Clinical trial NCT03708991: Effectiveness of PGT-A: IVF Versus ICSI
Official title: Effectiveness of PGT-A by Using IVF Versus ICSI for Non-male Factor Infertility: a Pilot Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Genetic Condition
Keywords: IVF
ICSI
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
First posted: 2018-10-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population is defined by all couples seeking a fertility treatment due to primary or secondary infertility in IVI RMA Abu Dhabi, for non-male factor infertility in combination with a PGT-A request.

Brief summary: The investigators want to investigate if the use of conventional in vitro fertilization (IVF) can generate more euploid embryos as compared to intracytoplasmic sperm injection (ICSI).

To verify this, the investigators will inject half of the oocytes by ICSI and the other half of the oocytes will be inseminated by conventional IVF. The most important aim is to see if IVF is able to generate more euploid embryos.

Detailed description: ICSI is commonly used in pre-implantation genetic testing (PGT) cases to eliminate any risk of sperm DNA contamination. With the switch from cleavage stage biopsy to biopsy of the full (hatching) blastocyst, this potential risk of contamination can be neglected and could allow the use of conventional IVF in PGT cases. Especially in cases of non-male factor infertility, the use of conventional IVF can be applied as a more 'natural' insemination method.

The investigators will perform a pilot study on sibling oocytes including participants with non-male factor infertility and requesting PGT-A (PGT for aneuploidy). If at least 10 cumulus oocyte complexes (COCs) are obtained after oocyte retrieval, half of the oocytes will be subjected to ICSI and the other half to conventional IVF. Preimplantation development is followed by time lapse imaging and blastocysts (day 5-7) fulfilling the biopsy criteria will undergo trophectoderm biopsy to detect the ploidy state and the mitochondrial DNA (mtDNA) copy number.

The main objective is to analyse if the use a more physiological insemination method (IVF) has a beneficial impact on the ploidy state of the blastocyst as compared to ICSI within the same participant. As the embryos will be cultured in a time lapse imaging system, annotations can be made and the differences in maturation rate, fertilization rate and embryo development between both insemination methods can be analysed as secondary outcome parameter. On top of this, the PGT-A outcome will also display the mtDNA copy number which can be compared between IVF and ICSI biopsied sibling blastocyst. Euploid blastocysts will be transferred in subsequent frozen embryo transfer (FET) cycles and give an indication on the clinical outcome between IVF and ICSI.

Eligibility criteria: Inclusion Criteria:

* Sperm parameters Sperm concentration before capacitation: \>15\*106 per ml (WHO) Total motility (PR+NP,%): \>40 (WHO) Progressive motility (PR,%):\>32 (WHO) Sperm concentration after capacitation: \>0.6\*106 per ml (not WHO defined) Progressive motility (PR,%):\>65 (WHO)
* ≥10 COCs after oocyte retrieval
* BMI ≤30 kg/m2
* Female age 18 to ≤ 40 years
* All ovarian stimulation protocols
* Fresh ejaculates
* Presence or absence of sperm morphology data: as the investigators do not have a diagnostic sperm analysis for all participants, the presence or absence of \>4% normal morphology (WHO) will not be taken into account, even with known low (\<4%) normal morphology
* Couples requesting PGT-A
* Arab population

Exclusion Criteria:

* If after denudation (ICSI) only 2 mature oocytes are obtained
* If all time lapse spaces are occupied
* If the volume to be added after IVF is insufficient to perform IVF on all needed oocytes
* Presence of \>1 \*106 per ml round cells in the ejaculate
* If a couple's previous cycle was included in the study

Primary outcomes:
measure: Ploidy state: euploid or aneuploid
timeFrame: 7 days
Secondary outcomes:
measure: mitoscore value: ranges from 10-1500
timeFrame: 1 day
measure: Maturation rate
timeFrame: 1 day
measure: Morphokinetic development
timeFrame: 7 days
measure: Fertilization rate
timeFrame: 1 day
measure: Embryo development up to day 3
timeFrame: 3 days
measure: Blastulation rate
timeFrame: 7 days
measure: Embryo development up to day 5
timeFrame: 7 days
measure: Pregnancy outcome
timeFrame: 3 months
Other outcomes:
measure: sperm concentration
timeFrame: 1 day
measure: sperm motility
timeFrame: 1 day
measure: Controlled ovarian stimulation: dosage
timeFrame: 2 weeks
measure: Controlled ovarian stimulation: days of stimulation
timeFrame: 2 weeks
measure: Controlled ovarian stimulation: hormonal profile
timeFrame: 2 weeks
measure: Controlled ovarian stimulation: type of trigger
timeFrame: 2 weeks
measure: Controlled ovarian stimulation: measurement of follicles
timeFrame: 2 weeks
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: IVI RMA Abu Dhabi
Study officials:
affiliation: IVIRMA Abu Dhabi
name: Neelke De Munck, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li Z, Wang AY, Bowman M, Hammarberg K, Farquhar C, Johnson L, Safi N, Sullivan EA. ICSI does not increase the cumulative live birth rate in non-male factor infertility. Hum Reprod. 2018 Jul 1;33(7):1322-1330. doi: 10.1093/humrep/dey118.
citation: Sahin L, Bozkurt M, Sahin H, Gurel A, Caliskan E. To compare aneuploidy rates between ICSI and IVF Cases. Niger J Clin Pract. 2017 Jun;20(6):652-658. doi: 10.4103/1119-3077.208959.
citation: Feldman B, Aizer A, Brengauz M, Dotan K, Levron J, Schiff E, Orvieto R. Pre-implantation genetic diagnosis-should we use ICSI for all? J Assist Reprod Genet. 2017 Sep;34(9):1179-1183. doi: 10.1007/s10815-017-0966-7. Epub 2017 Jun 13.
citation: De Munck N, El Khatib I, Abdala A, El-Damen A, Bayram A, Arnanz A, Melado L, Lawrenz B, Fatemi HM. Intracytoplasmic sperm injection is not superior to conventional IVF in couples with non-male factor infertility and preimplantation genetic testing for aneuploidies (PGT-A). Hum Reprod. 2020 Feb 29;35(2):317-327. doi: 10.1093/humrep/deaa002.