Live Birth After Letrozole-stimulated Cycles Versus Hormone Replacement Treatment Cycles for the First Frozen Embryo Transfer in Women With PCOS

Live Birth After Letrozole-stimulated Cycles Versus Hormone Replacement Treatment Cycles for the First Frozen Embryo Transfer in Women With PCOS: a Randomized Controlled Trial

This is a multicenter randomized controlled trial comparing the efficacy and safety of two endometrial preparation protocols for the first frozen embryo transfer cycle in PCOS with whole embryo freezing. Subjects will be randomized to letrozole-stimulated group or hormone replacement treatment group in their first frozen embryo transfer cycle, and their pregnancy and perinatal outcomes during this cycle will be followed up and analysis.

Study Overview

• Status: Recruiting
• Conditions: PCOS
• Intervention / Treatment: Procedure: Oral Letrozole; Procedure: Oral estradiol valerate

• Study Type: Interventional
• Enrollment (Estimated): 1078
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • Reproductive & Genetic hospital Of CITIC-Xiangya
      • Contact: Yuan Li, doctor; Phone Number: +86-731-84566688; Email: 1002251255@qq.com
      • Principal Investigator: Fei Gong, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. women diagnosed with PCOS according to modified Rotterdam criteria;
• 2. Women who are participating in their first cycle of IVF or ICSI.
• 3. Women whose IVF/ICSI ovarian stimulation protocol was either GnRH antagonist protocol or long agonist protocol.
• 4. Women with whole embryos freezing.
• 5. Women aged 20 to 38 years old;
• 6. Women BMI 18 kg/m2 to 30 kg/m2
• 7. Women with at least one good-quality embryo suitable for transfer, including day 3 cleavage stage embryo with grade 7CI /8CI and day 5 or day 6 blastocyst with grade 4BB or higher.

Exclusion Criteria:

• 1. Women who has a history of recurrent spontaneous abortion.
• 2. Women with unilateral/bilateral oophorectomy.
• 3. Women with untreated Hydrosalpinx.
• 4. Women with a uterine cavity abnormality, such as a uterine congenital malformation, untreated uterine septum (except shallow uterine septum), adenomyosis, submucous myoma, or moderate to severe intrauterine adhesions.
• 5. Women with uncontrolled diabetes mellitus, thyroid disease and hypertension.
• 6. Women who are indicated and planned to undergo preimplantation genetic test (PGT).

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole-stimulated group	Procedure: Oral Letrozole; Oral Letrozole at a dose of 2.5mg daily will be started on days 3-5 of the menstrual cycle and will be continued for 5 days.
Active Comparator: Hormone replacement treatment group	Procedure: Oral estradiol valerate; Oral estradiol valerate at a dose of 3mg twice daily will be started on days 3-5 of the menstrual cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate	Number of women with live birth/ number of women randomized to the specific group. Live birth is defined as the delivery of any viable infant at 28 weeks or more of gestation.	11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate	Number of women with clinical pregnancy /number of women randomized to the specific group. Clinical pregnancy was defined as the presence of at least one gestational sac in the uterine cavity on ultrasound at about 28 days after embryo transfer.	2 months
Biochemical pregnancy rate	Number of women with biochemical pregnancy /number of women randomized to the specific group. Biochemical pregnancy was defined as a human chorionic gonadotropin level of more than 10 milli-International unit (mIU) per milliliter (ml) as measured at about 14 days after embryo transfer.	1.5 months
Birth weight	Weight of newborns at delivery.	11 months
Incidence of obstetric and perinatal complications	Number of pregnancies with complications / number of clinical pregnancies.	11 months
Incidence of neonatal complications	Number of live births with neonatal complications / number of live births.	11 months
Miscarriage rate	Number of women with miscarrage / number of women with clinical pregnancy. Miscarriage refers to a complete spontaneous abortion or a nonviable pregnancy before 28 weeks of gestation.	9 months
Cycle cancellation rate	Number of women who initiated endometrial preparation without embryos transfer / number of women randomized to the specific group.	1 month
Ectopic pregnancy rate	Number of women with ectopic pregnancy /number of women randomized to the specific group. Ectopic pregnancy will be defined as implantation outside the uterine cavity, as confirmed by sonography or laparoscopy.	2 months

Collaborators and Investigators

• Sponsor: Reproductive & Genetic Hospital of CITIC-Xiangya

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 26, 2022
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Letrozole; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: P2022001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

All the individual participant data collected during the trial will be shared after deidentification upon request.

Study protocol, Statistical analysis plan, informed consent forms, and clinical study report will be available upon request.

Data will be available from 3 months following first publication and ending 5 years after the study has been concluded.

Individual participant data will be shared with researches who provide a methodologically sound proposal and whose proposed use of the data has been approved by an independent review committee.

• IPD Sharing Time Frame: Data will be available from 3 months following first publication and ending 5 years after the study has been concluded.
• IPD Sharing Access Criteria: Individual participant data will be shared with researches who provide a methodologically sound proposal and whose proposed use of the data has been approved by an independent review committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No