Follicular Size and Ploidy Observational Study

Follicle Size Clinical Trial

Official title:

Follicular Size and Ploidy: an Observational Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04052035
• Other study ID #: 1905-ABU-061-ND
• Status: Active, not recruiting
• Start date: February 10, 2020
• Est. completion date: August 30, 2023

Study information

• Verified date: June 2022
• Source: ART Fertility Clinics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: August 30, 2023
• Est. primary completion date: June 30, 2023
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Age, Parental
• Follicle Size

Intervention

Procedure:
• measuring the size of the follicle at time of follicle aspiration
While for an OPU out of the study the follicles are aspirated without measuring their sizes, now the follicles will be measured before they are aspirated. The measurement of the follicles is a non- invasive measurement: as the OPU is always performed under vaginal echo-guidance, the follicles are visible on the screen connected to the vaginal echo probe. By measuring two dimensions of the follicle, an average follicle diameter is registered for that follicle

Locations

Country	Name	City	State
United Arab Emirates	IVI Middle East Fertilty Clinic	Abu Dhabi

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Recovery rate	Number of COCs retrieved/ number of follicles aspirated	2 months
Secondary	Maturate rate	# of MII oocytes/ # of COCs retrieved	2 months
Secondary	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
Secondary	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
Secondary	Embryo development in time lapse incubators	assessing all specific time points	2 months
Secondary	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
Secondary	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
Secondary	Miscarriage rate after single euploid embryo transfer	loss of a pregnancy with hcg levels above 1000 IU after transfer	2 months
Secondary	pregnancy rate after euploid embryo transfer	presence of bhCG above 15IU 12 days after transfer	2 months
Secondary	biochemical pregnancy rate	characterized only by the presence of bhCG above 15 IU, no presence of gestational sac	2 months
Secondary	clinical pregnancy rate	hCG > 15 Iu/ml and ultrasound confirmation of a gestational sac	2 months
Secondary	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
Secondary	ectopic pregnancy rate	where the embryo attached outside the uterus	2 months