COMPARATIVE OUTCOMES OF NEW BCL6-GUIDED TREATMENT STRATEGIES IN WOMEN WITH UNEXPLAINED INFERTILITY: A MULTICENTER RETROSPECTIVE ANALYSIS OF 2,451 PATIENTS

Objective: To compare pregnancy and live birth outcomes across different treatment modalities in BCL6-positive patients with unexplained infertility (UI) undergoing IVF, and to contextualize outcomes relative to published untreated cohorts. Design: Retrospective multicenter cohort study. Materials and Methods: A total of 2,451 patients from 18 independent IVF centers undergoing BCL6 testing were included. Patients presented with UI, recurrent pregnancy loss (RPL), or recurrent implantation failure (RIF) along with BMI, age, prior history and embryo testing. The mean number of prior failed cycles was 1.8, and 85% underwent PGT-A. BCL6-positive patients received one of the following treatments prior to next embryo transfer: GnRH agonists, GnRH antagonists, letrozole, norethindrone, or laparoscopy. Patients receiving combination therapies or with incomplete clinical data were excluded. Primary outcomes were clinical pregnancy rate (PR) and live birth rate (LBR) per subsequent transfer. Outcomes were compared descriptively across treatment groups and against published untreated cohorts. Two proportion Z-test and Chi Square were used for statistical analysis. Results: Among 1,346 BCL6-positive patients, all treatments provided significant success compared to published data on untreated patients, PR 18% and LBR 11%. GnRH agonists (n=867) resulted in PR 74% and LBR 55%. Laparoscopy (n=76) demonstrated PR 78% and LBR 63%. Letrozole (n=169) yielded PR 66% and LBR 49%, while norethindrone (n=38) showed PR 58% and LBR 53%. GnRH antagonists (n=9) demonstrated PR 78% and LBR 78%, though interpretation is limited by small sample size. BCL6-negative patients (n=1,105) demonstrated PR 72% and LBR 53%, consistent with normal controls. Conclusions: In this large multicenter retrospective cohort, treatment of BCL6-positive patients was associated with significantly improved reproductive outcomes compared to published untreated cohorts. GnRH agonists and laparoscopy (current recommended published treatments) demonstrated the highest live birth rates compared to other treatment modalities. Differences between other treatment modalities (Letrozole and Norethindrone) require confirmation in prospective studies. However, all the treatment findings support the benefit from targeted intervention prior to embryo transfer on BCL6 positive patients. Financial Support: The author is an employee of Cicero Diagnostics, the licensee of the ReceptivaDx BCL6 test.