Endometrial BCL6 Expression and IVF Success or Failure

Sydney RunyansClemson University

Clemson, SC

Overview

• Endometriosis is an inflammatory condition associated with progesterone resistance

• Affects 176 million women worldwide• Costs $22 billion annually in US alone• Is a common finding in unexplained infertility

Nakagawa K et tal., 2007;33:665-70.Tsuji I et al., 2009;219:39-42.

Bonneau et a;., European journal of obstetrics, gynecology, and reproductive biology 2012;163:57-61.

Implantation Failure

• Implantation Window – “Frame Shift”

2 4 6 8 10

28

12

14

16

18

24

20

22

26

Ovulation

Menses

1

NormalDelayed implantationFailed implantation

Courtesy of Marc Fritz MD

Background

BCL6

• Nuclear factor associated in inflammation• Transcriptional gene repressor • Minimally regulated by progesterone in the

secretory phase• Dramatically up-regulated in endometriosis

Evans-Hoeker et al., submitted 2015

BCL6 and Endometriosis

Normal Subjects

mRNA IHC mRNA separated cells

BCL6 and Endometriosis

Endometriosis

BCL6

BCL6 in Endometriosis

Normal expression of BCL6 in:A. Proliferative phaseB. Early secretory phaseC. Mid-secretory phaseD. Late secretory phaseE. Endometriosis, Mid-secretory phaseF. Positive control (LN)G. Negative control

Objective

•To compare IVF and FET success rates in women based on prior endometrial BCL6 expression patterns

•Two groups were identified• Women with low BCL6 (< 1.4)• Women with high BCL6 (≥ 1.4)

Potential Confounders

•Women who were biopsied were more likely to have implantation failure or suspicious for poor outcomes

•Women with low BCL6 were in the minority

Demographics

Characteristic BCL6 Negative

BCL6 Positive P value

Mean Age (SD) 33.6 (2.9) 33.5 (3.4) 0.94 a

Mean BMI (SD) 25.8 (3.0) 26.1 (5.5) 0.31

Mean Parity (SD) 0 (0) 0.1 (0.3) 0.42

RaceCaucasian Afro AmericanOthers

34 (75.56%)9 (20%)

2 (4.44%)

7 (53.85%)4 (30.77%)2 (25.38%)

0.2

HSCORE Mean (SD) 0.75 (0.45) 3.4 (0.47 <0.0001

Percentage of Pregnancy

Results

-Patients BCL6 Negative (<1.4)-66% (4/6) of women who tested negative had a successful pregnancy while 33% (2/6) did not have a successful pregnancy.

-Patients BCL6 Positive (≥ 1.4)-10% (4/39) of women who tested positive had a successful pregnancy while 90% (35/39)

did not have a successful pregnancy.

DISCUSSION• LIMITATIONS

-Limited number of patients who were negative for BCL6-Patients were highly selected in the biopsy group-Did not control for endometriosis-Most but not all endometriosis was pathologically confirmed-Patients taken to L/S may have higher likelihood of finding endometriosis

• STRENGTHS-First study to be done that predicts outcome in IVF-Large sample size (at least for positive BCL6 samples)-The fact that the usual success in the GHS clinic is much higher supports these findings-Validation of findings of endometriosis by laparoscopy is reassuring -This new biomarker has been previously validated in separate studies

CONCLUSIONS-We have a potential test for predicting IVF outcome-BCL6 is potential marker for implantation failure and/or

endometriosis-If this test were implemented, surgery may be a better choice

than IVF as initial treatment-If we treated endometriosis in the first place, most likely we

would see even better implantation rates in the IVF program-IVF is not indicated in some women; up until now we did not

know who these women were

Future Directions

-Repeat in different population-Peform prospective studies-Examine BCL6 expression before and after surgery for endometriosis

-Examine fertility/implementation rates based on treating endometriosis via BCL6 score

-Cost-Effectiveness*-Determine whether medical suppression might improve IVF outcomes in BCL6 positive women

THANK YOU