Kovač, Viljem

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Rlldiol Oncol 1996: 30: 286-90. Prevention of fertility disturbances in oncological male patients Viljem Kovač Institute of' Oncology, Ljub(iana, Slovenia The modem therapelltic approaches to oncological plllients are not only aimed at cure hut also ensuring the least possible side e.ffects and the optimal q11ality <d' life which naturally includes preserved .fertility. Tile most e.ffective n1ea.rnre to prevent the occllrrence <�/' .rnrgery-relllled damage 1!f'.ferti!i1y in ma!e.1· is hy replacing radical retroperitonecd ly111phadenecto111y with seleclive or llnilateral lymplwdenectomy: mdio­thempy-related fertility damage can be prevenled hy shielding the remaining testicle .fi'Oln the sca/lered mdiation; and chenwthempy-related .fertility damage can be prevented by choosing the chemotherapelllic regimen which doesn 't contain alkylating agents. We have to con sider other modalities of prevention, including eliminating l(festyle and environment factors which can i1ifluence fertility, adeqllate sexual behaviour, early treatments of cryptorchidism and treatments of i1ifections. Key words: infertilily, male - prevention; neoplasms; radiotherapy - adverse effects; antineoplastic agents -adverse effects; lymph node excision - adverse effects Introduction The modem lherapeutic approaches to oncological patients are not only aimed al cure but also ensur­ing the least possible sillc elTects and thc optimal quality of life which naturally includes preserved fertility. 1 The best approach to reduce the sterilily prob­lems is to decrease lhe chance of occurrence of infertility2 since the cfficiency of treatment is un­certain and unpredictable.1In case of fertility impairment severa! methods of treatment exist. Following cancer lreatment fer­tility status is also frequently unpredictable, it is thereforc advisable for young male patients to store their deep-frozen sperm in a sperm bank prior to oncological therapy. ;., Correspon<lenee to: Assist. Yilje111 Kovač. M.D„ M.Se„ In­stitute of 0ncology, Zaloška 2. 1105 Ljubljana, Slovenia. Phone: +38661 1320 068. Fax: +38661 1314 180. E-111ail: vkovac (0mail .onco-i .si UDC: 616-006.6-08-06:6 l 6.697-084 Prevention of surgery-related damage It is important lhat patient with testicuiar tumours are operated transinguinally bul not transscrotally, otherwise the ipsilateral scrotal sac and inguinal lymph nodes must be postoperatively irradiated, which also mcans more scattered radiation to con­tralateral testis.1·"Radical retroperitoneal lymphadenectomy was usually performed on patients with testicular nonseminomatous tumours and Hodgkin's diseas­es 10· 12 and the most effective measure to preserve fertility in males is by replacing radical retro­peritoneal lymphadenectomy with selective or unilateral lymphadenectomy. 11·1• In patients withsuch operations it is possible to preserve emis­sion and ejaculation, most of semen analyses in majorily of patients are considered to be in nor­mal range aml most of them are potentially fer­tileY In this way the modified retroperitoneal lymph node dissection preserves the sympathetic outflow, retaining ejaculation in 75% of these men.1'Pre,·e11tio11 of)irtility disturhances in 011cologica/ 111a/e patients 287 In spite of lhe fact lhat ferlility is usually not the central problem in patients wilh prostate cancer because of their advanced age. early detection of this disorder allows less extensivc surgery. with fewer complications. For example. nerve-sparing radical retropubic prostatectomy. which preserves erectile function in many men by avoiding injury to the cavernosal neurovascular bundles. can be per­formed and prevent fertility disturbances. "'·17Prevention of racliotherapy-relatecl clamage The most effective measure to prevcnt the occur­rence of radiotherapy-related fertility damage can be by shielding the remaining testicle from scat­tered radiation. '-'1·18 Having already had unilateral semicastration pro­phylactically the retroperitoneal nodes only are treated and the irradiation of the remaining testicle should be avoided. The testicle is in any case ex­posed to the scattered radiation causing a degree of spermatogenesis impairment. 1'1-21 By shielding the remaining testicle gonadal dose should be kept low­er than I Gy in order to avoid prolonged and fre­quently permanent azoospermia or hypozoosper­niia. 10.22.2,In l-lodgkin's disease. when we irradiate the infradiaphragmatic region. the shielding of bolh tes­ticles from scattered radiation is necessary. Con­temporary radiotherapy techniques recommend the protection from scattered radiation. in case of go­nadal doze higher than 0,5% . 18 Attempls were made to reduce postirradiation inju­ry by reducing the size of target volume24·25 and thus decreasing the scattered radiation ancl in the same tirne increasing the distance between the target vol­ume and testes. ''1·1'' Additionally. reducing the tumour dose or even by the omission of the postoperative irradiation24·2' radiation side-clTect can be avoidecl al­togethcr. 27 Disease frce survival is rcduccd and further studies are nccessary to find patients where manage­ment by surveillance alonc should be su!Ticient.27•31Nevertheless, it is important to irradiatc paticnts with high energy photons because scallered radiation is reduced in such treatment.1'1Prevention of chemotherapy-relatccl clamage Chemotherapy-related fertility damage can be pre­vented by choosing the chemotherapeutic regimen which doesn't include alkylating agents.12·11Chemotherapy with alkylating agents is associ­ated wilh fertility problems in 60% of patients re­gardless whether it is given in combination with radiotherapy or not.34 Cisplatin. one of thc most efficient agent. has fortunately only moderate dam­aging effect on spermatogenesis.'·1'Limiling the number of cycles administrated to the minimum for achieving remission is also bene­ricial for prcserving male reproductive ability.'-1" Cytoprotective techniqucs to limit testicular inju­ry from the damaging effect 01· chemotherapy are currently ineffectual. The gonadal toxicity caused by chemotherapy and radiation was attempted to be reduced by luteinizing hormone releasing hormone (LI-IRI-1) analogues. It has been shown that non­pulsatile, chronic treatment with supraphysiologi­cal doses 01· LI-IRI-1 analogucs results in the sup­pression of the pituitary-gonadal axis and the sup­pression of spermatogenesis. Furthermore, there has been suggested that the inhibition of sperma­togenesis during exposure to cytotoxic drugs and radiation might rcduce or prevcnt gonadal toxicity. Experimental studies were encouraged,17 but in noneof clinical trials the influence on severity and dura­tion of spermatogenesis impairment has significant­ly been shown_Jx-,oThe administrations of some other clrugs (i.e. anti­oxidants N-acetylcystein and ascorbate) before the administration of procarbasine have been ellective by preserving spermatogenesis in an animal model. But the analogous studies in humans have not been published.'.,, During the oncological treatment there were also attempts to reduce spermatogenesis by adminis­trating of testosterone which can suppress gonado­tropin secretion and in this way protect testicular function. There is no clinical relevance up to now as well.42Others principles of prevention of fertility clisturbanees As thc causes or fertility disturbance are manifold'" we have to consider all other modalities of preven­tion, including the elimination of lifestyle and envi­ronment factors which can alTect fertility, more appropriate sexual behaviour. early treatments of cryptorchidism and treatments or infections. Elimination of l(festyle factors One of the most important steps of the prevention of fertility disturbances is to eliminate ali factors 288 Kovw' V that can affect fertility, such as bad nutrition,-lJA4cigarette smoking,45 alcohol abuse,4'' use of illicit drugs such us marijuana and cocaine_-lJ.-<-l and some drugs as anabolic steroids, antihypertensive medica­tions, cimetidine, antiholinergic drugs, etc_llW Elimination 1!( another e11viro11me11t .fr.1c:101:1· Oncological patients should not work with arsenic and lead. They should avoid exposure to heat, such as in saunas or working as plumbers and cooks. ioAsSexual behctviour According to Howards, sexual intcrcourse is rec­ommendcd evcry 48 hours in the middle of wom­an 's cycle or at the tirne of ovulation.-'1 Lower fre­qucncy or intercourse can result in missing thc ovu­lation tirne, and also diminish the quality of thc sperm (over 5 days or abstinence). In view of con­tradicting reports, namely, that rrcquent intercourse diminishes sperm concentration-l7 or even improve it,4" it should bc cautiously recommended more fre­quent intercourse during the tirne of woman's ovu­lation if their libido is adequate.H'1 Trea1111e111s of cr\'ptorchidism Cryptorchidism is firsl treated with gonadotropines (HCG. LH-RH) and later with orhiopexy.47·50 Orhi­opexy must be performed between the age of 5 and 9 or else as soon as possible. Some argue that cryptorchidism should be curcd by the age of 2, before histological changes occur,505' but at anyrate prior to puberty-47 Adcquate treatment reduees the chances of sterility, and also the incidence of malign alteration of testiclcs.5151 Only 75% and50% fertility ratc is rcported for patients with suc­cessful unilateral and bilateral orhiopexy. The re­sults, however, considerably improve if the proce­dure is performed beforc the age of 2. Hormona! treatment is recommcnded to start at the age of I O months.50Tren1111e111s c!f' i11/ec:1io11s It is imperative that uro-infections are treated effec­tively, preferably with regards to antibiogram of the agent.41 Trichomonas or gonorrhoea require thatthe sexual partner is treated as well. Conclusion Multimodality treatment has increased the survival or cancer patients in reccnt years. The quality of life should also be takcn into considcration during the cure. The maintenance of the reproductive ca­pacity is of grcat concern to many young patients. The cause of sterility was attributed to the long­term side effects of oncological treatment in spite of the fact that the step of fertility disturbances can be decreased by the selected treatment. One of the most important stcps of prcvcntion of fertility dis­turbanccs is also, if possible, to eliminatc ali fac­tors that can influence the fertility. References 1. Kovač V, Umek B, Marolt F. Škrk J, Reš P, Kuhelj J. 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Prevention of fertility disturbances in oncological male patients

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Prevention of fertility disturbances in oncological male patients

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