Medical or surgical treatment before embryo transfer improves outcomes in women with abnormal endometrial BCL6 expression

Abstract

Purpose To evaluate the effect of medical or surgical treatment prior to embryo transfer in women with elevated endometrial BCL6 expression and suspected endometriosis in a prospective, cohort study design at a university-associated infertility clinic. Methods All subjects had at least 1 year of unexplained infertility (UI) and each prospectively underwent endometrial biopsy and immunostaining for the oncogene BCL6, prior to embryo transfer during an assisted reproductive technology (ART) cycle. To be included, subjects had to have an abnormal BCL6 result, defined by elevated HSCORE ≥ 1.4. Women that were pre-treated with laparoscopy or medical suppression with GnRH agonist (depot leuprolide acetate; Lupron®, Abbvie, Inc., Chicago, IL) for 2 months were compared to a group that went untreated (controls). Endpoints included implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR), and as well as cycle characteristics. Miscarriage rate were also compared between treatment and control group. Results Women in each group had similar characteristics. Those treated by medical suppression and those undergoing laparoscopy for endometriosis had a significantly higher LBR, (5/10; 50%; 95%CI 23.7 to 76.3%) and (11/21; 52.4%; 95%CI 32.4 to 71.7), respectively, compared to controls (4/54; 7.4%; 95%CI 2.9 to 17.6). An absolute benefit of 44.2% (16/31; 95%CI 24.6 to 61.2) and a number need to treat of 3 for those that received treatment (medical suppression and laparoscopy), compared to no treatment. Miscarriages were significantly more common in the control group. Conclusions Women with suspected endometriosis and aberrant endometrial BCL6 expression have worse reproductive outcomes following embryo transfer, including a high miscarriage rate, poor IR, and low LBR and CPR compared to cycles pretreated with medical and surgical management.

What exactly is endometrial receptivity?

“…The BCL6 protein (vide supra) pairs with the histone deacetylase, SIRT1, to interfere with P signaling (70). A clinical study suggests that a positive test for BCL6 (high expression) is strongly predictive of poor reproductive outcomes in IVF (91), and another suggests that these women can be effectively treated using either GnRH agonist suppression or surgery for endometriosis before IVF (92). These findings also support the idea that some women with such defects could be treated without ART.…”

BCL-6 Overexpression as a Predictor for Endometriosis in Patients Undergoing In Vitro Fertilization

“…Endometriosis is a progressive, estrogen-dependent, chronic inflammatory disease affecting approximately 10% of reproductive age women, and over 200 million women worldwide. 1 – 3 It is an ancient disease described as early as 1855 BC by Egyptians as “suffocation of the womb” long before the histologic diagnosis of ectopic endometrial-like glands and stroma was described by Karl von Rokitansky in 1860. 4 Endometriosis has been reported in every organ in the human body, with clinically significant extragenital endometriosis leading to genitourinary, gastrointestinal, thoracic, and/or nervous system dysfunction.…”

“… 13 In fact, endometriosis is a leading cause of unexplained infertility, accounting for up to 50 – 80% of women struggling to conceive. 3 , 14 According to 2017 Society for Assisted Reproductive Technology data, only 2.5% of IVF cycles are performed in patients diagnosed with endometriosis, leading us to believe that endometriosis is grossly underdiagnosed in the setting of infertility. 15 , 16 …”

“… 14 , 22 , 25 Positive endometrial BCL-6 testing, defined as an HSCORE >1.4, has been associated with poor IVF outcomes and recurrent miscarriage. 3 , 18 , 25 By treating the underlying cause of endometrial inflammation secondary to endometriosis, whether medically or surgically, studies have shown improvement in subsequent live birth rates (LBR) (50 –76%) when compared to controls (7.4%). 3 , 12 This landmark study reported that 93.8% of patients that tested positive for BCL-6 had laparoscopic findings of endometriosis.…”

Successful Natural Pregnancy Using Whole Systems Traditional Chinese Medicine in a Complex Anovulatory Patient After Multiple Unsuccessful In Vitro Fertilization Treatments: A Case Report

“…Or she might have been tested for endometrial BCL6, and if positive, put on 2 months of leuprolide acetate (Lupron) or had laparoscopic surgery for her endometriosis. 13 Some clinics might also use endometrial receptivity testing to evaluate possible mistimed window of implantation.…”