Two Different Types of Luteal Phase Support in Natural Cycle Frozen Embryo Transfer and Its Effect on Pregnancy Rates

Study Overview
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Brief Summary
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The aim of the study is to compare the pregnancy rate between women treated with Gonadotropin Releasing Hormone (GnRH) agonist together with Human Chorionic Gonadotropin (HCG) and standard luteal support with progesterone following transfer of frozen embryos in in-vitro-fertilization (IVF) natural cycles.

Detailed Description
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The rate of frozen embryos transfer (FET) has increased in recent years due to a higher tendency of single embryo transfer, use of preimplantation genetic testing, and prevention of ovarian hyperstimulation. There are different methods to prepare the endometrium for FET: Natural cycle (NC) - natural preparation of the body for implantation without the need for medicinal intervention. Modified natural cycle (mNC) - Inducing ovulation by administration of Human Chorionic Gonadotropin (HCG) trigger. Medical - preparation of endometrium with hormones (estrogen and progesterone). Following embryo transfer, luteal phase support should be considered. Administration of treatment depends on the type of cycle chosen (either natural or medicated). Treatment options include progesterone, HCG and Gonadotropin Releasing Hormone (GnRH) analog - either one of them or combined. Different protocols (dosages and duration of use) with different pregnancy outcomes were explore before with inconclusive results. We wish to investigate administration of GnRH agonist+HCG vs. progesterone. Patients included in the study will be women undergoing natural cycle FET at the IVF center in Shaare Zedek, Jerusalem, Israel. All patients will be randomly divided into two groups, each will receive a different luteal treatment support as will be detailed later. Patients demographic data and pregnancy outcomes will be collected. Based on the clinical pregnancy rate in the prospective study by Bjuresten, et al [Fertil Steril, 2011], where a clinical pregnancy rate of 32% was found among women treated with progesterone for luteal support, and given an alpha of 5% and a power of 80%, 144 women (72 women in each group) are required in order to demonstrate a clinical pregnancy rate of 55% in the study group. Comparison of categorical variables will be carried out using the the chi-squared test. Comparison of continuous variables will be performed using the Students t-Test or Mann-Whitney U method depending on the variable distribution (normal vs. non-normal distribution, respectively). A multivariate regression will also be conducted in order to determine which variables are significantly and independently related. Statistical significance will be defined when P values are less than 0.05

Official Title
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Prospective Randomized Control Study of Two Different Types of Luteal Phase Support in Natural Cycle Frozen Embryo Transfer and Its Effect on Pregnancy Rates

Conditions
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Luteal Phase Support

Intervention / Treatment
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* Drug: GnRH agonist
* Drug: hCG
* Drug: Progesterone 100Mg Vag Tab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normo-ovulatory women Women undergoing frozen embryos transfer in a natural cycle Age 18-45 BMI 18-35 Exclusion Criteria: Women undergoing medicated frozen embryos transfer Women with a BMI over 35 or under 18. Women with hydrosalpinges Women with defects or uterine malformations (congenital) or acquired such as myomas Egg donation and surrogacy Use of preimplantation genetic testing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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
Interventional Model Description: All patients will be randomly divided into two groups, each will receive a different luteal treatment: Study group - patients will receive luteal support with GNRH agonist and HCG according to departmental protocol (described later). Control group - patients will receive luteal support with vaginal progesterone.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study group<br>Patients will receive luteal support with GNRH agonist and HCG according to departmental protocol: Cleavage stage embryo: ET day (embryo day 2-3) - Ovitrelle 125mcg Day 3 after ET - Ovitrelle 125mcg + Decapeptyl 0.1mg Day 6 after ET- Ovitrelle 125mcg Day 9 after ET - Ovitrelle 125mcg Embryo blastocyst stage: ET day (embryo day 5-6) - Ovitrelle 125mcg + Decapeptyl 0.1mg Day 3 after ET - Ovitrelle 125mcg Day 6 after ET - Ovitrelle 125mcg | Drug: GnRH agonist<br>* 125 mcg once at the day mentioned<br>Drug: hCG<br>* dose as mentioned<br>|
| Active Comparator: Control group<br>Patients will receive luteal support with vaginal progesterone - 100 mg Endometrin twice daily until week 8 of pregnancy. | Drug: Progesterone 100Mg Vag Tab<br>* dose as mentioned<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | visualization of intrauterine gestational sac on ultrasound divided by number of transfers | up to two month after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall pregnancy rate | number positive beta-hCG divided by total number of transfers | up to two month after embryo transfer | 
| Implantation rate | number of gestational sacs divided by number of embryos transferred | up to two month after embryo transfer | 
| Ectopic pregnancy rate | number of ectopic pregnancy divided by number of positive beta-hCG | up to two month after embryo transfer | 
| Miscarriage rate | number of non-viable before 24 weeks divided by total number of positive beta-hCG | up to 20 weeks after embryo transfer | 
| Live birth rate | number of live births after 24 weeks divided by number of transfers. | up to 42 weeks after embryo transfer |