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Effect of Estradiol Pretreatment on Antagonist ICSI Cycles

Primary Purpose

Female Infertility

Status
Completed
Phase
Phase 4
Locations
Egypt
Study Type
Interventional
Intervention
Estradiol Valerate 4mg
Sponsored by
Alexandria University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Female Infertility

Eligibility Criteria

20 Years - 37 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Women age 20-37 years.
  2. Anti-mullerian (AMH) level greater than 1.2 ng/ml.
  3. Body mass index between 18 and 29 kg/m2.
  4. Undergoing a first or second ICSI cycles.

Exclusion Criteria:

  1. Endometriosis.
  2. Uterine disorders such as fibroids and uterine anomalies.
  3. Antral follicular counts (AFC) less than 10.
  4. Azoospermic males.

Sites / Locations

  • IVF center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Group 1

group 2

Arm Description

Cases who received estradiol pretreatment then underwent ICSI.

Cases who underwent ICSI directly without receiving any pretreatment

Outcomes

Primary Outcome Measures

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
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
Total number of follicles by U/S on day of hCG.
number of follicles by ultrasound scan on day of hCG administration
Serum estradiol and progesterone level on day of hCG .
serum level of estradiol pg/dl and progesterone ng/dl on day of hCG administration
Endometrial thickness on day of hCG.
thickness of endometrium in mm on day of hCG
Number of mature oocytes
number of metaphase II oocytes after denudation
Number of good quality embryos.
number of grade 1 and grade 2 day 3 embryos

Secondary Outcome Measures

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.
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

Full Information

First Posted
January 5, 2022
Last Updated
January 20, 2022
Sponsor
Alexandria University
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1. Study Identification

Unique Protocol Identification Number
NCT05197374
Brief Title
Effect of Estradiol Pretreatment on Antagonist ICSI Cycles
Official Title
Studying The Effect of Estradiol Pretreatment on Follicular Synchronization and Intracytoplasmic Sperm Injection (ICSI) Outcome in Antagonist Cycles
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
June 1, 2020 (Actual)
Primary Completion Date
February 20, 2021 (Actual)
Study Completion Date
November 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexandria University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Female Infertility

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
114 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
Cases who received estradiol pretreatment then underwent ICSI.
Arm Title
group 2
Arm Type
No Intervention
Arm Description
Cases who underwent ICSI directly without receiving any pretreatment
Intervention Type
Drug
Intervention Name(s)
Estradiol Valerate 4mg
Other Intervention Name(s)
Progynova
Intervention Description
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.
Primary Outcome Measure Information:
Title
Days of stimulation.
Description
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
Time Frame
7-16 days after start of controlled ovarian stimulation.
Title
Total number of gonadotropin ampoules used.
Description
number of gonadotropin ampules used from the start of controlled ovarian stimulation on day 2 of menses until the day of hCG administration
Time Frame
7-16 days after start of controlled ovarian stimulation.
Title
Total number of follicles by U/S on day of hCG.
Description
number of follicles by ultrasound scan on day of hCG administration
Time Frame
7-16 days after start of controlled ovarian stimulation.
Title
Serum estradiol and progesterone level on day of hCG .
Description
serum level of estradiol pg/dl and progesterone ng/dl on day of hCG administration
Time Frame
7-16 days after start of controlled ovarian stimulation.
Title
Endometrial thickness on day of hCG.
Description
thickness of endometrium in mm on day of hCG
Time Frame
7-16 days after start of controlled ovarian stimulation.
Title
Number of mature oocytes
Description
number of metaphase II oocytes after denudation
Time Frame
36 hours after oocyte retrieval.
Title
Number of good quality embryos.
Description
number of grade 1 and grade 2 day 3 embryos
Time Frame
3 days after oocyte retrieval.
Secondary Outcome Measure Information:
Title
Pregnancy rate
Description
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.
Time Frame
14 days after embryo transfer
Title
Clinical pregnancy rate
Description
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
Time Frame
2 weeks after positive pregnancy test

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
37 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: Endometriosis. Uterine disorders such as fibroids and uterine anomalies. Antral follicular counts (AFC) less than 10. Azoospermic males.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sherif Hebisha, phD
Organizational Affiliation
Alexandria University
Official's Role
Principal Investigator
Facility Information:
Facility Name
IVF center
City
Alexandria
Country
Egypt

12. IPD Sharing Statement

Citations:
PubMed Identifier
10601087
Citation
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.
Results Reference
background
PubMed Identifier
11699127
Citation
Opsahl 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.
Results Reference
background
PubMed Identifier
29372156
Citation
Lee 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.
Results Reference
background
PubMed Identifier
22464760
Citation
Cedrin-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.
Results Reference
background
PubMed Identifier
31142165
Citation
Sefrioui 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.
Results Reference
background

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Effect of Estradiol Pretreatment on Antagonist ICSI Cycles

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