From the Guidelines
Not all patients with Klinefelter syndrome are infertile, although the majority experience significant fertility challenges due to the condition's impact on testicular function. Approximately 95-99% of men with Klinefelter syndrome have infertility issues, which are caused by the extra X chromosome (resulting in a 47,XXY karyotype) leading to progressive damage to the seminiferous tubules, reduced testosterone production, and impaired sperm development 1. However, some men with Klinefelter syndrome may have small numbers of functional sperm, particularly those with mosaic forms of the condition where some cells have normal chromosomal patterns.
Fertility Preservation Options
Fertility preservation options should be discussed early, ideally during adolescence, as sperm retrieval through testicular sperm extraction (TESE) or micro-TESE procedures may be successful in 30-50% of cases 1. When viable sperm are retrieved, they can be used with assisted reproductive technologies like intracytoplasmic sperm injection (ICSI).
- Early testosterone replacement therapy may help maintain secondary sexual characteristics and general health but doesn't typically improve fertility outcomes.
- Karyotype testing is recommended for males with primary infertility and azoospermia or sperm concentration <5 million sperm/mL when accompanied by elevated FSH, testicular atrophy, or a diagnosis of impaired sperm production 1.
- A meta-analysis assessing the frequency of Y-chromosome microdeletions in severely oligospermic males found that Y-chromosome microdeletions were found in 5% of males with sperm concentrations 0 to 1 million 1.
Diagnosis and Treatment
Azoospermia is defined as absence of sperm in the ejaculate, and when a semen analysis shows azoospermia, the laboratory should then centrifuge the ejaculate and re-suspend the pellet in a small volume of seminal plasma and examine under wet mount microscopy for the presence of rare sperm 1. Obstructive azoospermia is suspected if the physical examination reveals testes of normal size, fully descended into the scrotum and bilaterally dilated and/or indurated epididymides with or without absence of the vas deferens.
- In these cases, FSH levels are usually less than approximately 7.6 IU/L 1.
- When the testes are atrophic, especially in the presence of FSH greater than 7.6 IU/L, spermatogenic failure (non-obstructive azoospermia) is more likely the cause 1.
From the Research
Fertility in Klinefelter Syndrome Patients
- Patients with Klinefelter syndrome are not always infertile, as testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) can be used to achieve fatherhood 2, 3, 4, 5, 6.
- The success of TESE and ICSI in men with Klinefelter syndrome is comparable to other men with nonobstructive azoospermia 6.
- Several factors can influence the outcome of TESE, including age, clinical and hormonal parameters, and androgen therapy 2.
- Age is a significant prognostic factor for positive sperm retrieval rate, with TESE carried out before the age of 30 having a poorer prognosis 2.
- Approximately half of men with Klinefelter syndrome will ultimately fail fertility treatments 4.
- Individuals with Klinefelter syndrome have a relatively good prognosis for sperm recovery compared to other men with idiopathic nonobstructive azoospermia 4.
Treatment Options
- TESE and ICSI are the cornerstone of treatment for men with Klinefelter syndrome and nonobstructive azoospermia 4.
- Hormonal manipulation and timing of retrieval have also been suggested and evaluated as treatment modalities to optimize surgical success 4.
- Cryopreserving spermatozoa in adolescent patients may be a potential advantage in fertility treatment 5.