Vaginal Compared to Intramuscular Progesterone for Frozen Embryo Transfer

Study Overview
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Brief Summary
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To determine whether the of vaginal progesterone replacement for frozen embryo transfer results in equivalent live birth rates to intramuscular injection progesterone replacement.

Detailed Description
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The purpose of this ongoing study is to look at whether Endometrin® (vaginal micronized progesterone tablets) supplemented by intramuscular injection of progesterone in oil (PIO) work as well as PIO alone for women undergoing transfer of frozen-thawed blastocyst(s). Another goal of the study is to determine whether patients prefer Endometrin or PIO. Endometrin® has been approved by the United States Food and Drug Administration, or FDA, to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women. (FDA New Drug Approval Letter, Endometrin®, 2007). The use of Endometrin® (vaginal micronized progesterone tablets) in this study is investigational. An investigational use is one that is not approved by the U.S. Food and Drug Administration (FDA). Approximately 1170 women between the ages of 18-48 who are having difficulty becoming pregnant and wish to undergo frozen embryo transfer will be asked to participate. The participants will be recruited from among patients of Shady Grove Fertility. One-half of the participants who qualify and wish to take part in the ongoing study will be randomized (assigned by chance, like the flip of a coin) to receive Endometrin® and an intramuscular injection of PIO every third day. One-half will be randomized to receive an intramuscular injection of PIO every day. This study is a type of study called an open label, assessor-blind study. This means that you and your doctor will know which treatment you are assigned and receive; however, the person analyzing the information obtained from the study will not know which patients received which study treatments. Patients enrolling in the study will receive the medications for their frozen embryo transfer cycle free of charge.

Official Title
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A Randomized, Three-armed, Non-Inferiority Study of Vaginal Progesterone (Endometrin®) Compared to Intramuscular Progesterone in Oil (PIO) in Infertile Subjects Undergoing Frozen Embryo Transfer (FET)

Conditions
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Infertility

Intervention / Treatment
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* Drug: Endometrin® plus Progesterone in Oil (PIO)
* Drug: Progesterone in Oil (PIO) Only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Female age between 18 and 48 years Having available blastocyst(s) frozen by vitrification method at our center (Shady Grove Fertility). Standard eligibility criteria to undergo frozen blastocyst transfer at Shady Grove Fertility. Exclusion Criteria: Requires fresh embryos or surrogate carrier Embryos from frozen oocytes and embryos frozen more than once Any embryo cryopreserved by slow freeze method and/or prior to blastocyst stage Presence of any clinically relevant systemic disease contraindicated for ART History of more than 3 failed cycles in previous ART attempts and/or more than 3 recurrent pregnancy losses after ET Surgical or medical condition or requirement for medication, which may interfere with absorption, distribution, metabolism, or excretion of the drugs to be used Subjects with a body mass index (BMI) of <18 or >38 kg/m2 at screening Current or recent substance abuse, including alcohol and tobacco. (Note: Subjects who stopped tobacco usage at least 3 months prior to screening visit will be allowed) Currently breast feeding, pregnant, or having (a) contraindication(s) to pregnancy Refusal or inability to comply with the requirements of the protocol for any reason, including scheduled clinic visits and laboratory tests Trophectoderm or blastomere biopsy of the blastocyst(s) to be transferred. Documented intolerance or allergy to any of the medications used, including the study medication Participation in any experimental drug study within 60 days prior to screening If a subject undergoes more than two frozen blastocyst transfers meeting study criteria, she will only be eligible to enroll in the study for two of these.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 48 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 |
| --- | --- |
| Experimental: Endometrin® plus Progesterone in Oil (PIO)<br>Subjects in all arms will undergo the standard monitoring appointments and therapies involved in a frozen embryo transfer cycle. Patients randomized to the Endometrin® plus PIO arm will take progesterone as 2 100mg tablets of Endometrin® inserted vaginally twice daily. In addition, on the first day of Endometrin® therapy, patients randomized to this arm will take a 50mg intramuscular injection (1mL) of PIO and will repeat this injection every third day. Patients in this arm will undergo Frozen Embryo Transfer on the fifth day of Endometrin® therapy. | Drug: Endometrin® plus Progesterone in Oil (PIO)<br> <br> * Other names: Progesterone in Sesame Oil Injection;|
| Active Comparator: Progesterone in Oil (PIO) Alone<br>Subjects in all arms will undergo the standard monitoring appointments and therapies involved in a frozen embryo transfer cycle. Patients randomized to the PIO Only arm will take progesterone as a daily 50mg intramuscular injection (1mL) of PIO and will undergo Frozen Embryo Transfer on the sixth day of taking this medication. | Drug: Progesterone in Oil (PIO) Only<br> <br> * Other names: Progesterone in Sesame Oil Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live Birth | Live born infant at 23 weeks' estimated gestational age or greater. |  40 weeks post Frozen Embryo Transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing Implantation Rate | maximum # fetal heartbeats divided by total number of embryos transferred | 7-8 weeks after embryo transfer | 
| Implantation rate | Maximum number of gestational sacs, divided by total number of embryos transferred | 5-6 weeks post embryo transfer | 
| Biochemical pregnancy | detection of beta hCG (pregnancy hormone) above 5 IU/L |  10 days following embryo transfer | 
| Clinical pregnancy | Presence of gestational sac(s) at 5-6 weeks post ET | 5-6 weeks following embryo transfer | 
| Serum progesterone level | blood draw |  10 days following embryo transfer | 
| Patient satisfaction with Endometrin® vs. intramuscular progesterone in oil | As assessed by brief, optional online survey | between 0 and 10 days following embryo transfer | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infertility, Progesterone, ART, IVF, FET, FBT, Frozen Embryo Transfer