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Metabolic coenzyme shows promise for improved egg quality

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Despite advances in in vitro fertilisation (IVF) and growing success rates, age remains the single most important factor when it comes to fertility.
 
For women, egg quality declines relatively early from the age of 30 onward. As a result, success rates for IVF significantly drop from 35% in patients aged 30 and under, to 8% for women over 40 years of age.
 
But new research, published in the journal Nature, has found boosting levels of a common metabolic coenzyme may help improve egg quality and, in turn, chances of conception – both naturally and through IVF.
 
Researchers from the University of Queensland’s Centre for Clinical Research found that the quality of a woman’s eggs is significantly dependent on nicotinamide adenine dinucleotide (NAD+) – a chemical found in every cell of the body.
 
As eggs matured, increased levels of NAD+ were found to help ensure they retained the bulk of their cellular building blocks.
 
NAD+ is involved in hundreds of metabolic processes; however, with age its levels decline, as is the case with egg quality.
 
 Professor Hayden Homer, a scientist and lead researcher of the study, told newsGP the findings are ‘very promising’.
 
‘What are the options right now? For poor egg quality it’s either several rounds of IVF – and I mean several – or really the only medical option is to resort to donor eggs. What we are looking at is an opportunity to reverse poor egg quality for the first time,’ he said.
 
‘We have proof in an animal model, in a mouse model, that if we boost NAD+ in mice that are the equivalent of women who are in their mid-40s, we can revert their eggs to a 30-year-old quality.
 
‘We strongly believe that this is an agent that can bypass the need for IVF at all.’
The discovery, made as part of a four-year project, is considered to be the world’s most in-depth study of the final steps of egg maturation.
 
It involved taking high-resolution time-lapse imaging of live eggs lacking the NAD+ biosynthetic enzyme Nampt.
 
Researchers tracked the speed of spindles – the structure that pulls chromosomes apart – during the final stages of egg maturation.
 
They observed that a ‘burst’ of speed dependent upon NAD+ is required to prevent the egg from losing too much of its building blocks.
 
‘We expect that boosting NAD+ through oral agents that we hope to trial soon, will allow us for the first time to actually improve egg quality,’ Professor Homer said.
 
When it comes to natural ways of boosting NAD+ levels, Professor Homer says the only current evidence-backed option is intermittent fasting. But will it help sustain a successful pregnancy? He says likely not.
 
‘We know that when the body sees less calorie intake, one of the ways it compensates is to up NAD+ production to drive mitochondrial function. It seems to be a compensatory response that’s inbuilt and sort of hardwired into all of us,’ Professor Homer said.
 
‘The problem with that and pregnancy is that if you get pregnant whilst calorie restricted, the pregnancy doesn’t do well because of the lack of nutrients.
 
‘So although it can boost your NAD+ and sustain your egg quality, it doesn’t support actual pregnancy at the same time.’
 
Meanwhile, Professor Homer says there are also potential benefits for younger women.
 
While the best indicator of egg quality is a woman’s chronological age, he says there is a large group of women whose eggs age prematurely.
 
‘A lot of women come to IVF unknowingly because of poor egg quality,’ he said. ‘Remember, none of the tests we do can test the quality of your eggs; all you know is that you’re not getting pregnant. So you’ll be ovulating, tubes will be patent and sperm will be normal, but still not conceiving.
 
‘At least 10% of the women we see undergoing IVF have eggs that are older than you’d expect based on their age; they have a genetic predisposition to advanced ovarian ageing. So it applies more broadly.’
 
However, Dr Magdalena Simonis, a GP with a special interest in reproductive health, told newsGP it is important not to give women ‘a false sense of security’ when it comes to preserving their eggs or egg quality.
 
‘There are other factors at play,’ she said.
 
‘Much like co-enzyme Q10 has a central role in mitochondrial function, it was hypothesised that CoQ10 is also involved in infertility. Co-Q10 also decreases with age and rapidly drops in the 30s, then precipitously after that.’

 Dr Magdalena Simonis says lifestyle factors play a major role in fertility and pregnancy outcomes.
 
Rather, Dr Simonis suggests GPs, who are the first port of call for patients and their fertility, provide pre-pregnancy advice around the ‘window of opportunity’ and encourage healthy lifestyle choices.  
 
‘A good diet, maintaining a healthy weight and lifestyle factors … are key to achieving healthier pregnancy outcomes,’ she said. ‘The evidence exists already to support the importance of adequate levels of folic acid, iodine, vitamin D and avoiding chemical toxins, smoking and alcohol.
 
‘[Also] fertility is a female and a male issue so it is important to introduce the importance of a healthy lifestyle to both.’

To help patients maximise their fertility, Dr Simonis recommends GPs advise patients on the following:

• Maintaining a healthy weight and exercise: ‘Where the Body Mass Index (BMI) is high research shows that even losing a few kilos can improve pregnancy rates. The risk of gestational diabetes is reduced when a healthy weight is maintained and there is a regular exercise program.’ 
• Eating a healthy diet: ‘Simple recommendations include encouraging a variety of at least five vegetables throughout the day, and the dinner plate should have at least 2/3 vegetables or salad. Sugary drinks, fast food and processed foods should be limited.’
• Alcohol should be avoided: ‘Drinking alcohol reduces both women’s and men’s fertility, causing delays in conception and can affect the development of the fetus.’  
• Smoking should be stopped: ‘Women and men who smoke take longer to get pregnant than non-smokers, and the chemicals in cigarettes can damage eggs and sperm, which affects a future child’s health. Ideally, smoking cessation should occur at least three months prior to trying to conceive.’ 
• Folic acid supplementation: ‘Required at a minimum dose of 400 micrograms, in addition to 150 micrograms of iodine each day to support fetal development.’

Professor Homer also advises that GPs be proactive when it comes to specialist intervention.
 
‘My advice is really to be proactive about women who are seeking fertility advice in relation to their age; don’t hesitate to refer to specialists, especially as women get beyond 35,’ he said.
 
‘There is this window of egg quality and it’s about capitalising on it. One of the most stressful things is to see patients come in at 38, 39, 40, who really didn’t realise how quickly egg quality goes down.
 
‘As it stands now, once that’s gone down, without a therapeutically proven way to improve egg quality, then you’re really up against it.’
 
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egg quality fertility IVF pregnancy

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