The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Relationship between endometrial stem/progenitor cells in the endometrial scratch biopsy and live birth outcomes following IVF – a pilot study (#105)

Caroline E Gargett 1 2 , Ker Sin Tan 2 , Rue Ong 2 , Gareth Weston 1 3
  1. Department of Obstetrics and Gynaecology, Monash University , Clayton, VIC, Australia
  2. The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia
  3. Monash IVF, Clayton, Victoria, Australia

Endometrial injury (scratch) via a biopsy in the cycle prior to embryo transfer (ET) increases live birth rates. However the mechanism is unknown and the “scratch” is controversial. Human endometrium contains small populations of N-cadherin+ epithelial progenitor cells (eEPCs) located in the basalis and perivascular SUSD2+ mesenchymal stem cells (eMSCs) in both basalis and functionalis. We hypothesised that endometrial injury activates quiescent endometrial stem/progenitor cells to proliferate and regenerate the damaged endometrium, producing a thicker more responsive endometrium ‘ripe’ for embryo implantation in the following cycle. Scratch biopsies were collected from 31 women aged 27-41 years who had failed ≥1 IVF-ET cycle and were scheduled to receive an embryo in the subsequent cycle. Endometrial tissue was weighed, dissociated to single cells using collagenase and DNAse and cells counted. Aliquots of 105 cells were assessed for N-cadherin+ and SUSD2+ cells by single colour flow cytometry. Cell concentrations were calculated as number/mg tissue. Endometrial thickness was measured by ultrasound. Live birth/pregnancy outcomes were obtained from Monash IVF. 24 women underwent ET in the cycle following the scratch. Based on the distribution of tissue concentrations of N-cadherin+ and SUSD2+ cells, threshold values were >4500cells/mg for SUSD2hi , >3000 for N-cadherinhi and samples were categorised into 4 groups. Six of 9 samples with SUSD2hiN-cadherinlo concentrations resulted in live birth/pregnancy, 3/11 SUSD2loN-cadherinlo samples resulted in live births and there were no pregnancies/live births for SUSD2loN-Cadherinhi (n=3) or SUSD2hiN-Cadherinhi (n=1) samples. Age was similar between the groups, but endometrial thickness decreased from 11.8±1.5 to 7 mm across the 4 groups. This pilot data suggests that pregnancies/live births depend on the relative concentrations of eMSCs and eEPCs, with N-cadherinlo indicating a thicker endometrium and N-cadherinhi suggestive of thin basalis endometrium unable to support pregnancy. A fully powered study is required to confirm these findings.