Italiano
English
Clinical Rationale
Couple infertility affects approximately 15% of the reproductive-age population. Genetic causes account for a substantial proportion of cases (10–15% in male infertility; 8–10% in female infertility), while a meaningful share—around 20%—remains idiopathic even after a complete diagnostic work-up.1
In this context, having a single platform that integrates carrier screening and infertility genetics represents a major step forward, enabling optimized etiological assessment, stronger reproductive counseling, and more personalized assisted reproduction (ART) pathways.
1 Registro Nazionale PMA – Istituto Superiore di Sanità, Infertilità e tecniche di PMA, aggiornamento 09/03/2018.
Four Clinical Dimensions in a Single Analysis
CARRIERADVANCE Exome Infertility is a genetic test designed for couples with reproductive difficulties who are planning a pregnancy through ART.
The test integrates, in one analysis, four high-impact clinical areas:
Expanded Carrier Screening
Clinical Exome Sequencing:
- Clinical exome sequencing of 7,000+ genes associated with Mendelian disorders.
- Identification of the risk of transmitting genetic conditions to offspring, often in the absence of a family history.
Couple Infertility Genetics
- Diagnostic assessment of the main genetic causes of male and female infertility;
- Support in developing personalized clinical strategies.
TESE Prognosis in NOA
- Estimation of the likelihood of sperm retrieval in patients with non-obstructive azoospermia (NOA).
- Prognostic stratification TESE+/TESE− to support targeted clinical decisions.
Predisposition to Embryonic Aneuploidy
- Assessment of the risk of meiotic and post-zygotic mitotic errors.
- Useful in complex clinical scenarios (e.g., repeated implantation failure, recurrent pregnancy loss).
Expanded Carrier Screening: 7,000+ Genetic Disorders
CARRIERADVANCE Exome Fertility is among the most comprehensive carrier screening solutions currently available. Using Clinical Exome Sequencing, it analyzes the entire coding region of approximately 7,000 genes associated with Mendelian disorders. The test identifies couples at risk of transmitting genetic diseases, frequently even in the absence of a family history.
Key elements for counseling
- Most carriers are clinically asymptomatic and often unaware of their carrier status.
- Autosomal recessive inheritance: if both partners carry pathogenic variants in the same gene, the risk of having an affected child is 25% per pregnancy.
- X-linked inheritance: if the woman is a carrier, each male child has a 50% risk of being affected.
- Couple-based testing: maximizes clinical relevance and supports informed reproductive decisions (PGT-M, prenatal diagnosis, family counseling).
Couple Infertility Genetics
CARRIERADVANCE Exome Infertility enables an integrated assessment of the main genetic conditions associated with male and female infertility, helping reduce the proportion of idiopathic infertility and guiding therapeutic strategy.
Female infertility
- Primary ovarian insufficiency (POI)
- Gonadal dysgenesis and ovarian dysfunction
- Oocyte maturation defects
- Oocyte aneuploidy / embryonic lethality
- Recurrent pregnancy loss (monogenic causes)
Male infertility
- Non-obstructive azoospermia (NOA)
- Severe asthenozoospermia
- Sperm morphological defects
- Genetically determined spermatogenic failure
Clinical value: support for etiological diagnosis, reproductive risk stratification, and definition of personalized pathways (ART, targeted PGT-M when indicated, family counseling).
NOA and Prognostic TESE Stratification
Non-obstructive azoospermia (NOA) is the most severe form of male infertility (prevalence ~1% of the male population). In these patients, TESE/micro-TESE is often the only option to retrieve sperm usable for ICSI, with failure rates around 50% in idiopathic cohorts. First-line genetic tests (karyotype, AZF microdeletions) provide limited prognostic value in most cases.
CARRIERADVANCE Exome Fertility analyzes 200+ genes involved in key spermatogenic processes, enabling:
- Identification of the molecular cause of NOA/spermatogenic failure;
- Prognostic stratification of TESE outcome (probability of sperm retrieval) based on genes with evidence for TESE−/TESE+. (2)
TESE−
(Unfavorable Prognosis)
Pathogenic variants in genes consistently associated with failed sperm retrieval.
Clinical Utility: evaluate whether to avoid repeated invasive procedures with a poor risk/benefit ratio; redirect the couple toward alternative options.
TESE+
(Retrieval Possible)
Pathogenic variants in genes compatible with residual spermatogenesis.
Clinical Utility: TESE/micro-TESE may be justified. Success remains gene-dependent and influenced by phenotype/histology; overall andrological assessment remains decisive.
(2) Riera-Escamilla et al. Genetic determinants of testicular sperm extraction outcomes: insights from a large multicentre study of men with non-obstructive azoospermia. Hum Reprod Open. 2025 Aug 29;2025(3):hoaf049.
Predisposition to Embryonic Aneuploidy
Numerical chromosomal aneuploidies are a major cause of implantation failure and early miscarriage in ART. They may originate from:
- Meiotic errors: predominantly maternal, influenced by biological age with possible individual genetic modulation;
- Post-zygotic mitotic errors: resulting in mosaicism and complex chromosomal patterns.
CARRIERADVANCE Exome Fertility analyzes 13 genes selected on the basis of current scientific evidence to identify individual predisposition to:
- Meiotic aneuploidies (segregation errors in meiosis I/II).
- Post-zygotic mitotic errors (mosaicism, multiple aneuploidies, complex patterns).
The test does not diagnose embryonic aneuploidy; it provides an individual risk-stratification tool to be integrated with clinical phenotype, laboratory data, and previous investigations.
Carioscia et al. Nature 2026 doi: 10.1038/s41586-025-09964-2.
Sun et al. Am. J. Hum Genet 2023; 110:2092–2102.
Tyc et al. Hum Reprod. 2020 9;35:2134–2148.
Nguyen et al. Mol Hum Reprod 2017 13;23:406–416.
Biswas et al. Proc. Natl. Acad. Sci. U.S.A. (2024) 121(45) e2414963121.
Lledó et al. J Assist Reprod Genet. 2023;40:1755–1763.
McCoy et al. Science. 2015 10;348:235–238.
Technology Platform
CARRIERADVANCE
Exome Infertility is based on Clinical Exome Sequencing using state-of-the-art NGS technology, sequencing the entire coding region of ~7,000 genes. The integrated advanced bioinformatics pipeline enables detection of SNVs, indels, and CNVs in the investigated regions.
Advantage over targeted panels: no predefined mutation set; detection of any variant within the sequenced regions.
Report Interpretation
Carrier Screening & Infertility Genetics
POSITIVE: one or more variants identified (pathogenic or VUS).
Interpretation depends on the gene, inheritance mechanism, and clinical phenotype.
NEGATIVE: no relevant variants identified. Clinical decisions rely on comprehensive evaluation. Does not fully exclude genetic risk (the test does not cover the entire genome).
TESE Prognosis / Aneuploidy Predisposition
POSITIVE: pathogenic variant identified.
- NOA: contributes to TESE+/TESE− prognostic stratification.
- Aneuploidy: may indicate increased predisposition (to be integrated with clinical data and PGT-A results).
NEGATIVE: no variants detected in the analyzed genes.
Does not fully exclude genetic risk (the test does not cover the entire genome).
Indications for Testing
The test is recommended in the presence of:
ART pregnancy planning (preferred indication for the couple).
Idiopathic couple
infertility.
Donor conception: genetic matching of donor/partner.
Known or suspected family history of genetic disease.
Non-obstructive azoospermia (NOA): pre-TESE evaluation and post-negative TESE assessment.
Repeated implantation failures without apparent cause.
Recurrent miscarriage, particularly with evidence of embryonic aneuploidy.
High proportion of aneuploid embryos at PGT-A, especially if unexpected for maternal age.
PGT-A patterns suggestive of meiotic or mitotic errors (multiple aneuploidies, mosaicism).
A SIMPLE, STEP-BY-STEP WORKFLOW
Informational Brochure
CarrierAdvance Exome Infertility
Download brochureRequest information about CARRIERADVANCE
Fill in this form for a free consultation. One of our geneticists will contact you, free of charge and without obligation, to provide you with all the information you need.
