In-Vitro Fertilisation (IVF) and Intra-Cytoplasmic Sperm Injection (ICSI)

In-vitro fertilisation (IVF) is a process in which fertilisation of the eggs with sperm occur in a laboratory, ‘in vitro’.

Intra-cytoplasmic sperm injection (ICSI) is a process of injecting a single sperm into each egg to enhance fertilisation, during IVF. This technique may be recommended for specific problems.

In the IVF process, before fertilisation, hormonal injections are administered for about two to four weeks to stimulate the follicles within the ovaries. Eggs are then collected and inseminated (IVF) or injected (ICSI) with the husband’s sperm in the laboratory.

After fertilisation, the embryos are incubated for two to five days before being replaced into the womb in a process called embryo transfer. A successful pregnancy can be confirmed 17 days later via a blood test.

What causes of infertility can IVF treat?

IVF may be an option if either you or your partner has been diagnosed with any of the following conditions which may contribute to infertility:

• Tubal factor (e.g., tubal damage from previous infections / previous ligation / salpingectomy)
• Endometriosis
• Ovulatory problems and/or anovulation (e.g., in Polycystic Ovarian Syndrome [PCOS))
• Early menopause (premature ovarian failure)
• Male factor (e.g., low sperm count / absent sperm [azoospermia] / inability of sperm to penetrate or survive in the cervical mucous)
• Unexplained infertility

Other procedures involved in IVF

There are other procedures involved in IVF which are suitable for specific problems. Your doctor will advise you if any of the following are necessary for you:

• Intra-cytoplasmic sperm injection (ICSI)
  ICSI involves injecting a single sperm into each egg to allow fertilisation to occur in the laboratory. This is recommended if the man has poor quality sperm or if you have had difficulties with fertilisation previously.
  
  Injecting single sperm into an egg


• Blastocyst Culture
  Embryos are cultured for five days to become a blastocyst. The chances of pregnancy are much higher with a blastocyst transfer. This may be helpful for couples with repeated IVF failure, multiple eggs and if pre-implantation genetic diagnosis is required.

Who is suitable for IVF?

IVF is the only fertility treatment for women with irreparably damaged or blocked fallopian tubes. IVF is also offered when infertile women cannot conceive with simpler methods of treatment for conditions such as endometriosis, ovulatory dysfunction, unexplained infertility, sperm disorders and immunological problems.

Counselling and consent

There will be a session where the clinician will explain and discuss the procedure with you. Any questions that you have about the treatment can be raised at this time. This will enable you to fully understand the treatment you are about to embark on. You will also need to make some decisions regarding unfertilised eggs and abnormal/poor quality embryos.

A written consent for IVF/ICSI and cryopreservation/thawing of the embryos is also obtained.

You will also need a separate session by our IVF counsellor on the emotional and physical demands of undergoing the treatment programme and dealing with disappointments of failed attempts.

Pre-programme preparations

Blood tests have to be performed to exclude venereal diseases such as syphilis, human immunodeficiency viruses (HIV), hepatitis B and acquired immunodeficiency syndrome (AIDS). A rubella antibody test will also be carried out. You will be advised to have a rubella vaccination before the IVF procedure if you have no immunity against it. You should also start taking folate daily.

Your husband will have a pre-IVF semen analysis to determine any need for the sperms to be frozen and stored.

A typical IVF cycle

1. Controlled ovarian hyperstimulation and monitoring
   Hormone injections are administered to stimulate the production of multiple eggs in each ovary (versus the usual production of a single egg per month), which hence results in a better chance of pregnancy.
   
   This stimulation process usually requires the initial daily use of a GnRH agonist injections (e.g., Lucrin) to suppress the body’s spontaneous ovulation, and to ensure that the ovarian follicles grow in a synchronous fashion. It usually starts in the second half of your menstrual cycle and continues for about 14 to 20 days. Some patients may need to take this medication for longer periods. Blood tests and ultrasound scans will be done to ensure that the optimum response is reached. Once this is achieved, you will proceed to the gonadotrophin injections.
   
   Daily gonadotropin injections (e.g., Gonal-F or Puregon) into the muscle/subcutaneous tissue of your thigh or buttock are then added to stimulate growth of the follicles in the ovaries. After several days of gonadotrophin injections, an ultrasound scan is performed to determine the number and size of the growing follicles. You will need additional injections if the follicles have not reached the desired size.
   
   Transvaginal ultrasound scan showing follicles in the ovary after hormonal stimulation
   
   When the follicles have reached the desired size, an injection of human chorionic gonadotropin (hCG) is given, with the discontinuation of GnRH agonist and gonadotrophins. The hCG is required for the final maturation of eggs before egg collection. The egg collection is scheduled about 36 hours after the HCG injection.


2. Sperm preparation
   During the gonadotrophin injections, your husband need not abstain from sexual intercourse before the egg collection. On the day of the egg collection, your husband needs to produce a fresh masturbated semen sample.


3. Oocyte pick-up (egg retrieval)
   Oocyte pick-up is performed by placing a special needle attached to an ultrasound vaginal probe into the ovary, and removing the oocyte-cumulus complex (containing the egg). A mild sedative will be given to you, as only minimal discomfort will be experienced during the procedure.
   
   After the egg collection, you will be observed for a few hours before going home. Multiple eggs may be retrieved at a time depending on the success of the stimulation process. It is important to understand that not all follicles will necessarily contain an egg and that some of the eggs may not be ripe enough for fertilisation. An overnight fast is required before oocyte pick-up procedures.
   
   Hormonal stimulation induces superovulation; eggs aspirated from the mature follicles transvaginally with ultrasound-guided needle


4. Fertilisation
   Following egg retrieval, sperm is added to the eggs in a dish to allow fertilisation to occur by natural selection in the laboratory. A check to confirm that fertilisation has occurred is carried out the following day. Unfortunately, in about 10% of couples, there is no fertilisation at all.
   
   Intra-cytoplasmic sperm injection (ICSI) may be performed on the day of oocyte pick-up if the sperms quality is poor or if you have had difficulties with fertilisation in the past. During the procedure, a single sperm will be injected into each egg via a microneedle. On the following day, a check is made to confirm that fertilisation has occurred.


5. Embryo transfer
   Fertilised embryos are transferred into the uterus between day two and day five of fertilisation using a fine catheter. This is usually painless and takes only a few minutes. An overnight fast is recommended before the embryo transfer procedure. We encourage your husband to sit in during the embryo transfer.
   
   Usually, a maximum of two embryos are transferred at a time. A smaller number may be transferred if there are insufficient embryos or in younger patients. Up to three embryos may be transferred under exceptional circumstances (please ask your doctor for more information).
   
   You may go home shortly after the embryo transfer. You will be given hormones either orally, vaginally or even by injection to support the lining of the uterus and to enhance the chances of the embryos implanting. There is no restriction on activities including sexual intercourse.
   
   Eggs fertilised in-vitro (IVF) with sperms. Embryo transferred directly into uterus, bypassing tubal occlusion.


6. Freezing of extra embryos
   A proportion of patients may have excess good quality embryos. These may be frozen for future use. Patients do not need to undergo controlled ovarian hyperstimulation and egg collection again for these future thaw cycles. The survival rate for thawing these embryos is about 83%. There is an annual storage fee for these frozen embryos, and they can be stored up to 10 years at our facility.


7. Testing for Pregnancy
   You will need to come back between 14 to 17 days after the embryo transfer for a pregnancy test, which measures the pregnancy hormone b-hCG in the blood. If you are pregnant, subsequent ultrasound scans and blood tests will be arranged to ensure that the pregnancy is proceeding normally. If you are not pregnant, you may consider proceeding to a frozen (thaw) cycle of IVF if you have additional frozen embryos in storage.
   
   You should call your healthcare team if you are menstruating, so that further instructions can be given.

What are the possible complications and risks of IVF fertility treatment?

• Cancellation of the treatment cycle may occur due to various reasons, including poor follicular development. Our cancellation rate is approximately 5%.


• Ovarian Hyperstimulation Syndrome (OHSS)
  OHSS refers to excessive stimulation of the ovaries during ovulation induction. It is a side effect of the medications given to you. Symptoms include:
  • Abdominal discomfort and/or pain
  • Nausea and vomiting
  • Bloatedness or swelling of the abdomen and genital area
  • Shortness of breath
  • Dehydratio
  • Reduction of urine volume
  
  OHSS is usually mild and causes no more than slight lower abdominal discomfort in most cases. However, immediate medical attention is required should the symptoms persist or worsen. This includes:
  • Vomiting o Urinary problems
  • Severe discomfort from abdominal bloating
  • Chest pain or any difficulty in breathing
  
  Less than 1% of our patients undergoing IVF may need to be admitted due to severe symptoms of OHSS. If you experience any of the above symptoms, please inform your doctor.


• Multiple pregnancy
  When three embryos are replaced, there is a 10% risk of twins and a 3% risk of triplets. Although the prospect of twins or triplets may seem attractive to some couples, multiple pregnancies are associated with increased risks of maternal and foetal complications.
  
  These include an increased risk of:
  • Miscarriage
  • Premature labour which can result in a child with physical or learning disabilities
  • Pregnancy-associated problems such as bleeding, diabetes and high blood pressure
  • Caesarean section and its complications
  • Stillbirth
  
  With the increased risk of multiple pregnancies, babies born as a result of the assisted reproductive programme have a greater chance of being hospitalised in a neonatal ward or intensive care unit (ICU). Hence, as required by the Ministry of Health, all patients undergoing this treatment in Singapore must subscribe to neonatal insurance.


• Failure of fertility treatment
  The likely reasons for failure are:
  • Cancelled cycles
  • Failure to collect eggs
  • Failure of fertilisation
  • Failure of the embryo to implant
  
  This can be due to a significant portion of embryos being poor quality or abnormal. Failure of treatment can lead to emotional strain and depression. Psychological counselling and support is available. Do not hesitate to inform your doctors if you require help.


• Ectopic pregnancy
  IVF increases the likelihood of an ectopic pregnancy. The ectopic pregnancy rate is about 5%. Patients who become pregnant through IVF treatment are advised to schedule an early scan to make sure that the pregnancy is correctly positioned.
  
  If an ectopic pregnancy is detected at an early stage, a medication called methotrexate can be used to dissolve the pregnancy tissue. Otherwise, surgical procedures will be considered to treat the ectopic pregnancy. Your specialist will discuss the appropriate treatment with you, should this happen.


• Miscarriage
  Miscarriage is a common complication of pregnancy. The miscarriage rate is about 10-15%. You will experience some abdominal cramps and bleeding. This diagnosis needs to be confirmed by your doctor. Depending on your condition and assessment by your doctor, surgical procedures may be required. Please consult your specialist for further information.


• Risks of oocyte collection
  The risks of oocyte collection are very rare. As the procedure involves a needle entering the ovary, it may be complicated by bleeding from the ovaries, uterus or adjacent blood vessels and injury to the intestines. In such an instance, further treatment may be necessary.

What are the success rates?

At KKIVF

Our overall clinical pregnancy rate is about 40-44% per cycle and the take-home-baby rate is about 30%. Generally, patients who are below 36 years old have a better pregnancy chance. However, your chances of success will depend very much on your own individual circumstances.

At the SGH Centre for Assisted Reproduction

The centre reached an average of 41% pregnancy rate for fresh IVF cycles and 38% for frozen cycles in 2018, in comparison to the average of IVF pregnancy results in 2018 of 36% for Europe.

Regulatory and funding matters

For IVF:

IVF counselling is mandatory under Ministry of Health (Singapore) guidelines. There may be a waiting time before starting the programme.

For IVF and frozen embryo transfer (FET):

Government co-funding and Medisave can be used for Singapore Citizens, subject to conditions. For more details, please refer to the Ministry of Health (Singapore) website: http://www.pqms.moh.gov.sg

Under Ministry of Health (Singapore) guidelines, our institutions do not practise:

• Sex selection unless medically indicated
• Social storage of gamete or embryos unless medically indicated

Frequently asked questions (FAQ)

1. How much does IVF treatment cost?
   Currently, IVF costs* between $10,000 to $17,000 SGD depending on your selected treatment. There are government grants available for Singaporeans below the age of 40 to help cover the cost of your treatment provided you fulfil other criteria.
   
   Our staff will work closely with you to help you manage your costs. Please refer to this website for more information regarding using your MediSave for assisted conception procedures.
   
   *accurate as of 31 Dec 2023
   


2. Can I travel during my IVF fertility treatment?
   No. It is imperative that during the monitoring phase of the treatment cycle, patients should be available as multiple appointments will be made for mandatory tests and treatments. Our nursing staff will work closely with you in scheduling the appointments.


3. Can we choose the sex of the embryo?
   This is not allowed as the government of Singapore forbids sex selection procedures. The sex ratio is almost identical to that seen in the general population following standard IVF treatment.


4. Will my age affect my pregnancy chances with IVF fertility treatment?
   Pregnancy rates decrease and the incidence of miscarriage increases for patents above 40 years of age.


5. Does weight affect pregnancy chances with IVF fertility treatment?
   IVF is not recommended if body mass index (BMI) is more than 30 or less than 19 as the chance of success is significantly lower with higher risks.


6. Is there something we can do to improve our chances of success in IVF fertility treatment?
   Although IVF treatment is a medical process, some lifestyle and dietary modifications may improve the success rates. Patients should stop smoking and avoid inhaling passive smoke. Alcohol consumption and having an extreme BMI should also be avoided.
   
   A daily intake of 5 mg of folic acid is recommended for all patients trying to conceive as this prevents neural tube defects in the baby.


7. What should we expect after oocyte pick-up (egg retrieval)?
   It is not unusual to experience slight abdominal discomfort and/or bloating, which will usually subside in 48 hours. It is usually tolerable. If necessary, medications may be prescribed.
   
   The patient may also experience slight vaginal bleeding after the procedure which will subsequently resolve. However, please contact us if you have heavy vaginal bleeding or severe abdominal pain.


8. What should a patient take note of after the embryo transfer?
   Please avoid strenuous and high-impact activities and exercises. You will be provided with medical leave for rest. Is it normal to experience vaginal bleeding after embryo transfer? Light vagina bleeding often occurs within the first few days after an embryo transfer. This can be present as light bleeding (pink/red/brownish) or spotting/staining. In this instance, no intervention is usually required.
   
   Common causes include the implantation of the embryo onto the lining of the womb. The use of vaginal progesterone causing the cervix to be more delicate and thus cervical bleeding is another common cause.
   
   Patients may continue using vaginal progesterone tablets as directed. If the bleeding lasts longer than three days or becomes very heavy, you are advised to call the IVF centre.


9. Is it normal to experience pain after embryo transfer?
   Many women complain about non-specific abdominal discomfort after embryo transfer. If the discomfort is mild and not constant, it is unlikely to be of concern. Simple pain relief medications should be sufficient. If the pain is severe with or without heavy bleeding, please call your IVF centre for advice or seek medical attention in hospital.


10. When will I be able to tell if I am pregnant?
    A pregnancy test is normally scheduled 14 to 17 days after the embryo transfer. It is mandatory that you return for this test even if you are bleeding.