InfertilityPhase 3NCT03832894
Oestradiol Supplementation in Luteal Long Agonist Fresh In Vitro Fertilization/Intra Cytoplasmic Sperm Injection ( IVF/ICSI) Cycle .
A Phase 3 study testing Estradiol Valerate in people with Infertility, run by Cairo University at 1 site in Egypt.
Trial summary
Whether oestradiol administration affects the pregnancy rate in long agonist fresh IVF/ICSI cycles. Oestradiol level will be measured the day of HCG trigger to assess whether oestradiol level affects cycle outcome results. Read more about this study
- Who is it for?
- Ages 20 to 38 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility
- What is being tested?
- Estradiol Valerate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Dec 2018to 1 Jan 2020
- Phase
- Phase 3
- 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 38 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age group 20-38 years old.
- Patients Undergoing gonadotropin Releasing Hormone (Gn RH) long agonist protocol, with fresh embryo transfer.
- Day 3 Grade 1 embryos.
- Trilamellar endometrium with ranging endometrial thickness from 8 mm to 14 mm.
Who cannot join
- Karyotypic abnormalities in either partner.
- Patients with uterine abnormalities.
- G3-G4 quality embryos.
- Estradiol level 10,000 or more at time of trigger.
- Cases of egg donation/sperm donation/embryo donation.
- Polycystic ovary syndrome (PCOS )patients.
Show all 10Show fewer
- Poor responders (maternal age >40, Antral follicle counts (AFC )<5, Anti Mullerian Hormone (AMH )<1 and previous trial <5 oocyte retrieved ) (bologna criteria 2011)
- Those with 3 or more implantation failure.
- Endometrial thickness <8 or >14mm.
- Severe male factor.
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
Art Unit/ Obatetrics and Gynecology Department
Cairo, Cair0, 11542
Sherine H Hosny, 01097665573
About this study
Official title: Effects of Adding Oestradiol Supplementation in Luteal Phase in Patients Undergoing in Vitro Fertilization/ Intra Cytoplasmic Sperm Injection (IVF/ICSI ) Long Agonist Fresh Embryo Transfer Cycles
Whether oestradiol administration affects the pregnancy rate in long agonist fresh IVF/ICSI cycles. Oestradiol level will be measured the day of HCG trigger to assess whether oestradiol level affects cycle outcome results.
Read the detailed description
- Background and Rationale: Progesterone is essential for successful implantation and maintenance of early pregnancy . Although the oestrogen is not essential, it is important to maintain the progesterone level during the pregnancy and promote the transformation of the endometrium from the secretory to proliferative phase.
Compromised granulosa cells luteinisation could cause infertility or early miscarriage. In assisted reproductive technologies (ART) cycles, curettage of the granulosa cells during oocyte retrieval is thought to reduce corpora lutea function and thus progesterone production, resulting in a decrease in pregnancy rate.
Therefore, luteal support is routinely performed in ART cycles. Consensus has been reached on the supplementation of progesterone after the day of oocyte retrieval, which was performed in approximately 80% of the cycles and significantly improved clinical outcomes.However, the efficacy of oestradiol supplementation in luteal support remains controversial.
Previous studies have shown that the lower the serum estrogen level was at 4, 7 and 9 days following transplantation, the lower the clinical pregnancy rate. Previous studies showed that in patients with long or short duration ovulation induction, luteal support with oestradiol supplementation led to an increased serum estrogen level and an improved pregnancy rate . It was also found that patients having luteal support with estrogen (4 mg per day) had a significantly higher clinical pregnancy rate (40.6% vs 21.6%) and a significantly lower abortion rate (12.8% vs 38%) than those treated with progesterone alone.
In contrast, other investigators have failed to show any benefit of oestradiol supplementation during the luteal phase and a Cochrane review published in 2015 reported no differences in rates of live birth or ongoing pregnancy between the progesterone group and progesterone add oestrogen group. Hence, it remains unclear whether the addition of estrogen to progesterone for luteal support is associated with higher pregnancy rate and live birth rate.
In this study, the investigators will evaluate outcomes of patients undergoing IVF/ICSI-ET with oestradiol supplementation in addition to progesterone for luteal support. The investigators also report on the efficacy implications of oestradiol supplementation for patients undergoing IVF/ICSI-ET.
- Conditions
- Infertility
- Being tested
- Estradiol Valerate
- Keywords
- IVF, ICSI, oestradiol, long protocol
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol ValerateDrug
Also called Progynova, Progesterone vaginal suppositories
Oestradiol supplementation starting from day of trigger through out the luteal phase
| Study group | Role | What they receive |
|---|---|---|
| Group receiving oestradiol tablets in addition to progesterone | Active comparator | Group A :Will receive 400mg progesterone in the form of vaginal or rectal suppositories in addition to estradiol valerate oral tablets in a dose of 4mg/day(2x2), for luteal phase support. Starting from the day of ovum pickup and for 14 days after embryo transfer.
Group B : Will receive a dose of 400mg progesterone in the form of vaginal or rectal suppositories in addition to 2 placebo oral tablets(similar to estrogen tablets) for luteal phase support, from the day of Ovum pickup and for 14 days after embryo transfer. Receives: Drug: Estradiol Valerate |
| Group not receiving oestradiol tablets. | Placebo comparator | Group B : Will receive a dose of 400mg progesterone in the form of vaginal or rectal suppositories in addition to 2 placebo oral tablets(similar to estrogen tablets) for luteal phase support, from the day of Ovum pickup and for 14 days after embryo transfer Receives: Drug: Estradiol Valerate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Implantation rate
Number of gestational sacs per number of embryos transferred per cycle
Measured: 4 weeks after embryo transfer of each enrolled patient
Secondary outcomes (3)
Chemical pregnancy rate
Quantitative Beta Human Chorionic Gonadotropin (BHCG)
Measured: Two weeks after embryo transfer of each enrolled patient
Clinical pregnancy rate
Intrauterine gestational sac with fetal pole with positive pulsation
Measured: 4 weeks after embryo transfer of each enrolled patient with positive pregnancy test or 6 weeks from IVF cycle beginning in pregnant patients
Ongoing pregnancy rate
12 weeks gestation and more
Measured: 10 weeks after embryo transfer of each enrolled patient or 12 weeks from starting IVF cycle in pregnant patients
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2019
- Study start1 Dec 2018
- Primary completion1 Dec 2019 (estimated)
- Study completion1 Jan 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 2 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, sherine Hosny Mohamed Gad Allah, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03832894
- Sponsor's protocol ID
- MD IVF
- Status last verified
- Feb 2019
- First submitted
- 4 Feb 2019
- Last updated
- 7 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Adding Oestradiol Supplementation in Luteal Phase in Patients Undergoing in Vitro Fertilization/ Intra Cytoplasmic Sperm Injection (IVF/ICSI ) Long Agonist Fresh Embryo Transfer Cycles
- ClinicalTrials.gov ID
- NCT03832894
- Acronym / sponsor ID
- MD IVF
- Conditions
- Infertility
- Keywords
- IVF, ICSI, oestradiol, long protocol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2 participants (estimated)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- 1 Dec 2019 (estimated)
- Study completion
- 1 Jan 2020 (estimated)
- First posted
- 6 Feb 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.
Whether oestradiol administration affects the pregnancy rate in long agonist fresh IVF/ICSI cycles. Oestradiol level will be measured the day of HCG trigger to assess whether oestradiol level affects cycle outcome results.
Detailed description
- Background and Rationale: Progesterone is essential for successful implantation and maintenance of early pregnancy . Although the oestrogen is not essential, it is important to maintain the progesterone level during the pregnancy and promote the transformation of the endometrium from the secretory to proliferative phase.
Compromised granulosa cells luteinisation could cause infertility or early miscarriage. In assisted reproductive technologies (ART) cycles, curettage of the granulosa cells during oocyte retrieval is thought to reduce corpora lutea function and thus progesterone production, resulting in a decrease in pregnancy rate.
Therefore, luteal support is routinely performed in ART cycles. Consensus has been reached on the supplementation of progesterone after the day of oocyte retrieval, which was performed in approximately 80% of the cycles and significantly improved clinical outcomes.However, the efficacy of oestradiol supplementation in luteal support remains controversial.
Previous studies have shown that the lower the serum estrogen level was at 4, 7 and 9 days following transplantation, the lower the clinical pregnancy rate. Previous studies showed that in patients with long or short duration ovulation induction, luteal support with oestradiol supplementation led to an increased serum estrogen level and an improved pregnancy rate . It was also found that patients having luteal support with estrogen (4 mg per day) had a significantly higher clinical pregnancy rate (40.6% vs 21.6%) and a significantly lower abortion rate (12.8% vs 38%) than those treated with progesterone alone.
In contrast, other investigators have failed to show any benefit of oestradiol supplementation during the luteal phase and a Cochrane review published in 2015 reported no differences in rates of live birth or ongoing pregnancy between the progesterone group and progesterone add oestrogen group. Hence, it remains unclear whether the addition of estrogen to progesterone for luteal support is associated with higher pregnancy rate and live birth rate.
In this study, the investigators will evaluate outcomes of patients undergoing IVF/ICSI-ET with oestradiol supplementation in addition to progesterone for luteal support. The investigators also report on the efficacy implications of oestradiol supplementation for patients undergoing IVF/ICSI-ET.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group receiving oestradiol tablets in addition to progesterone | Active comparator | Drug: Estradiol ValerateGroup A :Will receive 400mg progesterone in the form of vaginal or rectal suppositories in addition to estradiol valerate oral tablets in a dose of 4mg/day(2x2), for luteal phase support. Starting from the day of ovum pickup and for 14 days after embryo transfer. Group B : Will receive a dose of 400mg progesterone in the form of vaginal or rectal suppositories in addition to 2 placebo oral tablets(similar to estrogen tablets) for luteal phase support, from the day of Ovum pickup and for 14 days after embryo transfer. |
| Group not receiving oestradiol tablets. | Placebo comparator | Drug: Estradiol ValerateGroup B : Will receive a dose of 400mg progesterone in the form of vaginal or rectal suppositories in addition to 2 placebo oral tablets(similar to estrogen tablets) for luteal phase support, from the day of Ovum pickup and for 14 days after embryo transfer |
Who may qualify
- Ages
- 20 to 38 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age group 20-38 years old.
- Patients Undergoing gonadotropin Releasing Hormone (Gn RH) long agonist protocol, with fresh embryo transfer.
- Day 3 Grade 1 embryos.
- Trilamellar endometrium with ranging endometrial thickness from 8 mm to 14 mm.
Key exclusion criteria (10 listed)
- Karyotypic abnormalities in either partner.
- Patients with uterine abnormalities.
- G3-G4 quality embryos.
- Estradiol level 10,000 or more at time of trigger.
- Cases of egg donation/sperm donation/embryo donation.
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 |
|---|---|---|
| Estradiol ValerateAlso: Progynova, Progesterone vaginal suppositoriesOestradiol supplementation starting from day of trigger through out the luteal phase | Drug | Group not receiving oestradiol tablets., Group receiving oestradiol tablets in addition to progesterone |
Primary outcome
Implantation rate
Time frame: 4 weeks after embryo transfer of each enrolled patient
Number of gestational sacs per number of embryos transferred per cycle
3 secondary outcomes
Chemical pregnancy rate
Time frame: Two weeks after embryo transfer of each enrolled patient
Clinical pregnancy rate
Time frame: 4 weeks after embryo transfer of each enrolled patient with positive pregnancy test or 6 weeks from IVF cycle beginning in pregnant patients
Ongoing pregnancy rate
Time frame: 10 weeks after embryo transfer of each enrolled patient or 12 weeks from starting IVF cycle in pregnant patients
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2019.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Estradiol Valerate in people with Infertility, run by Cairo University at 1 site in Egypt.
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 10 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 7 Feb 2019. 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 Egypt. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 SHERINE HOSNY (01097665573, sherinehosny@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Implantation rate (time frame: 4 weeks after embryo transfer of each enrolled patient). 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 7 Feb 2019.