Norethindrone Impact on Receptiva Outcomes (NIRO)

Inception Fertility Research Institute, LLC

Status: Active, not recruiting

Conditions: Infertility Female; Infertility (IVF Patients)

Study type: Observational

Funder types: Industry; Other

Identifiers

NCT07134920

IRI-MLF-2025-002

Details and patient eligibility

About

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.

Enrollment: 700 estimated patients

Sex: Female

Volunteers: No Healthy Volunteers

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)

Trial design

700 participants in 2 patient groups

Norethindrone acetate Group

Description:

Patients who received 6 and 8 weeks of suppression with norethindrone acetate prior to embryo transfer cycle

Depo Leuprolide Group

Description:

Patients who received two monthly injections of Depo Leuprolide Acetate prior to embryo transfer cycle