IVF have reached their teens now and have shown to be normal in every way.

Undesirable aspect of IVF

• Treatment is expensive
• The frequency of visits during treatment can disrupt professional and personal life.
• Injections may be painful and can cause localized skin reactions like redness and bruising.
• If the response is not good judging by the size and number of follicles the treatment cycle may be cancelled prior to the stage of oocyte recovery. This incidence is 10-15%.
• There is a possibility that some of the fertilized oocytes may be of a poor quality due to poor quality of either the sperm or the oocyte
• On occasions the response may be excessive leading to a condition termed ovarian hyperstimulation syndrome (OHSS). The ovaries enlarge, with fluid accumulation in the pelvis and abdominal cavity. Vigilance for the condition is mandatory as it can progress to a serious life threatening condition.
• Increased incidence of multiple pregnancies, because more than 1 embryo is transferred. This can be managed by fetal reduction at 9-10 weeks of gestation.

Success

At BACC the success rates approach global standards. Success rates depend on factors like age of the woman and indications for the procedure.Techniques like ICSI, Assisted laser hatching are additional techniques to IVF.  At BACC the IVF procedure will soon progress to a point wherein cells of the embryo can be studied in couples with a history of genetic disorder and hence chromosomally normal embryos may be selected for the procedure.