Implantation; PlacentaPhase 4NCT03948022
Luteal Support in Frozen-Thawed Embryo Transfer Cycles
A Phase 4 study testing Dydrogesterone 10Mg Tablet (duphaston), Progesterone 50Mg/mL Oil and Crinone 8% Vaginal Gel in people with Implantation; Placenta and Pregnancy Loss, run by Centrum Clinic IVF Center at 1 site in Turkey (Türkiye).
Trial summary
This study evaluates the clinical efficacy of 3 different luteal phase support in patients undergoing frozen-thawed embryo transfer cycles. Endometrium preparation will be hormone replacement in all cycles. Read more about this study
- Who is it for?
- Ages 20 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Implantation; Placenta, Pregnancy Loss, Frozen Embryo
- What is being tested?
- Dydrogesterone 10Mg Tablet (duphaston), Progesterone 50Mg/mL Oil and Crinone 8% Vaginal Gel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 30 Jun 2021to 20 Dec 2021
- 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 20 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- woman aged 20-40 years
- Having available blastocyst(s) cryopreserved by vitrification method.
Who cannot join
- requirement for fresh embryo(s);
- presence of any clinically relevant systemic disease contraindicated for assisted reproduction or pregnancy
- history of more than three failed cycles of IVF
- history of recurrent abortions
- allergy history for relevant drugs
- body mass index of <18 or >38 kg/m2 at screening
Show all 9Show fewer
- current breastfeeding or 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Which Luteal Support in Frozen-Thawed Embryo Transfer Cycles: A Randomized Controlled Trial
This study evaluates the clinical efficacy of 3 different luteal phase support in patients undergoing frozen-thawed embryo transfer cycles. Endometrium preparation will be hormone replacement in all cycles. Starting from day 11, group 1 will receive 100 mg micronized progesterone parenteral daily injections, group 2 will receive 90 mg bioadhesive gel vaginal twice daily and group 3 will receive 40 mg oral dydrogesterone daily tablets.
Read the detailed description
In natural pregnancy, successful implantation and pregnancy necessitates well-functioning corpus luteum. Luteal phase support (LPS) is critical in assisted conception cycles particularly for replacement frozen embryo transfer cycles owing to lack of corpus luteum. 3 different LPS options have been suggested:
- Progesterone in oil (intramuscular injections) is rapidly absorbed after i.m. injection and high progesterone plasma concentrations are reached after approximately 2h. Despite satisfactory plasma levels, the possible side-effects of pain and swelling are limiting the use.
- Vaginal application of progesterone is widely accepted with satisfactory endometrial levels and patient convenience. However, increased vaginal discharge and possible vaginal irritation are the most common side effects.
- Oral administration of synthetic progesterone (dydrogesterone) would offer a convenient way of progesterone administration. Better bioavailability than natural progesterone and less cost makes dydrogesterone preferable. Also, good quality evidence revealed satisfactory outcomes in fresh embryo transfer cycles. However, there is lack of good quality evidence for dydrogesterone as a LPS in frozen-thawed cycles.
The investigator's aim is to compare 3 widely used LPS in frozen-thawed embryo transfer cycles.
Following allocation of the subjects, hormone replacement will be scheduled for the endometrial preparation. Briefly; On day 2 of menstrual bleeding, endometrial preparation with oral estradiol (E2) (2 mg twice daily) will be initiated. Approximately 10 days after initiation of E2 administration, the subject will undergo a transvaginal ultrasound examination to assess endometrial development and serum progesterone (P) level will be checked. Once the subject achieved a trilaminar endometrium with a thickness of >7 mm with serum P levels <1.5 ng/ml, she will start the progesterone treatment to which she will be randomized to one of the 3 arms. After 3 days of P treatment along with E2 pills, cleavage embryo transfer will be performed. If the subject will receive blastocyst, 5 days of P treatment will be scheduled.
If these criteria were not met at the first evaluation, she will allowed up to 10 additional days (20 days total) of estrogen stimulation.
- Conditions
- Implantation; Placenta, Pregnancy Loss, Frozen Embryo, Luteal Support, Luteal Phase Defect, Assisted Reproduction
- Being tested
- Dydrogesterone 10Mg Tablet (duphaston), Progesterone 50Mg/mL Oil, Crinone 8% Vaginal Gel
- Keywords
- progesterone, implantation, pregnancy, abortion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dydrogesterone 10Mg Tablet (duphaston)Drug
40 mg daily oral tablets
Progesterone 50Mg/mL OilDrug
100 mg daily intramuscular injections
Crinone 8% Vaginal GelDrug
180 mg daily vaginal gels
| Study group | Role | What they receive |
|---|---|---|
| intramuscular progesterone | Active comparator | progestan (progesterone) 50 mg/ml ampoules, 2 ampoules (100 mg) intramuscular starting from day 11 of the endometrial preparation cycle. Receives: Drug: Progesterone 50Mg/mL Oil |
| vaginal progesterone | Active comparator | crinone %8 bioadhesive gel (progesterone) 90 mg, twice daily (180 mg/day) starting from day 11 of the endometrial preparation cycle. Receives: Drug: Crinone 8% Vaginal Gel |
| oral dydrogesterone | Experimental | oral dydrogesterone (progesterone) 10 mg tablets, 2x2 (40 mg total) Receives: Drug: Dydrogesterone 10Mg Tablet (duphaston) |
What is being measured
The primary outcome is the main question the study is designed to answer.
ongoing pregnancy rate
fetal cardiac activity beyond 12th week of gestation
Measured: 12th week of pregnancy
Secondary outcomes (2)
clinical pregnancy rate
fetal cardiac activity
Measured: 6th week of pregnancy
abortion rate
miscarriage of the pregnancy pregnancy recently confirmed with positive beta hCG blood test
Measured: during first 10 weeks of gestation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2019
- Study start30 Jun 2021
- Primary completion18 Dec 2021
- Study completion20 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Implantation; PlacentaStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centrum Clinic IVF Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Emre Göksan Pabuçcu, Centrum Clinic IVF Center
- Investigators
- Emre Pabuccu, Assoc. Prof., Study director, Ufuk University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03948022
- Sponsor's protocol ID
- centrumtupbebek
- Status last verified
- Dec 2021
- First submitted
- 9 May 2019
- Last updated
- 11 Jan 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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 29338855Griesinger G, Blockeel C, Sukhikh GT, Patki A, Dhorepatil B, Yang DZ, Chen ZJ, Kahler E, Pexman-Fieth C, Tournaye H. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Reprod. 2018 Dec 1;33(12):2212-2221. doi: 10.1093/humrep/dey306.
PubMed 30304457Zarei A, Sohail P, Parsanezhad ME, Alborzi S, Samsami A, Azizi M. Comparison of four protocols for luteal phase support in frozen-thawed Embryo transfer cycles: a randomized clinical trial. Arch Gynecol Obstet. 2017 Jan;295(1):239-246. doi: 10.1007/s00404-016-4217-4. Epub 2016 Oct 19.
PubMed 27761732
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Which Luteal Support in Frozen-Thawed Embryo Transfer Cycles: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03948022
- Acronym / sponsor ID
- centrumtupbebek
- Conditions
- Implantation; Placenta, Pregnancy Loss, Frozen Embryo, Luteal Support, Luteal Phase Defect, Assisted Reproduction
- Keywords
- progesterone, implantation, pregnancy, abortion
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 151 participants (actual)
- Lead sponsor
- Centrum Clinic IVF CenterUniversity, hospital or other
- Study start
- 30 Jun 2021 (actual)
- Primary completion
- 18 Dec 2021 (actual)
- Study completion
- 20 Dec 2021 (actual)
- First posted
- 13 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the clinical efficacy of 3 different luteal phase support in patients undergoing frozen-thawed embryo transfer cycles. Endometrium preparation will be hormone replacement in all cycles. Starting from day 11, group 1 will receive 100 mg micronized progesterone parenteral daily injections, group 2 will receive 90 mg bioadhesive gel vaginal twice daily and group 3 will receive 40 mg oral dydrogesterone daily tablets.
Detailed description
In natural pregnancy, successful implantation and pregnancy necessitates well-functioning corpus luteum. Luteal phase support (LPS) is critical in assisted conception cycles particularly for replacement frozen embryo transfer cycles owing to lack of corpus luteum. 3 different LPS options have been suggested:
- Progesterone in oil (intramuscular injections) is rapidly absorbed after i.m. injection and high progesterone plasma concentrations are reached after approximately 2h. Despite satisfactory plasma levels, the possible side-effects of pain and swelling are limiting the use.
- Vaginal application of progesterone is widely accepted with satisfactory endometrial levels and patient convenience. However, increased vaginal discharge and possible vaginal irritation are the most common side effects.
- Oral administration of synthetic progesterone (dydrogesterone) would offer a convenient way of progesterone administration. Better bioavailability than natural progesterone and less cost makes dydrogesterone preferable. Also, good quality evidence revealed satisfactory outcomes in fresh embryo transfer cycles. However, there is lack of good quality evidence for dydrogesterone as a LPS in frozen-thawed cycles.
The investigator's aim is to compare 3 widely used LPS in frozen-thawed embryo transfer cycles.
Following allocation of the subjects, hormone replacement will be scheduled for the endometrial preparation. Briefly; On day 2 of menstrual bleeding, endometrial preparation with oral estradiol (E2) (2 mg twice daily) will be initiated. Approximately 10 days after initiation of E2 administration, the subject will undergo a transvaginal ultrasound examination to assess endometrial development and serum progesterone (P) level will be checked. Once the subject achieved a trilaminar endometrium with a thickness of >7 mm with serum P levels <1.5 ng/ml, she will start the progesterone treatment to which she will be randomized to one of the 3 arms. After 3 days of P treatment along with E2 pills, cleavage embryo transfer will be performed. If the subject will receive blastocyst, 5 days of P treatment will be scheduled.
If these criteria were not met at the first evaluation, she will allowed up to 10 additional days (20 days total) of estrogen stimulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| intramuscular progesterone | Active comparator | Drug: Progesterone 50Mg/mL Oilprogestan (progesterone) 50 mg/ml ampoules, 2 ampoules (100 mg) intramuscular starting from day 11 of the endometrial preparation cycle. |
| vaginal progesterone | Active comparator | Drug: Crinone 8% Vaginal Gelcrinone %8 bioadhesive gel (progesterone) 90 mg, twice daily (180 mg/day) starting from day 11 of the endometrial preparation cycle. |
| oral dydrogesterone | Experimental | Drug: Dydrogesterone 10Mg Tablet (duphaston)oral dydrogesterone (progesterone) 10 mg tablets, 2x2 (40 mg total) |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- woman aged 20-40 years
- Having available blastocyst(s) cryopreserved by vitrification method.
Key exclusion criteria (9 listed)
- requirement for fresh embryo(s);
- presence of any clinically relevant systemic disease contraindicated for assisted reproduction or pregnancy
- history of more than three failed cycles of IVF
- history of recurrent abortions
- allergy history for relevant drugs
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 |
|---|---|---|
| Dydrogesterone 10Mg Tablet (duphaston)40 mg daily oral tablets | Drug | oral dydrogesterone |
| Progesterone 50Mg/mL Oil100 mg daily intramuscular injections | Drug | intramuscular progesterone |
| Crinone 8% Vaginal Gel180 mg daily vaginal gels | Drug | vaginal progesterone |
Primary outcome
ongoing pregnancy rate
Time frame: 12th week of pregnancy
fetal cardiac activity beyond 12th week of gestation
2 secondary outcomes
clinical pregnancy rate
Time frame: 6th week of pregnancy
abortion rate
Time frame: during first 10 weeks of gestation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2022.
- Results publication: PubMed 29338855Devine 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.
- Results publication: PubMed 30304457Griesinger G, Blockeel C, Sukhikh GT, Patki A, Dhorepatil B, Yang DZ, Chen ZJ, Kahler E, Pexman-Fieth C, Tournaye H. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Reprod. 2018 Dec 1;33(12):2212-2221. doi: 10.1093/humrep/dey306.
- Results publication: PubMed 27761732Zarei A, Sohail P, Parsanezhad ME, Alborzi S, Samsami A, Azizi M. Comparison of four protocols for luteal phase support in frozen-thawed Embryo transfer cycles: a randomized clinical trial. Arch Gynecol Obstet. 2017 Jan;295(1):239-246. doi: 10.1007/s00404-016-4217-4. Epub 2016 Oct 19.
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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.
Emre Pabuccu, Assoc. Prof. study director
Ufuk University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dydrogesterone 10Mg Tablet (duphaston), Progesterone 50Mg/mL Oil and Crinone 8% Vaginal Gel in people with Implantation; Placenta and Pregnancy Loss, run by Centrum Clinic IVF Center at 1 site in Turkey (Türkiye).
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 2 inclusion and 9 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 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). 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?
ongoing pregnancy rate (time frame: 12th week of pregnancy). 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 NCT03948022, which also lists 3 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 11 Jan 2022.