InfertilityNCT02078869
Uterine Contractions and Mode of Progesterone in Frozen Embryo Transfer (FET) Cycles: Randomized Clinical Trial
A study testing Progesterone in oil and vaginal progesterone suppositories in people with Infertility, run by Toronto Centre for Advanced Reproductive Technology.
Trial summary
When patients undergo in vitro fertilization (IVF), they often make more embryos than it is safe to transfer back in the womb all at once. These excess embryos are frozen and stored for future use. Frozen embryo transfer (FET) is therefore an important option of IVF where there are extra embryos. Read more about this study
- Who is it for?
- Ages 18 to 43 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Progesterone in oil and vaginal progesterone suppositories
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- No sites listed yet
- Study dates
- 15 May 2015to 1 Sep 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 43 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Female patients in the reproductive age group (18-43 years) undergoing IVF FET cycle, blastocyst stage.
Who cannot join
- History of reaction to either one of the P4 medication
- Current use of calcium channels blockers
- Uterine factor infertility
- Acupuncture therapy during current cycle
About this study
When patients undergo in vitro fertilization (IVF), they often make more embryos than it is safe to transfer back in the womb all at once. These excess embryos are frozen and stored for future use. Frozen embryo transfer (FET) is therefore an important option of IVF where there are extra embryos. FET should take place under ideal conditions when uterine receptivity and uterine endometrial lining thickness are at the appropriate developmental stage as the embryo. A common way of preparing the uterus for FET is by using medications (Estrogen and Progesterone) that imitate a normal menstrual cycle while monitoring the endometrial lining development by transvaginal ultrasound. Progesterone (P4) may be administered vaginally or intra-muscularly (IM). The mode of Progesterone administration is based upon local conventions, experts' opinion and patients' preferences. All the mentioned modalities are common in the daily practice of IVF clinics across the world.
The current medical literature does not present high quality evidence for the superiority of one form of Progesterone administration over the other for FET. The investigators know that in fresh embryo transfer cycles where natural follicles continue to function and produce Progesterone as corpora lutea, there were no reported differences in pregnancy rates when luteal vaginal P4 was compared with IM P4 support, but the investigators do not have the same reassurance regarding frozen embryo transfers. The aim of this study is to compare vaginal versus IM route of administration of P4 for FET cycle in a well-designed trial. Since many outcome variables are possible, the investigators have chosen to concentrate in the one that might shed light on a possible biological difference between the two modes of Progesterone administration; uterine contractions. Uterine contractions have been previously recognized as a possible factor that compromises success rates in patients undergoing IVF treatments. Progesterone is considered a uterine relaxant and its levels in the blood versus the levels in the uterus differ by its mode of administration: blood levels are higher when given IM whereas uterine P4 concentrations are higher when given vaginally. The investigators are interested to see whether IM progesterone in frozen embryo transfers presents a different uterine contraction pattern than the vaginal administration.
Read the detailed description
This is a randomized un-blinded clinical trial for comparing uterine contractions frequency in FET cycles between two medicated protocols of uterine lining programming. This study does not involve any new medications, nor mode of administration, but merely a designed array for evaluation of two existing well-established protocols.
Women undergoing Frozen embryo transfers (FET) at the blastocyst stage at the Toronto Centre for Advanced Reproductive Technologies (TCART) will be approached to take part in this study.
Pre-study Screening and Baseline Evaluation:
Study subjects will be recruited voluntarily at TCART clinic. The attending physician will screen and identify potential female patients undergoing in vitro fertilization (IVF) blastocyst FET cycles. The staff physician will explain the general rational. The protocol of the study and further explanations as well as the actual recruitment will be performed by a nurse or a fellow who are not part of the treating team. If the patient gives her consent, she will be randomized (computer generated block randomization) into one of the treatment groups (vaginal P4 or IM P4).
FET medicated cycle protocol includes ten days of Estrace (micronized 17b-estradiol) starting on day 3 of the cycle at a dose of 4 mg daily for 5 days followed by 8 mg daily for 5 days. Routine monitoring takes place after the 10th treatment day - cycle day 13 - and involves a longitudinal scan of the uterine cavity for endometrial thickness and pattern. This is not a study visit but a routine one that is part of the investigators standard of care. The study patients' monitoring will include one additional measurement (uterine contraction frequency counted by number of contractions per minute). After achieving sufficient endometrial proliferation (≥7 mm thickness with a triple layer pattern) with estrogen exposure, the patient starts progesterone use.
Patients randomized into the vaginal progesterone arm will start treatment with 200mg P4 suppositories 3 times a day. Patients randomized into the IM progesterone arm will start treatment with 50mg P4 IM injection once daily.
Blastocyst transfer is performed on the 6th day of P4 exposure. Standard of care is not subjected to any change in this study. The usual management though does not include a repeat Ultrasound imaging on the day of transfer: for the purpose of this study, ultrasound monitoring will be performed just before the embryo transfer and will document endometrial thickness, endometrial pattern and endometrial contractility (waves) as counted by number of contractions per minute. For uniformity of measurement purposes and objectivity, the monitoring will be performed at TCART by 2 highly qualified ultrasound technicians who are not involved in patient management and who will be blinded as to the route of P4 administration.
Routine management will follow the embryo transfer procedure: all patients will continue Estrace and Progesterone. All of the patients (study and control) will resume vaginal progesterone (200mg P4 suppositories 3 times a day).
- Conditions
- Infertility
- Being tested
- Progesterone in oil, vaginal progesterone suppositories
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Progesterone in oilDrug
Daily administration of 50 mg of IM Progesterone
vaginal progesterone suppositoriesDrug
Also called Prometrium
Vaginal Promterium 200 mg , 3 times a day
| Study group | Role | What they receive |
|---|---|---|
| intramuscular Progesterone in oil | Active comparator | 50mg of intramuscular Progesterone injection will be administered once daily for 6 days including the day of embryo transfer Receives: Drug: Progesterone in oil |
| vaginal progesterone suppositories | Active comparator | 200mg of progesterone suppositories will be administered 3 times a day for 6 days including the day of embryo transfer Receives: Drug: vaginal progesterone suppositories |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Uterine Endometrial Contractions Per Minute
The primary outcome will be the number of contractions per minute assessed over 5 minutes on the day of FET.
Measured: on the day of frozen embryo transfer
Secondary outcomes (1)
Implantation Rate
Four weeks after embryo transfer- routine ultrasound for pregnancy confirmation and number of sacs will be performed and the implantation rate will be calculated as number of sacs divided by number of patients who had embryos transferred
Measured: The outcome of the study cycle- tested 4 weeks after the transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2014 (estimated)
- Study start15 May 2015
- Primary completion1 Sep 2015
- Study completion1 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Toronto Centre for Advanced Reproductive Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Robert F. Casper, Toronto Centre for Advanced Reproductive Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02078869
- Sponsor's protocol ID
- PIO-wave
- Status last verified
- Apr 2023
- First submitted
- 3 Mar 2014
- Last updated
- 12 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Uterine Contractions and Mode of Progesterone in Frozen Embryo Transfer (FET) Cycles: Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02078869
- Acronym / sponsor ID
- PIO-wave
- Conditions
- Infertility
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Toronto Centre for Advanced Reproductive TechnologyUniversity, hospital or other
- Study start
- 15 May 2015 (actual)
- Primary completion
- 1 Sep 2015 (actual)
- Study completion
- 1 Sep 2016 (actual)
- First posted
- 5 Mar 2014 (estimated)
- Results
- Posted 12 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
When patients undergo in vitro fertilization (IVF), they often make more embryos than it is safe to transfer back in the womb all at once. These excess embryos are frozen and stored for future use. Frozen embryo transfer (FET) is therefore an important option of IVF where there are extra embryos. FET should take place under ideal conditions when uterine receptivity and uterine endometrial lining thickness are at the appropriate developmental stage as the embryo. A common way of preparing the uterus for FET is by using medications (Estrogen and Progesterone) that imitate a normal menstrual cycle while monitoring the endometrial lining development by transvaginal ultrasound. Progesterone (P4) may be administered vaginally or intra-muscularly (IM). The mode of Progesterone administration is based upon local conventions, experts' opinion and patients' preferences. All the mentioned modalities are common in the daily practice of IVF clinics across the world.
The current medical literature does not present high quality evidence for the superiority of one form of Progesterone administration over the other for FET. The investigators know that in fresh embryo transfer cycles where natural follicles continue to function and produce Progesterone as corpora lutea, there were no reported differences in pregnancy rates when luteal vaginal P4 was compared with IM P4 support, but the investigators do not have the same reassurance regarding frozen embryo transfers. The aim of this study is to compare vaginal versus IM route of administration of P4 for FET cycle in a well-designed trial. Since many outcome variables are possible, the investigators have chosen to concentrate in the one that might shed light on a possible biological difference between the two modes of Progesterone administration; uterine contractions. Uterine contractions have been previously recognized as a possible factor that compromises success rates in patients undergoing IVF treatments. Progesterone is considered a uterine relaxant and its levels in the blood versus the levels in the uterus differ by its mode of administration: blood levels are higher when given IM whereas uterine P4 concentrations are higher when given vaginally. The investigators are interested to see whether IM progesterone in frozen embryo transfers presents a different uterine contraction pattern than the vaginal administration.
Detailed description
This is a randomized un-blinded clinical trial for comparing uterine contractions frequency in FET cycles between two medicated protocols of uterine lining programming. This study does not involve any new medications, nor mode of administration, but merely a designed array for evaluation of two existing well-established protocols.
Women undergoing Frozen embryo transfers (FET) at the blastocyst stage at the Toronto Centre for Advanced Reproductive Technologies (TCART) will be approached to take part in this study.
Pre-study Screening and Baseline Evaluation:
Study subjects will be recruited voluntarily at TCART clinic. The attending physician will screen and identify potential female patients undergoing in vitro fertilization (IVF) blastocyst FET cycles. The staff physician will explain the general rational. The protocol of the study and further explanations as well as the actual recruitment will be performed by a nurse or a fellow who are not part of the treating team. If the patient gives her consent, she will be randomized (computer generated block randomization) into one of the treatment groups (vaginal P4 or IM P4).
FET medicated cycle protocol includes ten days of Estrace (micronized 17b-estradiol) starting on day 3 of the cycle at a dose of 4 mg daily for 5 days followed by 8 mg daily for 5 days. Routine monitoring takes place after the 10th treatment day - cycle day 13 - and involves a longitudinal scan of the uterine cavity for endometrial thickness and pattern. This is not a study visit but a routine one that is part of the investigators standard of care. The study patients' monitoring will include one additional measurement (uterine contraction frequency counted by number of contractions per minute). After achieving sufficient endometrial proliferation (≥7 mm thickness with a triple layer pattern) with estrogen exposure, the patient starts progesterone use.
Patients randomized into the vaginal progesterone arm will start treatment with 200mg P4 suppositories 3 times a day. Patients randomized into the IM progesterone arm will start treatment with 50mg P4 IM injection once daily.
Blastocyst transfer is performed on the 6th day of P4 exposure. Standard of care is not subjected to any change in this study. The usual management though does not include a repeat Ultrasound imaging on the day of transfer: for the purpose of this study, ultrasound monitoring will be performed just before the embryo transfer and will document endometrial thickness, endometrial pattern and endometrial contractility (waves) as counted by number of contractions per minute. For uniformity of measurement purposes and objectivity, the monitoring will be performed at TCART by 2 highly qualified ultrasound technicians who are not involved in patient management and who will be blinded as to the route of P4 administration.
Routine management will follow the embryo transfer procedure: all patients will continue Estrace and Progesterone. All of the patients (study and control) will resume vaginal progesterone (200mg P4 suppositories 3 times a day).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| intramuscular Progesterone in oil | Active comparator | Drug: Progesterone in oil50mg of intramuscular Progesterone injection will be administered once daily for 6 days including the day of embryo transfer |
| vaginal progesterone suppositories | Active comparator | Drug: vaginal progesterone suppositories200mg of progesterone suppositories will be administered 3 times a day for 6 days including the day of embryo transfer |
Who may qualify
- Ages
- 18 to 43 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Female patients in the reproductive age group (18-43 years) undergoing IVF FET cycle, blastocyst stage.
Key exclusion criteria (4 listed)
- History of reaction to either one of the P4 medication
- Current use of calcium channels blockers
- Uterine factor infertility
- Acupuncture therapy during current cycle
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Progesterone in oilDaily administration of 50 mg of IM Progesterone | Drug | intramuscular Progesterone in oil |
| vaginal progesterone suppositoriesAlso: PrometriumVaginal Promterium 200 mg , 3 times a day | Drug | vaginal progesterone suppositories |
Primary outcome
Number of Uterine Endometrial Contractions Per Minute
Time frame: on the day of frozen embryo transfer
The primary outcome will be the number of contractions per minute assessed over 5 minutes on the day of FET.
1 secondary outcome
Implantation Rate
Time frame: The outcome of the study cycle- tested 4 weeks after the transfer
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Progesterone in oil and vaginal progesterone suppositories in people with Infertility, run by Toronto Centre for Advanced Reproductive Technology.
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 1 inclusion and 4 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 12 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Uterine Endometrial Contractions Per Minute (time frame: on the day of frozen embryo transfer). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Apr 2023.