Stages of IVF
Stage 0 : Preparing for IVF
The steps for preparing for IVF are similar to the steps for preparing for IUI, and for getting pregnant in general.
To maximise the success rate of IVF, both parents should aim to be in an optimal physical condition. Eat healthy, and exercise regularly. Stop smoking, and reduce your intake of alcohol and caffeine.
Many ladies recommend reading the book “It starts with the egg” by Rebecca Fett on the types of supplements to take in the 3 months before you commence IVF.
Women should also take folic acid, to minimise birth defects such as spina bifida.
In addition, men should:
1. Take antioxidant supplements with vitamins A, C and E to improve the sperm quality.
2. Avoid hot baths, saunas and Jacuzzis. Sperm quality is badly affected by high temperatures.
3. Avoid medications that can adversely affect their sperm function.
Stage 1 : Stimulating the Ovaries
Most women produce only one egg each month. To increase the number of eggs which are produced, and accordingly the number of embryos that can be formed, hormonal injections are given.
The hormone injunctions usually start from the second day of the menstrual cycle. The injections are given daily, for about 10 to 12 days. Some women learn how to give themselves the injections, while other women let their husbands do it. Your clinic may also allow you to go to the clinic every day for the injections, but depending on your schedule, this may be quite troublesome.
You will be scanned once every few days to monitor how the eggs are growing and responding to the hormones. The scans are usually done trans-vaginally using a long and slim probe. Blood tests are also done to check for levels of certain hormones (oestradiol and LH) produced by the ovary and the brain.
Once the eggs are of a certain size, a second injection is given to stop the eggs from being released on their own. The eggs are then ready to be retrieved.
Some clinics offer either short or long IVF protocols, and your doctor will discuss with you to decide which is suitable. For the short protocol, the injections start on Day 2 of your menstrual cycle. For the long protocol, the injections start before your menstrual cycle commences, so as to prevent premature ovulation during the stimulation phase. A rough timeline is as follows:
Ovarian Hyperstimulation Syndrome (OHSS)
OHSS happens when too many ovarian follicles develop during the stimulation of the ovaries (Stage 1).
The symptoms of OHSS include:
Mild to moderate abdominal pain
Nausea / Vomiting
Tenderness in the area of your ovaries
Sudden weight increase of more than 3kg in a few days
It is not uncommon for younger women to have a mild form of OHSS. The severe form of OHSS is rarer, and it affects around 1% of all patients. OHSS (in any form) should be medically treated by your doctor until the complications have been treated.
Food – Maintain a healthy, balanced diet, and drink plenty of water.
Some clinics/women say you should eat:
1. Protein-rich food (e.g. tofu, eggs and beef) – to prevent Ovarian Hyperstimulation Syndrome
2. Folic acid and food rich in folic acid (e.g.peas, spinach, broccoli, kiwi, poultry products) – to prevent birth defects such as spina bifida and other developmental disorders
3. Food rich in zinc (e.g. dairy products, grains, potato and brazil nuts) - Helps to maintain and regulate hormone levels
Real women say…
“First day was full of screams. Then I sucked it up and just did it and it wasn't so bad… You get so scared but when the deed is done, it’s actually nothing!”
“I'm into day 4 of the injections. The bloated feeling gets worse as the day passes and today, it actually feels like menses cramps. The ache seems to spread up my spine and down my legs. And it was difficult to walk straight.”
“Being someone who is pretty terrified of needles, the first few times I had to inject myself was quite a frightening experience, I was also second guessing whether my way of doing was alright, or whether I will waste my medication if I do not respond well. Then as the days progresses, I do get a better hang of injecting myself, but as I inject myself more and more, bruises come along and I will be looking forward to the day I will have completed all the injections.
“Most people I know have a fear of needles, but once you get over the first few it becomes easier and less painful. Before injecting, use a small ice pack to numb the area. Hold it there for around 3-4 minutes, then clean with an alcohol swab and inject. This usually numbs the pain of the needle going in so you don’t feel it. I also used to put on music that I enjoy listening to when I had 2-3 injections to do each morning. It helped distract me and the music was uplifting.
“Try to make your skin as taut as possible ( pinch hard) to reduce the pain when the needle goes in. I got my husband to do the jabs, it’s the least he could do.”
“I’m not sure if this is practical or woo woo, but every time my husband poked me, I told myself “I’m nourishing myself”. The side effects for me were exhaustion, lower back ache, nausea, sore belly, bloatedness and that I looked pregnant when I’m not. Getting to know other women who were going through the same thing I was going through, made me feel kinda better. That I’m not alone.”
Stage 2 : Egg retrieval
Once the eggs have reached a minimum size of 17 to 18mm, they should be ready for fertilisation with the sperm.
Retrieving the eggs – Egg retrieval will be done in the hospital, under general anesthesia or sedation. The eggs will be retrieved from the egg follicles using a fine needle attached to a vaginal ultrasound probe. As you will be under general anesthesia or sedation, the procedure is generally pain-free.
Generally, you will be able to go home a few hours after the procedure, and you will be given some antibiotics to minimise any chance of infection. You will also be given Hospital Leave after the procedure.
Collecting the sperm – On the day of the egg retrieval, the husband has to produce a semen sample. To produce the best possible specimen, the husband should abstain from ejaculation or sexual intercourse for 3 to 5 days before the day of collection.
Semen can be collected at home and brought to the lab, but it should be kept warm at all times and it should reach the clinic as soon as possible. Alternatively, some private clinics and public hospitals may have a collection room - you should check in advance, to avoid having to use the toilets.
On the day of the procedure, you should come without any nail polish or makeup. You should also inform the nurses if you have any dentures or loose teeth.
After the procedure, some ladies say that you should:
Drink lots of water (at least 2 liters daily)
Continue to take a high protein diet.
Take ginger with longans
Avoid spicy or oily food.
Real women say…
I was so nervous when I went in for the egg retrieval. You had to be seated with your legs opened up and placed on a support. My heart rate was beating at 100bpm. But with the GA , everything happened really quickly and the process didn't take that long. Next moment I was in the recovery room.
“As everyone reacts differently to the medication given to sedate us, some people will take a longer time to wake up from the medication while some will wake up faster. There was once I woke up in the midst of the procedure, and they had to give me more medication to put me back under.”
“Before my egg retrievals, I did some guided meditation to help me calm my nerves and think of my happy place. My happy place is a stunning beach in Koh Lipe, Thailand. I imagine myself back there again, listening to the sound of the soothing ocean waves and I imagine that I can feel the soft sand between my toes. This strong and vivid scene gets me into a calm state and leaves me feeling less anxious about the entire process.”
“ Bring a pair of socks. Make sure your husband holds your phone for you, otherwise when you get out of the theatre, you won’t have anything to do while waiting to be discharged. (because your bag is in the locker.) Your bladder is supposed to be half full. Just in case you need to go before the procedure, have a bottle of water handy. Night before I usually listen to meditation and taking deep breaths (and a longer exhale) does help with anxiety.”
Stage 3 : Fertilising the Eggs
In the laboratory, the sperm sample is prepared and inspected. The most active / optimal sperm is then chosen to fertilise the egg. For cases where sperm quality is not that ideal, the sperm samples may be placed on a petri dish of Hyaluronan which will allow for selection of better sperms as the better sperm will be attached to the Hyaluronan (PICSI).
The fertilisation can be done in one of 2 ways:
Simply mixing the egg with the sperm (traditional IVF); or
by injecting a single sperm into each egg via a microneedle. This is called intra-cytoplasmic sperm injection (ICSI), and it is recommended for cases in which there is very poor sperm quality.
An embryo starts as a single cell, and then it divides every 12 to 24 hours. The embryos will be monitored daily by the embryologist, who might provide you with updates. You can expect the total number of embryos to decrease as the days go by.
The embryologist will advise you on when you should transfer the embryos – whether you should transfer at Day 3 or Day 5 Blastocyst stage. The exact day and time will depend on the quality of the embryos. The embryologist will determine the most suitable day for the transfers, and will also select the best quality embryos for transfer.
Stage 4 : Embryo Transfer
Embryo transfer is generally a painless procedure and usually no anaesthetic required. However, you will need to have a full bladder during the procedure so that the uterus can be seen properly. As the nurses will have to press on your uterus to perform the ultrasound scan during the procedure (while your bladder is full!), the procedure can be quite uncomfortable.
You will be asked to arrive at the clinic an hour before the procedure, with a full bladder. You may also be put on a drip to allow your uterus to relax. However, if you have a retroverted uterus, you will likely need to empty your bladder slightly. The nurses will check your uterus and let you know if this is necessary.
During the procedure, the embryos will be placed back into your womb, through the cervix, using a very thin, soft plastic tube. This procedure will feel similar to having a Pap smear. It is usually not painful, but it may be uncomfortable.
Day 3 Embryos or Day 5 Blastocyst?
By Day 3, the embryo will have around 4 to 8 cells.
Some of the reasons why a transfer may take place at Day 3 are as follows:
Some doctors prefer to transfer on Day 3 as they believe that the best place for an embryo to grow is inside the womb.
As the number of embryos decreases each day, there will be more embryos to transfer on Day 3, as compared to on Day 5. If there are only a few good quality embryos, a Day 3 transfer may be preferred.
As compared to a Day 5 transfer, there is a lower risk that there are no embryos to transfer at all, and that the cycle is cancelled altogether.
Similarly, there may be more embryos available for freezing after the Day 3 transfer.
On the other hand, if the transfer takes place on Day 3, it is more common to transfer 2 embryos (rather than 1). This results in a higher risk of a twin pregnancy.
By Day 5, the embryo will have around 70 to 100 cells, and it will become a blastocyst.
Some of the reasons why a transfer may take place at Day 5 are as follows:
Blastocysts are generally seen as being more viable and stable.
Embryos with chromosomal abnormalities are less likely to make it to the blastocyst stage.
It is easier to assess and select the better quality embryos. This allows for a single embryo to be transferred.
On the other hand, as fewer embryos make it to the blastocyst stage, there is a chance that none of the embryos make it to Day 5, and the cycle is cancelled altogether.
How many embryos to transfer?
Usually, 1 to 2 embryos are transferred.
If more than 1 embryo is transferred, the chances of pregnancy increase. However, there is also a higher chance of twins or triplets. The risks of carrying twins or triplets, which begin from the first trimester include:
Miscarriage of one or more babies
Caesarean section and haemorrhage after delivery
Premature babies which require admission to neonatal ICU * (about 60% of twins are born premature)
Growth restriction of the babies and low birth weight
Therefore, single embryo transfers are offered to women with the best chance of achieving a pregnancy. Single embryo transfers have shown to have good pregnancy rates with better long-term benefits in women who are suitable. Some factors which will be considered are:
Whether it is the first IVF cycle
Whether there are at least three good embryos on day 3 or three good blastocysts on day 5
Whether there are other embryos available for freezing
If you are suitable for a single embryo transfer, you are just as likely to conceive with two embryos as with a single embryo transfer, without the risks associated with multiple pregnancy.
Although the desire for parenthood can be strong and you have many decisions to make, it is important to choose the option that suits your personal and practical limits.
Genetic screening of IVF embryos
Genetic screening of the embryos allows only genetically healthy embryos to be implanted into the uterus, thus increasing the chances of a successful pregnancy.
In Singapore, it is possible to perform genetic screening of the embryo before it is implanted, but only under very limited circumstances. There are two methods of screening: Preimplantation genetic diagnosis (PGD) and Preimplantation genetic screening (PGS). Both methods of testing are basically the same - cells are taken from the embryo for testing before implantation. The difference lies in what the tests lookout for.
Preimplantation genetic diagnosis (PGD) tests for genetic disorders or chromosomal abnormalities. It is usually performed where one or both parents have a known genetic abnormality or are carriers of certain genetic diseases, such as:
Sickle cell anemia
Duchenne muscular dystrophy
Spinal muscular atrophy
Fragile X syndrome
Preimplantation genetic screening (PGS) tests for whether the cell has all 23 pairs of chromosomes, or whether there is an abnormal number of chromosomes in the cell (a condition known as Aneuploidy). However, the gender of the embryo is not made known to anybody who may have an influence on the selection of the embryos for implantation.
In 2017, the Ministry of Health started a 3-year pilot PGS program at the National University Hospital. Under the pilot programme, only patients who fulfill at least one of the following criteria will be eligible for PGS:
1. Age 35 years old and above, regardless of prognosis
2. Two or more recurrent implantation failures, regardless of age
3. Two or more recurrent pregnancy losses, regardless of age
Eligible patients from the 3 public hospitals (KKH, NUH, SGH) will be referred to the NUH lab to undergo PGS. Patients from private centers are referred to the 3 public hospitals for initial assessment.
Presently, the Ministry of Health is still evaluating the clinical outcomes from the pilot study to determine whether to offer PGS as a routine clinic service.
Real women say…
“I put in 2 day 3 embryos on my 2nd cycle and conceived with one healthy baby girl. Do try to rest as much and be stress-free. I watched a of Netflixed during the TWW! The embryos implant around day 8-9. So don't strain yourself too much during those few days.”
“Try and get some time to talk to your embryologist! My husband and I had so many questions around the embryos we had and the quality etc. We made sure that we scheduled time to speak to our embryologists to ask all our questions so that we felt at ease and more comfortable. We avoided forums and other opinions and what really matters is what your embryologist and IVF doctor have to say. They work as a team in your best interest to maximise your chances of getting pregnant. Trust them and don’t be afraid to ask them anything. No question is a silly question.”
Stage 5 : After the Embryo Transfer – the 2 week wait
You may go home shortly after the embryo transfer. You will be given daily hormonal support (progesterone or HCG) to support the uterus lining and increase the chances of the embryo implanting.
After the procedure, you should not do anything strenuous for the following few days. In fact, some clinics provide Hospital Leave for the two week wait. Rest well and be kind to yourself. Maintain a healthy, balanced diet and drink a lot of water. Avoid alcohol and coffee, and smoking, of course!
Some clinics will bring you in for a blood test 2 days after the embryo transfer, to check on your progesterone levels. If the levels are low, you will be given progesterone injections to increase the chance of a successful implantation.
Some women feel a whole host of symptoms, others feel nothing. The good or bad news is that the symptoms don’t indicate whether the transfer was successful. But do inform your doctor if you:
Experience vaginal itchiness
Run a fever
Have any strong menstrual cramps
Cramps – Generally, some cramps are normal and to be expected, especially in the days after the transfer. But tell your doctor if you feel any serious menstrual cramps.
Exercise – Most clinics will advise against doing exercise, especially strenuous exercise, or carrying heavy items. Some women also caution against swimming, yoga and going for massages.
Food – Maintain a healthy, balanced diet, and drink plenty of water.
Some clinics/women say you should eat:
Folic acid – to prevent birth defects such as spina bifida
Some clinics / women say you should NOT eat / drink:
Cocoa / chocolate
Cold and gassy drinks
Chinese herbal teas and soup (e.g. Bak Kut Teh)
Banana (with green skin)
Medications – Remember to take your medications regularly, as advised by your doctor.
Sexual intercourse – Some clinics recommend a 2-week restriction on sexual intercourse.
Stress – The 2 week wait is understandably nerve-wracking… but DON’T stress yourself!
Real women say…
“For my first failed cycle, I felt totally normal during the TWW. In my 2nd cycle, I had headaches and my tummy felt twitchy. I woke up one morning feeling super hungry. My boobs were tender and I was spotting 2 days before my blood test. Turned out that cycle was a BFP. Thank God.”
“For me, I usually do not feel anything or have any signs regardless whether there is any implantation. But I have the bad habit of testing with home pregnancy test before the blood test. I will suggest not to do the home pregnancy test unless you are sure you can handle the result of it, else it will just bring more unnecessary stress upon yourself.”
“As much as you are tempted to do an early pregnancy test during the 2WW, my advice is that you fill up your time doing things that you enjoy, will keep you calm and distracted. Doing a test at home may result in inaccurate results which will only cause more distress and can send your emotions spiraling.
I also avoid ‘Google’ as this can also send you a little crazy as the symptoms for early pregnancy can also mimic the symptoms of a BFN. Be patients as hard as it can be, you’ve done all that you can do and now it is out of your hands. Be sensible about what you eat, avoid alcohol and take nice long walks by yourself or with your partner. If it helps, do some visualisation exercises thinking about your little embaby all cosy and protected inside”
“All I can say, this is the most nerve-wrecking wait of my life and I did 5 of this. So I suggest that you find and do things that make you happy. Take up a new hobby maybe. Try not to over-analyse every “pregnancy” symptoms. Do not go on IVF forums because they can be very scary. Do restorative yoga for the 2WW or go walks with the husband.. Self-care and rest is very important. So do you what you need to put yourself first”
Stage 6: Pregnancy Test
Around 10 days after the embryo transfer, a blood test will be performed to confirm whether you are pregnant. If you are pregnant through IVF cycles, you will need to continue on the hormone medication until the pregnancy is at least 10-12 weeks.
Some bleeding from the vagina can occur even though you are pregnant, so it is important to do this test even if you think you are having your period.
It is important to realise that not every IVF cycle results in a successful pregnancy. Failure in one IVF cycle does not mean that you have a reduced chance of success in the next IVF cycle.
Frozen Embryo Transfer (FET) / Thaw IVF Cycles
Any extra embryos that are not transferred from the initial 'fresh' IVF cycle and are of sufficiently good quality may be frozen for future use. The frozen embryos can be used if the fresh IVF cycle fails, or after you deliver and want to get pregnant again.
The embryo storage needs to be renewed annually, up to a maximum of 5 to 10 years, depending on the storage facility. Further storage requires approval from the Ministry of Health.
There are generally three types of thaw cycles:
'Natural' thaw IVF cycles - you will be monitored to see when you ovulate. The egg in that cycle will not be collected but based on the time of ovulation, the embryos will be thawed for transfer into your uterus.
Letrozole-Thaw cycle - Letrozole will be taken for 5 days starting from around Day 2 of your menses. The doctor monitor for ovulation and thickness of lining, and the embryo transfer will be arranged based on the ovulation date and age of embryo (ie. Day 5 blastocyst will be arranged to be transferred 5 days after ovulation)
'Artificial' thaw IVF cycle - This may be advised if you have difficulty in having good ovulation. Hormonal medication will be given from day 2 of your menstrual cycle, and the embryos will be thawed and transferred when your womb lining is of sufficient thickness.
Real women say…
“I was so anxious to go ahead with the IVF cycle and finally be pregnant. So when my doctor recommended that we go for the frozen cycle, I was very disappointed that I would have to wait a further 2 months. But she explained that it would be best to let the lining be ideal for the transfer. Well, as it turns out, all of my transfers were successful - so no complaints!”
Egg / Sperm Donations
In Singapore, egg and sperm donation is permitted. However, commercial trading of egg and sperm is strictly prohibited in Singapore. So you cannot pay for the egg or sperm, nor can you pay the donor in any form. You can, however, reimburse the donor for his/her expenses incurred (e.g. transport costs).
The donor eggs can be sought from relatives or close friends, who might be willing to undergo the egg retrieval process (see Stage 1 and Stage 2 above). Most clinics will require you to find the egg donor yourself. Generally, the egg donor:
should not be related to the husband;
should be 35 years old or younger;
will have to complete a counseling and psychological assessment session;
will have to be screened for genetic risks and diseases;
will have to confirm that the donation is altruistic, such that she is not paid for the donation.
Alternatively, the donated eggs may be obtained from unrelated donors, such as ladies who are already undergoing fertility treatments and have eggs to spare.
It is easier to access donor sperm, than donor eggs. Some clinics will ask you to find your own sperm donor (such as relatives or close friends). Others will link you up with overseas sperm banks which have been approved by the Ministry of Health. However, there are some guidelines in place (e.g. there should be no more than 3 live births per sperm donor, to prevent the chance of half-siblings meeting).
In Singapore, it is not possible for a single lady to use donor sperm to get pregnant. It is also not possible for the clinics to carry out surrogacy arrangements (whereby another lady carries the child, and is paid for doing so).
Freezing your Eggs
Generally, the quality of the eggs decreases with age, especially after the woman turns 35 years old. Hence, some women wish to extract and freeze their eggs while they are relatively young.
In Singapore, the position is that you can only freeze your eggs for future use if there is a medical reason for you to do so. For example, you may freeze your eggs before undergoing chemotherapy and/or radiotherapy which may affect the quality of the eggs.
At present, “social egg freezing” is still not allowed in Singapore. So unless you have a medical reason for freezing your eggs, you will not be able to freeze your eggs (regardless of whether you are single or married) for use later, when you are ready to have kids.
Private or public treatment?
A common question is whether to go for treatment at a private clinic, or at a public hospital. Based on our own anecdotal evidence, here are some of the differences between the two:
Success Rate – IVF
In general, the most critical factor in determining a couple's fertility is female age. Generally, patients who are below 36 years old have a better chance of successful pregnancy. However, your chances of success will ultimately depend on your own individual circumstances.
The miscarriage rate is about 10-15%.