In-Vitro Fertilization

In-Vitro Fertilization (IVF) describes the process and techniques of fertility treatment through hormonal stimulation, egg retrieval, fertilisation and embryo transfer. The process does not have to involve vitrification and is about assisting fertilization.

Overview

IVF treatment cycle can be 
understood in four key stages.

1. Stimulate and Retrieve

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The treatment cycle is typically carried out over 2-4 weeks, beginning with your ovaries stimulated by hormonal injections to boost your egg production and help the eggs mature.

The process is monitored by blood tests and transvaginal ultrasound assessments of the ovaries.

Once the ovaries have grown sufficiently, the eggs are retrieved via an out-patient procedure. Sperm is also collected on the same day of egg retrieval and prepared for fertilization.

2. Assess and Freeze

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Mature eggs are selected and fertilized with sperm via standard insemination/”Traditional IVF” or Intracytoplasmic Sperm Injection (ICSI).

The fertilized eggs/zygotes are cultured in an incubator for further development and division to become blastocysts that could be ready for genetic testing and/or transfer.

3. Fertilize and Screen

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Embryos are screened and biopsy could be conducted to determine the presence of chromosomal abnormality and genetic disorders. In some countries, you can opt to find out the sex of the embryos at this stage.

If biopsy is conducted for Pre-implantation Genetic Testing, the embryos would be frozen in nitrogen to wait for the test results (typically around one to two weeks).

4. Transfer

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For a fresh embryo transfer, it would be conducted about five days later in a simple procedure to implant the embryo in the uterus.

For a frozen embryo transfer, the body needs to be prepared for the implantation procedures and may take another six weeks for the transfer to happen.

Reference Process and Timeline

There are a lot of factors that impact the timing of the treatment cycle. The below timeline is a generic process that is typical to patients but could vary for individuals.
1. First Consultation
  • Meet your doctor
  • Get medical advice
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The first appointment with your doctor helps you gain a thorough understanding of IVF, treatment procedures as well as the risks involved.
You should take this opportunity to evaluate if the doctor and clinic is right for you and the costs associated with your treatment.

You should form a view on the approximate treatment timeline, i.e. when you are starting your medication and when your egg retrieval date should be. The timeline would be refined as the treatment begins as it depends on the progress of your ovaries’ reaction to the medication.

Find out the preparation needed before treatment. Depending on your situation, they may ask you to get on or off birth control pills to regulate your cycle and provide specific dates on when to take your first and last oral contraceptives. Smoking could have an adverse impact on the egg retrieval count and quality and the doctor may advise you to refrain from smoking before and during your fertility treatment cycle.

Sometimes, some small operations may be needed, e.g. hysteroscopy, laparoscopic chromotubation, as part of the investigation before IVF.

2. Infectious Diseases and Fertility Tests
  • Complete health assessments
  • Prepare for treatment
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Typically, doctors would order testing of infectious diseases and your fertility level via blood and urine samples before you begin the fertility treatment. They could include the following assessments.

Infectious diseases
Hepatitis B, Hepatitis C, HIV, Syphilis, Chlamydia, Rubeola, Rubella

Fertility and reproductive health
AMH level, Prolactin, Vitamin D, FSH, Estrogen, Progesterone, Pap Smear, Ultrasound for antral follicle count

Genetic diseases
Genetic testing, conducted by analyzing saliva samples, could also be required, especially if you are freezing embryos and/or have a family history of genetic issues.

Male reproductive health
Semen Analysis and similar baseline lab work would be required from your partner/sperm provider.

3. First Day of Fertility Cycle
  • Conduct baseline test
  • Learn to inject medication
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Time: Usually within Day 1 – 3 of your menstrual cycle
The first day of your treatment cycle is usually within Day 1 – 3 of your period. The doctor or clinic would ask you to make an appointment during that time to conduct the baseline trans-vaginal ultrasound and blood assessment.

The nurse should work out a tentative calendar of your visits to the clinic for ultrasound and bloodwork and when to start the hormonal medication. The nurse would explain to you the hormonal medication you need to take and provide you the instructions for injection.

You should expect follow up visits to the clinic for ultrasound and blood work every 1-3 days during your treatment cycle to monitor your progress and determine when your ovaries are mature enough for egg retrieval.

4. Hormonal Stimulation
  • Inject medication
  • Continue ultrasound, blood tests
  • Manage side effects
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Time: 1 – 2 weeks
To retrieve eggs for IVF, the key to success lies in maturing multiple eggs at once. Injections of the natural hormones FSH and/or LH (gonadotropins) are used to stimulate the growth of the ovarian follicles where the eggs reside.

To prevent premature ovulation, other medications would be used to avoid release of the eggs before they are ready. Blood tests and ultrasound assessments are used to monitor the growth of follicles and ovarian response.

Typically, you will administer hormonal medication in the form of injections daily by yourself. The nurse would instruct you on how to manage each medication and the time and/or frequency you should take them. It is normal to have skin irritation, such as swelling, redness, bruising in the injection site. Ovarian hyperstimulation could be a risk so you should monitor any side effects you experience and reach out to the doctor or clinic if necessary.

5. Egg Retrieval
  • Retrieve eggs from ovaries
  • Prepare for recovery
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Time: 20 – 40 minutes
Before egg retrieval, you will administer the “trigger shot” as instructed by your nurse to prepare your ovaries for the out-patient operation. Pay attention to the time of the day in which you need to inject the “trigger shot” as it is critical for the egg retrieval success.

General or partial anesthesia is provided to reduce discomfort before the retrieval procedures begin. Under ultrasound guidance, a thin, long needle will penetrate through the vaginal wall into the individual follicles to remove the matured eggs. Risks associated include bleeding, infection and trauma if other intra-abdominal organs are damaged.

Medications may be prescribed to you to help manage side effects and support our recovery after the egg retrieval procedures.

6. Sperm Collection
  • Collect before egg retrieval
  • Prepare for insemination
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Sperm sample is collected on the day of egg retrieval. Your sperm provider or partner should have completed the necessary blood work and urine tests before the collection day. The sperm sample would be processed and prepared by a biologist to be used for insemination of the eggs.

7. Fertilization
  • Evaluate egg maturity
  • Inseminate eggs with sperm
  • Conduct fertilization assessment
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Time: Post-retrieval Day 0
After egg retrieval, the embryologist would examine the maturity of the eggs and prepare for insemination. If the egg is not mature, it will be discarded because it cannot be used for fertilization. The eggs are transferred to the embryology laboratory where they are kept in conditions that support their needs and growth which is very similar to the natural uterine environment. The eggs could be inseminated by one of two methods:

Standard insemination/conventional IVF
Sperm and eggs are cultured overnight in a dish together and the sperm have penetrate the eggs on their own, similar to natural insemination.

Intracytoplasmic sperm injection (ICSI)
ICSI is a technique in which individual sperm are injected directly into mature eggs with the aid of a microscope and fine instruments.

Your clinic or doctor may have preference on the use of one method over the other so it is important to discuss the method of fertilisation and associated risks before egg retrieval occurs.

8. Embryo Development
  • Divide and develop in culture
  • Check embryo development
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Time: Post-fertilization Day 1-7

Post-fertilization Day 1
Once insemination is complete, the eggs are returned to the incubators until fertilization is assessed the following morning.

Post-fertilization Day 2-4
After the fertilization assessment, the embryos remain in culture undisturbed to optimise development. The fertilised eggs/embryos should continuously be dividing and develop into the blastocyst stage.

Post-fertilization Day 5-7
Healthy embryos first reach the blastocyst stage (on Day 5, 6 or 7) and the embryos are removed from the incubators and their development is assessed. The age of the egg would be a key determining factor in blastocyst development and not all embryos in culture could develop into good quality blastocyst that can be transferred, biopsied or frozen. Day 7 is usually the final day of culture when all embryos that have not reached a developmental stage safe for biopsy or freeze will be discarded.

9. Pre-implantation Genetic Testing (PGT)
  • Examine chromosomal abnormalities
  • Identify genetic disorders
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Time: On or before Day 7 of fertilisation

Depending on the coverage you choose, PGT is an optional procedure typically used to assess the presence of genetic issues that could cause a higher chance of implantation failure or miscarriage and identify embryos with genetic mutations that lead to birth defects, such as cystic fibrosis. Embryo cells are analyzed to determine if there are chromosomal imbalances and/or specific genetic mutations that one or both of the parents are known to carry (via earlier genetic testing). The sex of the embryos can also be identified in the procedure.

The embryo biopsy is performed at the blastocyst stage (5, 6 or 7 days after fertilisation) before vitrification. The removed cells are sent for analysis, with results available in about 1 to 2 weeks.

Although current PGT techniques are mostly very accurate, the test may produce false-negative or false positive results (it may miss an abnormality or detect one that isn’t there). As the abnormal embryos will be discarded, you may end up with fewer embryos to freeze or use. You should discuss the risks of PGT with your doctor.

10. Embryo Transfer
  • Prepare for implantation
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Time: 15 – 30 minutes

Embryo transfer is a short procedure, similar to a pap smear, where fresh or thawed embryos are inserted into the uterine cavity via a catheter. Your doctor should discuss with you the optimal time of the transfer and how many embryos should be transferred.

If a fresh transfer is conducted, the highest quality embryo would be transferred into the uterus 3-5 days after fertilization. If the embryos underwent Pre-implantation Genetic Testing (PGT), they would be frozen for 1-2 weeks to wait for the results. Once the results are out, the embryos that are deemed healthy would be thawed for transfer. This could mean the frozen transfer takes place up to a month after fertilization.

The number of embryos transferred will increase the chances of pregnancy, but will also increase the risk of a multiple pregnancy (e.g., twins, triplets, etc.). Any embryos that are not transferred in the cycle can be frozen for future use.

11. Pregnancy Test
  • Take a pregnancy test
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Approximately two weeks after embryo transfer, a positive pregnancy test would signal if the implantation is successful. You may have a blood test to check the HCG (pregnancy hormone) levels and follow up with the first pregnancy ultrasound.

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