Follicular Size and Ploidy Observational Study

Follicular Size and Ploidy: an Observational Study

The primary objective is to determine which follicle sizes generate the highest rate of euploid blastocysts.

Study Overview

• Status: Active, not recruiting
• Conditions: Age, Parental; Follicle Size
• Intervention / Treatment: Procedure: measuring the size of the follicle at time of follicle aspiration

Detailed Description

The primary objective is to determine which follicle sizes generate the highest rate of euploid blastocysts.

Secondary objectives to be analysed between the different follicle sizes:

• The number of cumulus oocyte complexes (COCs) retrieved per aspirated follicle size
• The number of mature oocytes per COC retrieved (maturation rate)
• The number of normally fertilized oocytes per number of oocytes injected (fertilization rate)
• Embryo development up to the blastocyst stage
• Chromosomal status of the biopsied blastocysts
• Pregnancy rates after euploid blastocyst transfer
• Miscarriage rate after euploid blastocyst transfer

Most of the studies that looked at the relation between the follicular size and the developmental competence of the corresponding oocyte analysed normal responders with an average age of 35 years and normal BMI levels. However, during the last decades, a clear shift appeared in the patient population that present themselves for a fertility treatment. With many women delaying childbirth, we do not yet know how these advanced maternal age women may benefit from early or late trigger or from different follicular sizes.

Also, the rising prevalence of obesity may impact the follicular growth, which has not been analysed at the individual follicle size before.

For the above described reasons, we believe that the analysis of individual follicles and the developmental competence of the obtained oocyte, may guide us to improve individualized stimulation protocols for different subtypes of infertile patients. To guide us in this individualized process, this initial pilot study will be performed in a population of normal responders and will later be expanded to an infertile population with different characteristics.

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• United Arab Emirates
  • Abu Dhabi, United Arab Emirates
    • IVI Middle East Fertilty Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

The study is eligible to all patients undergoing a fertility treatment with PGT-A analysis at the blastocyst stage

Description

Inclusion Criteria:

Cycles with PGT-A analysis

• ICSI (intracytoplasmic sperm injection) only
• ICSI 40 hours after trigger
• Fresh oocytes
• Ejaculates: fresh or frozen: normozoospermia
• BMI ≤ 35kg/m 2
• Age ≤ 40 years
• AMH ≥ 1.1 ng/ml
• the number of follicles at the day of trigger: max 20 ≥ 11mm
• Stimulation protocol: Antagonist protocol with Menopur and and Dual trigger of (5.000-10.000IU) hCG and (0.2-0.3 mg) Gonapeptyl
• Final oocyte maturation trigger when 2-3 follicles reach size 17mm
• All races
• Embryo development in the Embryoscope with Global Total media

Exclusion Criteria:

• Inability to puncture all follicles from one ovary
• Endometriosis
• Hydrosalpinx
• History of uterine surgery
• History of previous treatment which may impact the ovarian reserve (adnexal surgery,
• chemotherapy, radiation…)
• Time between trigger and pick up deviating from 36 hours
• < 100.000 motile sperm
• Last follicular measurement day deviates more than 24 hours from the trigger day

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blastocyst ploidy outcome according to the follicular size at the OPU	Blastocyst ploidy is determined after biopsy of trophectoderm cells, taken from the blastocyst on day 5, 6 or 7 from development. A biopsy is only possible if an oocyte was retrieved from the follicle that was mature, normally fertilized and developed into a blastocyst of sufficient quality for biopsy). The following outcomes are possible: Normal; Abnormal; Inconclusive/No result	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery rate	Number of COCs retrieved/ number of follicles aspirated	2 months
Maturate rate	# of MII oocytes/ # of COCs retrieved	2 months
Fertilization potential ( normal and abnormal fertilization)	Normal fertilization is assessed by the presence of 2 pronuclei 16-20 hours post insemination. This is normal fertilization. Abnormal fertilization is a deviation from the presence of 2 pronuclei, this can be one or three or more.	2 months
Embryo development up to blastocyst stage	development of an embryo from day 0 to the blastocyst stage includes all developmental stages The embryo will make multiple divisions that will be recorded every day of development. It wll go from 1 cell, to 2 cells, 3 cells etc to be 8 cells on day 3 of development. On day 4, the morula will form and the embryo will start to compact, which is indicated as compacting or compacted. After this stage, we are around day 5 of development, the embryo will start to cavitate, this is the beginning of blastulation. Different stages are observed. Bl1: cavity is less than 50%, bl2: cavity is larger tan 50%, bl3: full blastocyst, bl4; expanded blastocyst, bl5: hatching balstocyst, bl6: hatched blastocyst, bl7: hatching through an artificail opening, bl8: collpased blastocyst. Blastocysts will be scored according to Gardner and Schoolcraft (1999).	2 months
Embryo development in time lapse incubators	assessing all specific time points	2 months
Chromosomal status of biopsied embryos	Blastocysts of sufficient quality will undergo trophectoderm biopsy. These 4-8 cells that are taken from the embryo are genitically tested for their chromosomal copy number. This will give an indication on the genetic status of the embryo. The embryo will be euploid if 23 pairs of intact chromosomes are present. If not, they are aneuploid.	2 months
mtDNA copy number	Mitoscore values is the ratio of the mitochondrial DNA over the nuclear DNA. This is presented as a value and has been linked to the implantation potential of the embryo. There is no unit.	2 months
Miscarriage rate after single euploid embryo transfer	loss of a pregnancy with hcg levels above 1000 IU after transfer	2 months
pregnancy rate after euploid embryo transfer	presence of bhCG above 15IU 12 days after transfer	2 months
biochemical pregnancy rate	characterized only by the presence of bhCG above 15 IU, no presence of gestational sac	2 months
clinical pregnancy rate	hCG > 15 Iu/ml and ultrasound confirmation of a gestational sac	2 months
implantation rate	• Implantation rate calculated by the number of gestational sacs observed at echographic screening at 6 weeks of pregnancy divided by the number of embryos transferred, multiplied by 100.	2 months
ectopic pregnancy rate	where the embryo attached outside the uterus	2 months

Collaborators and Investigators

• Sponsor: ART Fertility Clinics LLC
• Investigators: Study Chair: Ibrahim Elkhatib, MSc, IVIRMA Middle East Fertility Clinic

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 10, 2020
• Primary Completion (ANTICIPATED): June 30, 2023
• Study Completion (ANTICIPATED): August 30, 2023

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (ACTUAL): August 9, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: follicle size; maturity; euploid
• Other Study ID Numbers: 1905-ABU-061-ND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information regarding the size of follicle and the PGT-A results will be shared through the discussion part.

Further information regarding endocrine profile, fertilization and embryo development will be mentioned in the discussion as well, however, this data might be shared upon request after publication.

Personal information such as Name and contact details will not be mentioned or shared.

• IPD Sharing Time Frame: Undecided
• IPD Sharing Access Criteria: Undecided
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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