Small protein could solve big puzzle for unexplained infertility

A key protein that could help some women with unexplained infertility to achieve a healthy pregnancy has been identified.

Research into assisted reproductive technologies such as IVF has largely focused on the production of viable embryos. However, to achieve a pregnancy, it is essential to have both a quality embryo (the ‘seed’) and a healthy receptive endometrium (the ‘soil’). Failure of either the ‘seed’ or ‘soil’ compromises the likelihood of pregnancy.

Hudson Institute researcher Dr Tracey Edgell’s research is focused on providing the optimum environment within the endometrium, or womb, for an embryo to implant and form a healthy pregnancy.

In new research published in the journal Cytokine, Dr Edgell has identified that a number of small proteins, cytokines, chemokines and growth factors were elevated in the uterine fluid of women with unexplained infertility, including a protein called CSF3.

Dr Edgell examined how these elevated concentrations of CSF3 may influence the way a pregnancy is established. At levels seen in fertile women, CSF3 was shown to promote the growth of endometrial cells, but at the higher concentrations found in infertile women, this effect was lost. However, CSF3 at both high and low concentrations in the womb promoted the initial stages of embryo development, indicative of its importance at the time of embryo implantation.

Friend turns to foe

Currently, CSF3 is occasionally used in IVF as an additional treatment either prior to embryo transfer to promote development of a pregnancy, or in the early stages of pregnancy of women with a history of recurrent miscarriage.

In the latter group, clinical studies have shown that miscarriage rates decreased when CSF3 was given to women in the early stages of their pregnancy.

“However, in women trying to fall pregnant who already had naturally high levels of CSF3, the phrase ‘too much of a good thing can be a curse’ is certainly true,” Dr Edgell said.

“In these women, raising CSF3 levels could actually be detrimental to the establishment of a pregnancy.”

Treatment may alleviate need for IVF

Dr Edgell hopes to develop a treatment to ‘rebalance’ CSF3 concentrations in those women whose natural levels are too high to provide a better chance of falling pregnant ‘naturally’.

“This simple balancing action will strengthen production of endometrial cells to increase and thicken the lining of the womb. This would allow an embryo to implant and the pregnancy to occur,” Dr Edgell said.

“Our ultimate goal is to target CSF3 as treatment for women with unexplained fertility so they can become pregnant without having to resort to costly, invasive and stressful IVF procedures.”

Dr Edgell was awarded the 2017 Fielding Innovation Award which enabled her to undertake this research project, taking her a step closer to commercialising this research.

The financial and emotional cost of Infertility

An estimated 121 million couples experience infertility worldwide, with around half seeking medical assistance.

Victoria’s IVF success rate is about 28 per cent.

The costs of IVF to the Australian healthcare system are substantial. In 2015, the taxpayer contributed $254M to infertility treatment – a 50 per cent increase from 2007

Team: Dr Tracey Edgell, Dr Jemma Evans, Professor Lois Salamonsen (Hudson Institute),  Leah Lazzaro,  Kendra Boyes,  Meghana Sridhar, Dr Sally Catt (Monash University), Professor Luk Rombauts, Professor Beverley Vollenhoven (Hudson Institute, Monash University, Monash IVF, Monash Health)

Funding: Fielding Foundation, NHMRC, Monash IVF Research and Education Fund.

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