Frozen Embryo Transfer in Natural and Hormonal Replacement Cycles

Study Overview
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Brief Summary
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This study is a prospective randomized controlled trial to compare the pregnancy outcomes of frozen embryo transfer in natural and hormonal replacement cycles. The study population consisted of all infertile women with regular menstrual cycles who will undergo IVF/ICSI and frozen embryo transfer in Reproductive Biomedicine Research Center, Royan institute, Tehran Iran.

Detailed Description
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In this study all patients who will undergo frozen embryo transfer are randomly allocated to be prepared for transfer by using either natural cycle (with or without hCG for ovulation induction) or Hormonal cycle (with or without administration of GnRH-a) In natural cycle without hCG, daily monitoring of urinary LH is started from day eight of the cycle and frozen-thawed embryo transfer is planned 3-5 days after detection of LH surge, observing mature follicles in ultrasound and endometrial thickness over 7mm for cleavage embryos. In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed 3-5 days later in cleavage stage. In group 3, injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7 days if endometrial thickness is adequate, Estradiol administration will be continued with the same dose and 100mg Progesterone is administered before embryo transfer, otherwise patients are candidates for higher dosage of Estradiol till favourable endometrial thickness is achieved. In the hormonal group without GnRH-a, endometrial preparation will be started with daily administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for 6 days. Then treatment will be continued similar to the 3rd group.

Official Title
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Comparison of Pregnancy Outcomes in Frozen Embryo Transfer in Natural and Hormonal Replacement Cycles: a Randomized Controlled Trial

Conditions
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Infertility

Intervention / Treatment
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* Biological: frozen Embryo transfer
* Drug: 10,000U hCG injection
* Drug: GnRH agonist (Superfact)
* Drug: administration of 6 mg Estradiol valerate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with regular mensturation cycles Age 20-37 years Patients who underwent long protocol Body mass index (BMI) ≤ 30 kg/m2 Patients who will undergo frozen embryo transfer for the first time Exclusion Criteria: Oocyte or embryo donation cycles Uterine diseases or malformations Hyper prolactinemia Thyroid disorders Tuberculosis Recurrent abortion history Severe endometriosis Ovulation disorders

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 37 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Experimental: Natural cycle<br>In natural cycle without hCG, daily monitoring of urinary LH is started from day eight of the cycle and frozen-thawed embryo transfer is planned 3-5 days after detection of LH surge, observing mature follicles in ultrasound and endometrial thickness over 7mm for cleavage embryos. | Biological: frozen Embryo transfer<br>* In this study all patients who will undergo frozen embryo transfer are randomly allocated to be prepared for transfer by using either natural cycle (with or without hCG for ovulation induction) or Hormonal cycle (with or without administration of GnRH-a).<br>|
| Experimental: Natural cycle + hCG for ovulation induction<br>In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed 3-5 days later in cleavage stage. | Biological: frozen Embryo transfer<br>* In this study all patients who will undergo frozen embryo transfer are randomly allocated to be prepared for transfer by using either natural cycle (with or without hCG for ovulation induction) or Hormonal cycle (with or without administration of GnRH-a).<br>Drug: 10,000U hCG injection<br>* In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed 3-5 days later in cleavage stage.<br>|
| Experimental: Hormonally controlled cycle with GnRH-a<br>In this group , injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7 days if endometrial thickness is adequate, Estradiol administration will be continued with the same dose and 100mg Progesterone is administered before embryo transfer, otherwise patients are candidates for higher dosage of Estradiol till favourable endometrial thickness is achieved. | Biological: frozen Embryo transfer<br>* In this study all patients who will undergo frozen embryo transfer are randomly allocated to be prepared for transfer by using either natural cycle (with or without hCG for ovulation induction) or Hormonal cycle (with or without administration of GnRH-a).<br>Drug: GnRH agonist (Superfact)<br>* In group 3, injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7 days if endometrial thickness is adequate, Estradiol administration will be continued with the same dose and 100mg Progesterone is administered before embryo transfer, otherwise patients are candidates for higher dosage of Estradiol till favourable endometrial thickness is achieved.<br>|
| Experimental: Hormonally controlled cycle without GnRH-a<br>In the hormonal group without GnRH-a, endometrial preparation will be started with daily administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for 6 days. Then treatment will be continued similar to the 3rd group. | Biological: frozen Embryo transfer<br>* In this study all patients who will undergo frozen embryo transfer are randomly allocated to be prepared for transfer by using either natural cycle (with or without hCG for ovulation induction) or Hormonal cycle (with or without administration of GnRH-a).<br>Drug: administration of 6 mg Estradiol valerate<br>* In the hormonal group without GnRH-a, endometrial preparation will be started with daily administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for 6 days. Then treatment will be continued similar to the 3rd group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | The pregnancy rate will be evaluated in patients of each groups 4-6 weeks after embryo transfer. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate | Evaluation the implantation rate in patients of each groups 4-6 weeks after frozen embryo transfer | 4 weeks | 
| chemical pregnancy rates | Evaluation the chemical pregnancy rates in patients of each group 2 weeks after embryo transfer. | 2 weeks | 
| Ongoing pregnancy | Evaluation the ongoing pregnancy in patients of each group 12 weeks after embryo transfer. | 12 weeks | 
| miscarriage rate | Evaluation the miscarriage rate in patients of each group 12 weeks after embryo transfer. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infertility froze emberyo transfer hormone replacement