Luteal Phase Support During Frozen Embryo Transfer Cycle

Study Overview
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Brief Summary
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We aimed to decrease quantity of exogenous estrogen and evaluated the success rate of ongoing pregnancy in women undergone artificial FET who have a surplus embryos at previous fertility treatment cycles. In this study, endometrial prepared with standard long GnRH protocol and for luteal phase support patients received 6 mg oral E2 and intramuscularly P 100 mg/d and embryos on day 2-3 were transferred. Control group continued E2 until 12 week of pregnancy, while for cases after identify gestational sac with heart beat (the 6 week of pregnancy) by vaginal ultrasonography, E2 will discontinued.

Detailed Description
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Approval Status: Confirmed Approval reference Number: IR.ACECR.ROYAN.REC.1395.70 Board Name: Ethics committee of Royan infertility institute Board Affiliation: Reza Samani Phone: +982122305236 Email: samani@royaninstitute.org Yes Health, Treatment and Medical Education Ministry: Iran Hormones replace therapy (Artificial) is a method for endometrium preparation and embryo transfer. In this protocol for decrease of spontaneous ovulation, exogenous estrogen began in 2-3 days on follicular phase of the menstrual cycle which continue about 10 to 14 days. In the following luteal phase support by progesterone begins on 14 to 16 days of cycles. The luteal phase is supported with different dose and duration of estradiol (E2) and progesterone (P) until 8-12 week of pregnancy. Studied reported a higher risk of thromboembolism in pregnant women that using exogenous estrogen. Also, excess estrogen might be resulted fetus congenital anomalies, low birth weight and increased susceptibility to breast cancer in female fetuses. On the other hands, it seems placenta in early pregnancy duration synthesize estrogen and this time estrogen sufficient as a product of progesterone metabolism. We aimed to decrease quantity of exogenous estrogen and evaluated the success rate of ongoing pregnancy in women undergone artificial FET who have a surplus embryos at previous fertility treatment cycles. In this study, endometrial prepared with standard long GnRH protocol and for luteal phase support patients received 6 mg oral E2 and intramuscularly P 100 mg/d and embryos on day 2-3 were transferred. Control group continued E2 until 12 week of pregnancy, while for cases after identify gestational sac with heart beat (the 6 week of pregnancy) by vaginal ultrasonography, E2 will discontinued. The level of maternal estrogen and progesterone measured at progesterone days (day 15), the day of embryo transfer, 6 and 12 weeks of pregnancy. This study is a randomized clinical trial to investigate the duration of estrogen for luteal phase in pregnant women undergone frozen embryo transfer cycles- Randomized controlled trials phase III. The study protocol is approved by the Ethics Committee (Institutional Review Board) of Royan institute and all participants provide informed consent.

Official Title
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Duration of Estrogen for Luteal Phase in Pregnant Women Undergone Frozen Embryo Transfer Cycles- Randomized Controlled Trials Phase III

Conditions
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Infertility, Female, Frozen Embryo Transfer

Intervention / Treatment
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* Drug: Strogen
* Drug: Strogen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with surplus embryos undergone infertility treatment cycles (e.g. OHSS, inadequate endometrium, surplus frozen embryo from any cause) Age 21-37 years Normal BMI (18.5 <BMI <30) IVF / ICSI or IVF or ICSI cycles with antagonists or agonists protocols Frozen embryos on 2-3 days Exclusion Criteria: Endometrial thickness ≤7mm Egg Donors Surrogacy Male factor infertility with azoospermia Age <37 years old Hydrosalpinx Uterine anomalies Myoma with a compression effect or submocusa myoma PGD Blastocyst embryo transfer, ZIFT and GIFT

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 37 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FET cycle, discontinue estradiol after 6 gestational weeks<br>In patients 35 days after embryo transfer and observation of gestational sac with heart beat (6 weeks of pregnancy) by ultrasound, exogenous estrogen will discontinued while progesterone will remain daily use until twelfth week of pregnancy. | Drug: Strogen<br>* The OCP-LD begins in 2 to 3 days of the last menstrual cycle and then 500 μgr/d GnRH-a will received on day 17 for fourteen days. Then in 2-3 days of the next menstrual cycle, GnRH-a reduced to 200 μgr/d dose. the patients will receive 6 mg oral that will be continued for 14 days and during this time endometrium thickness evaluated by vaginal ultrasonography. If endometrial thickness is estimated ≥7mm, intramuscularly progesterone 100 mg/d will be started. After the onset of progesterone (days 17 to 18 cycles) frozen embryos transferred. In patients 35 days after embryo transfer and observation of gestational sac with heart beat (6 weeks of pregnancy) by ultrasound, exogenous estrogen will discontinued while progesterone will remain daily use until twelfth week of pregnancy. The levels of maternal estrogen and progesterone was measured at the time of the starting day of progesterone (day 15), the day of embryo transfer, 6 and 12 weeks of pregnancy.<br>* Other names: estradiol till 6 gestational weeks;|
| Active Comparator: FET cycle, continue estradiol till 12 gestational weeks<br>Control group receive 6 mg oral estrogen and 100 mg intramuscularly progesterone until 12 week of pregnancy. | Drug: Strogen<br>* The OCP-LD begins in 2 to 3 days of the last menstrual cycle and then 500 μgr/d GnRH-a will received on day 17 for fourteen days. Then in 2-3 days of the next menstrual cycle, GnRH-a reduced to 200 μgr/d dose. the patients will receive 6 mg oral that will be continued for 14 days and during this time endometrium thickness evaluated by vaginal ultrasonography. If endometrial thickness is estimated ≥7mm, intramuscularly progesterone 100 mg/d will be started. After the onset of progesterone (days 17 to 18 cycles) frozen embryos transferred. Control group receive 6 mg oral estrogen and 100 mg intramuscularly progesterone until 12 week of pregnancy. The levels of maternal estrogen and progesterone was measured at the time of the starting day of progesterone (day 15), the day of embryo transfer, 6 and 12 weeks of pregnancy.<br>* Other names: estradiol till 12 gestational weeks;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate after frozen embryo transfer | Ongoing pregnancy was defined when the pregnancy had completed ≥20 weeks of gestation. | ≥20 weeks of gestational age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal serum estrogen level | Maternal serum estrogen level | The start day of using progesterone for luteal support in FET cycle (day 15 after onset estradiol), the day of embryo transfer (approximately 17-18 days after onset estradiol), 6 and 12 weeks of gestational age | 
| Maternal serum progesterone level | Maternal serum progesterone level | The start day of using progesterone for luteal support in FET cycle (day 15 after onset estradiol), the day of embryo transfer (approximately 17-18 days after onset estradiol), 6 and 12 weeks of gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ongoing pregnancy rate, Estrogen, Frozen embryo transfer, Luteal phase support