Cryopreserved-thawed Embryo Transfer With or Without Gonadotropin Releasing Hormone Agonist

Cryopreserved-thawed Embryo Transfer in Down or Non-down Regulated Hormonally Controlled Cycles: a Prospective, Randomized Study

Traditionally, the use of GnRH-a suppression was considered essential for adequate endometrial hormonal modulation in cryopreserved-thawed embryo transfer cycles. Several studies, however, have questioned its necessity for controlled endometrial preparation. Using a high dose of estradiol from day 1 of the cycle will suppress the gonadotroph, preventing folliculogenesis and excessive secretion of LH, allowing adequate endometrial preparation without GnRH-a.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Procedure: Embryo transfer; Procedure: Serum Estradiol and Progesterone levels; Drug: GnRH agonist; Drug: External Estradiol; Drug: Progesterone

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 12411
    • IVF centre, Obstetrics and Gynaecology Department, Cairo University Hospitals (Kasr EL Aini)
  • Giza, Egypt, 12411
    • Nile IVF center
  • Giza, Egypt, 12411
    • Kamal Shaeer center of infertility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 20-35 years
• BMI 20-30
• Regular menses.
• No PCOS, no endometriosis
• No uterine anomalies or lesions
• No severe male factor
• All grade 1 cleaved stage embryos

Exclusion Criteria:

• Less than 20 or more than 35 years
• BMI less than 20 or more than 30
• Irregular cycles
• PCOS or endometriosis
• Uterine anomalies or lesions
• Severe male factor
• Poor quality embryos for transfer
• Severe

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
Active Comparator: With GnRHa; Cryopreserved-thawed embryo transfer cycle, with endometrial preparation using GnRHa followed by external estradiol and progesterone. The GnRHa depot from will be given on day 21 of the preceding cycle, on day 1 of the transfer cycle, the patient will receive 6 mg/ day of estradiol followed up on day 12 of the cycle, if the endometrium is less than 8 mm, till day 15 of the cycle estradiol will be increased to 8 mg/day until 8 mm or more. Then, serum estradiol and progesterone levels are collected, and progesterone 800 mg vaginal suppository will be added and embryo transfer performed 2 to 3 days later.	Procedure: Embryo transfer; The transfer of cryopreserved-thawed embryos inside the uterus aiming to achieve pregnancy; Procedure: Serum Estradiol and Progesterone levels; Serum estradiol and serum progesterone levels in blood on the day of start of progesterone supplementation; Drug: GnRH agonist; GnRH agonist given on day 21 of the cycle preceding the embryo transfer; Other Names: Decapeptyl SR; Drug: External Estradiol; Estradiol started on day1 of the cycle for endometrial prepartaion; Other Names: estradiol valerate of Cycloprogenova tablets; Drug: Progesterone; progesterone as luteal phase support start after endometrium is well prepared; Other Names: Cyclogest vaginal suppositories
Active Comparator: Without GnRHa; Cryopreserved-thawed embryo transfer cycle, with endometrial preparation using external estradiol and progesterone only. On day 1 of the transfer cycle, the patient will receive 6 mg/ day of estradiol and followed up on day 12 of the cycle, if the endometrium did not reach 8 mm, till day 15 of the cycle the dose will be increased to 8 mg/day until the endometrium is 8 or more mm. When the endometrium is ready, serum estradiol and progesterone levels are collected, then progesterone 800 mg vaginal suppository will be added and embryo transfer performed 2 to 3 days later.	Procedure: Embryo transfer; The transfer of cryopreserved-thawed embryos inside the uterus aiming to achieve pregnancy; Procedure: Serum Estradiol and Progesterone levels; Serum estradiol and serum progesterone levels in blood on the day of start of progesterone supplementation; Drug: External Estradiol; Estradiol started on day1 of the cycle for endometrial prepartaion; Other Names: estradiol valerate of Cycloprogenova tablets; Drug: Progesterone; progesterone as luteal phase support start after endometrium is well prepared; Other Names: Cyclogest vaginal suppositories

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate	the detection of intrauterine gestational sac with positive pulsations	5 weeks after embryo transfer]
Live birth rate	Pregnancy ending with a live birth	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estradiol and Progesterone levels on day of start of progesterone supplementation	The serum levels of estradiol and progesterone before embryo transfer	12 to 20 days
Endometrial thickness on day of start of progesterone supplementation	The endometrial thickness on the day of starting progesterone supplementation to transfer the embryos	12 to 20 days
Number of days needed for adequate (> 8mm) endometrial thickness	Number of days on external hormones to prepare endometrium	12 to 20 days
Cycle cancellation: not related to thawing, thin endometrium, high P. OR related to embryos not surviving thawing.	Cycle cancellation: not related to thawing, thin endometrium, high Progesterone. OR related to embryos not surviving thawing.	12 to 20 days
Chemical pregnancy rate	positive serum Beta HCG 14 days after embryo transfer	14 days after embryo transfer
Implantation rate.	the ratio between the number of embryos transferred and the number of sacs	5 weeks after embryo transfer
Early miscarriage rate	Pregnancy loss in the first 12 weeks gestation	3 months
Ongoing pregnancy rate	Pregnancy ongoing beyond 12 weeks gestation	3 months

Collaborators and Investigators

• Sponsor: Cairo University
• Collaborators: Nile Ivf Center, Cairo, Egypt; Kamal Shaeer center of infertility
• Investigators: Study Director: Eman K Shaeer, MD, Cairo university

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: March 30, 2016
• First Submitted That Met QC Criteria: April 12, 2016
• First Posted (Estimate): April 13, 2016

Study Record Updates

• Last Update Posted (Actual): May 17, 2018
• Last Update Submitted That Met QC Criteria: May 12, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Luteolytic Agents; Progestins; Estradiol; Triptorelin Pamoate; Progesterone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: 12016

Plan for Individual participant data (IPD)

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