We ensure that all the patients undergo a detailed work up so that the finer details are not missed and treatment can be individualised. The pre- IVF tests, which a patient may need include:
i. Blood Investigations– Blood level of Anti-Mullerian hormone (AMH), Day-2 FSH (Follicle Stimulating Hormone), LH (Luteinising Hormone) and E2 (Estradiol) is tested in the female partner. We also routinely test the female partner for blood levels of thyroid (TSH, T3 & T4) and prolactin hormones, complete blood count and status of Rubella infection. Thalassemia screening and a complete check for infectious diseases including HIV, Hepatitis B, Hepatitis C and Syphilis is also sometimes required.
ii. Transvaginal ultrasound– It is done to assess the anatomy of ovaries and uterus. An ultrasound scan done at the beginning of menstruation also helps in assessing the antral follicular count (AFC), which is a very good marker for ovarian reserve and a mid-cycle scan helps in assessing the endometrial status.
iii. Hysteroscopy– The best evaluation of uterine cavity is done by directly seeing it from inside. Several defects in the uterine cavity like polyps, adhesions, septum and fibroids can prevent the embryo from attaching in the uterine cavity. Hysteroscope is a very thin telescope which can be passed into the uterus through vagina and helps us study the structure of uterus from its inside. Hysteroscopy also allows surgical correction of many of the structural abnormalities in the same sitting. Hysteroscopy is performed under brief general anaesthesia and can be completed as a day care procedure.
iv. Sonosalpingography (SSG)– SSG is a simple diagnostic procedure primarily used for evaluating inside of uterine cavity for presence of submucous fibroids, polyps or other lesions inside uterus and check for patency of fallopian tubes. SSG is a very safe procedure and is generally conducted as an OPD procedure without need for any anaesthesia.
In SSG, a physiological liquid is pushed into the uterus under pressure using a catheter and the outlet of vagina is blocked using inflated balloon of the catheter. The liquid passes through the patent tubes under pressure and the flow of liquid through the patent tubes is detected using ultrasound scan.
The patients about to start the IVF should take special health precautions, avoid smoking and drinking and should maintain good healthy diet and hygiene. The patients should try and avoid any stress and anxiety.
A very important medication that is often started in the pre-stimulation phase is GnRH agonist- given either as injection or as nasal spray. The primary role of GnRH agonist is to prevent premature LH surge, which could result in premature ovulation before eggs are ready to be retrieved. There are many different protocols in which GnRH agonist play an important role. In the down regulation protocol, GnRH agonist is generally started from day 21 of the previous cycle on a daily basis and continued till the day of HCG trigger. It suppresses the pituitary so that there is no endogenous FSH and LH and the body is solely dependent of exogenous FSH and LH for egg growth and ovulation.
Some women planning for an IVF may also need pre-treatment with a birth control pill in the preceding cycle. This ensures that GnRH agonist therapy can be started on time in women who have irregular cycles. Another benefit of these pills is that they prevent the formation of ovarian cysts, which may develop with GnRH agonist or as a residual of previous ovulatory cycle.
Hormonal stimulation of the ovaries is the process of using hormone injections to help ovaries produce multiple eggs in one cycle. While only one egg is required for successful pregnancy, all eggs produced by the ovaries are not suitable to yield a pregnancy. Therefore gonadotropins injections are given to the patient so that her ovaries produce many eggs in a cycle. This improves the chances of getting enough good quality eggs for fertilisation, and therefore, of achieving a pregnancy. This is a very controlled process where injections are given not only to stimulate growth of eggs, but also to control the process of ovulation. Just like Gonadotropins are given to develop many follicles, injections are also needed to prevent LH surge in the body which may lead to premature ovulation before the eggs can be extracted. This is achieved either by GnRH Agonist which is started as discussed above or by giving GnRH antagonist injections daily once dominant follicle reaches 13-14mm in size. For a vast majority of patients the average duration of Gonadotropin stimulation is 10-12 days, where the aim is to produce 10-12 eggs and the patient is under regular monitoring to ensure good growth of follicles and also to time ovulation.
It is essential to regularly monitor the cycle using serial ultrasounds and periodic assessment of blood oestrogen level in order to optimise the outcome of ovarian stimulation. This assessment helps in tracking growth of the follicles and deciding when the eggs have become sufficiently big and mature. Once the majority of egg follicles are between 16 and 20 mm on average diameter, a final injection of Human Chorionic Gonadotropins (HCG) is given which prompts the eggs to mature and ovulate.
The eggs are likely to ovulate from the follicles 36 hours after the HCG injection. Therefore, we plan the egg retrieval 36 hrs from the time of HCG injection. This procedure is timed exactly according to the timing of the HCG injection, as we need the eggs to be mature but the follicle should not rupture.
Egg retrieval is the only time in the full IVF cycle, when we expect the patient to be admitted on day care basis. The patient is asked not to not eat or drink 6 to 8 hrs prior to the egg retrieval. During the egg retrieval procedure, short general anesthesia is administered to make the process comfortable and pain free for the lady. The vagina is then washed with a sterile water solution. A needle is placed under ultrasound guidance through the vagina into the ovary and fluid, and eggs from the follicles in the ovaries are collected into a test tube and sent to the IVF lab. The whole procedure takes about 30 minutes, and discomfort is generally very minimal.
A good IVF lab with trained personnel is the heart of a successful IVF program. In the IVF lab the eggs that have been retrieved from ovaries are kept in a culture medium in an incubator for some time and then every egg is overlaid with 50,000 to 10000 sperms from the partner. The sperm sample is also first prepared and washed to remove all the dead sperms, debris and liquid from the semen and then good quality sperms selected for fertilizing the eggs. Following this process of inseminating the egg petri dish is paced in the incubator again, for the sperms to enter and fertilize the egg.
The fertilized eggs called the embryos start dividing and become 4 celled by 2nd day, progressing to 8 cells by 3rd day and up to 100 cells by 5th day. The embryologist and the clinician keep a check on the growth and quality of the embryos. The final decision of embryo transfer and timing of the same is based on the embryo status & quality and the clinical details of the patient.
The embryo transfer can be done either on Day 2, Day 3 or Day 5 following the egg retrieval. We discuss with our patient to finalize the number of embryos to be transferred into the uterus of the recipient. The decision is generally based on the number and quality of embryos formed, patient’s age and clinical indication of IVF. The number of embryos to be transferred per cycle can range from a single embryo to up to 3 embryos. Any additional embryos are generally frozen and can be used in future, if required.
Preparing for Embryo Transfer- The day of embryo transfer is one of the most crucial days in the whole cycle. We expect the patient to relax and come to the centre with the urinary bladder at least half full in order to allow us to visualise the uterus using an abdominal ultrasound.
Embryo Transfer Procedure- The procedure of transfer is a gentle and simple procedure though needs a lot of precision by the doctor to be able to transfer at the correct spot in the uterus. After appropriate patient and embryo verification, the correct no of embryos are loaded in a thin catheter which is passed into the uterus through the cervix, simultaneously the passage of the catheter is checked by abdominal ultrasound and then embryos softly ejected from the catheter into the uterine cavity. The procedure is almost painless and takes less than 10 minutes time and is generally performed as an OPD procedure without requirement of any kind of anaesthesia.
After completing the transfer the patient rests in a relaxed position for 20 minutes and then can go home. The patients are given the following instructions to facilitate a better recovery:
a) Avoid any vigorous activity like aerobics or running. After 8 hours, they may gently increase their activity. The ovaries will still be full of fluid from the effects of the stimulation and one may feel some bloating or pelvic discomfort at this time. It is okay to take stairs slowly, and walk short distances.
b) Avoid vaginal creams, lubricants, or spermicides.
c) Avoid vaginal intercourse or orgasm for about a week after the transfer.
d) If the patient has to travel, allow twice as much time as usual and minimize stress.
e) Drink plenty of clear fluids to stay well-hydrated.
It is helpful to understand that at this point, successful embryo implantation and pregnancy will depend primarily on the health of the embryo rather than on patient’s activities.
A pregnancy test is performed around 12- 14 days after the embryo transfer. This test confirms the success of the IVF treatment, if positive. The patient is generally instructed to repeat the test after 2 days to be doubly sure of the outcome of the procedure. The doctor may instruct to stop the medications if the pregnancy test is negative.
Four weeks after the first positive blood pregnancy test, an ultrasound scan is performed to confirm a clinical pregnancy, which is the presence of a gestational sac in the uterine cavity (the gestational sac can be seen before the embryo is visible).