Frozen Embryo TransferPhase 4NCT05168865
Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients.
A Phase 4 study testing Letrozole 2.5mg in people with Frozen Embryo Transfer and Polycystic Ovarian Disease, run by Dubai Fertility Center.
Trial summary
One of the indications of freezing is to reduce the risk of ovarian hyperstimulation syndrome particularly in polycystic ovarian disease (PCOS) women. Very few RCTs addressed the issue of optimizing the endometrium for a frozen cycle. Read more about this study
- Who is it for?
- Ages 20 to 40 years, women only
- Conditions the study is for
- Frozen Embryo Transfer, Polycystic Ovarian Disease, Letrozole
- What is being tested?
- Letrozole 2.5mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2023to 1 Apr 2024
- 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
- No healthy volunteers
- Adult
Who may be able to join
- Women with PCOS diagnosed with Rotterdam criteria.
- Age between 20 to 40-year-old
- Undergoing frozen oocytes intracytoplasmic sperm injection transfer or frozen embryo transfer
- Willingly accept to participate in the study
Who cannot join
- Women > 40 years old or younger than 20.
- Uterine pathology that decreases the chance of pregnancy or increases risk of miscarriage such as
- Uterine fibroids (sub-mucous of any size or intramural of > 3 cm)
- Uncontrolled endocrinal-pathological disease like
- Cushing syndrome,
- Adrenal hyperplasia,
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- Hyperprolactinemia,
- Acromegaly,
- Thyroid disease,
- Diabetes mellitus, and
- Immune disorders.
- Presence of Hydrosalpinx
- Not willing or able to sign the consent form.
About this study
Official title: Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients. Randomized Controlled Study
One of the indications of freezing is to reduce the risk of ovarian hyperstimulation syndrome particularly in polycystic ovarian disease (PCOS) women. Very few RCTs addressed the issue of optimizing the endometrium for a frozen cycle. Interestingly, Letrozole for ovarian stimulation showed significantly better reproductive outcome when compared with hormone replacement therapy (HRT) cycle. In addition, HRT cycle has been associated with higher miscarriage rate when compared with natural cycle frozen embryo transfer. Nevertheless, there is not yet a well-designed prospective randomized study comparing letrozole and HRT in PCOS women undergoing frozen embryo transfer.
Read the detailed description
Freezing oocytes and embryos has become an integral part of the daily IVF practice. One of the indications of freezing is to reduce the risk of ovarian hyperstimulation syndrome particularly in polycystic ovarian disease (PCOS) women.
Very few randomized control trials addressed the issue of optimizing the endometrium for a frozen cycle. As PCOS women do not regularly ovulate, most of their frozen cycles are conducted after hormonal replacement therapy (HRT) preparation of the endometrium or after ovulation induction. In HRT cycle the endometrium is prepared using exogenous estradiol and progesterone. While HRT cycles requires less monitoring and easy scheduling, it is costly, associated with increased risk of thrombosis and women must continue using the exogenous hormones up to 10 to 12 weeks of gestation.
Interestingly, Letrozole for ovarian stimulation showed significantly better reproductive outcome when compared with HRT cycles. In agreement with the previous Chinese study, a retrospective Japanese ART registry data that included 110 722 frozen cycles confirmed the superiority of letrozole. Nevertheless, there is not yet a well-designed prospective randomized study.
In addition, HRT cycle has been associated with higher miscarriage rate when compared with natural cycle frozen embryo transfer. HRT is usually used in patients with PCOS. A retrospective study including 2664 PCOS patients showed significant decrease in the pregnancy loss when letrozole was used when compared with HRT in frozen cycles.
Investigators thought of comparing letrozole and HRT in women with PCOS who are undergoing frozen cycles in PCOS women. Live birth and miscarriage rates will be the primary outcomes.
- Conditions
- Frozen Embryo Transfer, Polycystic Ovarian Disease, Letrozole, Hormone Replacement Therapy, Live Birth, Miscarriage
- Being tested
- Letrozole 2.5mg
- Medical subject headings
- Polycystic Ovary Syndrome, Abortion, Spontaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Letrozole 2.5mgDrug
Also called estradiol and progesterone
Letrozole 5 mg starting on day 3 of spontaneous menstrual period or after progesterone withdrawal bleeding for five consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| PCOS women will receive letrozole ovarian stimulation. | Experimental | Polycystic ovarian disease (PCOS) women undergoing frozen embryo transfer (FER) will use Letrozole 5 mg starting on day 3 of spontaneous menstrual period or after progesterone withdrawal bleeding for five consecutive days. Receives: Drug: Letrozole 2.5mg |
| PCOS women will receive Estradiol and Progesterone (hormonal endometrial preparation). | Active comparator | PCOS women will use daily Cetorelix acetate 0.25 mg injections for 5 days from day 1-3 of the menstrual follow or after progesterone (P4) withdrawal bleeding. They will commence daily oral Estradiol Valerate (E2) 2 mg twice daily for 5 days starting from day 3 of the menstrual flow or after P4 withdrawal bleeding, then-after three times daily. When endometrial thickness reaches 7 mm or more, the dose of E2 will be reduced to 4 mg/ day. Women will start using vaginal micronized P4 100 mg three times daily starting from 8PM. After 48 hours of starting the vaginal P4, oral Dydrogesterone 10 mg three times daily will commence. Receives: Drug: Letrozole 2.5mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
livebirth rate per embryo transfer
A birth after 24 weeks gestation with a baby showing signs of life.
Measured: 9 months
Secondary outcomes (2)
miscarriage rate per embryo transfer
loss of pregnancy before 24 weeks gestation
Measured: 6 months
ongoing pregnancy per embryo transfer
ongoing viable pregnancy (by ultrasound examination at 12 weeks' gestation)
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2021
- Study start1 Aug 2023 (estimated)
- Primary completion1 Feb 2024 (estimated)
- Study completion1 Apr 2024 (estimated)
Why it stopped: unexpected slow recruitment and change of center frozen embryo transfer protocol
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Frozen Embryo TransferStudies 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
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dubai Fertility Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Elkalyoubi, Dubai Fertility Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05168865
- Sponsor's protocol ID
- DSREC-09/2020_16
- Status last verified
- Feb 2024
- First submitted
- 10 Dec 2021
- Last updated
- 20 Feb 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Letrozole Versus Hormonal Preparation in Frozen Cycles of PCOS Patients. Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT05168865
- Acronym / sponsor ID
- DSREC-09/2020_16
- Conditions
- Frozen Embryo Transfer, Polycystic Ovarian Disease, Letrozole, Hormone Replacement Therapy, Live Birth, Miscarriage
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: unexpected slow recruitment and change of center frozen embryo transfer protocol
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Dubai Fertility CenterUniversity, hospital or other
- Study start
- 1 Aug 2023 (estimated)
- Primary completion
- 1 Feb 2024 (estimated)
- Study completion
- 1 Apr 2024 (estimated)
- First posted
- 23 Dec 2021 (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.
One of the indications of freezing is to reduce the risk of ovarian hyperstimulation syndrome particularly in polycystic ovarian disease (PCOS) women. Very few RCTs addressed the issue of optimizing the endometrium for a frozen cycle. Interestingly, Letrozole for ovarian stimulation showed significantly better reproductive outcome when compared with hormone replacement therapy (HRT) cycle. In addition, HRT cycle has been associated with higher miscarriage rate when compared with natural cycle frozen embryo transfer. Nevertheless, there is not yet a well-designed prospective randomized study comparing letrozole and HRT in PCOS women undergoing frozen embryo transfer.
Detailed description
Freezing oocytes and embryos has become an integral part of the daily IVF practice. One of the indications of freezing is to reduce the risk of ovarian hyperstimulation syndrome particularly in polycystic ovarian disease (PCOS) women.
Very few randomized control trials addressed the issue of optimizing the endometrium for a frozen cycle. As PCOS women do not regularly ovulate, most of their frozen cycles are conducted after hormonal replacement therapy (HRT) preparation of the endometrium or after ovulation induction. In HRT cycle the endometrium is prepared using exogenous estradiol and progesterone. While HRT cycles requires less monitoring and easy scheduling, it is costly, associated with increased risk of thrombosis and women must continue using the exogenous hormones up to 10 to 12 weeks of gestation.
Interestingly, Letrozole for ovarian stimulation showed significantly better reproductive outcome when compared with HRT cycles. In agreement with the previous Chinese study, a retrospective Japanese ART registry data that included 110 722 frozen cycles confirmed the superiority of letrozole. Nevertheless, there is not yet a well-designed prospective randomized study.
In addition, HRT cycle has been associated with higher miscarriage rate when compared with natural cycle frozen embryo transfer. HRT is usually used in patients with PCOS. A retrospective study including 2664 PCOS patients showed significant decrease in the pregnancy loss when letrozole was used when compared with HRT in frozen cycles.
Investigators thought of comparing letrozole and HRT in women with PCOS who are undergoing frozen cycles in PCOS women. Live birth and miscarriage rates will be the primary outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PCOS women will receive letrozole ovarian stimulation. | Experimental | Drug: Letrozole 2.5mgPolycystic ovarian disease (PCOS) women undergoing frozen embryo transfer (FER) will use Letrozole 5 mg starting on day 3 of spontaneous menstrual period or after progesterone withdrawal bleeding for five consecutive days. |
| PCOS women will receive Estradiol and Progesterone (hormonal endometrial preparation). | Active comparator | Drug: Letrozole 2.5mgPCOS women will use daily Cetorelix acetate 0.25 mg injections for 5 days from day 1-3 of the menstrual follow or after progesterone (P4) withdrawal bleeding. They will commence daily oral Estradiol Valerate (E2) 2 mg twice daily for 5 days starting from day 3 of the menstrual flow or after P4 withdrawal bleeding, then-after three times daily. When endometrial thickness reaches 7 mm or more, the dose of E2 will be reduced to 4 mg/ day. Women will start using vaginal micronized P4 100 mg three times daily starting from 8PM. After 48 hours of starting the vaginal P4, oral Dydrogesterone 10 mg three times daily will commence. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Women with PCOS diagnosed with Rotterdam criteria.
- Age between 20 to 40-year-old
- Undergoing frozen oocytes intracytoplasmic sperm injection transfer or frozen embryo transfer
- Willingly accept to participate in the study
Key exclusion criteria (13 listed)
- Women > 40 years old or younger than 20.
- Uterine pathology that decreases the chance of pregnancy or increases risk of miscarriage such as
- Presence of Hydrosalpinx
- Not willing or able to sign the consent form.
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 |
|---|---|---|
| Letrozole 2.5mgAlso: estradiol and progesteroneLetrozole 5 mg starting on day 3 of spontaneous menstrual period or after progesterone withdrawal bleeding for five consecutive days. | Drug | PCOS women will receive Estradiol and Progesterone (hormonal endometrial preparation)., PCOS women will receive letrozole ovarian stimulation. |
Primary outcome
livebirth rate per embryo transfer
Time frame: 9 months
A birth after 24 weeks gestation with a baby showing signs of life.
2 secondary outcomes
miscarriage rate per embryo transfer
Time frame: 6 months
ongoing pregnancy per embryo transfer
Time frame: 3 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
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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 Phase 4 study testing Letrozole 2.5mg in people with Frozen Embryo Transfer and Polycystic Ovarian Disease, run by Dubai Fertility Center.
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 13 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: withdrawn, as of the sponsor's last update on 20 Feb 2024. 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.
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 was withdrawn before enrolling participants, so there are no results.
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?
livebirth rate per embryo transfer (time frame: 9 months). 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 20 Feb 2024.