Norethindrone Impact on Receptiva Outcomes (NIRO)

BCL6 Positivity and ART Outcomes: Comparing Norethindrone Acetate and Depo Lupron for Endometriosis Suppression Prior to Embryo Transfer

This retrospective study aims to evaluate pregnancy outcomes in patients with a positive BCL6 test (ReceptivaDx, who were treated with either norethindrone acetate or Depo Lupron prior to embryo transfer. The current standard of care involves treatment with Depo Lupron, a GnRH agonist associated with significant hypoestrogenic side effects that mimic menopausal symptoms. Additionally, Depo Lupron is costly, with a retail price exceeding $2,000 per dose. In contrast, norethindrone acetate is a well-tolerated oral progestin, available at a fraction of the cost (under $100 for a one-month course). While prior studies have demonstrated comparable efficacy between Depo Lupron and norethindrone for managing endometriosis-associated pain, their relative effectiveness in improving reproductive outcomes-particularly in BCL6-positive patients undergoing embryo transfer-remains underexplored. This study seeks to address that gap by comparing ongoing pregnancy, live birth, and miscarriage rates between the two treatment groups.

Hypothesis: IVF Patients testing positive for BCL6 and treated with norethindrone will not do worse than the current recommended treatment of 60 days Depo leuprolide as defined by two endpoint metrics, pregnancy rate and live birth rate.

Study Overview

• Status: Completed
• Conditions: Infertility (IVF Patients); Infertility Female

• Study Type: Observational
• Enrollment (Actual): 99

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Main Line Fertility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women with a ReceptivaDx BCL6-positive test who completed hormonal suppression therapy prior to embryo transfer cycle

Description

Inclusion Criteria:

• Diagnosis of recurrent pregnancy loss, recurrent implantation failure, unexplained infertility or severe dysmenorrhea and a positive BCL6 test Receptivadx
• Underwent assisted reproductive technology (ART or IVF)
• Treated with norethinedrone acetate 5 mg daily for 6 and 8 weeks or two monthly injections of Depo Leuprolide Acetate 7.5mg rior to embryo transfer cycle
• Euploid embryo transfer cycle was initiated within 1 week of completion of suppression protocol
• Adequate clinical documentation available, including treatment protocol, BCL6 results, and pregnancy outcomes
• If Endometrial Receptivity Analysis (ERA) was performed, result must be "receptive"
• A minimum uterine lining of 7.5mm was documented by ultrasound prior to the initiation of progesterone

Exclusion Criteria:

• Use of both norethinedrone acetate and Depo Leuprolide Acetate in the same treatment cycle
• Incomplete ART or outcome data
• Gestational carrier or egg donor
• No prescribed adjuvant therapy (e.g., Lovenox, Neupogen, IVIG)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Norethindrone acetate Group; Patients who received 6 and 8 weeks of suppression with norethindrone acetate prior to embryo transfer cycle
Depo Leuprolide Group; Patients who received two monthly injections of Depo Leuprolide Acetate prior to embryo transfer cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ongoing pregnancy rate	To compare ongoing pregnancy rates in BCL6-positive patients treated with norethindrone acetate versus Depo Lupron acetate	From beginning of treatment to 12 weeks post embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate	To compare live birth rates in BCL6-positive patients treated with norethindrone acetate versus Depo Lupron acetate	From start of treatment to 10 months post embryo transfer
Miscarriage Rate	Defined as the loss of a clinically confirmed pregnancy before 20 weeks of gestation	From start of treatment to 20 weeks post embryo transfer
Biochemical pregnancy rate	Defined as a low positive serum HCG with an inappropriate rise, spontaneous resolution	From start of treatment to 4 weeks post embryo transfer
Ectopic pregnancy rate		From start of treatment to 8 weeks post embryo transfer

Collaborators and Investigators

• Sponsor: Inception Fertility Research Institute, LLC
• Collaborators: Cicero Diagnostic

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2025
• Primary Completion (Actual): December 19, 2025
• Study Completion (Actual): December 19, 2025

Study Registration Dates

• First Submitted: August 14, 2025
• First Submitted That Met QC Criteria: August 14, 2025
• First Posted (Actual): August 21, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Norethindrone Acetate; Receptiva; Depo Lupron Acetate
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Infertility; Infertility, Female
• Other Study ID Numbers: IRI-MLF-2025-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No