Effect of Timing of Oocyte Denudation Before ICSI in an Oocyte Donation Model

Effect of Timing of Oocyte Denudation Before ICSI and Its Results in an Oocyte Donation Model: a Cluster Randomized Controlled Clinical Trial

Analyze the effect of preincubation time of oocyte on the results of ICSI in a oocyte donation model.

Study Overview

• Status: Completed
• Conditions: Fertility
• Intervention / Treatment: Procedure: timing for oocyte denudation and Intracytoplasmatic Sperm injection

Detailed Description

There is an intense communication inside the follicular structure. Bidirectional information between the oocyte and the granulosa cells is needed for a normal follicular development and oocyte competence.

There are conflicting results on the effect of pre-incubation time in ICSI.

It is not clear the proper time to denudate the oocyte from the somatic cells prior to ICSI, and some authors describe a negative impact of the premature cummulus removal on the ICSI results.

The aim of this study is to investigate wheter a preincubation time between oocyte retireval and injection has any effect on the ICSI ( intracytoplasmatic sperm injection) results .

• Study Type: Interventional
• Enrollment (Actual): 375
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad de buenos Aires, Buenos Aires, Argentina, C1199ABB
      • Hospital Italiano de Buenos Aires

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 32 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Oocytes retrieved from healthy donors, younger than 32 years old , with proven maternity(preference), who meet the admission criteria of ovodonation program:
• The oocytes included will be the product of antagonist stimulation protocol and with Gnrh agonists trigger. (see annex)
• Healthy women under 50 years of age , who meet the criteria as receptors into the ovodonation program.
• Oocytes retrieved after 36.5 h + -1 h of administration of triptorelin acetate.
• Only mature oocytes, in stage MII, will be included and injected.
• Use of fresh or thawed semen for the ICSI.

Exclusion Criteria:

• Cases of severe male factor such as azoospermia or severe oligo-astheno-teratospermia( alone or combinated)
• Sperm samples from surgical procedures (biopsy / testicular or epididymal puncture)
• Donors with a polycystic ovarian profile, according to The Androgen Excess and PCOS Society (AES), 2006.
• Thawed donated oocytes
• Oocytes from patients who have previously donated within a period of less than three months.
• Donors whith poor response (oocyte retrieved less than < 4 oocytes).
• Suspicion or signs of Endometriosis in donor patient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immediately oocyte denudation; After the retrieval , sybling oocytes were assigned to one o more recipient and then ,the oocytes were randomized in two arms . The first arm is the immediately denudation and immediately ICSI of the oocytes, and in the second arm the oocyte are denuded and injected after 4 hours from the pick up .	Procedure: timing for oocyte denudation and Intracytoplasmatic Sperm injection; Donated oocytes were randomly allocated to two groups concerning the time of cumulus corona removal. The first group: After oocyte retrieval, cumulus cells were immediately removed and then ICSI was performed; in the second group, the oocyte-cumulus complexes were incubated for 4 hours. Afterwards, the granulosa cells were removedand ICSI was immediately performed.; Other Names: cumulus corona removed; granulosa cells removed
Experimental: Delayed oocyte denudation; After the retrieval , sybling oocytes were assigned to one o more recipient and then ,the oocytes were randomized in two arms . In this arm, the oocyte are denuded and injected after 4 hours from the pick up .	Procedure: timing for oocyte denudation and Intracytoplasmatic Sperm injection; Donated oocytes were randomly allocated to two groups concerning the time of cumulus corona removal. The first group: After oocyte retrieval, cumulus cells were immediately removed and then ICSI was performed; in the second group, the oocyte-cumulus complexes were incubated for 4 hours. Afterwards, the granulosa cells were removedand ICSI was immediately performed.; Other Names: cumulus corona removed; granulosa cells removed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of M2 oocytes at injection	Asessment of the number of M2 oocytes was made after the oocyte denudation and ICSI	four hours after oocyte retrieval
Number of normal fertilized oocytes after ICSI	Asessment of the normal fertilization rate was made 24 hours after the intervention.	24 hours
Number of cleaving embryos	The embryo cleavage was evaluated after 48 hours and 72 hours after the ICSI was performed.	72 hours
Number of TOP embryos	The embryos were morfologically classified into 4 categories . It considered TOP embryos those correctly fertilized at day 1, and with regular 6 to 8 cells at day 2 with less than 20% fragmentation and without multinuclear blastomeres.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rate	The implantation rate was the ratio between the number of gestacional sacs and the number of transferred embryos.	14 days after embryo trasfer
Clinical pregnancy rate	Clinical pregnancy is confirmed by ultrasonography ,when one or more gestational sacs with heart activity are seen.	6 to 7 week

Collaborators and Investigators

• Sponsor: Hospital Italiano de Buenos Aires
• Investigators: Principal Investigator: Romina I Pesce, MD, Hospital Italiano de Buenos Aires

Publications and helpful links

General Publications

• Harrison KL, Wilson LM, Breen TM, Pope AK, Cummins JM, Hennessey JF. Fertilization of human oocytes in relation to varying delay before insemination. Fertil Steril. 1988 Aug;50(2):294-7. doi: 10.1016/s0015-0282(16)60076-6.
• Jacobs M, Stolwijk AM, Wetzels AM. The effect of insemination/injection time on the results of IVF and ICSI. Hum Reprod. 2001 Aug;16(8):1708-13. doi: 10.1093/humrep/16.8.1708.
• Rienzi L, Ubaldi F, Anniballo R, Cerulo G, Greco E. Preincubation of human oocytes may improve fertilization and embryo quality after intracytoplasmic sperm injection. Hum Reprod. 1998 Apr;13(4):1014-9. doi: 10.1093/humrep/13.4.1014.
• Van de Velde H, De Vos A, Joris H, Nagy ZP, Van Steirteghem AC. Effect of timing of oocyte denudation and micro-injection on survival, fertilization and embryo quality after intracytoplasmic sperm injection. Hum Reprod. 1998 Nov;13(11):3160-4. doi: 10.1093/humrep/13.11.3160.
• Yanagida K, Yazawa H, Katayose H, Suzuki K, Hoshi K, Sato A. Influence of oocyte preincubation time on fertilization after intracytoplasmic sperm injection. Hum Reprod. 1998 Aug;13(8):2223-6. doi: 10.1093/humrep/13.8.2223.
• Ho JY, Chen MJ, Yi YC, Guu HF, Ho ES. The effect of preincubation period of oocytes on nuclear maturity, fertilization rate, embryo quality, and pregnancy outcome in IVF and ICSI. J Assist Reprod Genet. 2003 Sep;20(9):358-64. doi: 10.1023/a:1025476910771.
• Hassan HA. Cumulus cell contribution to cytoplasmic maturation and oocyte developmental competence in vitro. J Assist Reprod Genet. 2001 Oct;18(10):539-43. doi: 10.1023/a:1011901923261.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: September 27, 2016
• First Submitted That Met QC Criteria: April 17, 2017
• First Posted (Actual): April 20, 2017

Study Record Updates

• Last Update Posted (Actual): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 27, 2020
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: oocyte donation; oocyte denudation; preincubation; icsi
• Other Study ID Numbers: 2500

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No