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

Study Overview
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Brief Summary
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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.

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

Conditions
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Infertility

Intervention / Treatment
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* Procedure: Embryo transfer
* Procedure: Serum Estradiol and Progesterone levels
* Drug: GnRH agonist
* Drug: External Estradiol
* Drug: Progesterone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: With GnRHa<br>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<br>* The transfer of cryopreserved-thawed embryos inside the uterus aiming to achieve pregnancy<br>Procedure: Serum Estradiol and Progesterone levels<br>* Serum estradiol and serum progesterone levels in blood on the day of start of progesterone supplementation<br>Drug: GnRH agonist<br>* GnRH agonist given on day 21 of the cycle preceding the embryo transfer<br>* Other names: Decapeptyl SR;Drug: External Estradiol<br>* Estradiol started on day1 of the cycle for endometrial prepartaion<br>* Other names: estradiol valerate of Cycloprogenova tablets;Drug: Progesterone<br>* progesterone as luteal phase support start after endometrium is well prepared<br>* Other names: Cyclogest vaginal suppositories;|
| Active Comparator: Without GnRHa<br>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<br>* The transfer of cryopreserved-thawed embryos inside the uterus aiming to achieve pregnancy<br>Procedure: Serum Estradiol and Progesterone levels<br>* Serum estradiol and serum progesterone levels in blood on the day of start of progesterone supplementation<br>Drug: External Estradiol<br>* Estradiol started on day1 of the cycle for endometrial prepartaion<br>* Other names: estradiol valerate of Cycloprogenova tablets;Drug: Progesterone<br>* progesterone as luteal phase support start after endometrium is well prepared<br>* Other names: Cyclogest vaginal suppositories;|

What is the study measuring?
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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 |