Post on 17-Feb-2017
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
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