One in seven couples in Singapore suffer from infertility. So, assisted reproductive technology offers hope to infertile couples. There are two types ― IVF (where the sperm and egg meet without any intervention in a petri dish) and intracytoplasmic sperm injection (or ICSI, an extension of IVF, in which the sperm is injected directly into the egg).

When Louise Brown, the world’s first “test-tube baby” was born via in-vitro fertilisation (IVF) on July 28, 1978, in the UK, there was controversy and fear that medicine was trying to “play God”. Nearly 40 years later, this medical phenom has improved, plus it’s more widely accepted within society.

To date, more than five million children have been conceived by assisted reproductive technology, notes Dr Pascal Gagneux, an evolutionary biologist and associate professor of pathology and comparative medicine in the US.

Indeed, mum of two, Maimunah Nasir, 35, will always be grateful that she has IVF to thank for blessing her with baby number two, who is now 3. She had her first child, a boy, now 10, soon after marriage and then tried to conceive her second child naturally for the next six years. However, her husband had some fertility issues. Maimunah says, “I’m so glad I live in a time that medicine has advanced so far that allowed me to have my daughter.”

Still, not everyone ― including the couples about to embark on their IFV journey ― know what this arduous procedure entails. Here are five lesser-known truths about IVF…

1) Expect plenty of tests, needles and doctor’s visits

First, you have to undergo various blood tests and scans to confirm that you’re infertile. In particular, hysterosalpingography (HSG) is an ultrasound where they inject dye into your fallopian tubes to check if they’re blocked. Some women have described it as “eye-wateringly painful” and “totally unexpected”.

Once you start on the stimulation phase (stims) you’ll need to inject yourself twice a day with hCG (human chorionic gonadotropin) hormones to stimulate your ovaries to boost egg production. Carried out after your last menstrual cycle, this can last 10 to 12 days. “I had to see my doctor every morning during my stims cycle, so that he could run tests and determine if everything was going according to plan,” Maimunah recalls.

To date, more than five million children have been conceived by assisted reproductive technology.

Next is egg-retrieval day, which takes place 36 to 38 hours after your last hCG jab. “The patient will be under sedation…with the help of an ultrasound, a vaginal probe is attached to the needle inserted into the vaginal walls, and into the ovary and follicle for egg retrieval,” explains Dr Yeong Cheng Toh, an IVF specialist at Virtus Fertility Centre.

A positive pregnancy doesn’t mean you can breathe easily just yet, by the way. All the hormones you took to suppress ovulation initially and manipulate your body for IVF will leave your body confused. It doesn’t know when to produce its own hormones to support your pregnancy. So, your fragile little embryo needs to be nurtured in the first few weeks of pregnancy with progesterone supplements.

Since you’ll receive this through suppositories or weekly injections at your doctor’s office, this can go for up to week 15, until your body has created the placenta. “IVF definitely isn’t for the faint-hearted or anyone who’s scared of needles, I’ll tell you that!” adds Maimunah.

2) It’s going to wreak havoc on your body

Before you can even start on stims, you’re required to take go through a two-week downregulation "long Lupron” protocol. During this time, you’ll be given drugs to stop the egg from being released and to prep your body for ovary stimulation later on. The Lupron is injected under the skin in your thigh or abdomen area, which can cause a whole host of side-effects including migraines, mood swings and early menopausal symptoms like hot flashes.

Dr Yeong quickly says that some clinics now offer the short protocol where just one injection will reach the same desired effects in half an hour and with less side-effects. “However, women with conditions such as endometriosis aren’t eligible for the short protocol,” he adds.

You are also at risk of Ovarian Hyperstimulation Syndrome (OHSS) when you’re going through the stims cycle. As the name suggests, this occurs when the hormones boosting your egg production go on overdrive and hyper-, or over-stimulate the number of eggs produced. Mild cases of OHSS can occur in about 10 to 20 per cent of cycles and symptoms include intermittent lower abdominal pain, nausea, vomiting and bloatedness. In severe cases, it can result in dizziness and shortness of breath.

3) You will be waiting ― a lot!

The irony of getting on the IVF roller coaster, is that once you’re on it, you will feel like you’re on a kiddie train ride going at 10 km/h. There is a lot of waiting and impatient anticipation for the next appointment, the next injection or the next scan.

“There so many pauses in-between each step ― first taking the downreg drug, then the jabs to increase my eggs, then the retrieval and insemination, then waiting to see if there are any viable embryos, followed by the implantation and the dreaded two-week wait to find out if I was pregnant or not,” Maimunah says. “Every step is so important that once you complete it, it’s a milestone on its own, it’s definitely not for emotionally-unresilient person.”

She also remembers buying cheap pregnancy test kids in bulk online that she would then pee on from the day she went through implantation. “The wait was killing me, I couldn’t take it. So, I used the cheap tests every day and inspected it closely for a positive reading. When I was nearing the two-week mark where a pregnancy diagnosis would be more accurate, I used the expensive test kit to confirm my pregnancy!”

“Every step is so important that once you complete it it’s a milestone on its own, it’s definitely not for emotionally-unresilient person.”

4) Results are not guaranteed

Since couples are counselled before they even start a cycle, they are more or less prepared in theory, but many of them are not prepared for emotional toil it takes.

Maimunah admits, “Not only can you go crazy with all the waiting, but when you realise that you after putting yourself, your family and your body through all of that it may actually not result in a pregnancy…it’s very depressing.”

Failed implantation could be due to embryos with significant genetic abnormalities. Age is a major factor in a successful pregnancy ― whether natural or IVF, Dr Yeong points out. “Results show that the younger you are, the higher your chances of success,” he adds. “If you are younger than 40, it’s an almost 50 per cent success rate, but if you’re 40 and older your chances are only 20 per cent per cycle.”

This is why in Singapore, a woman who is younger than 40 years is eligible for 10 rounds of IVF. Older women can only do five rounds. The Singaporean government only allows women younger than 45 years old to get IVF. You will need the government’s permission if you are above 45 years.

“In addition to preparing physically for IVF treatment, I also mentally prepare and manage my patient’s expectations as the diagnosis of infertility can be challenging,” says Dr Yeong. “That’s why at Virtus, all of our patients are offered private counselling sessions starting from the stage of hormone stimulation.”

"If you are younger than 40, it’s an almost 50 per cent success rate, but if you’re 40 and older your chances are only 20 per cent per cycle.”

5) You may be risking your baby’s health

An IVF procedure’s effect on the baby’s health is one area that has fully not been explored. Dr Gagneux, who has spent many years researching assisted reproductive technology, has found that it’s associated with an increased risk of multiple pregnancies, a higher chance of the woman being afflicted with pre-eclampsia, a greater likelihood of a C-section delivery. IVF babies also risk being born with malformations and even cancer in the long run.

According to him, IVF done in adult mice have shown that the females get heavier very late in life and have a dysregulated lipid metabolism, a hallmark of cancer cells. However, since the technology is about 40 year old and the oldest IVF baby is still in her 30s, not much is still known about the long-term health complications on an IVF baby.

Notes Dr Gagneux, “My research thus far has drawn attention to the fact that we might not be aware of the consequences of assisted reproduction due to the bypassing of the many quality control and compatibility checks that take place along the female reproductive tract during natural fertilisation.”

While pre-implantation genetic diagnosis can be used to test embryos for either a specific known genetic condition or chromosome abnormality, the biggest worry is the quality of the sperm. During natural conception, the strongest and healthiest sperm wins the race to fertilise the egg, ensuring a healthy pregnancy. However, in procedures like ICSI, where the tail is yanked off the sperm and the nucleus injected directly into the egg, one doesn’t know just how healthy the chosen sperm is, and what kind of a pregnancy and baby it will produce.

Another area of concern Dr Gagneux brings up is how the quality of the embryos are affected while sitting in a petri dish in the lab during the five days that it is being cultured. “We could be changing their imprint during that time,” he notes. “And that’s very troublesome.”

Pascal Gagneux, PhD, is an associate professor of Pathology in the Division of Comparative Pathology and Medicine, as well as associate director at the Center for Academic Research and Training in Anthropogeny (CARTA) at the University of California San Diego.

Dr Yeong Cheng Toh is an IVF specialist at Virtus Fertility Centre.

Photos: iStock

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