47,XYY Syndrome and Male Infertility

Men with 47,XYY syndrome present with varying physical attributes and degrees of infertility. A retrospective chart review was performed on a male infertility and genetic anomaly database. Three patients with 47,XYY were found. Each presented with > 2 years of infertility. All were tall with elevated body mass indices. Scrotal findings ranged from normal to atrophic testicles. Semen analyses demonstrated oligospermia and varying endocrine profiles. Because of the diverse phenotype and potential lack of symptoms, identification and diagnosis of men with 47,XYY syndrome may be difficult. We recommend careful screening of 47,XYY patients and referral to primary physicians for long-term follow-up for increased incidence of health-related comorbidities.Key words: Infertility syndromesThe 47,XYY sex chromosome variation is the most common sex chromosome anomaly after Klinefelter syndrome (47,XXY),^1–3 occurring in approximately 1 out of 1000 live male births.^4,5 Parental nondisjunction at meiosis II resulting in an extra Y chromosome produces a 47,XYY karyotype in the affected offspring.^6–8 46,XY/47,XYY mosaics from parental nondisjunction during cell division after postzygotic mitosis can result in addition of the extra Y chromosome in early embryonic development.^6,8Most patients with 47,XYY have a delayed diagnosis, with a median age of 17.1 years at diagnosis, as was shown in a Danish cohort study.⁹ Although most have no phenotypic abnormalities, XYY boys are at greater risk for behavioral problems, mild learning disability, delayed speech and language development, and tall stature.¹⁰ Studies have increasingly reported an association between 47,XYY and fertility problems, noting an increased incidence of chromosomally abnormal spermatozoa in the semen of men with 47,XXY syndrome.^7,11–15 This greater prevalence of hyperhaploid sperm results in an increased risk of passing the extra Y chromosome to offspring.¹⁴ Men with 47,XXY syndrome can have variable sperm counts, ranging from normal to azoospermia.^{3,8,14,16–18}Here we review pertinent findings on physical examination and laboratory evaluation in three men with 47,XXY syndrome diagnosed during infertility evaluation as well as review the available literature on the subject, with special emphasis on male fertility effects.