Comparison of Vaginal and Intramuscular Progesterone in Vitrified-warmed Blastocyst Transfer Cycles

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to test the hypothesis that the pregnancy rates of women (ages 18-50 years) undergoing transfer of vitrified-warmed blastocysts (frozen at less than 41 years of age) as part of their IVF treatment are not different with respect to the administration of progesterone (Crinone® 8% vaginal gel versus intramuscular progesterone).

Detailed Description
-----------------
The hypothesis of this study is that the type of progesterone administered (intramuscular progesterone or Crinone® 8% vaginal gel) does not affect implantation and clinical pregnancy rates in women receiving cryo-thawed blastocysts that were produced using their own eggs and frozen before age 41 years. Both intramuscular progesterone (25-100 mg compounded in oil) or vaginal progesterone (Crinone® 8% vaginal progesterone gel) are widely used for luteal phase support in patients receiving vitrified-warmed embryos. Crinone® 8% is FDA approved for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (ART) treatment for infertile women with progesterone deficiency (FDA approval letter, 1997).

Official Title
-----------------
Comparison of Vaginal Progesterone Gel (Crinone 8%®) and Intramuscular Progesterone in Vitrified-Warmed Blastocyst Transfer Cycles

Conditions
-----------------
Infertility

Intervention / Treatment
-----------------
* Drug: Vaginal progesterone gel (Crinone® 8%)
* Drug: Intramuscular Progesterone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent Patient age at time of embryo freezing: 18 to 40.9 years Patient age at embryo transfer: 18 to 50 years (i.e. women currently ages 18-50 years who are transferring embryos created using eggs retrieved from women aged 18-40.9 years) Blastocysts frozen by vitrification at Brigham and Women's Hospital Standard eligibility criteria for blastocyst transfer at Brigham and Women's Hospital Exclusion Criteria: Fresh or cleavage-stage embryo transfer planned Gestational carrier cycles Natural and modified natural cycles Embryos frozen more than once or derived from thawed oocytes Embryos frozen at centers other than Brigham and Women's Hospital Embryos frozen using techniques other than vitrification (i.e. slow frozen) Patients with recurrent pregnancy loss, defined as failure of 3 or more clinical pregnancies Uterine factor infertility: Asherman's, submucosal fibroids, polyp greater than 1 cm at time of embryo transfer, uninterrupted hydrosalpinx Patients with three prior failed embryo transfers (fresh or frozen) BMI<18 or >40 kg/m2 at screening Currently breast feeding or pregnant Embryo biopsy performed Current smoking, alcohol or illicit drug use Allergy to study drugs Refusal or inability to adhere to study protocol Participation in other experimental drug trials concurrently within the past 60 days

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Vaginal progesterone gel (Crinone® 8%)<br>Crinone® 8% (90 mg of micronized progesterone in a bioadhesive vaginal gel contained in a single use, one piece applicator) is administered once 5 days prior to embryo transfer, then twice per day until the pregnancy test is negative or until the 10th week of pregnancy. | Drug: Vaginal progesterone gel (Crinone® 8%)<br>* Crinone® 8% (90 mg of micronized progesterone in a bioadhesive vaginal gel contained in a single use, one piece applicator) is administered once 5 days prior to embryo transfer, then twice per day until the pregnancy test is negative or until the 10th week of pregnancy.<br>* Other names: Crinone;|
| Active Comparator: Intramuscular Progesterone<br>Progesterone-25 mg intramuscularly once 5 days prior to embryo transfer, then 50 mg once per day until the pregnancy test is negative or until the 10th week of pregnancy. | Drug: Intramuscular Progesterone<br>* Progesterone-25 mg intramuscularly once 5 days prior to embryo transfer, then 50 mg once per day until the pregnancy test is negative or until the 10th week of pregnancy.<br>* Other names: progesterone;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | Percentage of patients with intrauterine gestational sac by ultrasound | 5-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate | Maximum number of gestational sacs divided by total number of embryos transferred | 5-6 weeks | 
| Sustained implantation rate | maximum number of fetal heartbeats divided by total number of embryos transferred | 7 weeks | 
| Biochemical pregnancy | Positive serum b-hCG (above 5 IU/L) without subsequent ultrasound evidence of pregnancy | 6 weeks | 
| Ongoing pregnancy rate | Live intrauterine pregnancy at the time of transfer to obstetrical care | 7-8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Infertility, In vitro fertilization, Embryo transfer, Blastocyst, Progesterone, Crinone