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InfertilityPhase 4NCT02254577

Vaginal Compared to Intramuscular Progesterone for Frozen Embryo Transfer

A Phase 4 study testing Endometrin® plus Progesterone in Oil (PIO) and Progesterone in Oil (PIO) Only in people with Infertility, run by Shady Grove Fertility Reproductive Science Center at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To determine whether the of vaginal progesterone replacement for frozen embryo transfer results in equivalent live birth rates to intramuscular injection progesterone replacement. Read more about this study

Who is it for?
Ages 18 to 48 years, women only
Conditions the study is for
Infertility
What is being tested?
Endometrin® plus Progesterone in Oil (PIO) and Progesterone in Oil (PIO) Only
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,139 participants
Where
14 sitesUnited States
Study dates
Oct 2014to 27 Apr 2018
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 48 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 14Show fewer
  • 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.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Shady Grove Fertility Center

    Annandale, Virginia, 22003

  • Shady Grove Fertility Center

    Annapolis, Maryland, 21401

  • Shady Grove Fertility Center

    Baltimore, Maryland, 21202

  • Shady Grove Fertility Center

    Bel Air, Maryland, 21015

  • Shady Grove Fertility

    Camp Hill, Pennsylvania, 17011

  • Shady Grove Fertility Center

    Chesterbrook, Pennsylvania, 19087

  • Shady Grove Fertility Center

    Columbia, Maryland, 21044

  • Shady Grove Fertility Center

    Frederick, Maryland, 21702

  • Shady Grove Fertility Center

    Leesburg, Virginia, 20176

  • Shady Grove Fertility Center

    Rockville, Maryland, 20850

  • Shady Grove Fertility Center

    Towson, Maryland, 21204

  • Shady Grove Fertility Center

    Washington D.C., District of Columbia, 20006

  • Shady Grove Fertility Center

    Washington D.C., District of Columbia, 20016

  • Shady Grove Fertility Center

    Woodbridge, Virginia, 22192

Other trials in United States

About this study

Official title: 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)

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

Read the detailed description

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.

Conditions
Infertility
Being tested
Endometrin® plus Progesterone in Oil (PIO), Progesterone in Oil (PIO) Only
Keywords
Infertility, Progesterone, ART, IVF, FET, FBT, Frozen Embryo Transfer
Medical subject headings
Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Endometrin® plus Progesterone in Oil (PIO)Drug

    Also called Vaginal Micronized Progesterone Tablet, Progesterone in Sesame Oil Injection

  • Progesterone in Oil (PIO) OnlyDrug

    Also called Progesterone in Sesame Oil Injection

Study groups in NCT02254577
Study groupRoleWhat they receive
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.
Receives: Drug: Endometrin® plus Progesterone in Oil (PIO)
Progesterone in Oil (PIO) AloneActive 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.
Receives: Drug: Progesterone in Oil (PIO) Only

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Live Birth

    Live born infant at 23 weeks' estimated gestational age or greater.

    Measured: ~40 weeks post Frozen Embryo Transfer

Secondary outcomes (6)

  1. Ongoing Implantation Rate

    maximum # fetal heartbeats divided by total number of embryos transferred

    Measured: 7-8 weeks after embryo transfer

  2. Implantation rate

    Maximum number of gestational sacs, divided by total number of embryos transferred

    Measured: 5-6 weeks post embryo transfer

  3. Biochemical pregnancy

    detection of beta hCG (pregnancy hormone) above 5 IU/L

    Measured: ~10 days following embryo transfer

  4. Clinical pregnancy

    Presence of gestational sac(s) at 5-6 weeks post ET

    Measured: 5-6 weeks following embryo transfer

  5. Serum progesterone level

    blood draw

    Measured: ~10 days following embryo transfer

  6. Patient satisfaction with Endometrin® vs. intramuscular progesterone in oil

    As assessed by brief, optional online survey

    Measured: between 0 and 10 days following embryo transfer

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Oct 2014 (estimated)
  2. Study startOct 2014
  3. Primary completion27 Apr 2018
  4. Study completion27 Apr 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,139 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02254577
Sponsor's protocol ID
13-0028
Other IDs
SUSTAIN
Status last verified
Jul 2018
First submitted
29 Sep 2014
Last updated
2 Aug 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 24847018

  • Feinberg 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.

    PubMed 23137759

  • Paulson 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.

    PubMed 24606090

  • Devine 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.

    PubMed 33992421

  • Devine 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.

    PubMed 29338855

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Endometrin® plus Progesterone in Oil (PIO) and Progesterone in Oil (PIO) Only in people with Infertility, run by Shady Grove Fertility Reproductive Science Center at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Live Birth (time frame: ~40 weeks post Frozen Embryo Transfer). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02254577, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2018.

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