Vaginal Compared to Intramuscular Progesterone for Frozen Embryo Transfer
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)
2 other identifiers
interventional
1,139
1 country
14
Brief Summary
To determine whether the of vaginal progesterone replacement for frozen embryo transfer results in equivalent live birth rates to intramuscular injection progesterone replacement.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Oct 2014
Longer than P75 for phase_4
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 29, 2014
CompletedStudy Start
First participant enrolled
October 1, 2014
CompletedFirst Posted
Study publicly available on registry
October 2, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 27, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
April 27, 2018
CompletedAugust 2, 2018
July 1, 2018
3.6 years
September 29, 2014
July 31, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Live Birth
Live born infant at 23 weeks' estimated gestational age or greater.
~40 weeks post Frozen Embryo Transfer
Secondary Outcomes (6)
Ongoing Implantation Rate
7-8 weeks after embryo transfer
Implantation rate
5-6 weeks post embryo transfer
Biochemical pregnancy
~10 days following embryo transfer
Clinical pregnancy
5-6 weeks following embryo transfer
Serum progesterone level
~10 days following embryo transfer
- +1 more secondary outcomes
Study Arms (2)
Endometrin® plus Progesterone in Oil (PIO)
EXPERIMENTALSubjects 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.
Progesterone in Oil (PIO) Alone
ACTIVE COMPARATORSubjects 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
Shady Grove Fertility Center
Washington D.C., District of Columbia, 20006, United States
Shady Grove Fertility Center
Washington D.C., District of Columbia, 20016, United States
Shady Grove Fertility Center
Annapolis, Maryland, 21401, United States
Shady Grove Fertility Center
Baltimore, Maryland, 21202, United States
Shady Grove Fertility Center
Bel Air, Maryland, 21015, United States
Shady Grove Fertility Center
Columbia, Maryland, 21044, United States
Shady Grove Fertility Center
Frederick, Maryland, 21702, United States
Shady Grove Fertility Center
Rockville, Maryland, 20850, United States
Shady Grove Fertility Center
Towson, Maryland, 21204, United States
Shady Grove Fertility
Camp Hill, Pennsylvania, 17011, United States
Shady Grove Fertility Center
Chesterbrook, Pennsylvania, 19087, United States
Shady Grove Fertility Center
Annandale, Virginia, 22003, United States
Shady Grove Fertility Center
Leesburg, Virginia, 20176, United States
Shady Grove Fertility Center
Woodbridge, Virginia, 22192, United States
Related Publications (5)
Shapiro DB, Pappadakis JA, Ellsworth NM, Hait HI, Nagy ZP. Progesterone replacement with vaginal gel versus i.m. injection: cycle and pregnancy outcomes in IVF patients receiving vitrified blastocysts. Hum Reprod. 2014 Aug;29(8):1706-11. doi: 10.1093/humrep/deu121. Epub 2014 May 20.
PMID: 24847018BACKGROUNDFeinberg EC, Beltsos AN, Nicolaou E, Marut EL, Uhler ML. Endometrin as luteal phase support in assisted reproduction. Fertil Steril. 2013 Jan;99(1):174-178.e1. doi: 10.1016/j.fertnstert.2012.09.019. Epub 2012 Nov 6.
PMID: 23137759BACKGROUNDPaulson RJ, Collins MG, Yankov VI. Progesterone pharmacokinetics and pharmacodynamics with 3 dosages and 2 regimens of an effervescent micronized progesterone vaginal insert. J Clin Endocrinol Metab. 2014 Nov;99(11):4241-9. doi: 10.1210/jc.2013-3937. Epub 2014 Feb 25.
PMID: 24606090BACKGROUNDDevine K, Richter KS, Jahandideh S, Widra EA, McKeeby JL. Intramuscular progesterone optimizes live birth from programmed frozen embryo transfer: a randomized clinical trial. Fertil Steril. 2021 Sep;116(3):633-643. doi: 10.1016/j.fertnstert.2021.04.013. Epub 2021 May 13.
PMID: 33992421DERIVEDDevine K, Richter KS, Widra EA, McKeeby JL. Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with Endometrin have inferior ongoing pregnancy rates: results from the planned interim analysis of a three-arm randomized controlled noninferiority trial. Fertil Steril. 2018 Feb;109(2):266-275. doi: 10.1016/j.fertnstert.2017.11.004. Epub 2018 Jan 17.
PMID: 29338855DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 29, 2014
First Posted
October 2, 2014
Study Start
October 1, 2014
Primary Completion
April 27, 2018
Study Completion
April 27, 2018
Last Updated
August 2, 2018
Record last verified: 2018-07