Brain activity may hold the secret to helping infertile couples

by Nicky Pellegrino / 19 January, 2018

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Sometimes, there is no obvious reason a seemingly fertile couple are struggling to conceive. His sperm is healthy; she has no history of pelvic infection or endometriosis; everything seems as it should be, yet there’s still no pregnancy.

Now, Professor Allan Herbison and his team at the University of Otago’s Centre for Neuroendocrinology have taken a significant step in helping these couples – who make up about a third of infertility cases in New Zealand. They have identified crucial information about the way our brains control fertility.

It’s not exactly news that the brain has a role to play here. The idea that it controls the pituitary gland, prompting it to send out hormones, has been around since the 1940s. But for a long time, scientists have been trying to understand the mechanism behind that control: what exactly is going on in the brain that makes this happen?

It’s a question Herbison has been asking for about 25 years. “We know so much about other organs, such as the heart and liver, but when it comes to the brain, we’re cavemen,” he says. “It’s incredibly complex and we’ve been really struggling. But now, new techniques have been developed and we’ve been able to apply them to the brain. This is an exciting time to be in neuroscience.”

For a while, research was centred on the gonadotropin-releasing hormone (GnRN) neuron, which occasionally sends out pulses that activate the pituitary gland to release the hormones that control the testes and ovaries. Herbison admits that researchers went down a bit of a blind alley there, because it turns out that a couple of thousand other neurons drive the GnRH by releasing a chemical called kisspeptin. “The GnRH neuron just sits there and does what [the other neurons] tell it to do,” says Herbison.

Working with mice, he has been able to show that the kisspeptin neurons located in the hypothalamus area of the brain somehow synchronise and become active for about a minute every hour. This is what drives the pulses. The key question now is how they manage to do that.

Professor Allan Herbison. Photo/Sharron Bennett

“The more detail we can find about the mechanisms involved, the more chance we have of manipulating them to generate or stop synchronisation,” says Herbison.

For some women, the problem is that the neurons are too active: they generate pulses far too quickly, which confuses the ovaries. These women – sufferers of polycystic ovary syndrome (PCOS) – deal with other unpleasant symptoms, including acne, excess facial hair and weight gain, and treatments only manage the symptoms rather than offering a cure.

In other women, the pulses have stopped or start too slowly, often as a result of environmental factors such as not eating enough or doing too much exercise.

“There’s a huge link with stress,” says Herbison.

“It’s very clear that brain cells involved with stress also regulate the kisspeptin neurons. A number of animal studies show a wide variety of stressors stop the pulses completely or slow them down.”

From an evolutionary perspective, this makes sense: pregnancy is a vulnerable time and, for our forebears, it was preferable if it happened only when health and external circumstances were optimal.

There’s plenty of anecdotal evidence that if you remove stress, couples can find it easier to conceive. When Herbison talks to groups of infertile couples, he often hears stories about people who gave up on IVF after several rounds and fell pregnant naturally when the stress of treatment ceased.

The pharmaceutical industry is hugely interested in kisspeptin’s potential. It is already being seen as a potential method of stimulating ovulation in women undergoing IVF that would be safer than some of the drugs now in use, which increase the risk of ovarian cancer and can be used for only a short time. In trials at Imperial College London, volunteers were injected with kisspeptin and an encouraging number of healthy babies were born.

“The closer we can get to mimicking nature, the more sophisticated fertility treatments are going to be,” says Herbison, who hopes that within the next decade, these new discoveries will be making a positive difference to many couples trying to conceive.

This article was first published in the December 16, 2018 issue of the New Zealand Listener.

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