New fertility treatments could offset the problems of ageing

In recent years, a social phenomenon has emerged: men and women are waiting longer and longer to start a family. Gone are the days when the majority would settle down early in their 20s and promptly begin having children. Today, we want to live our lives to the fullest before making lifelong commitments. We want to focus on our careers, and we want to find the right partner to share our futures with, rather than the one that is most judicious and timely.

While greater financial security and life experience make for an ideal environment in which to raise children, nature unfortunately has its own schedule, and an obdurate one at that. As we age, it becomes increasingly difficult to fall pregnant, not to mention risky. The likelihood of genetic disorders increases dramatically over time, particularly after the age of 35, which is now around the time many people plan to have children. This seismic shift in social norms and expectations, together with the mounting cost of living, has led to fewer people having children, while those who do have children generally have fewer than previous generations. Aside from the emotional turmoil this can cause for individuals, the cumulative result has been a decline in birth rates in numerous countries around the world. This phenomenon has direct economic repercussions that may well result in demographic disasters in the not-too-distant future.

Age-related fertility problems
Women are born with a finite number of egg cells, or oocytes, in their uterus – between one and two million. This number, however, soon begins to fall, and by adolescence, only some 300,000 eggs remain. While the quantity remains abundant during a woman’s 20s, the rate of decline begins to accelerate at the age of 32, speeding up even more so just five years later. By menopause, which usually takes place around the age of 50, all oocytes are gone.

What’s more, not all oocytes mature into eggs, while those that do are usually released one at a time during the monthly menstrual cycle. Eggs thus stay dormant until they are released, making them some of the longest living cells in the body. Herein lies the crux of the problem: as dormant eggs do not perform cellular repair, the likelihood of damage grows with each passing year.

Although these biological truths remain, our attitudes and the choices we make have changed – and drastically at that. “Many women are waiting until their 30s and 40s to have children. In fact, about 20 percent of women in the US now have their first child after 35, and this leads to age becoming a growing cause of fertility problems”, said Dr Sheree Boulet, Senior Epidemiologist at the Centre of Disease Control (CDC) Division of Reproductive Health.

About 20 percent of women in the US now have their first child after 35, and this leads to age becoming a growing cause of fertility problems

According to Boulet, in the US, around one in three couples in which the woman is older than 35 experience fertility problems. Indeed, becoming pregnant is but the first hurdle to overcome. Boulet stated: “Ageing not only decreases a woman’s chances of having a baby, but also increases her chances of miscarriage and of having a child with a genetic abnormality.”

The causes of female infertility are generally associated with ovarian function, and include diminished ovarian reserve, premature ovarian failure and, the most common cause of infertility in women, polycystic ovary syndrome. Also presenting a problem is tubal patency, which refers to how open, swollen or blocked fallopian tubes are. Under this category falls endometriosis, a common condition in which tissue and cells similar to those of the womb lining (the endometrium), are found outside it. Finally, uterine contours, namely the physical characteristics of the uterus, can also cause issues such as fibroids and other abnormalities.

With such conditions increasing in prevalence with age, and the changing of social norms, rates of pregnancy and childbirth continue to decline around the world. For example, recent estimates by the CDC’s National Survey of Family Growth indicate six percent of married women between the ages of 15 and 44 are unable to fall pregnant after one year of unprotected sex (which is how infertility is commonly defined). “This figure is generally considered an underestimate”, said Boulet. “Results from a few cohort studies and a cross-sectional study using a current duration approach, [which] considers time to pregnancy suggest that the prevalence of infertility is closer to 15 percent.”

In Japan, a plunging population rate has become a national concern of grave economic importance. At present, Japan’s birth rate is 1.4 children per woman – far lower than the 2.1 average needed to ensure stability in one of the world’s largest economies. Since the country’s population peak of 128.1 million in 2008, Japan has become increasingly skewed towards an older populace. Today, around 25 percent of the population is over the age of 64, while the number of children below 15 is at an historic low. Based on the current trajectory, Japan’s population is expected to plummet to 86 million by 2060, 40 percent of whom will be over 65. Such a demographic will place incredible pressure on the state, particularly in terms of medical and pension systems.

Gender parity
Contrary to common misconceptions, the fault does not lie with the age of the woman alone, as men also experience increasing fertility problems as they grow older. The CDC’s analysis of the 2002 National Survey of Family Growth found that 7.5 percent of sexually experienced men under the age of 45 in the US (around 3.3 to 4.7 million men) have seen a fertility doctor at some point in their lives. Of those men, 18 percent were diagnosed with an infertility problem, including semen problems and varicoceles. “Varicoceles are overly large veins on a man’s testicles, which cause them to overheat; the heat may affect the number or shape of the sperm”, Boulet explained.

During evaluation practitioners will assess the concentration of sperm, as well as its motility and morphology – both of which can affect chances of insemination. That said, as Boulet explained: “A slightly abnormal semen analysis does not mean that a man is necessarily infertile. Instead, a semen analysis helps determine if and how male factors are contributing to infertility.”

Issues related to sperm can be caused by various factors. As with women, lifestyle plays an important role; habits such as heavy alcohol use, smoking, drug abuse, and anabolic steroid or testosterone supplementation can have a detrimental impact on the concentration and motility of sperm. Likewise, environmental factors are relevant, particularly in terms of exposure to pesticides, lead and other toxins.

As far as male infertility is concerned, we are not yet able to choose the best spermatozoa for use

Various medical conditions, such as diabetes, cystic fibrosis and infections, can also contribute to abnormal semen analyses, as can cases in which a man has received chemotherapy or been exposed to radiation. Of course, the likelihood of any of the above taking place swells as the years march on. Moreover, the cessation of sperm production altogether also becomes more likely with age, and is caused by a condition called male hypogonadism, which, according to a study published by the International Journal of Clinical Practice in 2006, affects 40 percent of men over the age of 45.

And yet, at present, treating male infertility remains highly problematic. “As far as male infertility is concerned, we are not yet able to choose the best spermatozoa for use”, said Dr Kostandinos Sfakianoudis, an obstetrician and gynaecologist specialising in human infertility at Greek fertility clinic Genesis Athens.

Fixes and breakthroughs
At present, in vitro fertilisation (IVF) is the most common treatment for fertility. First used in 1978, the process involves surgically removing eggs from the ovaries, then fertilising them with sperm within a laboratory setting. The fertilised eggs, or embryos, are then implanted into the womb in the hope that one will take. The process involves taking daily injections of follicle-stimulating hormones, which can be emotionally punishing and lead to a reduced libido, and can be an issue itself when trying to conceive. In fact, IVF can sometimes lead to depression or anxiety during or after treatment. And, despite such an uncomfortable and gruelling process, it does not always result in pregnancy; in the UK, for example, only 20 to 25 percent of cases are successful.

Moreover, due to the private costs and various rules for state-sponsored IVF, many people do not even have access to fertility treatments. For instance, in the UK, patients over the age of 43 or with a BMI over 30 are unlikely to receive IVF treatment from the state, and instead face a private healthcare cost of £5,000. Given this is the age at which an increasing number of couples try to have children, a large portion of the population is thus prevented from receiving treatment – and this issue isn’t exclusive to the UK. “As we all know, most patients delay the onset reproductive pursuit, and therefore they are always confronted with the problem of age and time, yet still, there are many societies and governments that do not allow the performance of IVF even in advanced age”, Sfakianoudis said.

However, while governments may be slow to change their rules, medical research is taking a leap forward. In particular, 2016 has been a significant year for innovations in fertility treatment. Take Genesis Athens, which recently pioneered a method to reverse menopause through platelet-rich plasma (PRP) therapy. PRP, which is made by centrifuging a blood sample to isolate growth factors, is currently used in conditions such as osteoarthritis, tennis elbow and rotator cuff tears. The therapy is proven to be highly effective, utilising platelets from the patient’s own blood in order to rebuild damaged cartilage and tendons.

Genesis Athens recently pioneered a method to reverse menopause through platelet-rich plasma therapy

“We know that the PRP helps tissue recovery very well; it enhances healing procedures and stimulates tissues. So we thought: ‘Why not test that on menopausal ovaries?’ We have already tested it on more than 30 patients, and it seems that in many among them, it works”, said Sfakianoudis. “It works in terms of improving hormonal parameters and recovering menses after menopause; there are patients who do not respond, but it seems promising.”

PRP also appears to be an effective treatment for women whose embryos refuse to attach to the uterus. This condition often arises as a result of scarring from miscarriages, thin uterine lining, or cysts. Naturally, as with any medical breakthrough, more steps are needed until widespread access is available. “Larger studies need to be implemented”, Sfakianoudis said. “For the moment, we are recruiting patients and enlarging our samples. If it is proved to be working then it will certainly get a clean clarification and commercial use, but for the moment, it needs to be investigated further.”

Treatments for male infertility have also shown great potential this past year. In June, New Scientist revealed progress had been made to help men who cannot produce viable sperm. The method extracts the stem cells that produce sperm, and then corrects the mutations in vitro, before implanting them back into the testicles. Through this method, not only is a couple spared IVF treatment, but the child they produce will also benefit from no longer having the faulty gene present in the father. Genome editing does, however, raise ethical questions, with many opposing the idea of ‘designer babies’.

Nonetheless, the ability to prevent faulty genes being passed on to a child offers a wealth of opportunities in preventative care, as well as enabling more couples to have children. This area in particular was the subject of the media spotlight at the end of September, when it was revealed New York’s New Hope Fertility Clinic had successfully carried out the world’s first birth involving three parents. So as not to pass on a lethal genetic disorder from the mother, the nucleus from her egg was removed and implanted into a donor egg, which was then fertilised with the father’s sperm. This technique was successful in removing the genes carrying Leigh syndrome, while still carrying traits of the couple. Although such procedures are currently illegal in the US (it was done in Mexico for this reason), it holds great promise for countless couples around the world who refrain from producing offspring for fear of the genetic disorders their children might inherit.

Blurred lines
When it comes to fertility treatments, there is a fine ethical line to tread. Some argue a couple should not be allowed to give birth after a certain age, as their own health may become an issue; they may not be able to run around after toddlers or indeed survive until the child’s teen years or adulthood. Of course, such scenarios can transpire for young couples as well – and they do, every day.

That said, many still argue it is unfair to purposefully put a child in an unstable or uncertain environment. Misfortune is all too frequent; when it comes to children, as a society, we strive to ensure their wellbeing at all times.

Some argue a couple should not be allowed to give birth after a certain age, as their own health may become an issue

When asked about this particular issue, Sfakianoudis was clear in his conviction: “We deal with lots of women every day and their desire is enormous. It’s a life dream that we are pursuing for each one of them, and I cannot deny it to any of them. I understand the ethical issues, but I cannot condemn a patient who wasn’t able to find the right person to construct her family in the right time as our society implements.”

He is right to a certain extent: who are we to judge another on the path their life has taken? Whether it’s due to choice or chance, a couple should not be denied the greatest gift that life has to offer.

Moral issues regarding the age of new parents aside, the truth of the matter is infertility is a colossal problem. It affects millions of people around the world every day. It can disrupt lives, cause depression, and wreak havoc on an economy. As such, governments and scientists have a responsibility to tackle this escalating problem, not only to help potential parents realise their dreams, but to ensure economic stability in the long term. The saying ‘children are our future’ may be a cliché, but it is as true today as it has ever been.

Society has changed; the social norms and customs associated with decades gone-by cease to function in the modern climate. It is becoming increasingly difficult to buy a home, have a steady income, and pay for childcare and schooling, not to mention everything else that comes in between. For these reasons, and so many more, people are delaying parenthood – this is a fact. But, when all is said and done, it is a fact that we must address if we are to balance our personal aspirations with societal needs, now and into the future.