Effect of Estradiol Pretreatment on Antagonist ICSI Cycles

Female Infertility Clinical Trial

Official title:

Studying The Effect of Estradiol Pretreatment on Follicular Synchronization and Intracytoplasmic Sperm Injection (ICSI) Outcome in Antagonist Cycles

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05197374
• Other study ID #: 0106351
• Status: Completed
• Phase: Phase 4
• Start date: June 1, 2020
• Est. completion date: November 15, 2021

Study information

• Verified date: January 2022
• Source: Alexandria University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 injection (ICSI) outcome in antagonist cycles

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: November 15, 2021
• Est. primary completion date: February 20, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 37 Years

Eligibility

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.

Related Conditions & MeSH terms

• Female Infertility
• Infertility
• Infertility, Female

Intervention

Drug:
• Estradiol Valerate 4mg
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.

Locations

Country	Name	City	State
Egypt	IVF center	Alexandria

Sponsors (1)

Lead Sponsor	Collaborator
Alexandria University

Country where clinical trial is conducted

Egypt, 

References & Publications (5)

Cédrin-Durnerin I, Guivarc'h-Levêque A, Hugues JN; Groupe d'Etude en Médecine 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	7-16 days after start of controlled ovarian stimulation.
Primary	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	7-16 days after start of controlled ovarian stimulation.
Primary	Total number of follicles by U/S on day of hCG.	number of follicles by ultrasound scan on day of hCG administration	7-16 days after start of controlled ovarian stimulation.
Primary	Serum estradiol and progesterone level on day of hCG .	serum level of estradiol pg/dl and progesterone ng/dl on day of hCG administration	7-16 days after start of controlled ovarian stimulation.
Primary	Endometrial thickness on day of hCG.	thickness of endometrium in mm on day of hCG	7-16 days after start of controlled ovarian stimulation.
Primary	Number of mature oocytes	number of metaphase II oocytes after denudation	36 hours after oocyte retrieval.
Primary	Number of good quality embryos.	number of grade 1 and grade 2 day 3 embryos	3 days after oocyte retrieval.
Secondary	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.	14 days after embryo transfer
Secondary	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	2 weeks after positive pregnancy test