The Effects of Two Endometrium Preparation Protocols in Frozen-thawed Embryo Transfer in Women With Irregular Cycles

Study Overview
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Brief Summary
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There are two main cycle regimens used for endometrial preparation for frozen embryo transfer （FET) in women with irregular cycles: hormone replacement therapy cycles (HRT) in which the endometrium is artificially prepared by estrogen and progesterone hormones with/without a gonadotrophin releasing hormone agonist (GnRH-a) down regulation, and ovulation induced cycles (OI) in which follicular development is supported with increasing doses of gonadotrophin hormones and ovulation is induced. At present, there is still no sufficient evidence that which kind of frozen embryo transfer cycle regimen to plan more advantage. The purpose of this study was to compare the pregnancy outcome of hormone replacement therapy cycles (HRT) and ovulation induced cycles (OI) in women with irregular cycles.

Detailed Description
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This study is a prospective randomized controlled trial. Patients with irregular cycles undergoing FET in reproductive medicine renter of Sun Yat-sen Memorial Hospital will be recruited who should not be elder than 40 and had more than 3 frozen embryos. They will be randomized to receive either the OI-FET cycle (group OI-A) or the HRT-FET cycle (group HRT-B). In group OI-A, the follicular development is supported by Letrozole(LE) 2.5mg,once daily,is introduced on cycle day 3 .And on cycle day 10 , a Vagina ultrasound is introduced to monitor the development of the follicular ,following by intramuscular gonadotrophin 37.5 75 IU/d until there is a Luteinizing Hormone(LH) surge or ovulation .On the day appearing Luteinizing Hormone surge，patient is always introduced intramuscular human chorionic gonadotrophin(HCG) 10000 IU.If there is sill no Luteinizing Hormone surge when the follicle is 20-24mm ,the ovulation will be induced by HCG.Then the luteum is supported by HCG 2000-2500 IU/3d.Transfer of thawed embryos will be performed 3 days after ovulation is observed. In group HRT-B, oral estradiol, 2 mg, once daily, is introduced on cycle day 3 with an increasing doses protocol. If the endometrial thickness is greater than 7mm, progesterone 40-60 mg in oil will be administered via intramuscular injection. Transfer of thawed embryos will be performed 3 days later.

Official Title
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The Effects of Two Endometrium Preparation Protocols in Frozen-thawed Embryo Transfer in Women With Irregular Cycles

Conditions
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Infertility

Intervention / Treatment
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* Drug: Letrozole and human chorionic gonadotrophin
* Drug: estradiol and progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age forty years old or less Has irregular Menstruation (cycle more than 35 days or less than 24 days ) or has regulation Menstruation but previous data suggest that abnormal ovulation Frozen embryos number more than three Exclusion Criteria: Has Chocolate cyst or adenomyosis of uterus Clear hydrosalpinx Uterine scar or intrauterine adhesion and endometrial thickness <7mm before ovulation recur thick endometrium（<7mm） repeated implantation failure（≥3 times） Cancel the cycle because of having no dominant follicle in the ovulation induction（OI)+FET before or the growth of endometrium not good in the HRT+FET before

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: group OI-A<br>Patients with irregular cycles undergoing FET in reproductive medicine renter of Sun Yat-sen Memorial Hospital will be recruited , who should not be elder than 40 and had more than 3 frozen embryos.They will be randomized to receive the Letrozole and human chorionic gonadotrophin ovulation induced cycles. | Drug: Letrozole and human chorionic gonadotrophin<br>* the follicular development is supported by Letrozole(LE) 2.5mg,once daily is introduced on cycle day 3 .And on cycle day 10 , a Vagina ultrasound is introduced to monitor the development of the follicular ,following by intramuscular gonadotrophin 37.5 75 IU/d until there is a Luteinizing Hormone(LH) surge or ovulation .On the day appearing Luteinizing Hormone surge，patients is always introduced intramuscular human chorionic gonadotrophin(HCG) 10000 IU.If there is sill no Luteinizing Hormone surge when the follicle is 20-24mm ,the ovulation will be induced by HCG.Then the luteum was supported by HCG 2000-2500 IU/3d.Transfer of thawed embryos will be performed 3 days after ovulation is observed.<br>* Other names: Chorionic gonadotropic hormone;|
| Other: group HRT-B<br>Patients with irregular cycles undergoing FET in reproductive medicine renter of Sun Yat-sen Memorial Hospital will be recruited, who should not be elder than 40 and had more than 3 frozen embryos will be randomized to receive the estradiol and progesterone replacement therapy cycles. | Drug: estradiol and progesterone<br>* oral estradiol, 2 mg, once daily, was introduced on cycle day 3 with an increasing doses protocol. If the endometrial thickness was greater than 7mm, progesterone 40-60 mg in oil was administered via intramuscular injection. Transfer of thawed embryos was performed 3 days later<br>* Other names: luteal hormone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ongoing pregnancy rate | 12 weeks after pregnancy,people go Vaginal B ultrasonic examination，being saw gestational sac and heart tube beat as ongoing pregnancy | 12 weeks after pregnancy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pregnancy rate | 2 weeks after Embryo transplantation, people go urine HCG and blood HCG test，positive as pregnancy | 2 weeks after Embryo transplantation | 
| clinical pregnancy rate | 5 weeks after Embryo transplantation,people go Vaginal B ultrasonic，being saw the gestation sac as clinical pregnancy | 5 weeks after Embryo transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endometrium preparation protocols, frozen-thawed embryo transfer, irregular cycle, randomized controlled trial