Impact of chemotherapy and radiotherapy for testicular germ cell tumors on spermatogenesis and sperm DNA: a multicenter prospective study from the CECOS network

Bujan, Louis; Walschaerts, Marie; Moinard, Nathalie; Hennebicq, Sylviane; Saïas, Jacqueline; Brugnon, Florence; Auger, Jacques; Berthaut, Isabelle; Szerman, Ethel; Daudin, Myriam; Rives, Nathalie

doi:10.1016/j.fertnstert.2013.05.018

Cited by 111 publications

(105 citation statements)

References 45 publications

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“…29–32 In 129 patients referred to the Centres d’Etudes et de Conservation des Oeufs et du Sperme Humain for sperm banking before testicular germ cell tumour treatment who provided serial semen specimens, spermatogenesis recovered after two or fewer cycles of bleomycin, etoposide, and cisplatin (BEP regimen) at 12 months after the start of treatment, and there was slower, but complete, recovery at 24 months after the start of therapy in those who received radiation therapy or three or four courses of BEP. 33 …”

Section: Discussionmentioning

confidence: 99%

Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study

Green

Liu

Kutteh

et al. 2014

The Lancet Oncology

286

197

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Summary Background Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer. Methods We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01–20·3] at diagnosis, 29·0 years [18·4–56·1] at assessment, and a median of 21·0 years [10·5–41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for oligospermia (sperm concentration >0 and <15 million per mL) and azoospermia were calculated with logistic regression modelling. Findings Azoospermia was noted in 53 (25%) of 214 participants, oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m2 were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=–0·37, p<0·0001). Mean CED was 10 830 mg/m2 (SD 7274) in patients with azoospermia, 8480 mg/m2 (4264) in patients with oligospermia, and 6626 mg/m2 (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m2 CED for azoospermia (OR 1·22, 95% CI 1·11–1·34), and for oligospermia (1·14, 1·04–1·25), but age at diagnosis and age at assessment were not. Interpretation Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m2. Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services.

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Section: Discussionmentioning

confidence: 99%

Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study

Green

Liu

Kutteh

et al. 2014

The Lancet Oncology

286

197

View full text Add to dashboard Cite

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“…1, 2, 3 Cancer therapies such as radiation often lead to a temporary disruption or a complete arrest of spermatogenesis. 4 In major cases, detrimental effects of ionizing radiation (IR) on biological tissue are mediated via indirect interactions, which increased production of hydroxyl radicals (•OH) by radiolysis of H 2 O, followed by the abnormal elevation of cytotoxic reactive oxygen species (ROS) and oxidative damage. 5, 6 The latter results in a cell cycle block, followed by apoptosis if the damage is severe.…”

mentioning

confidence: 99%

Upregulation and nuclear translocation of testicular ghrelin protects differentiating spermatogonia from ionizing radiation injury

Zeng

Zhao

et al. 2014

Cell Death Dis

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Proper control of apoptotic signaling is important for maintenance of testicular homeostasis after ionizing radiation (IR). Herein, we challenged the hypothesis that ghrelin, a pleiotropic modulator, is potentially involved in IR-induced germ cell injury. Lower body exposure to 2 Gy of IR induced a notable increase of ghrelin expression in the nuclear of differentiating spermatogonia at defined stages, with an impairment in the Leydig cells (LCs)-expressing ghrelin. Unexpectedly, inhibition of the ghrelin pathway by intraperitoneal injection of a specific GHS-R1α antagonist enhanced spermatogonia elimination by apoptosis during the early recovery following IR, and thereafter resulted in impaired male fertility, suggesting that the anti-apoptotic effects of evoked ghrelin, although transient along testicular IR injury, have a profound influence on the post-injury recovery. In addition, inhibition of ghrelin signaling resulted in a significant increase in the intratesticular testosterone (T) level at the end of 21 days after IR, which should stimulate the spermatogenic recovery from surviving spermatogonia to a certain extent during the late stage. We further demonstrated that the upregulation and nuclear trafficking of ghrelin, elaborately regulated by IR-elicited antioxidant system in spermatogonia, may act through a p53-dependent mechanism. The elicitation of ghrelin expression by IR stress, the regulation of ghrelin expression by IR-induced oxidative stress and the interaction between p53 and ghrelin signaling during IR injury were confirmed in cultured spermatogonia. Hence, our results represent the first evidence in support of a radioprotective role of ghrelin in the differentiating spermatogonia. The acutely, delicate regulation of local-produced ghrelin appears to be a fine-tune mechanism modulating the balance between testicular homeostasis and early IR injury.

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“…Bujan ve ark. yaptığı bir çalışmada TK'lı erkeklerde kemoterapi ve radyoterapi sonrasında sperm DNA yapısı üzerindeki etkilenmeler incelemiş ve 6 ay içerisinde sperm DNA fagmantasyonunu en yüksek düzeyde olduğunu tespit etmişlerdir (29). Radyasyonun DNA hasarı potansiyeli fertilite tedavisinde üremeye yardımcı teknikler kullanımı sırasında dikkate alınmalıdır.…”

Section: Radyoterapi Ve Kemoterapinin Fertilite üZerinde Etkisiunclassified

“…Sperm sayılarının normal sınırlara 5 yıl içerisinde %58 erkekte ulaştığı bildirilmiştir. Başka bir çalışmada iki siklus BEP tedavisi gören erkeklerde sperm sayılarının tedavi öncesi sayılara ulaşması 1 yıl sürerken, iki siklustan fazla BEP alanlarda sperm sayılarının 24 aya kadar uzayan sürede tedavi öncesi değerlere ulaştığı görülmüştür (29). Sisplatin yerine karboplatin kullanımının fertilite üzerinde etkisi, tedavi öncesi normospermik olan yüksek riskli evre I non-seminomatöz germ hücre tümörleri (NSGCT) olan erkeklerde incelenmiştir.…”

Section: Radyoterapi Ve Kemoterapinin Fertilite üZerinde Etkisiunclassified

Testis Kanserli Hastalarda Sperm Dondurma ve İnfertilite

Bakircioglu¹,

Alıcı²

2014

uob

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Güncel kanser tedavileri ile genç erkeklerin yaşam süreleri uzamasına karşın kullanılan kemoterapi ve radyoterapi infertiliteye neden olabilmektedir. Bu derlemede amacımız testis kanserli erkeklerde fertilite potansiyelinin tedavi öncesinde ve sonrasında korunması hakkında literatür bilgilerini incelemektir. Testis kanserli erkeklerde sperm konsantrasyonları diğer kanser tiplerine göre daha düşük olduğu tespit edilmiştir. Tedavi için kullanılan kemoterapi ve radyoterapi spermatogenezi negatif olarak etkilemektedir. Buna rağmen kemoterapi gören erkeklerin sperm parametreleri 1 yıl sonra, radyoterapi görenlerde ise 2 yıl sonra tedavi öncesi değerlere geri dönebilir. Erkeklerde tedavi öncesinde azoospermi görüldüğü durumlarda orşiektomi ile eş zamanlı testisten sperm elde ederek (TESE) sperm saklama uygulanabilir. Sperm dondurma kanser hastalarında fertilite potansiyelinin korunması için hala altın standarttır. Bu nedenle testis kanseri teşhis edilen erkeklerin tedavilerine başlamadan önce mevcut potansiyellerinin anlaşılması ve sperm dondurma işlemi için infertilite merkezlerine başvurmaları desteklenmelidir. (Üroonkoloji Bülteni 2014;13:176-181) Anah tar Ke li me ler: Testis kanseri, sperm dondurma, infertilite Modern cancer therapies have greatly improved survival rates in men of reproductive age and younger; however, surgery, chemotherapy and radiation therapy may lead to male infertility. In this review, we would like to investigate fertility status of men with testicular cancer and sperm preservation options before and after cancer treatment. Sperm concentration of patients diagnosed with testicular cancer is lower than other cancer patients. In addition to that chemotherapy and radiotherapy negatively affect spermatogenesis. Radiotherapy have a much more deleterious effect on fertility compared with chemotherapy alone. However, after one year of chemotherapy or two years of radiotherapy, semen parameters may return to basal levels before cancer therapy. If the patient is azoospermic before any cancer specific treatment, testicular sperm extraction (TESE) for cryopreservation is an option at the time with orchiectomy operation. Sperm cryopreservation is still a gold standard to preserve fertility potential for cancer patients before the cancer specific treatments. Therefore, men diagnosed with testicular cancer should be encouraged to contact with infertility clinics to understand their fertility potentials and for sperm cryopreservation. (Bulletin of Urooncology 2014;13:176-181)

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Impact of chemotherapy and radiotherapy for testicular germ cell tumors on spermatogenesis and sperm DNA: a multicenter prospective study from the CECOS network

Cited by 111 publications

References 45 publications

Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study

Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study

Upregulation and nuclear translocation of testicular ghrelin protects differentiating spermatogonia from ionizing radiation injury

Testis Kanserli Hastalarda Sperm Dondurma ve İnfertilite

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