The Effectiveness of the Letrozole-induced Endometrial Preparation Protocol in Frozen-thawed Embryo Transfer (FET)

Clinical Outcomes of Letrozole-induced Endometrial Preparation Regimens Versus Conventional Endometrial Preparation Regimens Including Natural Cycle, Hormone Replacement Regimens in FET, a Randomized Controlled Study

The goal of this single center, non-blinded, randomized controlled clinical trial to comparison of pregnancy outcomes and perinatal outcomes in patients undergoing IVF treatment (including ICSI) with FET with letrozole-induce endothelial preparation protocol versus natural cycles, hormone replacement protocol.

The main questions it aims to answer are:

• To investigate whether letrozole-induce endothelial preparation is effective in improving the live birth rate and clinical pregnancy rate.
• To explore its possible impact on clinically important indicators such as spontaneous abortion rate, implantation cycle cancellation rate, days of endothelial preparation, and number of visits to the clinic.

The study subjects were randomized into groups starting at D1-D3 of the menstrual cycle. The study subjects were stratified according to whether their menstrual cycles were regular or not, and were divided into the following endothelial preparation regimens according to the pre-prepared stratified zoned randomized group numbers: (1) regular menstrual cycles (25-35 d): letrozole ovulation-promoting cycles, natural cycles, and hormone-replacement cycles; and (2) irregular menstrual cycles (<25 d or >35 d): letrozole ovulation-promoting cycles, hormone-replacement cycle.

Study Overview

• Status: Recruiting
• Conditions: Infertility, Female; Letrozole
• Intervention / Treatment: Drug: Letrozole

• Study Type: Interventional
• Enrollment (Estimated): 858
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chengliang Zhou, Dr.; Phone Number: 08613758240793; Email: chengliang_zhou@163.com
• Study Contact Backup: Name: Xiaojun Chen, Dr.; Phone Number: 19921917097; Email: cxj8012@hotmail.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Yu Xiao
    • Contact: Yu Xiao, Dr.; Email: ethanhsiao@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Women <40 years of age undergoing IVF or ICSI at our reproductive center with a total of ≤3 superovulation cycles , and with ≥2 cleavage embryos or ≥1 blastocyst were cryopreserved. Previous cycles of embryo transfer ≤ 2 and only one transfer cycle with 1-2 embryos per study subject was enrolled.

Exclusion Criteria:

1. Patients with chromosomal abnormalities in either spouse, hydrosalpinx, severe endometriosis, adenomyosis, and uterine and uterine cavity organic diseases such as uterine malformations, endometrial polyps, and uterine adhesions;
2. patients who underwent pre-implantation genetic diagnosis (PGT);
3. patients who underwent ICSI using surgically obtained epididymal or testicular spermatozoa;
4. patients with a Body mass index (BMI, = weight/height2 ) > 30 kg/m2;
5. patients with recurrent spontaneous abortions;
6. patients with sequential embryo transfer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole-induced endometrial preparation protocol; Starting at D3 of the menstrual cycle, letrozole 2.5 mg po qd was administered for 5 days. After 1 week, ultrasound was performed to dynamically monitor follicular development, and 75-150 IU im qd of human menopausal gonadotrophin (hMG) given to continue ovulation stimulation as needed, and oestradiol valerate 2 mg po qd was given to regulate endometrial thickness until the follicle developed to 16 mm in diameter and 7 mm in endometrial thickness. The follicles developed to ≥16 mm in diameter and ≥7 mm in lining thickness and were dynamically monitored by ultrasound and serum sex hormone levels to determine the day of ovulation. From the day of ovulation, dexamethasone 10 mg po tid was administered, and cleavage-stage embryos were transferred 2 or 3 days later, or blastocysts were transferred 5 days later. Deferiprone 10 mg po tid was continued for 14 days after transfer.	Drug: Letrozole; Different endothelial preparations according to groups, see arm descriptions for details
No Intervention: Natural cycles endometrial preparation protocol; Follicular development was monitored dynamically by ultrasound from D8-D11of the menstrual cycle until the follicles developed to ≥16 mm in diameter and ≥7 mm in endothelial thickness, and the day of ovulation was determined by dynamic ultrasound monitoring and detection of serum sex hormone levels. Deferiprone 10 mg po tid was administered from the day of ovulation, and D2 or D3 cleavage stage embryos were transferred 2 or 3 days later, or blastocysts were transferred 5 days later. Deferiprone 10 mg po tid was continued for a total of 14 days after transfer. Cycles were canceled if endothelial thickness was <7 mm on the day of ovulation or if serum progesterone levels were 5 nmol/L before ovulation.
No Intervention: Hormone replacement cycles endometrial preparation protocol; Starting from D1-D5 of the menstrual cycle, estradiol valerate 2 mg po bid was administered for 7 days, followed by ultrasound for dynamic monitoring of endothelial and follicular development, and if the endothelial thickness was <7 mm, the dosage of estradiol valerate was increased to 3-4 mg po bid as appropriate. The number of days of hormone replacement ranged from 11-20 days, and when the endothelial thickness was 7 mm, luteinizing hormone vaginal slow-release gel 90 mg pv qd was added, as well as dexedrine and progesterone 10 mg po bid to transform the endothelium 2 or 3 days later or 5 days later. Progesterone 10 mg po bid was added to transform the endothelium, and cleavage stage embryos were transferred 2 or 3 days later, or blastocysts were transferred 5 days later. Luteal support as described above was continued for a total of 14 days after transfer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth	The number of deliveries resulting in at least one live birth	40-42 weeks'estimated gestational age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy	Clinical pregnancies diagnosed by ultrasonographic visualisation of gestational sacs, the number of clinical pregnancies expressed per 100 embryo transfer cycles	5-7 weeks' estimated gestational age
embryo implantation	Serum Human Chorionic Gonadotropin levels >10 IU/L, the number of gestational sacs observed divided by the number of embryos transferred	14 day after embryo transfer

Collaborators and Investigators

• Sponsor: International Peace Maternity and Child Health Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: July 31, 2023
• First Submitted That Met QC Criteria: August 16, 2023
• First Posted (Actual): August 23, 2023

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Frozen-thawed embryo transfer; Letroziole; Endothelial preparation protocol
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Infertility; Infertility, Female; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: InternationalPMCHH-1

Drug and device information, study documents

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