Comparison of Pregnancy Rates in Modified Natural Frozen Embryo Transfer (FET) Cycle After Luteal Support with GnRH Agonist Versus Progesterone

NCT06870266 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 0357-24-SZMC
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: The capability to transfer frozen embryos reduces embryo loss following in vitro fertilization (IVF) and results in higher pregnancy rates compared to a single IVF cycle. Endogenous progesterone from the corpus luteum, following frozen embryo transfer in natural or modified natural cycles, is expected to provide sufficient luteal support, as observed in spontaneous pregnancies. Nevertheless, research has demonstrated higher pregnancy success rates with additional luteal support. The current standard for luteal phase support involves vaginal progesterone administration. Several case reports have indicated that administering a gonadotropin-releasing hormone (GnRH) agonist during the luteal phase does not compromise pregnancy continuation achieved through IVF and may, in fact, enhance implantation success. Studies have shown that the luteal phase can be maintained with a GnRH agonist alone, without the need for progesterone supplementation. A recent prospective randomized controlled trial compared standard progesterone support with GnRH agonist support in fresh embryo transfers. The group receiving GnRH agonist support demonstrated a significantly higher pregnancy rate. Given the studies proving the positive impact of GnRH agonist, there is a need for a prospective randomized controlled trial to evaluate the use of GnRH agonist support in frozen embryo transfers. Aims and Significance: This study aims to compare pregnancy rates between women receiving GnRH agonist treatment and those receiving standard progesterone-based luteal support during frozen embryo transfers in natural cycles as part of IVF treatments. Conducting a prospective comparative study will enable us to assess the effectiveness of GnRH agonist treatment relative to standard luteal phase support. Based on the results, the investigators may consider treatment with intranasal GnRH agonist, which improves quality of life and may also enhance pregnancy and live birth rates. Methods: The study will be conducted on patients scheduled to undergo modified natural cycles. Participants will be randomly allocated into two groups:

1. 1.Study Group: Luteal phase support will begin on the day of ovulation with Nafarelin nasal spray (200 mcg twice daily) for two weeks, until pregnancy blood test (hCG).
2. 2.Control Group: Luteal phase support will be provided through vaginal progesterone. Endometrin 100 mg twice daily. If the hCG test is positive, the supportive treatment will continue until the 8th week of pregnancy, as per the attending physician's instructions.

Conditions

Ivf; Frozen Embryo Transfer (FET)

Outcome Measures

Primary Outcomes (1)

• clinical pregnancy rate

  positive fetal heart beat

  two months after ET

Secondary Outcomes (4)

• positive pregancny

  two weeks after ET

• implantation rate

  two months after ET

• live birth rate

  9 months after the treatment

• miscarriage rate

  up to 24 weeks pregnancy

Study Arms (2)

SYNAREL

ACTIVE COMPARATOR

LUTEAL PHASE SUPPORT WITH SYNAREL 200 MCG X2 DAY

Drug: Nafarelin nasal spray

UTEROGESTAN

ACTIVE COMPARATOR

LUTEAL PHASE SUPPORT WITH UTEROGESTAN 200 MG X2 DAY

Drug: Utrogestan®

Interventions

Nafarelin nasal spray DRUG

NAFARLIN 200 MCG X2 DAY

SYNAREL

Utrogestan® DRUG

UTROGESTAN 200 MG X2 DAY

UTEROGESTAN

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women treated at the Shaare Zedek IVF clinic scheduled for frozen embryo transfer
• Normo-ovulatory women
• Women undergoing frozen embryo transfer in a modified natural cycle
• BMI 18-35
• Age 18-40

You may not qualify if:

• Women undergoing medicated FET cycles
• BMI \>35 or \<18
• Women with hydrosalpinx
• Women with congenital or acquired uterine anomalies (e.g., myomas)
• Egg donation or surrogacy
• Women with endometriosis
• Intolerance to GnRH agonists
• Nasal congestion or respiratory conditions affecting nasal absorption

Sponsors & Collaborators

• Shaare Zedek Medical Center: lead

MeSH Terms

Conditions

Long Qt Syndrome 3

Interventions

Utrogestan

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 20, 2025
• First Posted: March 11, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share