Co-incubation of Oocytes With Sperm: Defining the Optimal Incubation Time
Primary Purpose
Infertility
Status
Recruiting
Phase
Not Applicable
Locations
United Arab Emirates
Study Type
Interventional
Intervention
2h exposure to sperm for IVF
overnight exposure to sperm for IVF
Sponsored by
About this trial
This is an interventional treatment trial for Infertility
Eligibility Criteria
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
- Globozoospermia
- PCO according to the Rotterdam criteria
- Progesterone >1.5 ng/ml on the day of trigger
Sites / Locations
- ART Fertility ClinicsRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
IVF: 2h exposure
IVF: overnight exposure
Arm Description
Half of a patients' oocytes will be subjected to 2h exposure to sperm
Half of a patients' oocytes will be subjected to overnight incubation with sperm (=usual practice).
Outcomes
Primary Outcome Measures
Normal fertilization rate
presence of two pronuclei per inseminated oocyte
Secondary Outcome Measures
Number of COCs assigned to each group
number of oocytes, per patient, assigned to each exposure group
Maturation rate
number of mature oocytes obtained in each arm
Fertilization
Number of abnormally fertilized oocytes and failed fertilization
Total fertilization failure
Number of cycles with complete fertilization failure (in one arm or in both arms)
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
Embryo quality on day 5
defined by a modified model of Gardner and Schoolcraft,1999
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)
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)
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
Day of trophectoderm biopsy
Day at which the blastocyst reaches sufficient expansion to perform biopsy of trophectoderm cells
Euploid rate
Number of genetically normal embryos per total number of blastocysts biopsied, stratified per day of biopsy
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
Pregnancy outcome
dichotomous variable defined by the presence of βhCG test of > 15IU 12-15 days after embryo transfer
Biochemical pregnancy
dichotomous variable defined as a pregnancy in which the hCG levels start do decrease after 1 week
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
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.
Full Information
NCT ID
NCT04627545
First Posted
November 3, 2020
Last Updated
March 23, 2023
Sponsor
ART Fertility Clinics LLC
1. Study Identification
Unique Protocol Identification Number
NCT04627545
Brief Title
Co-incubation of Oocytes With Sperm: Defining the Optimal Incubation Time
Official Title
Co-incubation of Oocytes With Sperm: Defining the Optimal Incubation Time
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 3, 2020 (Actual)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ART Fertility Clinics LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Oocytes of one patient will be evenly and randomly distributed between two timings of exposure to sperm: 2h exposure versus overnight exposure (16-20h)
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IVF: 2h exposure
Arm Type
Experimental
Arm Description
Half of a patients' oocytes will be subjected to 2h exposure to sperm
Arm Title
IVF: overnight exposure
Arm Type
Active Comparator
Arm Description
Half of a patients' oocytes will be subjected to overnight incubation with sperm (=usual practice).
Intervention Type
Other
Intervention Name(s)
2h exposure to sperm for IVF
Other Intervention Name(s)
short exposure
Intervention Description
Oocytes will only be briefly (2h) exposed to progressive motile sperm for insemination
Intervention Type
Other
Intervention Name(s)
overnight exposure to sperm for IVF
Other Intervention Name(s)
long exposure
Intervention Description
Oocytes will be exposed for a longer duration (overnight, 16-20h) to progressive motile sperm for insemination
Primary Outcome Measure Information:
Title
Normal fertilization rate
Description
presence of two pronuclei per inseminated oocyte
Time Frame
2 days
Secondary Outcome Measure Information:
Title
Number of COCs assigned to each group
Description
number of oocytes, per patient, assigned to each exposure group
Time Frame
2 days
Title
Maturation rate
Description
number of mature oocytes obtained in each arm
Time Frame
2 days
Title
Fertilization
Description
Number of abnormally fertilized oocytes and failed fertilization
Time Frame
3 days
Title
Total fertilization failure
Description
Number of cycles with complete fertilization failure (in one arm or in both arms)
Time Frame
3 days
Title
Embryo quality on day 3
Description
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
Time Frame
5 days
Title
Embryo quality on day 5
Description
defined by a modified model of Gardner and Schoolcraft,1999
Time Frame
8 days
Title
blastulation rate I
Description
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)
Time Frame
8 days
Title
blastulation rate II
Description
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)
Time Frame
8 days
Title
Utilization rate
Description
number of embryos that can be used for the patient (=number of embryos that can be biopsied)/number of oocytes assigned to the group
Time Frame
8 days
Title
Day of trophectoderm biopsy
Description
Day at which the blastocyst reaches sufficient expansion to perform biopsy of trophectoderm cells
Time Frame
8 days
Title
Euploid rate
Description
Number of genetically normal embryos per total number of blastocysts biopsied, stratified per day of biopsy
Time Frame
8 days
Title
Morphokinetic parameters
Description
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
Time Frame
10 days
Title
Pregnancy outcome
Description
dichotomous variable defined by the presence of βhCG test of > 15IU 12-15 days after embryo transfer
Time Frame
60 days
Title
Biochemical pregnancy
Description
dichotomous variable defined as a pregnancy in which the hCG levels start do decrease after 1 week
Time Frame
70 days
Title
Implantation rate
Description
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
Time Frame
80 days
Title
Clinical pregnancy Fetal Heart beat positive
Description
dichotomous variable defined by the ultrasonographic visualization of one or more gestational sacs, with fetal heart beat at 7 weeks.
Time Frame
80 days
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Female patients seeking fertility treatment
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
43 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Globozoospermia
PCO according to the Rotterdam criteria
Progesterone >1.5 ng/ml on the day of trigger
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Neelke De Munck, PhD
Phone
+971501982760
Email
Neelke.demunck@artfertilityclinics.com
First Name & Middle Initial & Last Name or Official Title & Degree
Barbara Lawrenz, PhD, MD
Phone
+971526500757
Email
Barbara.lawrenz@artfertilityclinics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neelke De Munck, PhD
Organizational Affiliation
ART Fertility Clinics
Official's Role
Principal Investigator
Facility Information:
Facility Name
ART Fertility Clinics
City
Abu Dhabi
Country
United Arab Emirates
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neelke De Munck, PhD
Phone
+971501982760
Email
Neelke.demunck@artfertilityclinics.com
First Name & Middle Initial & Last Name & Degree
Barbara Lawrenz, PhD, MD
Phone
+971526500757
Email
Barbara.Lawrenz@artfertilityclinics.com
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Learn more about this trial
Co-incubation of Oocytes With Sperm: Defining the Optimal Incubation Time
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