Norethindrone Impact on Receptiva Outcomes

Inception Fertility Research Institute, LLC99 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

Conditions

Infertility (IVF Patients)Infertility Female

Eligibility

Sex: FEMALE

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Ongoing pregnancy rate

To compare ongoing pregnancy rates in BCL6-positive patients treated with norethindrone acetate versus Depo Lupron acetate

Time frame: From beginning of treatment to 12 weeks post embryo transfer

Secondary Outcomes

Live birth rate

To compare live birth rates in BCL6-positive patients treated with norethindrone acetate versus Depo Lupron acetate

Time frame: 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

Time frame: 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

Time frame: From start of treatment to 4 weeks post embryo transfer

Ectopic pregnancy rate

Time frame: From start of treatment to 8 weeks post embryo transfer