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

Nezhat, Camran; Rambhatla, Anupama; Miranda-Silva, Catarina; Asiaii, Atena; Nguyen, Kimsa; Eyvazzadeh, Aimee D.; Tazuke, Salli I.; Agarwal, Shruti; Jun, Suckjoon; Nezhat, Azadeh; Roman, Robert

doi:10.4293/jsls.2020.00064

Cited by 21 publications

(18 citation statements)

References 36 publications

(51 reference statements)

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“…Women with at least six months of postoperative follow-up were assessed for reproductive outcomes (n=40), resulting in a clinical pregnancy rate of 90.0%. The positive predictive value (PPV) of BCL-6 testing was found to be as high as 96% for the diagnosis of endometriosis, similar to previously reported rates ( 19 , 22 ).…”

Section: Introductionsupporting

confidence: 87%

“…Testing for endometrial BCL-6 may help determine high-risk endometriosis patients with other inflammatory pathologies who could be good surgical candidates. Endometrial BCL-6 testing has a high PPV that could help physicians and patients undergoing infertility treatment to seek surgical evaluation for endometriosis, to improve their reproductive outcomes ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, 93.8% of patients that tested positive for BCL-6 had laparoscopic findings of endometriosis ( 19 ). A retrospective study by Nezhat et al ( 22 ) on reproductive age females going through IVF treatment with endometrial BCL-6 overexpression who underwent laparoscopic surgery for treatment of suspected endometriosis showed that three-quarters of patients (74.7%, n=56) had a histologically confirmed diagnosis, while 21.3% were diagnosed visually through the presence of ovarian endometriotic implants (n=16). Women with at least six months of postoperative follow-up were assessed for reproductive outcomes (n=40), resulting in a clinical pregnancy rate of 90.0%.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Can we accurately diagnose endometriosis without a diagnostic laparoscopy?

Nezhat¹,

Agarwal²,

Lee³

et al. 2022

J Turkish German Gynecol Assoc

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Endometriosis is a progressive, estrogen-dependent, chronic inflammatory disease that affects approximately 6-10% of reproductive age women. Patients usually presents with symptoms, such as non-menstrual pelvic and abdominal pain, ovulatory pain, dyspareunia, dysmenorrhea, dyschezia, and/or changes to bowel or bladder function, which can be exacerbated during ovulation or menses. Endometriosis is a leading cause of unexplained infertility, accounting for up to 50-80% of cases. Currently, altered endometrial receptivity and progesterone resistance are some of the leading theories that could explain endometriosis-related implantation failure. In the endometrium, the B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL-6) protein forms a complex that binds to and inactivates regulators of the progesterone pathway, leading to progesterone resistance, aberrant decidualization, implantation failure, and recurrent miscarriages in women diagnosed with endometriosis. Surgical diagnosis consisting of laparoscopy, with or without histologic confirmation, is still considered the gold standard for diagnosis of endometriosis. Development of noninvasive screening and diagnostic tests to accurately identify patients with endometriosis has become increasing popular. A screening test for endometriosis has been developed to detect endometrial BCL-6 overexpression in asymptomatic women with unexplained infertility or recurrent pregnancy loss. Positive endometrial BCL-6 testing has been associated with recurrent miscarriages and poor in vitro fertilization outcomes. When the underlying cause of endometrial inflammation secondary to endometriosis was treated, an improvement in subsequent live birth rates was seen. Endometrial BCL-6 testing has a high positive predictive value that could help physicians and patients undergoing infertility treatment to seek surgical evaluation for endometriosis, to improve their reproductive outcomes.

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Section: Introductionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Can we accurately diagnose endometriosis without a diagnostic laparoscopy?

Nezhat¹,

Agarwal²,

Lee³

et al. 2022

J Turkish German Gynecol Assoc

Self Cite

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show abstract

“…Further research incorporating additional parameters that might influence IVF outcome in endometriosis patients, such as the parameters of autoimmune pathologies (B-cell chronic lymphocytic leukemia/lymphoma 6-BCL-6, interleukins, etc.) and their correlations with basal hormonal status, should be performed [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Predictive Value of Basal Serum Progesterone for Successful IVF in Endometriosis Patients: The Need for a Personalized Approach

Bila

Dotlić

Radjenović

et al. 2022

JPM

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The data regarding the role of progesterone (P4) in reproductive events of endometriosis patients are limited. This prospective study aimed to examine the predictive value of basal P4 serum levels for successful in vitro fertilization (IVF) in patients with primary infertility and endometriosis. The study included 73 patients divided according to endometriosis treatment (surgery vs. control—no treatment). The general data, basal hormonal status, and pregnancy rates were determined for every patient. Clinical pregnancy was achieved in 40.3% of patients, and more often in patients treated for endometriosis before IVF. The regression analysis showed that higher basal P4 serum levels were associated with achieving pregnancy through IVF. When regression was adjusted for the patient and IVF characteristics, higher basal P4 serum levels were associated with pregnancy achievement in both groups of women, along with the basal serum levels of FSH, LH, and AMH; EFI score; and stimulation protocol. The ROC analysis showed that the basal P4 serum level for successful IVF should be ≥0.7ng/mL. The basal P4 serum level cut-off for IVF success in endometriosis patients was determined for the first time. Constructed models for IVF success prediction emphasize the importance of determining the basal P4 serum levels for the personalized treatment of endometriosis-related infertility.

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“…Initially described as a proto-oncogene and transcriptional repressor implicated in the pathogenesis of B-cell lymphoma, BCL6 has recently been identified as a promising tissular biomarker which could be used to diagnose women affected by endometriosis [ 1 , 2 , 3 , 4 ]. The recent identification of actors acting in conjunction with BCL6, and the delineation of several target genes have helped to better determine its biological functions [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Morphological and Digital-Assisted Analysis for BCL6 Endometrial Expression in Women with Endometriosis

Squatrito

Blacher

Henry

et al. 2022

JCM

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BCL6 (B-cell lymphoma 6) is a proto-oncogene and transcriptional repressor initially described as being involved in B-cell lymphoma. Recently, this factor has been identified as a promising tissue biomarker which could be used to diagnose women affected by endometriosis. Previous studies used HSCORE for BCL6 staining quantification in the endometrium. However, this semi-quantitative technique of analysis has some limitations, including a lack of objectivity, robustness, and reproducibility that may lead to intra- and inter-observer variability. Our main goal was to develop an original computer-assisted method to quantify BCL6 staining from whole-slide images reliably. In order to test the efficiency of our new digital method of quantification, we compared endometrial BCL6 expression between fertile and infertile women without or with different stages of endometriosis by using the widely used HSCORE analysis and our new automatic digital image analysis. We find a higher expression of BCL6 in the endometrium of infertile women with endometriosis and women with stage IV endometriosis. Furthermore, we demonstrate a significant correlation between the two types of independent measurements, indicating the robustness of results and also the reliability of our computer-assisted method for BCL6 quantification. In conclusion, our work, by using this original computer-assisted method, enables BCL6 quantification more objectively, reliably, robustly, and promptly compared to HSCORE analysis.

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

Cited by 21 publications

References 36 publications

Can we accurately diagnose endometriosis without a diagnostic laparoscopy?

Can we accurately diagnose endometriosis without a diagnostic laparoscopy?

Predictive Value of Basal Serum Progesterone for Successful IVF in Endometriosis Patients: The Need for a Personalized Approach

Comparison of Morphological and Digital-Assisted Analysis for BCL6 Endometrial Expression in Women with Endometriosis

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