Co-incubation of Oocytes With Sperm: Defining the Optimal Incubation Time

The current pilot study aims to evaluate the fertilization rates between sibling oocytes subjected to short incubation (2h) versus overnight incubation (16-20h). As secondary objectives, the abnormal fertilization, embryo development, blastocyst biopsy and euploid rates will be analyzed.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Other: 2h exposure to sperm for IVF; Other: overnight exposure to sperm for IVF

Detailed Description

All patients for whom at least 6 cumulus oocytes complexes (COCs) are assigned to IVF, with normal sperm parameters, are eligible for the study. An electronically generated randomization list will allocate the first half of the oocytes to one arm and the other half of the oocytes to the second arm. In case an odd number of oocytes will be inseminated, one extra oocyte will be allocated to the first arm. In this prospective observational pilot study, the fertilization potential of 40 patients will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Arab Emirates
  • Abu Dhabi, United Arab Emirates
    • ART Fertility Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Sperm parameters

  • Sperm concentration before capacitation: >15 million per ml (WHO) Total motility (PR+NP %): >40 (WHO) Progressive motility (PR %):>32 (WHO)
  • Sperm concentration after capacitation: >0.6 million per ml (not WHO defined) Progressive motility (PR %):>65 (WHO)
• ≥6 COCs assigned to IVF
• BMI ≤35 kg/m2
• Female age 18 to ≤ 43 years
• All ovarian stimulation protocols
• Fresh ejaculates
• Abstinence duration 2-5 days
• Presence or absence of sperm morphology data: as we do not have a diagnostic sperm analysis for all patients, the presence or absence of >4% normal morphology (WHO) will not be taken into account, even with known low (<4%) normal morphology
• Couples requesting Preimplantation Genetic Testing for Aneuploidies
• Arab population

Exclusion Criteria:

• If the volume to be added after IVF is insufficient to perform IVF on all needed oocytes
• Presence of >1 million per ml round cells in the ejaculate
• If a couple's previous cycle was included in the study
• Previous history of fertilization failure or <50% fertilisation
• Globozoospermia
• PCO according to the Rotterdam criteria
• Progesterone >1.5 ng/ml on the day of trigger

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IVF: 2h exposure; Half of a patients' oocytes will be subjected to 2h exposure to sperm	Other: 2h exposure to sperm for IVF; Oocytes will only be briefly (2h) exposed to progressive motile sperm for insemination; Other Names: short exposure
Active Comparator: IVF: overnight exposure; Half of a patients' oocytes will be subjected to overnight incubation with sperm (=usual practice).	Other: overnight exposure to sperm for IVF; Oocytes will be exposed for a longer duration (overnight, 16-20h) to progressive motile sperm for insemination; Other Names: long exposure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normal fertilization rate	presence of two pronuclei per inseminated oocyte	2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of COCs assigned to each group	number of oocytes, per patient, assigned to each exposure group	2 days
Maturation rate	number of mature oocytes obtained in each arm	2 days
Fertilization	Number of abnormally fertilized oocytes and failed fertilization	3 days
Total fertilization failure	Number of cycles with complete fertilization failure (in one arm or in both arms)	3 days
Embryo quality on day 3	defined by the Istanbul consensus (Alpha Scientists, 2011) The number of blastomeres and their division pattern, fragmentation, presence of compaction, vacuoles, granulation and nuclei will divide the embryos into 3 categories: good, fair or poor	5 days
Embryo quality on day 5	defined by a modified model of Gardner and Schoolcraft,1999	8 days
blastulation rate I	number of embryos reaching at least the BL1 stage/ number of oocytes assigned to that group: defined by a 1 (yes, the embryo is blastulating) or 0 (no, the embryo is not blastulating)	8 days
blastulation rate II	number of embryos reaching at least the BL1 stage/ number of mature oocytes in that group: defined by a 1 (yes, the embryo is blastulating) or 0 (no, the embryo is not blastulating)	8 days
Utilization rate	number of embryos that can be used for the patient (=number of embryos that can be biopsied)/number of oocytes assigned to the group	8 days
Day of trophectoderm biopsy	Day at which the blastocyst reaches sufficient expansion to perform biopsy of trophectoderm cells	8 days
Euploid rate	Number of genetically normal embryos per total number of blastocysts biopsied, stratified per day of biopsy	8 days
Morphokinetic parameters	As embryos will be monitored in a time lapse imaging system, morphokinetic parameters will be compared between both exposure arms: o t2: the timing to two cells; t3: the timing to three cells; t4: the timing to four cells; t5: the timing to five cells; t8: the timing to eight cells; SC: starting to compact; M: the timing to morula; SB: starting to blastulate; B: reaching a BL3 according to Gardner and Schoolcraft, 1999; F: reaching a BL4 according to Gardner and Schoolcraft, 1999; cc2: t3-t2; s2: t4-t3	10 days
Pregnancy outcome	dichotomous variable defined by the presence of βhCG test of > 15IU 12-15 days after embryo transfer	60 days
Biochemical pregnancy	dichotomous variable defined as a pregnancy in which the hCG levels start do decrease after 1 week	70 days
Implantation rate	defined by the number of gestational sacs/number of embryos transferred • Clinical pregnancy (yes or no) defined by the ultrasonographic visualization of one or more gestational sacs, including ectopic pregnancies	80 days
Clinical pregnancy Fetal Heart beat positive	dichotomous variable defined by the ultrasonographic visualization of one or more gestational sacs, with fetal heart beat at 7 weeks.	80 days

Collaborators and Investigators

• Sponsor: ART Fertility Clinics LLC
• Investigators: Principal Investigator: Neelke De Munck, PhD, ART Fertility Clinics

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2020
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): July 30, 2023

Study Registration Dates

• First Submitted: November 3, 2020
• First Submitted That Met QC Criteria: November 8, 2020
• First Posted (Actual): November 13, 2020

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 9, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility
• Other Study ID Numbers: 2010-ABU-010-ND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The principal investigator will gather all data for the study and prepare the database for the statistician, who will be blinded for patient information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No