IVF treatment: Where to draw the line?

After returning home from a holiday with her new husband, Lee Cowden was hit with chest pains - it turned out to be a heart attack due to a high dose of In Vitro Fertilisation (IVF) drugs.

Facing ovarian problems Cowden, 33, had taken the drugs to improve her chances of conceiving a child. She didn’t think it would end in a heart attack, but she is one of many women who are facing serious side effects from IVF.

“I was diagnosed with poly cystic ovarian syndrome (PCOs) when I was 15 and was told at that point that I would need to have fertility treatment to have a family. I married at 25 and straight away started to undergo the fertility treatment,” Cowden, a music teacher, said.   

Cowden’s initial attempt to conceive had failed and the clinic in London where she was taking treatment had doubled the dose for the next cycle to stimulate her ovaries, as part of IVF.

“After the heart attack, I was told that I could no longer have conventional IVF. Because of the PCOs, my body is more likely to over stimulate - OHSS,” Cowden said.

Side effects

The treatment which resulted in the world’s first successful birth of test tube baby - Lusie Brown -  in July 1978, has helped so many couples to conceive babies. Every year, more than 3.7 million babies are born across the world with the help of fertility treatments, but today, experts are increasingly wary of side effects associated with the treatment.

In the UK, nearly 60,000 cycles of IVF are carried out per year and a recent inquiry into maternal deaths in the United Kingdom found that Ovarian Hyper Stimulation Syndrome (OHSS), following high-dose IVF is now one of the leading causes of maternal mortality in England and Wales.

“In most of the cases, it is possible to predict the complications involved. It’s very necessary to monitor women undergoing treatment for the OHSS, as it gives rise to other related complications,” Dr Sadoon Sadoon, Consultant gynaecologist, Medway NHS Foundation Trust, London, said.

According to the National Institutes of Health, high-dose stimulation leads to OHSS in 10 per cent of IVF patients. The severe form of the condition occurs in about 2 per cent. The ovaries become swollen with the shift of the body fluid (intravascular) to the chest and abdomen.

“If it is not addressed immediately, there is a risk of kidney failure, clotting problems, including pulmonary embolism and liver disorder. It is potentially fatal and women can end up in intensive care unit with long- term consequences,” Dr Geeta Nargund, president of International Society for Mild Approaches in Assisted Reproduction (ISMAAR), and medical director of Create Health Clinics, London, said.

“It can result in poor pregnancy outcome, including miscarriages,” adds Dr Sadoon, who is an expert in infertility management and minimal access surgery.

Birth defects

Besides, a recent study suggested that high-dose IVF contributes to lower birth weights, compared with the babies of women who receive minimal doses of hormonal drugs.

In 2008, an analysis of the data of the National Birth Defects Study in the US found that certain birth defects were significantly more common in babies conceived through IVF, notably septal heart defects, cleft lip with or without cleft palate, esophageal atresia and anorectal atresia.

“… it is still important for parents who are considering using ART [Assisted Reproductive Technology, which includes all fertility treatments such as IVF] to think about all of the potential risks and benefits of this technology,” said Jennita Reefhuis, epidemiologist at CDC’s National Centre on Birth Defects and Developmental Disabilities, and the lead author of the report published in the Human Reproduction journal.

Added to these, a new Australian study published in the New England Journal of Medicine examined birth defects associated with different types of assisted reproductive technology.

Researchers compared risk of major birth defects - such as cerebral palsy or heart or gastrointestinal defects - among babies born with help of the most commonly available types of fertility treatments, including IVF, ICSI (intracytoplasmic sperm injection) and ovulation induction.

"While assisted reproductive technologies are associated with an increased risk of major birth defects overall, we found significant differences in risk between available treatments," said the lead author of the study, Associate Professor Michael Davies from the University of Adelaide's Robinson Institute and School of Paediatrics and Reproductive Health.

And only two years ago, the inventor of ICSI, Dr André van Steirteghem, had warned it was being “overused”. He had told the American Association for the Advancement of Science (AAAS) meeting at San Diego in 2010 that he believed “ICSI was being used too often” and had warned that it should be “used when absolutely necessary”.

Unaware of complications

Not all the times women are aware of the complications associated with the IVF treatment and the moment they are unable to conceive naturally, they blindly think of IVF. Not many realize that they always end up going for the standard IVF treatment and end up facing several complications associated with it.

“When we offer IVF, we should give women options of having Natural (drug-free) IVF , Mild IVF (small amount of drugs) and conventional IVF (high dose drugs),” Dr Geeta Nargund, who has published more than 100 peer-reviewed scientific papers including abstracts and several book chapters in the field of Assisted Reproduction and Advanced Ultrasound in reproductive medicine, said.

The way of stimulation always plays a major role in the IVF treatment. In high-dose IVF, women are first given drugs to suppress ovaries, causing temporary menopausal symptoms. Later, ovaries are stimulated to produce more eggs.

“Women normally produce one egg per cycle, but when they are given high dose drugs to stimulate ovaries, they end up producing many eggs and sometimes 20 to 30 eggs, sometimes even more. Some of them are donated during egg donation programme,” Dr Sadoon said.

Even though more eggs are produced after stimulation, collection also comes with risks.

“The egg collection carries a small risk of bleeding, infection and internal injury,” said Dr Nargund.

Switching to mild IVF 

Many countries, including Holland, Denmark, Sweden, the UK, Japan and South Korea, are switching to mild or soft IVF from aggressive forms of conventional IVF, and other countries are yet to think on those lines.

Even though there are complications in high dose IVF treatment, why do women prefer it? Is it something to do with cost factor? According to Dr Nargund, “it is because of higher number of eggs and embryo obtained in conventional high-dose IVF” and the feeling that chances of getting pregnant are more.

Many patients and doctors believe that high-dose drugs will increase the chances of conceiving in lesser cycles. But contrary to the general opinion, low-dose IVF drugs are less expensive, costing only about a third of standard IVF, according to Cowden.

"Women undergoing IVF treatment forums want 20-30 eggs so that embryos could be freezed. They fail to realise the risks and the sky-high cost of the high-dose drugs. I calculated and realized I could have four cycles of mild IVF for the cost of one standard IVF," Cowden said.

Mild or soft IVF uses very low dose stimulation for a shorter period of time within a woman's own menstrual cycle which can reduce the burden and discomfort of treatment, including the risk of OHSS. “It is also associated with healthier eggs, embryos and the lining of the uterus,” says Dr Nargund.

Women want their own biological baby and will be ready to go through any amount of turmoil - financial and mental. “The ultimate joy I got when I saw the face of my babies, nothing matters, not even the amount of complications I went through during the treatment," 35-year-old Lisa (name changed to protect the identity), who suffered three miscarriages, before giving birth to twins recently, in New York, said.

Overcoming the stigma
Reducing cost and increasing accessibility and safety are the key priorities in fertility treatment. Welfare of the mother and child should be taken into account before the treatment.

Cowden, who was asked to stop standard IVF drugs, started having mild dose of IVF treatment a year later. "I was given small doses of fertility drugs and carefully monitored. I conceived within three months of the treatment with Molly, who is now five,” Cowden, mother of two, said. "I cried my eyes out when the nurse finally said, ‘Test is positive, you are pregnant’. I was more than happy."

“Natural cycle IVF can be more successful in older women and in women with low egg reserve,” says Dr Nargund, adding, “We must do no harm while offering this treatment.”

To some extent, IVF treatment has become commercialized. “It shouldn’t be used for no reason. Both doctors and patients should realize that IVF is not the only way to conceive, there are many other ways. Mild IVF drugs can achieve the same if not better outcome and aggressive use of ovarian stimulation should be avoided," Dr Sadoon said.

Plus, there is a need to overcome the stigma of being infertile and thinking IVF as the only solution for the problems. There’s a need to understand how to deal with the most painful part - infertility - in life. Many women do not even make it public that they are undergoing IVF treatment, let alone discussing the complications.

“Women are very sensitive, they would not want to talk about it,” said Angie (name changed to protect the identity), working as a secretary in a firm in London, who has also faced complications and has given up the IVF treatment altogether and adopted childfree lifestyle, said.

Becoming parents through IVF treatment can be financially - given the fact that insurances do not cover IVF treatments - and emotionally a draining process. “It’s been a roller-coaster ride for me. I have gone through agonizing times, but I’m happy, rather say lucky, I have a happy ending for my story,” Cowden said.

With many women around the world desperate to have children, it seems Cowden and millions like her will continue using the technique, regardless of the risks.