Research

Dr Sacks completed his PhD in reproductive immunology at Oxford University in 1998. His research began in the field of pre-eclampsia (a potential complication of pregnancy characterised by high blood pressure). However, he became increasingly drawn to the challenges of early pregnancy implantation – an embryo must implant (embed) in the wall of the uterus to lead to a successful pregnancy. His initial studies demonstrated that pregnancy is not an ‘immune suppressed state’, as was believed at the time, but actually an ‘inflammatory state’. This new finding changed the way we view and manage pregnancy.

The inflammation that occurs during pregnancy is partly created by natural killer (NK) cells, which are the main immune cells in the uterus. In some cases, this inflammation is excessive and may be the cause of implantation failure and other complications of pregnancy such as pre-eclampsia.

Dr Sacks’ research identified that NK cell activity in the blood can be reliably tested, providing a simple method by which we can diagnose women who are likely to benefit from immune suppressive therapy as part of their fertility treatment. Without such therapy, these women have fewer babies, more miscarriages, and more IVF failures.

In previous decades, the male was largely ignored as a potential cause or target for treatment in infertility. Today, males are recognised as 50% of the problem, and tests and treatments for male factor infertility have become increasingly sophisticated. Dr Sacks’ initial research in this area was one of the first-ever studies to show that sperm DNA fragmentation (lesions, damage or breaks in the genetic material of the sperm), is the sole cause of miscarriage in 6% of cases of recurrent miscarriage.

Sperm has now become one of Dr Sacks’ main areas of research, in collaboration with the bioengineering department at UTS. Together with Professor Majid Warkiani, Dr Sacks is jointly supervising three PhD projects investigating the use of artificial intelligence (AI) to detect sperm more effectively (in the setting of low sperm quantity); to select better sperm for use in ICSI (an advanced IVF technique where a single, high-quality sperm is precisely injected into a mature egg); and to improve the long-term storage of small numbers of sperm (to aid fertility preservation, e.g. for men undergoing medical treatment such as chemotherapy or radiation that may affect the quality or quantity of sperm).

IVF treatment protocols have become fairly standardised throughout the world. But that does not mean that they are perfect, or that we can’t try to get the best outcomes for particular patients by modifying them.

Dr Sacks’ initial interest in this area was progesterone. He found that measuring levels of progesterone in the blood is a useful way to assess the likelihood of embryos implanting successfully. However, serum progesterone levels are not so useful as an indicator of treatment adequacy. This is because progesterone, when delivered by vaginal pessary, will go straight to the uterus, where it is most needed.

Dr Sacks has also studied the implications of other hormone levels in IVF success. For a woman’s eggs to develop and mature, two hormones are required: follicle-stimulating hormone (FSH) and luteinising hormone (LH). Throughout the IVF process, it has been clear for some time that FSH is by far the most important hormone for egg development, so in most modern IVF treatment protocols, it is the only stimulation hormone given to women. But small amounts of LH do also seem to be important, and in most cases, low levels are produced naturally by the woman’s own pituitary gland. However, in some IVF treatment protocols (e.g. the commonly used ‘antagonist protocol’), profound suppression of this natural LH can occur. In these women, administering LH by injection may improve the hormonal stimulation of egg development.

In an early study, Dr Sacks investigated whether adding LH makes a significant difference to IVF outcomes by comparing this practice with a colleague. They found that there was indeed a marked increase in live birth rate when LH was added to the treatment protocol in IVF cycles where a woman’s natural LH had dropped to very low levels.

This finding was the basis for a much larger study, which was, in part, funded by Merck Pharmaceuticals. In one of the largest studies of its kind, over 12,000 cycles, involving more than 20 doctors at IVF Australia, were analysed. This brand new research showed that when LH levels drop, adding LH back by injection increases live birth rates in younger women. It also increases the number of eggs retrieved and the number of useable embryos in all women.

There has been a genetics revolution in the last few years, bringing the power of this technology to the clinic. It is now possible to test for most specific genetic diseases in embryos using pre-implantation genetic diagnosis (PGT-M). In couples planning to start a family, it has become standard practice to consider screening them for risk of having a child with a genetic disease. This is called genetic carrier screening. This revolution in human reproduction poses significant challenges to the evolutionary framework that has produced all of life so far, and is one of the themes covered in Dr Sacks’ upcoming book (The Origin of Hope).

Dr Sacks has formed a partnership with the genetics start-up company, 23strands. Together, they are researching the whole genome (all genes) in couples experiencing unexplained infertility and repeated IVF failure. They are hoping to find new genetic causes for these issues, so that in the future, genetic testing may be used to identify couples at risk, assisting with treatment and reproductive decisions. Dr Sacks and 23strands have also recently received a $5 million research grant from the National Health & Medical Research Council (NHMRC) to investigate whether a combination of genome testing and AI can help identify the optimal IVF treatment protocol and hormone stimulation doses for patients undergoing IVF.

Patients frequently consult alternative practitioners during their fertility and IVF journeys. The support these practitioners provide can sometimes make the difference. However, it has been very difficult to prove if interventions such as acupuncture and naturopathy can improve IVF success rates or reduce the chance of miscarriage. But it is important to acknowledge the support of alternative practitioners, and to try to demonstrate the effectiveness of their interventions, wherever possible.