HRT Versus MOS for Endometrial Preparation Prior to FET in Non PCOS Patients

Study Overview
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Brief Summary
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Evaluation of endometrial preparation using either hormonal therapy or ovarian stimulation prior to frozen-thawed embryo transfer (FET) in patients without polycystic ovarian syndrome (PCOS)

Detailed Description
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Women will be randomly divided into two groups; one will be subjected to endometrial preparation by hormone replacement therapy (HRT) and the other will be subjected to minimal ovarian stimulation (MOS). Women in the HRT group will be given estradiol valerate 4 mg daily from day 2 to day 12 of the cycle then the endometrial thickness will be assessed on day 13 by transvaginal sonography (TVS). If the endometrium is ≥ 8 mm and of moderate echogenicity, luteal phase support (using progesterone supplements) will be started but if the endometrium is < 8 mm, estradiol valerate will be continued until reaching appropriate endometrial thickness and echogenicity then the luteal phase support will be started. Women in the MOS group will be given clomiphene citrate in dose of 100-150 mg daily for 5 days (from day 2 to day 6 of the cycle) then switched to low dose gonadotropin (75-150 IU daily) followed by monitoring of the follicular growth (folliculometry) ); starting from day 10 of the stimulation cycle and repeated every 2 days. Final oocyte maturation will be induced by administration of human chorionic gonadotropin (HCG) when there will be at least one leading follicle > 18 mm in diameter followed by luteal phase support (using progesterone supplements) after 48 hours. In both groups, FET will be planned in the appropriate day according to the stage that the embryos have been cryopreserved in it.

Official Title
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Hormone Replacement Therapy Versus Minimal Ovarian Stimulation for Endometrial Preparation Prior to Frozen-thawed Embryo Transfer in Non Polycystic Ovarian Syndrome Patients

Conditions
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Infertility

Intervention / Treatment
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* Drug: Estradiol valerate
* Drug: Sequential Clomiphene citrate and Gonadotropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women without PCOS as defined by the Rotterdam criteria. Presence of at least 2 cryopreserved good quality cleavage-stage embryo (good quality cleavage-stage embryos display stage-specific cell division, have blastomeres of fairly equal size with few to no cytoplasmic fragments). Exclusion Criteria: PCOS or polycystic ovary on ultrasound scan. Moderate or severe endometriosis. Hydrosalpinx. Uterine abnormalities or myoma. Previous uterine surgery.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 38 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: HRT group<br>Women will be subjected to HRT using Estradiol valerate before FET | Drug: Estradiol valerate<br>* Women will be given estradiol valerate 4 mg daily from day 2 to day 12 of the cycle then the endometrial thickness will be assessed on day 13 by transvaginal sonography (TVS). If the endometrium is ≥ 8 mm and of moderate echogenicity, luteal phase support (using progesterone supplements) will be started but if the endometrium is < 8 mm, estradiol valerate will be continued until reaching appropriate endometrial thickness and echogenicity then the luteal phase support will be started.<br>* Other names: Cycloprogynova (white tablets);|
| Active Comparator: MOS group<br>Women will be subjected to MOS using sequential clomiphene citrate and gonadotropin before FET | Drug: Sequential Clomiphene citrate and Gonadotropin<br>* Women will be given clomiphene citrate in dose of 100-150 mg daily for 5 days (from day 2 to day 6 of the cycle) then switched to low dose gonadotropin (75-150 IU daily) followed by monitoring of the follicular growth (folliculometry) ); starting from day 10 of the stimulation cycle and repeated every 2 days. Final oocyte maturation will be induced by administration of human chorionic gonadotropin (HCG) when there will be at least one leading follicle > 18 mm in diameter followed by luteal phase support (using progesterone supplements) after 48 hours.<br>* Other names: Sequential Clomid and Menogon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | Number of clinical pregnancies (defined as presence of at least one intrauterine gestational sac with fetal pole and cardiac activity on TVS scan at 4-6 weeks after the ET) divided by the number of ET procedures | 6 weeks after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate | Number of gestational sacs on TVS scan at 4-6 weeks after ET divided by the number of transferred embryos | 6 weeks after embryo transfer | 
| Miscarriage rate | Number of first trimester miscarriages (before 12 weeks gestational age) divided by the number of clinical pregnancies | 12 weeks gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Frozen-thawed embryo transfer, FET protocols