Telomere Length in Human Polar Body and Telomere Length in Cumulus Cells: A Clinical Validation Study

Study Overview
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Brief Summary
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To investigate whether telomere length (TL) of the first Polar body (PB) correlates with TL in Cumulus cells (CC)

Detailed Description
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With the present study we want to analyze, as a primary objective, whether telomere length (TL) in the first Polar Body (PB) correlates with TL in the corresponding Cumulus cells (CC). As a secondary objective, a possible correlation between TL in PBs and blastocyst TL and ploidy will be evaluated. To our best knowledge, there are no studies evaluating TL in CC and TL in PBs of the corresponding oocyte. With the present prospective study, we sought to investigate whether there is a correlation between CC-TL and PB-TL. If a correlation exists, CC-TL assessment would serve as a valuable non-invasive technique to gain information about oocyte competence.

Official Title
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Does the Telomere Length in First Human Polar Body Correlates With the Telomere Length in Cumulus Cells: A Clinical Validation Study

Conditions
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Telomere Length

Intervention / Treatment
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* Genetic: First polar body biopsy in MII oocytes
* Genetic: PGT-A blastocyst


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI 18- 30kg/m2 Expected normo/high responders Normal female/male karyotype Antagonist protocol with agonist trigger. PGT-A: NGS in blastocysts Fresh autologous ejaculates (≥5 mill/ml) Primary and secondary infertility Only ICSI as insemination technique Exclusion Criteria: • PCOS patients according to International evidence-based guideline for the assessment and management of polycystic ovarian syndrome 2018.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 43 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MII with PB biopsy<br>Five selected MII will undergo sequential polar biopsy; on day 0 [PB1] (36-42 hours post trigger injection) and if fertilization occurred on day 1 [PB2] (17-20 hours post ICSI). On day 5, 6 or 7, the resulting blastocyst will be biopsied. | Genetic: First polar body biopsy in MII oocytes<br>* Since PBs are by-products of the meiotic division of the oocyte and are not required for fertilization and subsequent embryo development, they can be removed to assess exclusively maternal chromosomal information without harming the embryo integrity. As previously described, PB biopsy does not impact the morphokinetic parameters of the embryo development and can be safely applied without the risk of impairing the reproductive potential of the embryo.<br>* Other names: telomere lenght;Genetic: PGT-A blastocyst<br>* preimplantation genetic screening for aneuploidies<br>|
| Experimental: MII with no PB biopsy<br>MII will not go under polar body biopsy. On day 5, 6 or 7, the resulting blastocyst will be biopsied. | Genetic: PGT-A blastocyst<br>* preimplantation genetic screening for aneuploidies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| telomere length (TL) of the first Polar body (PB) and TL in Cumulus cells (CC) | Correlation between telomere length (TL) of the first Polar body (PB) and TL in Cumulus cells (CC) | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To correlate TL between both polar bodies | If the MII fertilize after performing ICSI, polar body biopsy for the second PB will be performed | 8 weeks | 
| To correlate TL in male WBC and TL in sperm | TL will be assess in leukocytes (male´s blood sample) and in the sperm (fresh ejaculate) | 8 weeks | 
| To correlate TL in female WBC and TL in CC | TL will be assess in leukocytes (female´s blood sample) and in the cumulus cells (CC) from the retrieved oocytes. | 8 weeks | 
| To evaluate a possible correlation between TL-CC and TL-TE | Correlation between TL-CC and TL in trophectoderm biopsy performed in the developed blastocysts | 8 weeks | 
| To evaluate a possible correlation between TL-CC and ploidy TE | Correlation between TL-CC and PGT-A results in trophectoderm biopsy performed in the developed blastocysts | 8 weeks | 
| To evaluate telomerase activity (TA) in CC and a possible correlation with CC-TL | Telomerase is a ribonucleoprotein complex responsible for de novo telomere synthesis and addition of telomeric repeats to existing telomeres | 8 weeks | 
| To evaluate FSH/LH gene expression in CC | During the follicular phase LH whose receptors (LHR) are expressed in granulosa cells under the influence of FSH, plays an important role in the regulation of ovarian function and is essential to promote the growth of the dominant follicle, final oocyte maturation as well as ovulation induction | 8 weeks | 
| To evaluate a possible correlation between ploidy in PBs and ploidy in TE biopsy | PGT-A in PB and PGT-A in TE biopsy | 8 weeks | 
| PB biopsy and embryo development | To validate that PB biopsy does not impair embryo development compared to their sibling embryos with no PB biopsied | 8 weeks | 
| To evaluate TL in sperm + TL-PB and TL in TE | TL in sperm + TL-PB and TL in the resulting biopsied | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PGT-A, telomere length, cumulus cells, polar body