Female InfertilityPhase 4NCT05197374
Effect of Estradiol Pretreatment on Antagonist ICSI Cycles
A Phase 4 study testing Estradiol Valerate 4mg in people with Female Infertility, run by Alexandria University at 1 site in Egypt.
Trial summary
Depended on the hypothesis that growth asynchrony of antral follicles is a consequence of the gradual follicle stimulating hormone (FSH) elevation that occurs during the late luteal phase, the aim of this work is to study the effect of estradiol pretreatment on follicular synchronization and intracytoplasmic sperm… Read more about this study
- Who is it for?
- Ages 20 to 37 years, women only
- Conditions the study is for
- Female Infertility
- What is being tested?
- Estradiol Valerate 4mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jun 2020to 15 Nov 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 37 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women age 20-37 years.
- Anti-mullerian (AMH) level greater than 1.2 ng/ml.
- Body mass index between 18 and 29 kg/m2.
- Undergoing a first or second ICSI cycles.
Who cannot join
- Endometriosis.
- Uterine disorders such as fibroids and uterine anomalies.
- Antral follicular counts (AFC) less than 10.
- Azoospermic males.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Studying The Effect of Estradiol Pretreatment on Follicular Synchronization and Intracytoplasmic Sperm Injection (ICSI) Outcome in Antagonist Cycles
Depended on the hypothesis that growth asynchrony of antral follicles is a consequence of the gradual follicle stimulating hormone (FSH) elevation that occurs during the late luteal phase, the aim of this work is to study the effect of estradiol pretreatment on follicular synchronization and intracytoplasmic sperm injection (ICSI) outcome in antagonist cycles
Read the detailed description
Gonadotropin-releasing hormone antagonist (GnRH-ant) cycles are characterized by higher patient acceptability with more attention being directed to the potential effect of steroid pretreatment to program antagonist protocol cycles, as marked size discrepancies of growing follicles reflect incoordinated maturation of follicular-oocyte complexes and complicates clinical criteria for human chorionic gonadotropin (hCG) administration. This phenomenon is associated with fewer mature oocytes and resulting embryos, which limits sufficient embryo selection for embryo transfer. Indeed, the large number of available embryos represented an important prognostic factor of invitro-fertilization (IVF) outcome, particularly in poor prognosis patients, possibly by increasing the probability that at least one good-quality embryo will be selected for embryo transfer. During COH, a better understanding of follicular development has resulted in the improvement of strategies for ovarian stimulation. This approach represents a potential and more physiological alternative to GnRH agonist or oral contraceptive pills pre-treatment in a trial to synchronize multi-follicular development and improve controlled ovarian hyperstimulation (COH) results. The present study is a randomized controlled trial that investigated whether E2 pre-treatment during the luteal phase affects developmental characteristics of growing follicles during COH. It depended on the hypothesis that growth asynchrony of antral follicles is a consequence of the gradual FSH elevation that occurs during the late luteal phase, thus testing for detection of the effect of luteal estradiol on follicular synchronization and its effect on ICSI outcome.
- Conditions
- Female Infertility
- Being tested
- Estradiol Valerate 4mg
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol Valerate 4mgDrug
Also called Progynova
Estradiol valerate 2 mg (two tablet once daily) started 5 days before expected menses (or 7 days after ovulation of previous cycle). After start of menses, estradiol pretreatment was stopped and controlled ovarian stimulation started.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Cases who received estradiol pretreatment then underwent ICSI. Receives: Drug: Estradiol Valerate 4mg |
| group 2 | No intervention | Cases who underwent ICSI directly without receiving any pretreatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days of stimulation.
number of days from the start of controlled ovarian stimulation on day 2 of menses until the day of hCG administration until day of hCG administration
Measured: 7-16 days after start of controlled ovarian stimulation.
Total number of gonadotropin ampoules used.
number of gonadotropin ampules used from the start of controlled ovarian stimulation on day 2 of menses until the day of hCG administration
Measured: 7-16 days after start of controlled ovarian stimulation.
Total number of follicles by U/S on day of hCG.
number of follicles by ultrasound scan on day of hCG administration
Measured: 7-16 days after start of controlled ovarian stimulation.
Serum estradiol and progesterone level on day of hCG .
serum level of estradiol pg/dl and progesterone ng/dl on day of hCG administration
Measured: 7-16 days after start of controlled ovarian stimulation.
Endometrial thickness on day of hCG.
thickness of endometrium in mm on day of hCG
Measured: 7-16 days after start of controlled ovarian stimulation.
Number of mature oocytes
number of metaphase II oocytes after denudation
Measured: 36 hours after oocyte retrieval.
Number of good quality embryos.
number of grade 1 and grade 2 day 3 embryos
Measured: 3 days after oocyte retrieval.
Secondary outcomes (2)
Pregnancy rate
the number of positive pregnancies (defined as serum B-hCG more than 5 miu/ml measured 14 days after embryo transfer) divided by the number of embryo transfer procedures.
Measured: 14 days after embryo transfer
Clinical pregnancy rate
The number of clinical pregnancies (defined as the presence of a gestational sac with positive heart beat detected by transvaginal ultrasound scan 2 weeks after positive pregnancy test) divided by the number of embryo transfer procedures
Measured: 2 weeks after positive pregnancy test
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2022
- Study start1 Jun 2020
- Primary completion20 Feb 2021
- Study completion15 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Female InfertilityStudies of the same condition, open and under way.
- More trials run by Alexandria 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexandria University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sherif Hebisha, phD, Principal investigator, Alexandria University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05197374
- Sponsor's protocol ID
- 0106351
- Status last verified
- Jan 2022
- First submitted
- 5 Jan 2022
- Last updated
- 3 Feb 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Devreker F, Pogonici E, De Maertelaer V, Revelard P, Van den Bergh M, Englert Y. Selection of good embryos for transfer depends on embryo cohort size: implications for the 'mild ovarian stimulation' debate. Hum Reprod. 1999 Dec;14(12):3002-8. doi: 10.1093/humrep/14.12.3002.
PubMed 10601087Opsahl MS, Blauer KL, Black SH, Lincoln SR, Thorsell L, Sherins RJ. The number of embryos available for transfer predicts successful pregnancy outcome in women over 39 years with normal ovarian hormonal reserve testing. J Assist Reprod Genet. 2001 Oct;18(10):551-6. doi: 10.1023/a:1011906024170.
PubMed 11699127Lee H, Choi HJ, Yang KM, Kim MJ, Cha SH, Yi HJ. Efficacy of luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist priming protocol in poor responders undergoing in vitro fertilization. Obstet Gynecol Sci. 2018 Jan;61(1):102-110. doi: 10.5468/ogs.2018.61.1.102. Epub 2017 Dec 19.
PubMed 29372156Cedrin-Durnerin I, Guivarc'h-Leveque A, Hugues JN; Groupe d'Etude en Medecine et Endocrinologie de la Reproduction. Pretreatment with estrogen does not affect IVF-ICSI cycle outcome compared with no pretreatment in GnRH antagonist protocol: a prospective randomized trial. Fertil Steril. 2012 Jun;97(6):1359-64.e1. doi: 10.1016/j.fertnstert.2012.02.028. Epub 2012 Mar 28.
PubMed 22464760Sefrioui O, Madkour A, Kaarouch I, Louanjli N. Luteal estradiol pretreatment of poor and normal responders during GnRH antagonist protocol. Gynecol Endocrinol. 2019 Dec;35(12):1067-1071. doi: 10.1080/09513590.2019.1622086. Epub 2019 May 29.
PubMed 31142165
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studying The Effect of Estradiol Pretreatment on Follicular Synchronization and Intracytoplasmic Sperm Injection (ICSI) Outcome in Antagonist Cycles
- ClinicalTrials.gov ID
- NCT05197374
- Acronym / sponsor ID
- 0106351
- Conditions
- Female Infertility
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Alexandria UniversityUniversity, hospital or other
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 20 Feb 2021 (actual)
- Study completion
- 15 Nov 2021 (actual)
- First posted
- 19 Jan 2022 (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.
Depended on the hypothesis that growth asynchrony of antral follicles is a consequence of the gradual follicle stimulating hormone (FSH) elevation that occurs during the late luteal phase, the aim of this work is to study the effect of estradiol pretreatment on follicular synchronization and intracytoplasmic sperm injection (ICSI) outcome in antagonist cycles
Detailed description
Gonadotropin-releasing hormone antagonist (GnRH-ant) cycles are characterized by higher patient acceptability with more attention being directed to the potential effect of steroid pretreatment to program antagonist protocol cycles, as marked size discrepancies of growing follicles reflect incoordinated maturation of follicular-oocyte complexes and complicates clinical criteria for human chorionic gonadotropin (hCG) administration. This phenomenon is associated with fewer mature oocytes and resulting embryos, which limits sufficient embryo selection for embryo transfer. Indeed, the large number of available embryos represented an important prognostic factor of invitro-fertilization (IVF) outcome, particularly in poor prognosis patients, possibly by increasing the probability that at least one good-quality embryo will be selected for embryo transfer. During COH, a better understanding of follicular development has resulted in the improvement of strategies for ovarian stimulation. This approach represents a potential and more physiological alternative to GnRH agonist or oral contraceptive pills pre-treatment in a trial to synchronize multi-follicular development and improve controlled ovarian hyperstimulation (COH) results. The present study is a randomized controlled trial that investigated whether E2 pre-treatment during the luteal phase affects developmental characteristics of growing follicles during COH. It depended on the hypothesis that growth asynchrony of antral follicles is a consequence of the gradual FSH elevation that occurs during the late luteal phase, thus testing for detection of the effect of luteal estradiol on follicular synchronization and its effect on ICSI outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Estradiol Valerate 4mgCases who received estradiol pretreatment then underwent ICSI. |
| group 2 | No intervention | –Cases who underwent ICSI directly without receiving any pretreatment |
Who may qualify
- Ages
- 20 to 37 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Women age 20-37 years.
- Anti-mullerian (AMH) level greater than 1.2 ng/ml.
- Body mass index between 18 and 29 kg/m2.
- Undergoing a first or second ICSI cycles.
Key exclusion criteria (4 listed)
- Endometriosis.
- Uterine disorders such as fibroids and uterine anomalies.
- Antral follicular counts (AFC) less than 10.
- Azoospermic males.
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 Valerate 4mgAlso: ProgynovaEstradiol valerate 2 mg (two tablet once daily) started 5 days before expected menses (or 7 days after ovulation of previous cycle). After start of menses, estradiol pretreatment was stopped and controlled ovarian stimulation started. | Drug | Group 1 |
Primary outcome
Days of stimulation.
Time frame: 7-16 days after start of controlled ovarian stimulation.
number of days from the start of controlled ovarian stimulation on day 2 of menses until the day of hCG administration until day of hCG administration
Total number of gonadotropin ampoules used.
Time frame: 7-16 days after start of controlled ovarian stimulation.
number of gonadotropin ampules used from the start of controlled ovarian stimulation on day 2 of menses until the day of hCG administration
Total number of follicles by U/S on day of hCG.
Time frame: 7-16 days after start of controlled ovarian stimulation.
number of follicles by ultrasound scan on day of hCG administration
Serum estradiol and progesterone level on day of hCG .
Time frame: 7-16 days after start of controlled ovarian stimulation.
serum level of estradiol pg/dl and progesterone ng/dl on day of hCG administration
Endometrial thickness on day of hCG.
Time frame: 7-16 days after start of controlled ovarian stimulation.
thickness of endometrium in mm on day of hCG
Number of mature oocytes
Time frame: 36 hours after oocyte retrieval.
number of metaphase II oocytes after denudation
Number of good quality embryos.
Time frame: 3 days after oocyte retrieval.
number of grade 1 and grade 2 day 3 embryos
2 secondary outcomes
Pregnancy rate
Time frame: 14 days after embryo transfer
Clinical pregnancy rate
Time frame: 2 weeks after positive pregnancy test
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 3 Feb 2022.
- Background: PubMed 10601087Devreker F, Pogonici E, De Maertelaer V, Revelard P, Van den Bergh M, Englert Y. Selection of good embryos for transfer depends on embryo cohort size: implications for the 'mild ovarian stimulation' debate. Hum Reprod. 1999 Dec;14(12):3002-8. doi: 10.1093/humrep/14.12.3002.
- Background: PubMed 11699127Opsahl MS, Blauer KL, Black SH, Lincoln SR, Thorsell L, Sherins RJ. The number of embryos available for transfer predicts successful pregnancy outcome in women over 39 years with normal ovarian hormonal reserve testing. J Assist Reprod Genet. 2001 Oct;18(10):551-6. doi: 10.1023/a:1011906024170.
- Background: PubMed 29372156Lee H, Choi HJ, Yang KM, Kim MJ, Cha SH, Yi HJ. Efficacy of luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist priming protocol in poor responders undergoing in vitro fertilization. Obstet Gynecol Sci. 2018 Jan;61(1):102-110. doi: 10.5468/ogs.2018.61.1.102. Epub 2017 Dec 19.
- Background: PubMed 22464760Cedrin-Durnerin I, Guivarc'h-Leveque A, Hugues JN; Groupe d'Etude en Medecine et Endocrinologie de la Reproduction. Pretreatment with estrogen does not affect IVF-ICSI cycle outcome compared with no pretreatment in GnRH antagonist protocol: a prospective randomized trial. Fertil Steril. 2012 Jun;97(6):1359-64.e1. doi: 10.1016/j.fertnstert.2012.02.028. Epub 2012 Mar 28.
- Background: PubMed 31142165Sefrioui O, Madkour A, Kaarouch I, Louanjli N. Luteal estradiol pretreatment of poor and normal responders during GnRH antagonist protocol. Gynecol Endocrinol. 2019 Dec;35(12):1067-1071. doi: 10.1080/09513590.2019.1622086. Epub 2019 May 29.
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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.
Sherif Hebisha, phD principal investigator
Alexandria University
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 Estradiol Valerate 4mg in people with Female Infertility, run by Alexandria 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 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 3 Feb 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 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. 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?
Days of stimulation. (time frame: 7-16 days after start of controlled ovarian stimulation.). The study lists 7 primary outcomes in all. 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 NCT05197374, which also lists 5 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 3 Feb 2022.