Effect of Estradiol Pretreatment on Antagonist ICSI Cycles

Overview

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

Full Title of Study: “Studying The Effect of Estradiol Pretreatment on Follicular Synchronization and Intracytoplasmic Sperm Injection (ICSI) Outcome in Antagonist Cycles”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 20, 2021

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.

Interventions

  • 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.

Arms, Groups and Cohorts

  • Experimental: Group 1
    • Cases who received estradiol pretreatment then underwent ICSI.
  • No Intervention: group 2
    • Cases who underwent ICSI directly without receiving any pretreatment

Clinical Trial Outcome Measures

Primary Measures

  • 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

Secondary Measures

  • Pregnancy rate
    • Time Frame: 14 days after embryo transfer
    • 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
    • Time Frame: 2 weeks after positive pregnancy test
    • 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

Participating in This Clinical Trial

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.

Gender Eligibility: Female

Minimum Age: 20 Years

Maximum Age: 37 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Alexandria University
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Sherif Hebisha, phD, Principal Investigator, Alexandria University

References

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.

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.

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.

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.

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.

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