The Impact of Duration of Gonadotropin-Releasing Hormone Agonist Pretreatment and Letrozole Supplementation on Pregnancy Outcomes in Frozen-Thawed Embryo Transfer Cycles for Patients With Adenomyosis: A 2 by 2 Factorial Multicenter, Randomized Controlled Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 432
- Locations
- 1
- Primary Endpoint
- Live birth rate
Study Overview
Brief Summary
This randomized clinical trial aims to assess the comparative effectiveness of different pre-treatment protocols prior to frozen embryo transfer (FET) among women with adenomyosis, providing evidence-based guidance for clinical decision-making. The main questions it aims to answer are:
Does the protocol involving two doses of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment result in a higher live birth rate compared to one dose of GnRH-a pretreatment in women with adenomyosis undergoing frozen embryo transfer? Does the protocol involving GnRH-a with letrozole supplementation result in a higher live birth rate compared to GnRH-a monotherapy in women with adenomyosis undergoing frozen embryo transfer? Eligible participants will undergo screening before endometrial preparation for FET, following which they will be randomly assigned to one of four groups: GnRH-a-1M, GnRH-a-2M, GnRH-a+LE-1M or GnRH-a+LE-2M. In the GnRH-a-1M group, participants will be pre-treated with one dose GnRH agonist before endometrial preparation. In the GnRH-a-2M group, participants will be pre-treated with two doses GnRH agonist before endometrial preparation. In the GnRH-a+LE-1M group, participants will be pre-treated with one dose GnRH agonist and letrozole 28 days before endometrial preparation. In the GnRH-a+LE-2M group, participants will be pre-treated with two doses GnRH agonist, along with daily 2.5 mg letrozole for 28 days since the first injection of GnRH agonist before endometrial preparation. After pre-treament, all participants will return for endometrial preparation in artificial cycles.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to 38 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Sonographically diagnosed adenomyosis via transvaginal ultrasound;
- •Candidates scheduled for frozen single blastocyst (Day5, Day6) transfer
- •Age 20-38 years
- •Previous embryo transfer attempts: ≤2 cycles
Exclusion Criteria
- •Patients diagnosed with Recurrent pregnancy loss, Autoimmune disorders (e.g., systemic lupus erythematosus), Uterine fibroids ≥5 cm, Cervical incompetence, Cesarean scar niche
- •History of Myomectomy and/or adenomyosis lesion excision, Cervical conization
- •Patients presenting with Congenital Müllerian anomalies (unicornuate uterus, septate uterus, etc.), Endometrial atypical hyperplasia, malignancy or defects
- •Sperm retrieval method: Micro-TESE (microdissection testicular sperm extraction)
- •Fertilization method: Rescue ICSI
- •Endometrial thickness <7 mm, Intrauterine adhesions, Intrauterine fluid
- •Contraindications to exogenous hormone administration
- •Use of GnRH within 3 months prior to enrollment
Arms & Interventions
GnRH-a-1M
Intervention: GnRH-a-1M (Drug)
GnRH-a-2M
Intervention: GnRH-a-2M (Drug)
GnRH-a+LE-1M
Intervention: GnRH-a+LE-1M (Drug)
GnRH-a+LE-2M
Intervention: GnRH-a+LE-2M (Drug)
Outcomes
Primary Outcomes
Live birth rate
Time Frame: 40 weeks after embryo transfer
Secondary Outcomes
- Cycle Cancellation Rate(3 weeks after initiating artificial cycle)
- Hypoestrogenic Adverse Event Rate(4 weeks after 3.75mg GnRH-a intramuscular injection)
- Embryo Implantation Rate(3 weeks post embryo transfer)
- Positive Pregnancy Test Rate(2 weeks post embryo transfer)
- Clinical Pregnancy Rate(5 weeks post embryo transfer)
- Ectopic Pregnancy Rate(7 weeks' gestation)
- Ongoing Pregnancy Rate(10 weeks post embryo transfer)
- Miscarriage Rate(Prior to 28 weeks' gestation)
- Drug-Related Venous Thromboembolism (VTE) Rate(Treatment initiation until 10 weeks' gestation)
- Preterm Birth Rate(22, 28, 32, 37 weeks' gestation)
- Gestational Diabetes Mellitus (GDM) Incidence(24-28 weeks' gestation)
- Rate of Hypertension in Pregnancy(20 weeks' gestation to delivery)
- Low Birth Weight Rate(Delivery)
- Very Low Birth Weight Rate(Delivery)
- Macrosomia Rate(Delivery)
- Extreme Macrosomia Rate(Delivery)
- Multiple Pregnancy Rate(6-8 weeks' gestation)
- Stillbirth Rate(28 weeks' gestation to delivery)
- Neonatal Mortality Rate(First 28 days postnatal)
- Adverse Event Incidence(Enrollment until 6 months postpartum)
Investigators
Yanwen Xu
Director of the Reproductive Medical Center, the First Affliated Hospital of Sun Yat-sen University
First Affiliated Hospital, Sun Yat-Sen University