Process of In Vitro Fertilisation(IVF)

Dr.Taruna (Infertility &IVF specialist, INDIRA IVF, UDAIPUR) explained Today I will take you through the steps of in-vitro fertilization in detail. Every couple that visits our clinic will initially be given an educational lecture highlighting the causes of infertility and the basis of how we individualize our plans. This is followed by a one on one meeting with each couple to discuss their case.

After this, we carry out basic blood tests for the couple, an Anti- Muellerian hormone test for the female partner and semen analysis of the male partner. The female partner then gets a baseline ultrasound done.

• After the couple has finished their screening, an individualized treatment plan will be developed. They will follow their plan until pregnancy is achieved. Since each case is different, each treatment plan will be different.

An example of the Process of IVF treatment

• Baseline ultrasound
• Initiation of hormonal pills as per requirements
• Ovarian stimulation and follicular monitoring
• Trigger shot for maturation, rupture of follicle and oocyte retrieval
• Fertilization and embryo formation
• Embryo transfer (Fresh or Frozen)
• Pregnancy test (15 days after transfer)
• Early antenatal ultrasound (4-5 weeks gestation)

Baseline ultrasound

Whenever the patient visits our center, we carry out a transvaginal ultrasound scan to examine their ovaries and take an antral follicular count which gives an idea of the patient’s ovarian reserve. We also look at the uterus, if the endometrial thickness is appropriate for that phase of the menstrual cycle and if any pathologies of the Fallopian tube are visible.

In some cases, patients may develop uterine fibroids, infections of the fallopian tubes or ovarian cysts or endometriomas. If we detect any ovarian pathology, we may not continue therapy until the cysts resolve on their own or advise the right medical or surgical treatment as deemed necessary. If the baseline ultrasound is normal, we will begin injections for ovarian stimulation.

Initiation of hormonal medication

Some patients are advised hormonal medications at the start of their IVF cycle. The reasons are listed as follows

• This reduces the use of GnRH-agonists
• This reduces the chances of developing ovarian cysts before IVF
• This is associated with better ovarian response during ovarian stimulation and finally, number of eggs are retrieved
• This also assists in synchronous follicle growth, which means all follicles are of similar size which eventually leads to better retrieval rates when ovum or egg pick up is done.

Ovarian stimulation

The stimulatory medication prescribed for a patient is individualized.

. It may include all or any combination or one of the following medications:

• GnRH-AGONISTS (e.g. Leuprolide, Triptorelin) – This acts by preventing premature release of the developing eggs. This medication suppresses the master hormonal control gland of the body-the pituitary gland. This leads to improved recruitment of multiple follicles which finally results in better egg retrieval.
• GnRH ANTAGONISTS (e.g. Cetrotide) – This medication can also improve ovarian response by acting in a way similar to agonists.
• Gonadotropins (e.g. Gonal-f, Follis, menopur)– This medication includes Recombinant, Highly Purified or Urinary FSH and LH. It also includes HMG and helps promote follicle development and egg maturation. Recombinant injections provide the benefit of minimal side effects with a better response to stimulation.

The medicines are injected subcutaneously that is just below the surface of the skin

Follicular monitoring

Along with the injections which are given for stimulation, simultaneously the monitoring of the patient in the clinic using ultrasounds and if required hormonal measurements are done. Patients are usually seen between one to four days apart depending on follicle growth. This frequency is necessary to adjust the dose of injections which in turn to improves follicular development and assists in deciding when to add medications as well as when to give the trigger injection to rupture the follicles.

Final maturation / Trigger injection

Oocyte retrieval

Trigger injections include HCG or GnRH Agonist. Thirty-six hours after the trigger injection, under short general anesthesia, an oocyte retrieval or ovum pick-up procedure, which involves removing eggs from the ovary is performed. An anesthetist will monitor the patient while the procedure is ongoing.

A thin needle attached to a transvaginal ultrasound probe is inserted through the vagina into the ovary. The contents from each ovarian follicle are suctioned into a test tube and immediately transferred to the embryo laboratory and examined to find a number of as well as the grading of oocytes or eggs. The egg retrieval takes approximately 10-15 minutes.

The patient can return home the same day. They may experience some grogginess, soreness, cramping and mild vaginal bleeding. This is common on the night of egg pick up or retrieval. We prescribe pain medication before the patient is discharged and usually they feel back to normal the next morning.

After the retrieval, the ovaries remain enlarged for the next several weeks. There may be side effects such as mild bloating, abdominal pain or spotting per vaginum which disappear in a few days after the ovum pick up.

Fertilization and Blastocyst Culture

The male partner is expected to provide a semen sample on the day of retrieval which is processed by the embryology laboratory. In some cases, a frozen sample can be used, such as when the husband stays abroad or if semen sample from a sperm donor is necessary. Intracytoplasmic Sperm Injection or ICSI procedure is carried out on each oocyte in our laboratory and the egg is inseminated with a single sperm.. On the third or fifth day after the retrieval, we inform the couple about the number of eggs that fertilized and if they choose which developed into day Five embryos or blastocysts.

Embryo transfer-fresh or frozen

If fresh embryo transfer is advised then the procedure is carried out between three and six days after the oocyte retrieval procedure. Whether the fresh or frozen transfer is to be carried out depends on the retrieval, the number, and quality of embryos produced and the patient’s preference.

However, we prefer frozen embryo transfer as it provides better results so the patient is called after giving medications for endometrial preparation either in the next menstrual cycle or as per their convenience

An embryo catheter (tube) is inserted into the uterine cavity under ultrasound guidance to place the embryos chosen for transfer. In this case, we use an abdominal ultrasound to follow the catheter and to place embryos in the right position. This procedure thus requires a full bladder. We either transfer a single embryo or two embryos at a time depending on the case and the couple’s choice,

A number of factors will be looked at in making this decision:

• Quality of each embryo and number of embryos
• Age of the patient
• The previous number and outcome of pregnancies.
• Whether they have had a previous transfer

Embryos that are not chosen for the transfer and that are good quality are frozen and stored for use at a later time, if desired by the patient.

On the day of the embryo transfer, we provide the patient with specific instructions. These include- whether bed rest is necessary, how to take their medications and other precautions they can take until the day of their pregnancy test.

Progesterone support

Progesterone is a hormone which helps to support the uterine lining during pregnancy and helps a healthy pregnancy develop in the early stages. Progesterone supplementation is known to improve the chance of success of IVF.

For this reason, we prescribe progesterone injections around the time the embryo transfer is planned and after the transfer patients will take it either by injection and/or orally or by the vaginal route.

Progesterone is the same hormone the ovaries produce and is used in a dose that is not excessive. It is usually continued at least until the pregnancy test and longer once the patient is confirmed to be pregnant, for the first three months.

Pregnancy test

A blood test confirming pregnancy is performed approximately fifteen days after the egg retrieval. In this period the patient is advised to continue with their normal routine. Some patients may experience pregnancy symptoms which are not necessarily a confirmatory sign of pregnancy.

Vaginal bleeding after the transfer does not mean that the procedure had any complications or it was unsuccessful. A blood pregnancy test (B-hCG level), approximately 15 days after embryo transfer confirms the pregnancy. If the hCG level is borderline we may ask the patient to repeat the test after 48 hours.

Early antenatal ultrasound

Fifteen days after a positive pregnancy test, an early antenatal ultrasound is scheduled. This will be about one month following the embryo transfer. This ultrasound is done trans vaginally to. look for an early fetal heartbeat, a yolk sac, and gestational sac.

If the ultrasound confirms a normal pregnancy, we start oral as well as vaginal medications to support the pregnancy and those recommended in early pregnancy. Since these pregnancies are precious, we ask the patient to follow up with us in the antenatal period and we look after each case carefully till term.