World-leading gynaecology research recognised

Professor Cindy Farquhar and her team have received the Health Research Council of New Zealand (HRC) Beaven Medal for their research into the treatment of gynaecological and fertility conditions that has transformed clinical practice worldwide.

The team of Waipapa Taumata Rau, University of Auckland and international researchers ¹ were presented with the Beaven Medal for excellence in translational health research at the Royal Society Te Apārangi Research Honours ceremony at Auckland Museum on 20 November 2024.

HRC Chief Executive Professor Sunny Collings says over the past 30 years Professor Farquhar’s team has led 12 clinical trials into gynaecology and fertility treatments. Many of these trials have changed how women and couples with unexplained infertility are treated and led to less invasive treatments and better health outcomes for women and their families.

As the medical director of Fertility Plus in Auckland and deputy chair of the World Health Organization’s Fertility Guidelines, Professor Farquhar has a keen interest in helping the approximately one in seven couples who experience infertility, and this has been a key driver behind her team’s research, especially in more recent times.

In vitro fertilisation (IVF), a type of fertility treatment where an egg is removed from a woman’s ovaries and fertilised with sperm in a laboratory, was a huge game-changer when it was first introduced 40 years ago. However, Professor Farquhar says the reality is that a woman is “more likely not to get pregnant with an IVF cycle than they are to get pregnant”.

These odds have led to a raft of IVF ‘add-ons’ to try to improve one’s chance of conceiving, such as ‘endometrial scratching’, which involves sampling the tissue lining the womb (endometrium).

“The process of endometrial scratching takes a few minutes and is like having a smear test, but more painful. The action of taking the biopsy sample was thought to result in a ‘scratch’ or ‘injury’ to the lining of the womb, possibly making the womb more receptive to an embryo implanting. Our team knew that most clinics were offering this to their patients, and we wanted to find out if it really helped women to conceive from IVF,” Farquhar says.

In 2014, Farquhar, with colleague Dr Sarah Lensen, in Australia, and a large international team began recruiting for a clinical trial looking into this procedure, in which 1364 women from New Zealand, Australia, UK, Sweden and Belgium were randomly allocated to either receive or not receive an endometrial scratch before their IVF cycle.

Their findings, published in the New England Journal of Medicine in 2019,² showed no benefit from endometrial scratching: the live birth rate was the same among women who did and didn’t have it (26.1 percent); nor was there any subgroup of women who appeared to benefit, including women with previous IVF failure.

Their recommendation for IVF clinics to stop using endometrial scratching was widely heeded, and the practice is no longer used in countries such as New Zealand, Australia and the UK, with the possible exception of women with recurrent implantation failure.

“We have a responsibility to provide people seeking fertility treatments with robust scientific evidence so that they don’t go down the path of trying every unproven add-on,” says Professor Farquhar.

The team’s research has also led to renewed interest in intrauterine insemination (IUI), where sperm is placed directly into the womb using a small catheter, as a cheaper and less invasive adjunct or possible alternative to IVF.

“In New Zealand, people with unexplained infertility need to have been trying to get pregnant for five years before they can even get on the waiting list for IVF. We wanted to explore if there was a treatment that people could have earlier that was just as good as IVF.”

In 2013, IUI was no longer recommended by guidelines in the UK because of a lack of evidence. However, Professor Farquhar and her team’s clinical trial comparing three cycles of IUI with the ‘just keep trying’ approach showed a three-fold increase in pregnancy with IUI.

The results of this trial, published in the Lancet in 2017,³ led to the European Society of Human Reproduction and Embryology recommending IUI as a first-line treatment in 2023. This guideline has also been adapted for Australia with the same recommendation.

The team has recently recruited 737 couples in New Zealand for an HRC-funded clinical trial comparing one cycle of IVF with four cycles of IUI for the same group of patients with unexplained infertility. If the pretrial predictions are correct, then Professor Farquhar estimates that about one-third of patients will get pregnant with IUI and won’t have to wait for IVF.

“Increasingly people understand that if you wait until after 35 to try to get pregnant, then you’re limiting your options. Both natural conception and IVF success rates decline after 35. And we can’t afford to be complacent. New Zealand’s fertility rate has been below the replacement level of 2.1 children per woman since 2013 and we had a record low of 1.52 for the year ending March 2024, lower than Australia at 1.784,” says Professor Farquhar.

“We need to do more to improve access to fertility treatments both for our patients’ sakes and so that we don’t fall further behind in our fertility rate. Affordable, effective fertility treatments are part of the solution.”

One of the team’s early trials looked at the use of the drug methotrexate to treat ectopic pregnancies,⁵ which is where the fertilised egg grows outside the womb, making it unviable and potentially causing life-threatening complications. This trial and others have led to methotrexate being recommended as part of the clinical guidelines for treating some women with early-stage ectopic pregnancy. In many cases, this treatment can avoid the need for surgery to remove the ectopic and often the fallopian tube.

The team was also successful in leading the development of the New Zealand Guidelines on Heavy Menstrual Bleeding, which supported non-surgical options for treating heavy periods such as the levonorgestrel intrauterine device. Since these changes were made, New Zealand’s rate of hysterectomy surgery to remove a woman’s womb to manage heavy menstrual bleeding has declined from one of the highest rates in the world in the early 1990s, to one of the lowest rates in the OECD.⁶

Professor Collings says, “Cindy and her team have made it their mission to highlight the importance of having good scientific evidence for clinical decisions in maternity care, gynaecology and sexual reproductive health. Their efforts span the research cycle and focus strongly on leading or assisting in the development of national and international clinical guidelines to get evidence into practice so that patients can ultimately benefit.”

Footnotes

1. Professor Cindy Farquhar, New Zealand-based colleagues: Associate Professor Vanessa Jordan, Marian Showell, Helen Nagels, Dr Magda Bofill, Dr Lynn Sadler, Dr Lucy Prentice, Melissa Vercoe, Dr Karyn Anderson.
International collaborators: Dr Sarah Lensen (Australia), Dr Sarah Armstrong (Bristol University, UK), Dr James Duffy (University of London, UK), Professor Ben Mol (Monash University, Australia), Dr Jack Wilkinson and Professor Andy Vail (University of Manchester), Professor Rick Legro (Pennsylvania State College of Medicine, USA), Professor Madelon van Wely (University of Amsterdam, Netherlands).

2. A randomised trial of endometrial scratching before In Vitro Fertilization
3. Intrauterine insemination with ovarian stimulation versus expectant management for unexplained infertility (TUI): a pragmatic, open-label, randomised, controlled, two-centre trial - ScienceDirect
4. Births and deaths: Year ended March 2024, Statistics NZ.
5. An economic evaluation of single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured ectopic pregnancy - ScienceDirect.
6. obgyn.onlinelibrary.wiley.com/doi/10.1111/ajo.13478