Luteal Phase SupportNCT05838105
Two Different Types of Luteal Phase Support in Natural Cycle Frozen Embryo Transfer and Its Effect on Pregnancy Rates
A study testing GnRH agonist, hCG and Progesterone 100Mg Vag Tab in people with Luteal Phase Support, run by Shaare Zedek Medical Center at 1 site in Israel.
Trial summary
The aim of the study is to compare the pregnancy rate between women treated with Gonadotropin Releasing Hormone (GnRH) agonist together with Human Chorionic Gonadotropin (HCG) and standard luteal support with progesterone following transfer of frozen embryos in in-vitro-fertilization (IVF) natural cycles. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Luteal Phase Support
- What is being tested?
- GnRH agonist, hCG and Progesterone 100Mg Vag Tab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Oct 2022to 1 Jan 2025
- Phase
- Interventional
- 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 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Normo-ovulatory women
- Women undergoing frozen embryos transfer in a natural cycle
- Age 18-45
- BMI 18-35
Who cannot join
- Women undergoing medicated frozen embryos transfer
- Women with a BMI over 35 or under 18.
- Women with hydrosalpinges
- Women with defects or uterine malformations (congenital) or acquired such as myomas
- Egg donation and surrogacy
- Use of preimplantation genetic testing
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Shaare Zedek medical center
Jerusalem, 91031
Heli Alexandroni, MD, +972549900913, heli.alexandroni@gmail.com
About this study
Official title: Prospective Randomized Control Study of Two Different Types of Luteal Phase Support in Natural Cycle Frozen Embryo Transfer and Its Effect on Pregnancy Rates
The aim of the study is to compare the pregnancy rate between women treated with Gonadotropin Releasing Hormone (GnRH) agonist together with Human Chorionic Gonadotropin (HCG) and standard luteal support with progesterone following transfer of frozen embryos in in-vitro-fertilization (IVF) natural cycles.
Read the detailed description
The rate of frozen embryos transfer (FET) has increased in recent years due to a higher tendency of single embryo transfer, use of preimplantation genetic testing, and prevention of ovarian hyperstimulation.
There are different methods to prepare the endometrium for FET:
- Natural cycle (NC) - natural preparation of the body for implantation without the need for medicinal intervention.
- Modified natural cycle (mNC) - Inducing ovulation by administration of Human Chorionic Gonadotropin (HCG) trigger.
- Medical - preparation of endometrium with hormones (estrogen and progesterone).
Following embryo transfer, luteal phase support should be considered. Administration of treatment depends on the type of cycle chosen (either natural or medicated). Treatment options include progesterone, HCG and Gonadotropin Releasing Hormone (GnRH) analog - either one of them or combined. Different protocols (dosages and duration of use) with different pregnancy outcomes were explore before with inconclusive results. We wish to investigate administration of GnRH agonist+HCG vs. progesterone.
Patients included in the study will be women undergoing natural cycle FET at the IVF center in Shaare Zedek, Jerusalem, Israel. All patients will be randomly divided into two groups, each will receive a different luteal treatment support as will be detailed later. Patients demographic data and pregnancy outcomes will be collected.
Based on the clinical pregnancy rate in the prospective study by Bjuresten, et al [Fertil Steril, 2011], where a clinical pregnancy rate of 32% was found among women treated with progesterone for luteal support, and given an alpha of 5% and a power of 80%, 144 women (72 women in each group) are required in order to demonstrate a clinical pregnancy rate of 55% in the study group.
Comparison of categorical variables will be carried out using the the chi-squared test. Comparison of continuous variables will be performed using the Students t-Test or Mann-Whitney U method depending on the variable distribution (normal vs. non-normal distribution, respectively). A multivariate regression will also be conducted in order to determine which variables are significantly and independently related. Statistical significance will be defined when P values are less than 0.05
- Conditions
- Luteal Phase Support
- Being tested
- GnRH agonist, hCG, Progesterone 100Mg Vag Tab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GnRH agonistDrug
125 mcg once at the day mentioned
hCGDrug
dose as mentioned
Progesterone 100Mg Vag TabDrug
dose as mentioned
| Study group | Role | What they receive |
|---|---|---|
| Study group | Active comparator | Patients will receive luteal support with GNRH agonist and HCG according to departmental protocol:
Cleavage stage embryo:
* ET day (embryo day 2-3) - Ovitrelle 125mcg
* Day 3 after ET - Ovitrelle 125mcg + Decapeptyl 0.1mg
* Day 6 after ET- Ovitrelle 125mcg
* Day 9 after ET - Ovitrelle 125mcg
Embryo blastocyst stage:
* ET day (embryo day 5-6) - Ovitrelle 125mcg + Decapeptyl 0.1mg
* Day 3 after ET - Ovitrelle 125mcg
* Day 6 after ET - Ovitrelle 125mcg Receives: Drug: GnRH agonist; Drug: hCG |
| Control group | Active comparator | Patients will receive luteal support with vaginal progesterone - 100 mg Endometrin twice daily until week 8 of pregnancy. Receives: Drug: Progesterone 100Mg Vag Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pregnancy rate
visualization of intrauterine gestational sac on ultrasound divided by number of transfers
Measured: up to two month after embryo transfer
Secondary outcomes (5)
Overall pregnancy rate
number positive beta-hCG divided by total number of transfers
Measured: up to two month after embryo transfer
Implantation rate
number of gestational sacs divided by number of embryos transferred
Measured: up to two month after embryo transfer
Ectopic pregnancy rate
number of ectopic pregnancy divided by number of positive beta-hCG
Measured: up to two month after embryo transfer
Miscarriage rate
number of non-viable before 24 weeks divided by total number of positive beta-hCG
Measured: up to 20 weeks after embryo transfer
Live birth rate
number of live births after 24 weeks divided by number of transfers.
Measured: up to 42 weeks after embryo transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2023
- Study start1 Oct 2022
- Primary completion1 Jan 2025 (estimated)
- Study completion1 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Luteal Phase SupportStudies 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
- Model description
- All patients will be randomly divided into two groups, each will receive a different luteal treatment: 1. Study group - patients will receive luteal support with GNRH agonist and HCG according to departmental protocol (described later). 2. Control group - patients will receive luteal support with vaginal progesterone.
- Masking
- None (open label)
- Enrolment
- 144 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shaare Zedek Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Heli Alexandroni, Shaare Zedek Medical Center
- Investigators
- Keren Rotshenker Olshnika, MD, Principal investigator, Sharee Zedek Medical Center, Israel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05838105
- Sponsor's protocol ID
- LutealSupport
- Status last verified
- Apr 2023
- First submitted
- 20 Apr 2023
- Last updated
- 1 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013 Sep-Oct;19(5):458-70. doi: 10.1093/humupd/dmt030. Epub 2013 Jul 2.
PubMed 23820515Le Lannou D, Griveau JF, Laurent MC, Gueho A, Veron E, Morcel K. Contribution of embryo cryopreservation to elective single embryo transfer in IVF-ICSI. Reprod Biomed Online. 2006 Sep;13(3):368-75. doi: 10.1016/s1472-6483(10)61441-1.
PubMed 16984767Loutradi KE, Kolibianakis EM, Venetis CA, Papanikolaou EG, Pados G, Bontis I, Tarlatzis BC. Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril. 2008 Jul;90(1):186-93. doi: 10.1016/j.fertnstert.2007.06.010. Epub 2007 Nov 5.
PubMed 17980870Weissman A, Horowitz E, Ravhon A, Steinfeld Z, Mutzafi R, Golan A, Levran D. Spontaneous ovulation versus HCG triggering for timing natural-cycle frozen-thawed embryo transfer: a randomized study. Reprod Biomed Online. 2011 Oct;23(4):484-9. doi: 10.1016/j.rbmo.2011.06.004. Epub 2011 Jun 15.
PubMed 21840758Mackens S, Stubbe A, Santos-Ribeiro S, Van Landuyt L, Racca A, Roelens C, Camus M, De Vos M, van de Vijver A, Tournaye H, Blockeel C. To trigger or not to trigger ovulation in a natural cycle for frozen embryo transfer: a randomized controlled trial. Hum Reprod. 2020 May 1;35(5):1073-1081. doi: 10.1093/humrep/deaa026.
PubMed 32395750Ghobara T, Gelbaya TA, Ayeleke RO. Cycle regimens for frozen-thawed embryo transfer. Cochrane Database Syst Rev. 2017 Jul 5;7(7):CD003414. doi: 10.1002/14651858.CD003414.pub3.
PubMed 28675921Montagut M, Santos-Ribeiro S, De Vos M, Polyzos NP, Drakopoulos P, Mackens S, van de Vijver A, van Landuyt L, Verheyen G, Tournaye H, Blockeel C. Frozen-thawed embryo transfers in natural cycles with spontaneous or induced ovulation: the search for the best protocol continues. Hum Reprod. 2016 Dec;31(12):2803-2810. doi: 10.1093/humrep/dew263. Epub 2016 Oct 25.
PubMed 27798046Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: 10.1016/j.fertnstert.2009.11.036. Epub 2010 Jan 25.
PubMed 20097333
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Randomized Control Study of Two Different Types of Luteal Phase Support in Natural Cycle Frozen Embryo Transfer and Its Effect on Pregnancy Rates
- ClinicalTrials.gov ID
- NCT05838105
- Acronym / sponsor ID
- LutealSupport
- Conditions
- Luteal Phase Support
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- Shaare Zedek Medical CenterUniversity, hospital or other
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 1 Jan 2025 (estimated)
- Study completion
- 1 Jan 2025 (estimated)
- First posted
- 1 May 2023 (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.
The aim of the study is to compare the pregnancy rate between women treated with Gonadotropin Releasing Hormone (GnRH) agonist together with Human Chorionic Gonadotropin (HCG) and standard luteal support with progesterone following transfer of frozen embryos in in-vitro-fertilization (IVF) natural cycles.
Detailed description
The rate of frozen embryos transfer (FET) has increased in recent years due to a higher tendency of single embryo transfer, use of preimplantation genetic testing, and prevention of ovarian hyperstimulation.
There are different methods to prepare the endometrium for FET:
- Natural cycle (NC) - natural preparation of the body for implantation without the need for medicinal intervention.
- Modified natural cycle (mNC) - Inducing ovulation by administration of Human Chorionic Gonadotropin (HCG) trigger.
- Medical - preparation of endometrium with hormones (estrogen and progesterone).
Following embryo transfer, luteal phase support should be considered. Administration of treatment depends on the type of cycle chosen (either natural or medicated). Treatment options include progesterone, HCG and Gonadotropin Releasing Hormone (GnRH) analog - either one of them or combined. Different protocols (dosages and duration of use) with different pregnancy outcomes were explore before with inconclusive results. We wish to investigate administration of GnRH agonist+HCG vs. progesterone.
Patients included in the study will be women undergoing natural cycle FET at the IVF center in Shaare Zedek, Jerusalem, Israel. All patients will be randomly divided into two groups, each will receive a different luteal treatment support as will be detailed later. Patients demographic data and pregnancy outcomes will be collected.
Based on the clinical pregnancy rate in the prospective study by Bjuresten, et al [Fertil Steril, 2011], where a clinical pregnancy rate of 32% was found among women treated with progesterone for luteal support, and given an alpha of 5% and a power of 80%, 144 women (72 women in each group) are required in order to demonstrate a clinical pregnancy rate of 55% in the study group.
Comparison of categorical variables will be carried out using the the chi-squared test. Comparison of continuous variables will be performed using the Students t-Test or Mann-Whitney U method depending on the variable distribution (normal vs. non-normal distribution, respectively). A multivariate regression will also be conducted in order to determine which variables are significantly and independently related. Statistical significance will be defined when P values are less than 0.05
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- All patients will be randomly divided into two groups, each will receive a different luteal treatment: 1. Study group - patients will receive luteal support with GNRH agonist and HCG according to departmental protocol (described later). 2. Control group - patients will receive luteal support with vaginal progesterone.
| Arm | Type | Receives |
|---|---|---|
| Study group | Active comparator | Drug: GnRH agonist, Drug: hCGPatients will receive luteal support with GNRH agonist and HCG according to departmental protocol: Cleavage stage embryo: * ET day (embryo day 2-3) - Ovitrelle 125mcg * Day 3 after ET - Ovitrelle 125mcg + Decapeptyl 0.1mg * Day 6 after ET- Ovitrelle 125mcg * Day 9 after ET - Ovitrelle 125mcg Embryo blastocyst stage: * ET day (embryo day 5-6) - Ovitrelle 125mcg + Decapeptyl 0.1mg * Day 3 after ET - Ovitrelle 125mcg * Day 6 after ET - Ovitrelle 125mcg |
| Control group | Active comparator | Drug: Progesterone 100Mg Vag TabPatients will receive luteal support with vaginal progesterone - 100 mg Endometrin twice daily until week 8 of pregnancy. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Normo-ovulatory women
- Women undergoing frozen embryos transfer in a natural cycle
- Age 18-45
- BMI 18-35
Key exclusion criteria (6 listed)
- Women undergoing medicated frozen embryos transfer
- Women with a BMI over 35 or under 18.
- Women with hydrosalpinges
- Women with defects or uterine malformations (congenital) or acquired such as myomas
- Egg donation and surrogacy
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 |
|---|---|---|
| GnRH agonist125 mcg once at the day mentioned | Drug | Study group |
| hCGdose as mentioned | Drug | Study group |
| Progesterone 100Mg Vag Tabdose as mentioned | Drug | Control group |
Primary outcome
Clinical pregnancy rate
Time frame: up to two month after embryo transfer
visualization of intrauterine gestational sac on ultrasound divided by number of transfers
5 secondary outcomes
Overall pregnancy rate
Time frame: up to two month after embryo transfer
Implantation rate
Time frame: up to two month after embryo transfer
Ectopic pregnancy rate
Time frame: up to two month after embryo transfer
Miscarriage rate
Time frame: up to 20 weeks after embryo transfer
Live birth rate
Time frame: up to 42 weeks after embryo transfer
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2023.
- Background: PubMed 23820515Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013 Sep-Oct;19(5):458-70. doi: 10.1093/humupd/dmt030. Epub 2013 Jul 2.
- Background: PubMed 16984767Le Lannou D, Griveau JF, Laurent MC, Gueho A, Veron E, Morcel K. Contribution of embryo cryopreservation to elective single embryo transfer in IVF-ICSI. Reprod Biomed Online. 2006 Sep;13(3):368-75. doi: 10.1016/s1472-6483(10)61441-1.
- Background: PubMed 17980870Loutradi KE, Kolibianakis EM, Venetis CA, Papanikolaou EG, Pados G, Bontis I, Tarlatzis BC. Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril. 2008 Jul;90(1):186-93. doi: 10.1016/j.fertnstert.2007.06.010. Epub 2007 Nov 5.
- Background: PubMed 21840758Weissman A, Horowitz E, Ravhon A, Steinfeld Z, Mutzafi R, Golan A, Levran D. Spontaneous ovulation versus HCG triggering for timing natural-cycle frozen-thawed embryo transfer: a randomized study. Reprod Biomed Online. 2011 Oct;23(4):484-9. doi: 10.1016/j.rbmo.2011.06.004. Epub 2011 Jun 15.
- Background: PubMed 32395750Mackens S, Stubbe A, Santos-Ribeiro S, Van Landuyt L, Racca A, Roelens C, Camus M, De Vos M, van de Vijver A, Tournaye H, Blockeel C. To trigger or not to trigger ovulation in a natural cycle for frozen embryo transfer: a randomized controlled trial. Hum Reprod. 2020 May 1;35(5):1073-1081. doi: 10.1093/humrep/deaa026.
- Background: PubMed 28675921Ghobara T, Gelbaya TA, Ayeleke RO. Cycle regimens for frozen-thawed embryo transfer. Cochrane Database Syst Rev. 2017 Jul 5;7(7):CD003414. doi: 10.1002/14651858.CD003414.pub3.
- Background: PubMed 27798046Montagut M, Santos-Ribeiro S, De Vos M, Polyzos NP, Drakopoulos P, Mackens S, van de Vijver A, van Landuyt L, Verheyen G, Tournaye H, Blockeel C. Frozen-thawed embryo transfers in natural cycles with spontaneous or induced ovulation: the search for the best protocol continues. Hum Reprod. 2016 Dec;31(12):2803-2810. doi: 10.1093/humrep/dew263. Epub 2016 Oct 25.
- Background: PubMed 20097333Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: 10.1016/j.fertnstert.2009.11.036. Epub 2010 Jan 25.
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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.
Keren Rotshenker Olshnika, MD principal investigator
Sharee Zedek Medical Center, Israel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GnRH agonist, hCG and Progesterone 100Mg Vag Tab in people with Luteal Phase Support, run by Shaare Zedek Medical Center at 1 site in Israel.
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 6 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: status not confirmed, as of the sponsor's last update on 1 May 2023. 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 Israel. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Heli Alexandroni, MD (+972549900913, heli.alexandroni@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical pregnancy rate (time frame: up to two month after 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 NCT05838105, which also lists 8 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 1 May 2023.