PreventionGenetics Releases New Panels for Infertility and
Disorders of Sex Development
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Infertility is a disorder of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. It affects 10-20% of couples worldwide and is generally attributed to males and females equally. Infertility evaluations can be an emotional and financial burden for couples. An infertility evaluation can involve extensive tests including imaging, blood work, semen analysis, biopsies, laparoscopies and more, costing thousands of dollars without a promise to result in a successful pregnancy. It is estimated that genetic abnormalities including both chromosomal and single-gene alterations can account for up to 30% of cases of infertility (Hotaling 2014). At PreventionGenetics we are committed to helping couples find these genetic answers, offering a Comprehensive Panel, as well as sub panels for Female Infertility, Male Infertility and Disorders of Sex Development.
Our Comprehensive Panel
Our comprehensive Disorders of Sex Development (DSD) and Infertility Sequencing Panel is a 207 gene panel that combines genes involved in DSD as well as genes associated with both female and male infertility. 64 genes in this panel account for approximately 35% of cases of DSD (Baxter et al. 2015). Pathogenic variants in 28 genes cause hypogonadotropic hypogonadism in about 40-50% of patients. Pathogenic variants in 14 genes cause gonadal failure in 15% of affected females with hypergonadotropic hypogonadism (Layman 2013).
Indications
• Symptoms consistent with DSDs including both non-syndromic DSD with ambiguous or abnormal genitalia and syndromic conditions that involve additional congenital anomalies
• Individuals with Genetic Infertility
• Cases where there is a family history of DSD, infertility and/or premature menopause
Sex chromosome aneuploidy, structural abnormality and copy number variation are common genetic causes of DSDs and infertility. For this reason, we include copy number variation (CNV) detection as part of our panels.
Our Disorders of Sex Development Panel
DSD Panel is a multi-gene panel analyzes genes involved in both syndromic and non-syndromic DSDs. 64 genes in this panel account for approximately 35% of cases of 46,XY DSD (Baxter et al. 2015).
Indications
• Ambiguous genitalia
• Gonadal dysgenesis
• Hypospadias
• Reduced to no sperm production
• Müllerian structures
More on Sex Development
Sex development is a complex process under genetic control directing the initially bi-potential gonad to develop into either a testis or an ovary (sex determination), and the consequent differentiation of internal ducts and external genitalia (sex differentiation) (Laino et al 2014). Disruption of either determination or differentiation can lead to disorders of sex development (DSDs) which are congenital conditions with atypical development of chromosomal, gonadal, or anatomic sex (Hughes et al. 2006). DSDs, ranging in severity from genital abnormalities to complete sex reversal, include congenital development of ambiguous genitalia, disjunction between the internal and external sex anatomy, incomplete development of sex anatomy, sex chromosome anomalies (Turner Syndrome; Klinefelter Syndrome) and disorders of gonadal development (Park et al. 2006).
Our Infertility Panels
Female Infertility Panel is a multi-gene panel analyzes genes involved in both syndromic and non-syndromic female infertility (Baxter 2015). The detection rate of this NGS panel in a large cohort of female patients is unavailable in the literature. However, in patients with hypogonadotropic hypogonadism, 40-50% of patients have pathogenic variants in 28 genes in this panel. For woman with hypergonadotropic hypogonadism and especially 46,XX ovarian failure, about 15% of women have pathogenic variants in 14 genes in this panel (Layman 2013).
Testing for FMR1 CGG Repeat Expansion is also available. Premature Ovarian Failure (POF type 1) or Primary Ovarian Insufficiency (POI) refers to ovarian dysfunction that results in infertility or menopause before the age of 40 in women. FMR1 premutation alleles were found in 2-8% of idiopathic POI cases (Ferrarini et al. 2013; Bachelot et al. 2009).
Male Infertilty Panel analyzes genes involved in both syndromic and non-syndromic male infertility (Baxter 2015). The detection rate of this NGS panel in a large cohort of infertile male patients is unavailable in the literature. However, in patients with hypogonadotropic hypogonadism, 40-50% of patients have pathogenic variants in 28 genes in this panel.
Y chromosome deletion analysis is also available. Y chromosome deletions are typically characterized by azoospermia, severe to moderate oligozoospermia, and/or abnormal sperm morphology/motility. Males with Y chromosome deletions usually have no obvious symptoms, although physical examination may reveal small testes. Y chromosome deletions are the most frequent cause of spermatogenic failure in infertile men with normal cytogenetic chromosomes. Incidence of these deletions in infertile men is about 3-10% (Silber and Disteche 2012).
Indications
• Determine the cause of infertility
• Identify risk of passing to offspring
• Influence treatment plans
Background on Infertility
In humans, sexual development and reproductive function occur by the actions of the hypothalamin-pituitary-gonadal axis induced by gonadotropin releasing hormone (GnRH). Aberrations in this axis can lead to pubertal and reproductive deficiencies. Diagnoses of infertility include hypogonadotrophic hypogonadism, hypergonadotrophic hypogonadism, and obstructive disorders (Layman 2002). Patients with hypogonadotrophic hypogonadism present with absent or deficient puberty and poorly defined secondary sexual characteristics owing to low serum gonadotrophin, follicle stimulating hormone (FSH), and luteinizing hormone (LH); while infertility in patients with hypergonadotrophic hypogonadism is usually caused by gonadal defect (primary amenorrhea and premature ovarian failure in females; oligospermia, azoospermia, or other abnormalities of sperm morphology or motility in males).
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References:
Baxter R.M. et al. 2015. The Journal of Clinical Endocrinology and Metabolism. 100: E333-44. PubMed ID: 25383892
Hotaling J.M. 2014. The Urologic Clinics of North America. 41: 1-17. PubMed ID: 24286764
Hughes I.A. et al. 2006. Journal of Pediatric Urology. 2: 148-62. PubMed ID: 18947601
Laino L. et al. 2014. Endocrine Connections. 3: 180-92. PubMed ID: 25248670
Layman L.C. 2002. Journal of Medical Genetics. 39: 153-61. PubMed ID: 11897813