Cause of polycystic ovary syndrome discovered at last

The most common cause of female infertility – polycystic ovary syndrome – may be caused by a hormonal imbalance before birth. The finding has led to a cure in mice, and a drug trial is set to begin in women later this year.

Polycystic ovary syndrome affects up to one in five women worldwide, three-quarters of whom struggle to fall pregnant. The condition is typically characterised by high levels of testosterone, ovarian cysts, irregular menstrual cycles, and problems regulating sugar, but the causes have long been a mystery. “It’s by far the most common hormonal condition affecting women of reproductive age but it hasn’t received a lot of attention,” says Robert Norman at the University of Adelaide in Australia.

Treatments are available for helping affected women get pregnant, but their success rates are typically less than 30 per cent across five menstrual cycles.

Polycystic ovaries are the most common cause of fertility issues in women

Womb changes
Now, Paolo Giacobini at the French National Institute of Health and Medical Research and his colleagues have found that the syndrome may be triggered before birth by excess exposure in the womb to a hormone called anti-Müllerian hormone.

The researchers discovered that pregnant women with polycystic ovary syndrome have 30 per cent higher levels of anti-Müllerian hormone than normal. Since the syndrome is known to run in families, they wondered if this hormonal imbalance in pregnancy might induce the same condition in their daughters.

To test this idea, they injected excess anti-Müllerian hormone into pregnant mice. As their female offspring grew up, they displayed many of the hallmarks of polycystic ovary syndrome, including later puberty, infrequent ovulation, delays in falling pregnant, and fewer offspring.

The excess hormone seemed to trigger this effect by overstimulating a set of brain cells that raise the level of testosterone.

Cure in mice
The team were able to reverse this effect in the mice using cetrorelix, an IVF drug routinely used to control women’s hormones. After treatment with this drug, the mice stopped showing symptoms of polycystic ovary syndrome.

The team is now planning a clinical trial of cetrorelix in women with the condition, which they hope to start before the end of the year. “It could be an attractive strategy to restore ovulation and eventually increase the pregnancy rate in these women,” says Giacobini.

“It’s a radical new way of thinking about polycystic ovary syndrome and opens up a whole range of opportunities for further investigation,” says Norman.

If the syndrome is indeed passed from mothers to daughters via hormones in the womb, that could explain why it’s been so hard to pinpoint any genetic cause of the disorder, says Norman. “It’s something we’ve been stuck on for a long time,” he says.

The findings may also explain why women with the syndrome seem to get pregnant more easily in their late 30s and early 40s, says Norman. Anti-Müllerian hormone levels are known to decline with age, usually signalling reduced fertility. But in women who start out with high levels, age-related declines may bring them into the normal fertility range – although this still needs to be tested, says Norman.

(Source: NS)

Why PCOS is on the rise among Indian women

One in every 10 women in India has polycystic ovary syndrome (PCOS), a common endocrinal system disorder among women of reproductive age, according to a study by PCOS Society. And out of every 10 women diagnosed with PCOS, six are teenage girls.

PCOS was described as early as 1935. However, even today there is a general lack of awareness regarding the condition in India and it often remains undetected for years. This health condition is estimated to affect about 10 million women globally.

A study conducted by the department of endocrinology and metabolism, AIIMS, shows that about 20-25 per cent of Indian women of childbearing age are suffering from PCOS. While 60 per cent of women with PCOS are obese, 35-50 per cent have a fatty liver. About 70 per cent have insulin resistance, 60-70 per cent have high level of androgen and 40-60 per cent have glucose intolerance.

In studies conducted in South India and Maharashtra, prevalence of PCOS was reported as 9.13 per cent and 22.5 per cent, respectively.

Many aspects of the disorder are not understood properly as its symptoms and severity vary greatly. Women with PCOS are often found to have higher than normal insulin levels. Insulin is a hormone that’s produced in the pancreas. It helps the body cells turn sugar (glucose) into energy.

If you don’t produce enough insulin, your blood sugar levels can rise. This can also happen if you’re insulin resistant, meaning you aren’t able to use the insulin you do produce effectively. If you’re insulin resistant, your body may try to pump out high levels of insulin in an effort to keep your blood sugar levels normal.

Too-high levels of insulin can cause your ovaries to produce more androgens, such as testosterone. Insulin resistance may also be caused by having a body mass index above the normal range. Insulin resistance can make it harder to lose weight, which is why women with PCOS often struggle with this issue.

The incidence of PCOS among women and teenage girls has risen to such an extent that the Indian Council of Medical Research (ICMR) has taken up a nationwide survey. The reason it is dangerous is that if this condition is left unchecked or undiagnosed, it can lead to infertility among other long-term health concerns.

Early diagnosis and treatment is key to help prevent health problems. At Motherhood Hospitals alone, we have seen 4-5 cases of teenage girls suffering from PCOS, which is significantly high compared to 10 years ago. This is mostly due to unhealthy lifestyles, unhealthy diets and lack of exercise.

Spectrum of symptoms
Girls and women suffering from PCOS exhibit a range of symptoms such as weight gain, fatigue, unwanted hair growth, thinning hair, infertility, acne, pelvic pain, headaches, sleep problems and mood changes. Most symptoms begin shortly after puberty and they can also develop during late teens and into early adulthood.

Girls with PCOS typically have irregular periods or amenorrhea, and heavy or scanty bleeding during menses. Doctors also look for elevated levels of the male hormone androgen (testosterone) and polycystic ovaries.

With PCOS, women can develop cysts due to ovaries not being released on time. The follicles keep growing and form multiple cysts, which appear like “a string of pearls”. Women are likely to develop PCOS if their mother or sister also has the condition.

Not just that, women with PCOS have a higher risk of developing other health complications such as hypertension, high cholesterol, anxiety and depression, sleep apnea, heart attack, diabetes and endometrial, ovarian and breast cancer. Women who have PCOS have a higher rate of miscarriage, gestational diabetes, and premature delivery.

Recommended treatment
Unfortunately, PCOS cannot be cured. It can, however, be managed to a large extent by controlling symptoms. Exercise and a healthy diet are the best bet for women with PCOS as this will help to regulate their menstrual cycle and lower blood glucose levels.

High-fibre foods can help combat insulin resistance by slowing down digestion and reducing the impact of sugar on the blood. This may be beneficial to women with PCOS. Great options for high-fibre foods include broccoli, cauliflower and sprouts, red leaf lettuce, green and red peppers, beans and lentils,  tomatoes, spinach, almonds and walnuts, olive oil, fruits, such as blueberries and strawberries, and fatty fish high in omega-3 fatty acids, such as salmon.

Lean protein sources like tofu, chicken and fish don’t provide fibre but are filling and a healthy dietary option for women with PCOS.

Instead of three big meals they should have five small meals, which helps metabolise food and in maintaining weight.

If women with PCOS are suffering from infertility, then fertility drugs may be administered to aid ovulation. On the other hand, if a woman does not want to get pregnant, then birth control pills may be prescribed.

In order to stop excess hair growth and help reduce acne, using anti-androgens is the recommended course of action. While many women have been recommended to regularly exercise, (minimum 45 minutes a day, five times a week) one refrain that we commonly hear is that they don’t have time.

Up to 5-10 per cent of weight loss will help improve the symptoms, hormonal balance and regularisation of menstrual cycle. PCOS among women, especially adolescents, is an urgent public health problem that needs careful assessment, timely intervention and appropriate treatment.

Promotion of healthy lifestyles, the need for regular exercise and increased awareness programmes on PCOS is the need of the hour to enable a holistic solution to this problem.

(Source: Daily O)

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. 

Women brave IVF complications for children

Women continue to use In Vitro Fertisilation to conceive, despite increasing evidence of dangerous side effects.

After returning home to London from a holiday with her new husband in 2004, Lee Cowden was hit with crippling chest pains. It turned out to be a heart attack that had been caused by a high dose of In Vitro Fertilisation (IVF) drugs.

Facing ovarian problems, the 33-year-old had taken the drugs to improve her chances of conceiving a child, but has become one of many women who are facing serious side effects from IVF.

Each year, more than 3.7 million babies are born across the world with the help of fertility treatments, but experts are increasingly wary of side effects associated with the treatment.

"I was diagnosed with Polycystic 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," Cowden, a music teacher, told Al Jazeera. "I married at 25 and straight away started to undergo the fertility treatment."   

Louise Brown, the world's first "test tube baby", was born in July 1978, and the process has since helped many couples conceive. Robert Edwards, who is credited with developing IVF, won the Nobel Prize in Medicine for his work. 

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