Sperm aneuploidy frequencies analysed before and after chemotherapy in testicular cancer and Hodgkin's lymphoma patients

Abstract

BACKGROUND Multicolour fluorescent in situ hybridization was utilized to detect sperm aneuploidy for chromosomes 13, 21, X and Y in testicular cancer and Hodgkin's lymphoma chemotherapy patients. METHODS Aneuploidy was assessed before, and 6, 12 and/or 18-24 months after, the initiation of chemotherapy, and compared with age matched controls. 635 396 sperm were scored blindly with 5000 sperm/patient/chromosome/ time point, where sperm was available. (First two phrases have been reversed). RESULTS Comparing testicular cancer and Hodgkin's lymphoma patients to each other and with controls, cancer-specific differences were identified. Hodgkin's lymphoma patients, particularly, exhibited significantly increased aneuploidy frequencies for all chromosomes throughout treatment. At 6 months, all cancer patients showed significantly increased frequencies of XY disomy and nullisomy for chromosomes 13 and 21. In general, aneuploidy frequencies declined to pretreatment levels 18 months after treatment initiation, but increased aneuploidy frequencies persisted in some chromosomes for up to 24 months. CONCLUSIONS Because of elevated aneuploidy frequencies prior to and up to 24 months from the start of chemotherapy, patients should receive genetic counselling about the potentially increased risk of an aneuploid conceptus from sperm cryopreserved prior to chemotherapy, and for conceptions up to 2 years after the initiation of treatment.

Scoring of sperm chromosomal abnormalities by manual and automated approaches: qualitative and quantitative comparisons

“…It has been well documented that severe male infer tility correlates with a significant increase in sperm aneuploidy; in addition, other factors such as paternal age, chemotherapy treatment, smoking and alcohol have also been associated with increased sperm aneuploidy [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Given the significant increased risk of sperm aneuploidy in infertile men, concerns have been raised regarding whether these individuals are at a higher risk of giving rise to aneuploid pregnancies when treated by intracytoplasmic sperm injection (ICSI) [17].…”

“…Sperm FISH screening in the clinical setting has the potential to provide individuals with valuable information to enable informed decisions to be made regarding their reproductive choices. Patients who may benefit from such screening include cancer patients, recurrent pregnancy loss or repeated unexplained IVF failure patients, patients with structural chromosome aberrations and constitutional sex chromosome aneuploidies [4,8,16,[22][23][24]. Given that the practicalities involved in scoring sperm FISH preparations may impede its introduction into the clinic, an obvious solution is automated 'spot counting' of FISH signals in each cell.…”

Effect of temozolomide on male gametes: an epigenetic risk to the offspring?

“…The total sperm count and the motile sperm counts remained above the normal range values throughout the treatment. The decline in sperm quantity was not associated with increased DNA fragmentation but, similar to other chemotherapeutic regimes, the aneuploidy frequency increased immediately after treatment and then declined to pre-treatment levels [11].…”

Using decision trees to enhance interdisciplinary team work: the case of oncofertility

“…2 Male fertility preservation decision tree. The patient may attempt natural pregnancy after appropriate treatment or disease specific waiting period, and subsequent to the completion of his cancer therapy and in consultation with his treating physician, approximately 2 years [1,22,23]. If attempting natural pregnancy, preimplantation diagnosis may also be recommended depending on cancer type and treatment regimen [21] Decision trees as a way to enhance interdisciplinary work in the clinical setting Interdisciplinary team work has the potential to offer great benefits for researchers and patients alike, creating novel treatments and providing specialized, expert care.…”