Dr Bruce Lessey, Reproductive Endocrinologist and Researcher, Greenville, US says, “One of the toughest conversations you can have with your patient is why their IVF transfer failed.” Yet this conversation takes place around 100,000 times every year in the US. Many of those conversations take place when the patient is diagnosed with unexplained infertility (UI).
Wouldn’t it be great to cut down on the number of those type of conversations? Perhaps recognising the impact of BCL6 levels can help.
What is BCL6 and what is the link to unexplained infertility?
BCL6 (B-cell lymphoma 6 protein) is a protein that in humans is encoded by the BCL6 gene. This protein is postulated to act as a repressor of transcription. It has been shown to modulate the Interleukin-4 (IL4) responses of B-cells.
Recently, BCL6 has been found to be highly over-expressed in the endometrium for women with endometriosis during the secretory phase of the menstrual cycle, compared to women without endometriosis1. The presence of BCL6 can be demonstrated in tissue sections of the endometrium using immunohistochemistry.
The eutopic endometrium of women with endometriosis exhibits inflammation, aberrant oestrogen activity, cellular proliferation and a resistance to progesterone (P4)2. In fact, 75% of women diagnosed with UI will test positive for BLC6.
This is postulated as the main reason why BCL6 has now been shown to be a prognostic marker for unexplained fertility. Clinically, there can be little doubt that the endometrium of women with endometriosis is less receptive to embryo implantation. Strong evidence exists to suggest that endometrial changes are associated with decreased cycle fecundity as a result of this disease3.
BCL6 as a predictor of IVF success
A study this year investigated whether high levels of BCL6 could predict IVF outcomes in women who have unexplained infertility4. The researchers investigated women over 8 years who were still infertile after undergoing IVF for a year or more. Of these women, 75% had high levels of BCL6, while 25% had normal BCL6 levels.
Results
- Women who had low levels of BCL6 had a significantly higher pregnancy rate, at 64.7%
- Women who had high levels of BCL6 had a pregnancy rate of only 17.3%.
The live birth rate was also significantly higher in women with low BCL6 at 58.8%. This compared to just 11.5% for women with high BCL6. From this it is clear that high BCL6 levels are associated with poor pregnancy outcomes.
The authors concluded, “High levels of BCL6 expression in this cohort suggests that undiagnosed endometriosis may be a common factor that needs to be considered in women before undergoing IVF.”
How to test for BCL6?
A diagnostic test called ‘ReceptivaDx’5, which can be used to test patients for BCL6 prior to their first IVF treatment. It provides physicians in IVF centres the ability to diagnose endometriosis with a simple biopsy, with results taking 3-5 days.
The case for ReceptivaDX
Dr. Lessey, speaking of ReceptivaDX said, “This test provides an opportunity for couples to better understand the basis of their infertility and will provide more options and higher success rates.”
It seems something of a no-brainer that women considering IVF should have access to this highly predictive test. Given the high cost of treatment and the emotional cost of IVF failure, it makes sense to invest a little extra in the test.
Knowing their BCL6 status gives women the opportunity to increase their chances of success if they test positive, and peace of mind if they test negative. Either way, testing for BLC6 would seem a positive step before IVF treatment.
References
- Evans-Hoeker, E. et al. 2016. Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis. Reprod Sci. 23, 1234–1241, doi:10.1177/1933719116649711 (2016).
- Bulun, S. E. 2009. Endometriosis. N Engl J Med 360. 268–279, doi:10.1056/NEJMra0804690 360/3/268 [pii] (2009)
- Bruce A. Lessey, J. Julie Kim. 2017. Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why. July 2017. Volume 108, Issue 1, Pages 19–27
- Laura D. Almquist, Creighton E. Likes, Benjamin Stone, Kaitlin R. Brown, Ricardo Savaris, David A. Forstein, Paul B. Miller, Bruce A. Lessey. 2017. Endometrial BCL6 testing for the prediction of in vitro fertilization outcomes: a cohort study. Fertility and Sterility. December 2017. Volume 108, Issue 6, Pages 1063–1069
- https://www.receptivadx.com
