WHERE WERE YOU BEFORE RECEIVING THIS AWARD?
I had commenced my research project as a clinical fellow in the National Maternity Hospital and Merrion Fertility Clinic, Dublin studying endometrial markers of implantation. I had funding to undertake RNA-sequencing on 16 samples initially. However, with the help of the Clinical Primer Scheme, I was able to expand the cohort and perform validation work on an expanded cohort of 50 samples.
YOUR RESEARCH PROJECT IN LAY TERMS
Embryo implantation represents a critical step in the reproductive process. Successful implantation requires a receptive endometrium, a normal and functional embryo and a synchronized dialogue between maternal and embryonic tissues. A critical need exists to evaluate endometrial receptivity in spontaneous pregnancy and in assisted reproduction to provide a clearer understanding of the role of the endometrium in normal implantation. Endometrial receptivity is mediated by a number of complex signalling pathways. However, this area is poorly understood, and implantation failure is common. There is a lack of evidencedbased therapies for implantation failure, particularly in the area of reproductive immunology. This work highlights interleukin-17 (IL-17) signalling as an important candidate pathway that may contribute to dysregulated immune function in the endometrium of women with unexplained infertility who fail to conceive following assisted reproductive therapy. Importantly, this work demonstrates that changes in IL-17A levels in the local endometrial microenvironment are reflected in the systemic circulation, corroborating serum IL-17A as a potential robust and minimally invasive predictor of endometrial function. These novel findings have the potential to lead to the development of new therapeutic strategies to treat underlying dysfunction and improve pregnancy outcomes in women with unexplained infertility.
HOW HAS ISSF HELPED YOUR RESEARCH CAREER?
I was able to expand my study cohort to 50 samples and perform important validation work. The scheme also gave me the opportunity to expand my network within UCD through presentation of this work and ongoing mentorship which has resulted in significant outputs from this work and strong collaborations in UCD for the future. I presented this work at the British Fertility Society (BFS) Meeting in 2019 and it was very well received, highlighted by the fact that I was awarded the BFS Best Early Career Clinician Award for best oral presentation. This work was published in Human Reproduction in 2020 in a paper entitled “Dysregulation of the interleukin-17A pathway in endometrial tissue from women with unexplained infertility affects pregnancy outcome following assisted reproductive treatment” and I was awarded the prestigious Harold Malkin Prize 2021 from the Royal College of Obstetrics and Gynaecology for the best original work while being of a Specialty Trainee grade in a hospital in the UK or Republic of Ireland. Following this research opportunity, I was awarded and undertook a clinical fellowship in Reproductive Genetics and Genomics at Columbia University Irving Medical Center and New York Presbyterian Hospital.
TANGIBLE OUTPUTS AS A RESULT OF RECEIVING THE AWARD
Higher Qualification
Doctorate of Medicine (MD) Awarded June 2019, University College Dublin, Ireland. Thesis: “Endometrial markers of implantation and subsequent pregnancy – is dysregulation of inflammatory pathways the key?”
Original, Peer-Reviewed Publications
- Mid-luteal uterine artery Doppler indices in the prediction of pregnancy outcome in nulliparous women undergoing assisted reproduction. Crosby DA, Glover LE, Downey P, Mooney EE, O’Farrelly C, McAuliffe FM, Brennan DJ, Wingfield M. Hum Fertil (Camb). 2021 Jan 13:1-11. PMID: 33439056
- The impact of accurately timed mid-luteal endometrial injury in nulligravid women undergoing their first or second embryo transfer. Crosby DA, Glover LE, Downey P, Mooney EE, McAuliffe FM, O’Farrelly C, Brennan DJ, Wingfield M. Ir J Med Sci. 2020 Oct 22. PMID: 33090349
- Dysregulation of the interleukin-17A pathway in endometrial tissue from women with unexplained infertility affects pregnancy outcome following assisted reproductive therapy. DA Crosby, LE Glover, EP Brennan, P Kelly, P Cormican, B. Moran, F. Giangrazi, P. Downey, EE Mooney, BJ Loftus, FM McAuliffe, M. Wingfield, C. O’Farrelly, DJ Brennan. Hum Reprod. 2020 Aug 1;35(8):1875-1888. PMID: 32614049 Oral Presentations to Learned Societies
- Dysregulation of IL-17A and calprotectin in the female reproductive tract affects pregnancy outcome following assisted reproductive therapy. F Giangrazi, DA Crosby, F Reidy, M Wingfield, L Glover, C O’Farrelly. FERTILITY 2021. Online. January 2021
- Dysregulation of the Interleukin-17 pathway affects pregnancy outcome following assisted reproductive therapy. DA Crosby, LE Glover, E Brennan, E Mooney, P Downey, B Loftus, C O’Farrelly, FM McAuliffe, DJ Brennan, M Wingfield. 18th World Congress of the Academy of Human Reproduction, Dublin. April 2019
- Dysregulation of the Interleukin-17 pathway in women with unexplained infertility affects pregnancy outcome following assisted reproductive therapy. DA Crosby, LE Glover, E Brennan, E Mooney, P Downey, B Loftus, C O’Farrelly, FM McAuliffe, DJ Brennan, M Wingfield. FERTILITY 2019. Birmingham, UK. January 2019. Awarded British Fertility Society Young Clinician Award for Best Oral Presentation
- Dysregulation of IL-17A pathway affects ART pregnancy outcome in unexplained infertility. DA Crosby, LE Glover, E Brennan, E Mooney, P Downey, B Loftus, C O’Farrelly, FM McAuliffe, DJ Brennan, M Wingfield. Junior Obstetrics and Gynaecology Society (JOGS) Scientific Meeting. November 2018. Awarded Second Prize Best Oral Presentation
- Dysregulation of metabolic pathways in endometrium of women with unexplained infertility affects embryo implantation and subsequent pregnancy. DA Crosby, LE Glover, EP Brennan, P Cormican, P Downey, E Mooney, C O’Farrelly, B Loftus, FM McAuliffe, DJ Brennan, M Wingfield. 11th Irish Fertility Society Scientific Meeting, Dublin. May 2018. Awarded First Prize Best Oral Presentation
- Endometrial injury in nulliparous women may increase success rates in ART. DA Crosby, LE Glover, EP Brennan, P Cormican, P Downey, E Mooney, C O’Farrelly, B Loftus, FM McAuliffe, DJ Brennan, M Wingfield. 11th Irish Fertility Society Scientific Meeting, Dublin. May 2018
- Identification of whole transcriptomic changes in mid-luteal endometrium associated with successful implantation in assisted reproductive technology. DA Crosby, LE Glover, E Brennan, B Loftus, DJ Brennan, M Wingfield. FERTILITY 2018, Liverpool, UK. January 2018
- Identification of whole transcriptomic changes in mid-luteal endometrium associated with successful implantation in assisted reproductive technology. DA Crosby, L Glover, E Brennan, A Murphy, C Moss, B Loftus, MB Wingfield, DJ Brennan. UCD Conway Festival of Research and Innovation, Dublin. September 2017. Selected for moderated poster presentation. Poster Presentations to Learned Societies
- Influence of body mass index on the relationship between endometrial thickness and pregnancy outcome in frozen blastocyst embryo cycles. Crosby DA, O’Brien YM, Glover LE, Martyn F, Wingfield MB. FERTILITY 2018. British Fertility Society, Liverpool, UK. January 2018
- Identification of whole transcriptomic changes in mid-luteal endometrium associated with successful implantation in UCD-Wellcome Institutional Strategic Support Fund 11 assisted reproductive technology. Crosby DA, LE Glover, E Brennan, B Loftus, MB Wingfield, D Brennan. Fourth Irish Congress of Obstetrics, Gynaecology & Perinatal Medicine, Kilkenny. December 2017
- Identification of whole transcriptomic changes in mid-luteal endometrium associated with successful implantation in assisted reproductive technology. Crosby DA, LE Glover, E Brennan, B Loftus, MB Wingfield, D Brennan. Moderated poster presentation, UCD Conway Festival. September 2017
WHAT DID THE AWARD MEAN TO YOU PERSONALLY?
I am extremely grateful to the UCD-Wellcome Institutional Strategic Support Fund for awarding me the Clinical Primer Scheme. This has significantly benefited my career through funding and advancing my work, through the mentorship I was given and allowing me to develop research networks nationally and internationally. My passion for clinical and reproductive genetics began while I was undertaking this work thanks to this award and I was fortunate to further my training by undertaking a clinical fellowship in genetics and genomics at Columbia University Irving Medical Center and New York Presbyterian Hospital and an MSc in Genomic Medicine. By combining the skillset learned from this published work and my clinical fellowship in Reproductive Genetics and Genomics, I hope to establish, develop and deliver a specialised academic reproductive genetics service to enable the timely realisation of the benefits for individual patients and their families in the National Maternity Hospital, where I commenced work as a Consultant Obstetrician & Gynaecologist with special interest in Reproductive Medicine and Genetics in January 2022. I hope to combine the skillset I have developed with further opportunities to continue this research in collaboration with UCD in the future.