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Follicular Size and Ploidy Observational Study

Conditions
Age, Parental
Follicle Size
Registration Number
NCT04052035
Lead Sponsor
ART Fertility Clinics LLC
Brief Summary

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

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
24
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Blastocyst ploidy outcome according to the follicular size at the OPU2 months

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:

1. Normal

2. Abnormal

3. Inconclusive/No result

Secondary Outcome Measures
NameTimeMethod
Recovery rate2 months

Number of COCs retrieved/ number of follicles aspirated

Maturate rate2 months

# of MII oocytes/ # of COCs retrieved

Embryo development in time lapse incubators2 months

assessing all specific time points

Miscarriage rate after single euploid embryo transfer2 months

loss of a pregnancy with hcg levels above 1000 IU after transfer

Fertilization potential ( normal and abnormal fertilization)2 months

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.

Embryo development up to blastocyst stage2 months

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).

ectopic pregnancy rate2 months

where the embryo attached outside the uterus

Chromosomal status of biopsied embryos2 months

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.

mtDNA copy number2 months

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.

pregnancy rate after euploid embryo transfer2 months

presence of bhCG above 15IU 12 days after transfer

implantation rate2 months

• 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.

biochemical pregnancy rate2 months

characterized only by the presence of bhCG above 15 IU, no presence of gestational sac

clinical pregnancy rate2 months

hCG \> 15 Iu/ml and ultrasound confirmation of a gestational sac

Trial Locations

Locations (1)

IVI Middle East Fertilty Clinic

🇦🇪

Abu Dhabi, United Arab Emirates

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