Methods of Protecting Ovaries from Radiation Therapy

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GYNAECO LOGY

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METHODS OF PROTECTING OVARIES FROM RADIATION THERAPY A. Covens, MD, FRCSC, Assistant Professor, Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology, University of Toronto, Head, Division of Gynaecologic Oncology, Toronto-Sunny brook Regional Cancer Centre, Toronto, Ontario ABSTRACT

Preservation of ovarian function is both safe and feasible in many young women with pelvic malignancies. Of the methods used to preserve ovarian function after radiation, only surgically transposing the ovary from its site within (or close to) the radiated field to a distant site has withstood the test of time. Despite trans positioning and the use of blocks, the ovaries are still subject to the following sources of radiation; head leakage, the collimator assembly, air scattering, and internal scattering (the most significant). Ovarian failure secondary to radiation is dependent not only on the dose of radiation received, but also the age at exposure, and the use of concomitant chemotherapy. Sites of ovarian transposition are midline and lateral. Although midline transpositions are technically easier to perform and require no further intervention for pregnancy to occur, they are associated with a low rate of efficacy (0 to 67% in Hodgkin's patients) , and are contra-indicated in patients requiring whole pelvic radiation. Lateral ovarian transpositions have been associated with modest success rates in cervical cancer patients ( 15 to 50%) . Despite preservation of ovarian tissue, studies in cervical cancer patients have found only 30 to 60 percent of patients have continued long term ovarian function after transposition alone, and 15 to 50 percent after transposition and external pelvic radiation. Furthermore, up to 25 percent of nonirradiated patients experience complications from the retained ovarian tissue later in life. Laparoscopy appears to be an ideal method for performing ovarian transpositions as its preliminary morbi&ty is low, and it can be combined with other staging, diagnostic, and therapeutic interventions including pelvic and para-aortic lymphadenectomy. With more experience and longer follow-up confirming its safety and efficacy in comparison to laparotomy, it will likely replace laparotomy as the predominant method of ovarian transposition in the future. Despite the above innovations, ovarian transposition is at best fair in preventing radiation induced menopause (after external pelvic radiation), and is associated with a potential for an increase in ovarian complications. Future efforts should be directed towards improving patient selection, while increasing the efficacy and decreasing the long-term morbi&ty associated with this procedure. RESUME

Il est possible de conserver Ia fonction ovarienne de maniere securitaire chez de nombreuses jeunes femmes presentant des malignites pelviennes. Parmi 1es methodes utilisees pour proteger Ia fonction ovarienne durant !'irradiation, seule Ia transposition chirurgicale des ovaires al' ecart du champ d' irradiation a resiste al' epreuve du temps. T outefois, malgre Ia transposition des ovaires et l' utilisation de blindages, les ovaires res tent exposes ades fuites au niveau de Ia tete de l' appareil et du collimateur et aux rayonnements diffuses par !'air et les tissus (Ia cause Ia plus importante d'irradiation). L'apparition d'une

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iOt entkJmetrlosiS the Se1Jerity of ~

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tlys'JI(mon'hea, pel""ie pain, timtdyspareunia .ls not necessarily associated with the stage of the disease. 1,2

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' ' ' insuffisance ovarienne a Ia suited' une irradiation depend non seulement de Ia dose de rayonnements rec;ue, mais mmi de l' iige a l' exposition et d'une chimiotherapie concomitant£. Les ovaires peuvent etre transposes dans le plan median ou lateralement. La transposition dans le plan median est techniquement plus simple et ne requiert pa..1 d' autre intervention pour n€aliser une grossesse; son taux d' efficacite est cependant faible (de 0 a 67tJour 100 dans le traitement de Ia maladie de Hodgkin) et elle est contre-indiquee lorsqu' on doit irradier toutle bassin. La transposition laterale s' accompagne d' un taux d' efficacite modeste dans les cas de cancer du col de l' uterus ( 15 a 50 pour 100) . Malgre Ia preservation des tissus ovariens, les etudes effectuees dans les cas de cancer du col montrent que Ia function ovarienne n' est maintenue a long terme que chez 30 a 60 pour 100 des patientes apres transposition seule et chez 15 a 50 pour 100 des patientes apres transposition et irradiation pelt•ienne exterieure. En outre, jusqu' a 25 pour 100 des patientes non irradiees presentent des complications au niveau des tissus ovariens consert•es plus tard au cours de leur vie. La laparoscopie semble constituer Ia methode parfaite pour les transpositions ovariennes, du fait que Ia morbidite preliminaire est faible et qu' on peut l' associer ad' autres interventions tels Ia classification du cancer, le diagnostic ou les interventions therapeutiques, dont Ia l)·mphadenectomie pelvienne et para-aortique. Avec l' experience et des sui vis prolonges concernant son efficacite et son innocuite /Jar ra/Jilort a Ia laparotomie, cette methode finira probablement par remplacer Ia laparotomie comme methode principale de transposition omrienne. Malgre les innovations ci-dessus, Ia transposition ovarienne donne des resultats pluwt mO)ens dans Ia prevention de Ia menopause iatrogene (apres irradiation pelvienne exteme) et s' accompagne d' un risque accru de complications ovariennes. L' effort a l' at·enir det m s' orienter vers une meilleure selection des patientes, tout en augmentant l' efficacite de cette procedure et en en reduisant Ia morbidite a long terme.

J SOGC 1995;17:975-84 KEY WORDS Radiation, menopause, surgery.

INTRODUCTION

FIGURE 1

Methods of protecting ovaries from radiation have been investigated since 1956 when Batten described encasing ovaries in lead shells in an eight-year-old girl prior to radiation for a pelvic neuroblastoma. 1 Nonsurgical methods which include birth control pills and gonadotrophin-releasing hormone analogues have not proven effective (despite encouraging preliminary results in experimental animals and humans) and, thus, will not be discussed any further. 24 In 1970, Ray reported the first series of midline ovarian transposition with shielding prior to pelvic radiation for Hodgkin's disease.i Since then, numerous methods of ovarian transposition and transplantation have been described including laparoscopic approaches. 61 ' Historically, various locations in the body have been used as recipient sites for transposed ovaries. Figure 1 depicts the most common ones and their relationship to the bony structures of the pelvis and spine. These can be summarized as midline, lateral, and high lateral sites.

Anatomical location of midline, lateral, and high lateral ovarian transposition sites, including the location of the non-transposed ovary

ation to lymph node bearing areas.i He reported an ovarian function retention rate of 59 percent. As many of these women were young and the uterus not involved, transposing the ovaries either in front or behind the uterus and subsequently shielding them represented a simple method of moving the ovaries out of the radiated field (Figure 2). Technically, this method is the simplest, requiring no division of ligaments, and allows for

TECHNIQUES/SITES MIDLINE OVARIAN TRANSPOSITION

Midline ovarian transpositions were popularized in the '70s, when Ray reported the first of many such series in women with Hodgkin's disease about to undergo radi-

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' ' ' postoperative adjuvant pelvic radiation for cervical cancer. As the lateral transposition described by Nahhas did not place the ovaries superiorly enough, he transposed the ovaries lateral to the ascending and descending colons.ll Seven of nine patients thus treated had "no signs or symptoms of hormonal deficiency." In 1988, Belinson revised Hodel's transposition, by tunnelling the ovary and its pedicle retroperitoneally before suturing it intraperitoneally in the paracolic gutters (Figure 3 ). 9 Dosimetric calculations for pelvic (4,500 rads) with or without para-aortic irradiation was 158 rads and 460 rads, respectively. However, of 13 patients thus treated, only three received pelvic radiation postoperatively, of whom none became menopausal. More recently, Anderson found that only four of 24 patients ( 17%) retained ovarian function after radical hysterectomy, lateral ovarian transposition, and postoperative adjuvant pelvic radiation, while Feeney reported that 12 of 24 (50%) patients retained ovarian function after similar treatment.20'21

conception to occur without the need for subsequent intervention. However, the proximity of the pelvic lymph node bearing areas to the midline, resulting in substantial internal scatter and radiation exposure of the transposed ovaries (see below), has lead to a high incidence of ovarian failure. This has been reported in many small series to range from 33 to 100 percent. 5·14- 16 Furthermore, Hadar found that only three of 13 ovaries identified by CT scan were completely outside the radiation field, while Hunter noted that only 60 percent of patients undergoing midline oophoropexies had their ovaries sufficiently displaced from their normal position that, had an inverted 'Y' field of irradiation been applied, the ovaries would have been spared. 1m Sharma measured doses of radiation as a function of the distance from the edge of typical radiation fields-periaortic, and inverted 'Y' using phantom-loaded thermoluminescent LiF dosimeters. He reported that the amount of radiation received by ovaries transposed behind the uterus was four to five times that received by laterally transposed ovaries. 19

LAPAROSCOPIC OVARIAN TRANSPOSITION

Experience using laparoscopy to perform ovarian transpositions has been reported by Williams and Prouvost.12'13 Although neither of these two reports placed the ovaries in the traditional high lateral positions described above, they have stimulated renewed interest in ovarian transpositions using laparoscopy. One of the disadvantages

FlGURE3

LATERAL OVARIAN TRANSPOSITIONS

Nahhas reported the first lateral ovarian transposition in 1971 in 18 patients with Hodgkin's disease. The ovaries were sutured to the peritoneum, lateral to the common iliac vessels, and below the iliac crest. All but one patient continued to menstruate. Dosimetric measurements estimated the dose to the transposed ovaries to be eight percent of the prescribed dose. 7 Hodel revised the method described by Nahhas, in patients requiring

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~~~~~'!iJralpnl)f laparo~ic ~~ ovar1an transposition; id$cntify b~ips ovarian ligament$

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' ' ' being placed outside the radiation field and shielded by a lead block. 14· 19 These alternate sources of radiation to the transposed gonads include; head leakage, scattering from the collimator assembly and the field shaping blocks, air scattering, and most significantly, internal scattering. The latter event occurs as photons bounce off internal structures and become redirected to sites outside the radiated field. Logically, organs closest to the field edge receive the greatest amount of scattered radiation. This phenomenon has been quantitated by numerous investigators using dosimeters in phantoms (Figure 4 ).14,19 Empirically, it has become evident that the likelihood of ovarian failure after exposure of the ovaries to radiation is dependent on three factors: the dose of radiation received by the ovaries, the age at exposure, and the presence or absence of concomitant chemotherapy. 24 Radiation sensitivity is oocyte dependent and, therefore, age at irradiation is important. As the number of oocytes within the ovary decline exponentially from approximately 2,000,000 at birth to 2,000 at menopause, the sensitivity of the ovary to radiation increases with age. The approximate dose of radiation to the ovary and its effect on ovarian function in relation to age have been well documented by Baker and Ash (Table 1). 2s. 26 Wallace calculated the LDso of the human oocyte not to exceed four Gy. 27 This calculation was, however, based upon a number of assumptions such as the rate of exponential atresia of surviving follicles post-irradiation to be similar to non-irradiated ovaries, and the number of oocytes at

to traditional ovarian transpositions has been the need for a laparotomy. While this is justifiable when other therapeutic or diagnostic procedures must be performed, the procedure becomes difficult to rationalize in their absence. Our division has performed five laparoscopic ovarian transpositions (8 ovaries) on three patients with cervical cancer and two patients with Hodgkin's disease (manuscript submitted). After a follow-up of three to 27 months, four patients are menstruating without exogenous hormones, while one patient has become menopausal after her ovaries slipped back into the pelvis postoperatively. In our series, the ovaries were transposed a mean distance of 14.5 em from their original position, by measurement from plain abdominal x-rays (Figure 3 ). Dosimetric estimates revealed the mean dose of radiation each ovary would have received after external pelvic irradiation (4,500 cGy) to be 135 to 190 cGy, and paraaortic nodal irradiation (4,500 cGy) to be 230 to 310 cGy. Including the pelvic lymphadenectomies which were performed in addition to the transpositions in three patients, the operative times and blood loss ranged :&om 1.5 to four hours, and 50 to 300 mls, respectively. Most importantly, the postoperative hospital stay ranged from zero to two days, and no operative or postoperative complications were encountered. Although the methods of ovarian transfixation need to be refined, and more experience is required, this approach seems promising in light of the preliminary morbidity. Given that this method can be combined with other staging, diagnostic, and therapeutic interventions such as pelvic and para-aortic lymphadenectomy, and can be performed on a short-stay basis (possibly outpatient), it will likely replace laparotomy as the predominant method of performing ovarian transpositions in the future.

FIGURE4 100 80

~ :J: 60

CAUSES OF OVARIAN FAILURE AFTER TRANSPOSITION

0

0

"

,§ 40

When an ovarian transposition fails to preserve ovarian function, it is usually due to the fact that the ovaries received a sufficient amount of radiation to cause radiation-induced menopause, or the vascular pedicles were compromised. The ovaries will receive a significant amount of radiation if they are not moved an adequate distance from the radiated field, or if they slip back to their original location from their transposed site. This amount of radiation can be substantial, despite the ovary

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Distance from Edge of Block (em)

Demonstration of the relationship between distance from the edge of a 10 em block and the radiation received expressed as % midline dose. modified from Le Floch et al. Cancer 1976;38:2265. 14

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' ' ' ovarian failure, and methods of therapy received is portrayed diagrammatically in Figure 6. Factors to consider prior to performing an ovarian transposition are: the age of the patient; the prognosis of her disease; the radiation field size to be used; the dose of radiation to be delivered and; whether chemotherapy is to be given (and if so, the drugs). Technically, it is crucial to transpose the ovary as far as possible from the border of the radiation field to minimize the likelihood of the ovary being included in the field, and to minimize the amount of radiation it will receive from internal scatter. The vascular pedicle should be handled carefully to avoid torsion and trauma which could compromise the viability of the ovary. Similarly, the pedicle should be placed either retroperitoneally or fixed to the peritoneum to avoid formation of a potential internal hernia. Once transposed, a secure method of transfixing the ovary in situ is essential as slippage can occur and render the procedure unsuccessful. Application of a radiological marker to the ovary (such as haemoclips) is helpful to the radiation oncologist in planning the patient's radiation and the use of blocks. Inherently, it seems important to place the ovary intraperitoneally to prevent retroperitoneal ovulation and subsequent cyst formation, although nonintraperitoneal locations have been used. 8 Consideration of the patient's fertility wishes (where appropriate) are important in terms of the future needs for conception to occur (i.e. oocyte aspiration and in vitro fertilization versus reversal of transposition).

TABLE 1 EFFECTS OF IONIZING RADIATION ON OVARIAN FUNCTION OVARIAN DOSE

RESULTS

0.6Gy

No deleterious effect

1.5Gy

No deleterious effect in young women, some risk of sterilization in women >40 yrs.

2.5-5.0 Gy

In women 15-40 yrs, 60% sterilized, remainder may suffer temporary amenorrhoea. In women >40 yrs, 100% sterilized.

5.0-8.0 Gy

In women 15-40 yrs, 60-70% sterilized, remainder may experience temporary amenorrhoea.

>8.0 Gy

100% sterilized.

Reproduced with permission.

birth to be 2,000,000 while those at age 50 are assumed to be approximately 2,200. With this information, if the dose received by the ovary furthest from the radiation field is calculated, then the predicted age of premature ovarian failure can be determined by assuming an average complement of oocytes for age at the time of irradiation. Figure 5 graphically depicts the relationship between age at irradiation and likelihood of ovarian failure. The use of chemotherapy in combination with radiation has been demonstrated in numerous studies in Hodgkin's disease and other tumour sites to be associated with a higher likelihood of ovarian failure than irradiation alone. 2224 Histologically, chemotherapy (most notably, alkylating agents) results in ovarian fibrosis and follicular destruction. 28 11 As with radiation, the likelihood of ovarian failure after chemotherapy is age dependent. The relationship between age, probability of

FIGURE6 FIGURES High High

Low Young

Low

0

10

20

30

Age at Treatment

Old

40

Schematic representation of additive relationship of chem'otherapy and radiation, and likelihood of menopause with respect to age at treatment. Chemotherapy -Radiation - Chemo +Rads Modified from Horning et al. N Engl J Med 1981;304:1379. 23

Age (yrs)

Schematic representation of the relationship between fractionated radiation required to induce menopause and age of treatment.

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' ' ' incidence of ovarian failure (10%). In contrast, Feeney reported 104 patients treated by ovarian transposition after radical hysterectomy and no adjuvant radiation and found that only three percent experienced menopausal symptoms and three percent adnexal disease requiring analgesics or surgery. 21 Unfortunately, the small numbers of patients in these studies, and their conflicting results have been unhelpful in resolving the issues addressed above.

PREGNANCY AFTER RADIATION

Concerns have been raised about the radiation exposure of the transposed ovaries in patients contemplating pregnancy. Although the mutagenic effects of radiation to the gonadal tissues have long been recognized in experimental animals, there is little evidence in humans to support these effects. A review of 31,150 atomic bomb survivors reveals no excess in stillbirths, major congenital defects, cancer with onset prior to 20 years, death among live-born children up to age 26 years, or the presence of chromosomal abnormalities and mutations.ll,l4 Additionally, the pregnancy outcomes of women irradiated for Hodgkin's disease have not demonstrated any fetal wastage or birth defects in 24 infants in one series. 21 Nevertheless, as recessive mutations may take several generations to become manifest, caution is still required.

SUMMARY

Preservation of ovarian function allows the patient to benefit from physiologic endogenous hormones rather than to suffer estrogen deprivation or accept exogenous hormones where side effects, cost, and compliance can be problematic. In those cases where preservation of fertility is feasible, the benefits of ovarian transposition are even greater. However, these benefits must be weighed against the immediate complication rate and the long-term rate of retained ovarian function and painful cyst formation. Many factors are contributory: the age of the patient; the technique of transposition and; the dose, size, and type of radiation fields chosen. Internal scatter can contribute a significant amount of radiation to the transposed ovary, and methods to minimize this must be taken. It is evident from the literature that current methods are modestly successful at best in preventing radiation induced menopause. Not entirely clear is the question of the life- span of transposed ovaries relative to retained ovaries following hysterectomy. New methods including laparoscopy may help in decreasing the morbidity associated with this procedure, and will likely become the predominant method of performing this operation in the future.

LONG-TERM RESULTS

Whether the lifespan of transposed ovaries is shorter than non-transposed ovaries, and if so, the cause, be it radiation, vascular compromise, or other factors continues to be debated. Similar questions about the long-term complication rates (cyst formation) in transposed ovaries versus non-transposed ovaries remain unanswered. Chambers compared the sequelae of 25 laterally transposed ovaries after radical hysterectomy to 59 non-transposed ovaries after radical hysterectomy. 35 As none of the patients received adjuvant pelvic radiation, differences in ovarian complication rates could be attributed to the surgical procedure. After a mean follow-up of 38 months, a three-fold increase in the incidence of symptomatic ovarian cysts was noted in the transposed ovaries (24%) versus the non-transposed ovaries (7.4%). The incidence of early menopause in patients not incurring any additional surgery or radiation was similar between the transposed (4.3%) and non-transposed patients (4.1 %). Anderson found that of 58 patients with ovarian transposition and no adjuvant radiation, 18 percent required oophorectomy for management of painful ovarian cysts, while another 14 percent required medical management for the same, and 15 percent spontaneously became menopausaU 0 Thus, only 53 percent of ovarian transposition patients were left with no problems. However, this is not substantially different from patients who did not undergo ovarian transposition after radical hysterectomy for the incidence of similar problems (21 %), nor the

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REFERENCES 1. 2.

3.

4.

Batten R, Brown DEM. Protection of ovaries from radiation. Lancet 1956; 1:939-40, Whitehead E, Shalet SM, Blackledge G, Todd I, Crowther D, Beardwell CG. The effect of combination chemotherapy on ovarian function in women treated for Hodgkin's disease. Cancer 1983;52:988-93, Chapman RM, Sutcliffe SB. Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin's disease. Blood 1981 ;58(4):849-51. Jegou B, de Ia Calle JFV, Bauche F, Protective effect of medroxyprogesterone acetate plus testosterone against radiation-induced damage to the reproductive function of male rats and their offspring, Proc Natl Acad Sci 1991 ;88:8710-14.

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' ' ' 5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

Ray GR, Trueblood HW, Enright LP, Kaplan HS, Nelson TS. Oophoropexy: a means of preserving ovarian function following pelvic megavoltage radiotherapy for Hodgkin's disease. Radiology 1970;96:175-80. Krebs C, Blixenkrone-Moller N, Mosekilde V. Preservation

21. Feeney DD, Moore DH, Look KY, Stehman FB, Sutton GP. The fate of the ovaries after radical hysterectomy and ovarian transposition. Gynecol Oncol1995;56:3-7. 22. Haie-Meder C, Mlika-Cabanne N, Michel G, Briot E, Gerbaulet A, Lhomme C, Cosset JM, Sarrazin D, Flamant F, Hayat M. Radiotherapy after ovarian transposition: ovarian function and fertility preservation. lnt J Radiat On col Bioi Phys 1993;25:419-24. 23. Horning SJ, HoppeRT, Kaplan HS, Rosenberg SA. Female reproductive potential after treatment for Hodgkin's disease. N Engl J Med 1981;304:1377-82. 24. Stillman RJ, Schinfeld JS, Schiff I, Gelber RD, Greenberger J, Larson M, Jaffe N, Li FP. Ovarian failure in long-term survivors of childhood malignancy. Am J Obstet Gynecol 1981;139:62-6. 25. Baker TG. Radiosensitivity of mammalian oocytes with particular reference to the human female. Am J Obstet Gynecol1971;110:746-61. 26. Ash P. The influence of radiation on fertility in man. Brit J of Radiol1980;53:271-8. 27. Wallace WHB, Shalet SM, Hendry JH, Morris-Jones PH, Gattamaneni HR. Ovarian failure following abdominal irradiation in childhood: the radiosensitivity of the human oocyte. Brit J Radial 1989;62:995-8. 28. Miller JJ, Williams GF, Leissring JC. Multiple late complications of therapy with cyclophosphamide, including ovarian destruction. Am J Med 1971;50:530-5. 29. Morgenfeld MC, Goldenberg V, Parisier H, Bugnard SC, BurGE. Ovarian lesions due to cytostatic agents during the treatment of Hodgkin's disease. Surg Gynecol Obstet 1972; 134(5):826-8. 30. Nicosia SV, Matus-Ridley M, Meadows AT. Gonadal

of ovarian function in early cervical cancer after surgical lifting of the ovaries and radiation therapy. Acta Radio Ther Phys Bioi 1963;1 :176-82. Nahhas WA, Nisce LZ, D'Angio GJ, Lewis JL Jr. Lateral ovarian transposition: ovarian relocation in patients with Hodgkin's disease. Obstet Gynecol 1971 ;38(5):785-8. Leporrier M, von Theobald P, Roffe J, Muller G. A new technique to protect ovarian function before pelvic irradiation. Cancer 1987 ;60:2201-4. Belinson JL, Doherty M, McDay JB. A new technique for ovarian transposition. Surg Gynecol Obstet 1984;159:157-60. Cantor B. Transplantation and replantation of the fallopian tubes and ovaries: a technique for patients undergoing pelvic irradiation. Fertil Steril1983;39:231-4. Hodel K, Rich WM, Austin P, DiSaia PJ. The role of ovarian transposition in conservation of ovarian function in radical hysterectomy followed by pelvic radiation. Gynecol Oncol1982;13:195-202. Williams RS, Mendenhall N. Laparoscopic oophoropexy for preservation of ovarian function before pelvic node irradiation. Obstet Gynecol1992;80(3):541-3. Prouvost MA, Canis M, Le Bouedec G, Achard JL, Mage G, Dauplat J. Transposition ovarienne per-coelioscopique avant curietherapie dans les cancers du col uterin stade lA et lB. J Gynecol Obstet Bioi Reprod 1991;20:361-5. Le Floch 0, Donaldson SS, Kaplan HS. Pregnancy following oophoropexy and total nodal irradiation in women with Hodgkin's disease. Cancer 1976;38:2263-8. Thomas PRM, Winstanly D, Peckham MJ, Austin DE, Murray MAF, Jacobs HS. Reproductive and endocrine function in patients with Hodgkin's disease: effects of oophoropexy and irradiation. Br J Cancer 1976;33: 226-31. Numann PJ, Aust JC. Details of technique and results of staging laparotomy in the diagnosis of Hodgkin's disease. Am Surg 1978;44:723-6. Hadar H, Loven D, Herskovitz P, Bairey 0, Yagoda A, Levavi H. An evaluation of lateral and medial transposition of the ovaries out of radiation fields. Cancer 1994; 7 4:77 4-9. Hunter MCH, Glees JP, Gazet JC. Oophoropexy and ovarian function in the treatment of Hodgkin's disease. Clin Radiol1980;31:21-6. Sharma SC, Williamson JF, Khan FM, Lee CKK. Measurement and calculation of ovary and fetus dose in extended field radiotherapy for 10 MV x rays. lnt J Radiat Oncol Bioi Phys 1981;7:843-6.

effects of cancer therapy in girls. Cancer 1985;55(1 0):2364-72. 31. Kuhajda FP, Haupt HM, Moore WG, Hutchins GM. Gonadal morphology in patients receiving chemotherapy for leukemia. Evidence for reproductive potential and against a testicular tumor sanctuary. Am J Med 1982;72(5):759-67. 32. Sobrinho LG, Levine RA, DeConti RC. Amenorrhea in patients with Hodgkin's disease treated with antineoplastic agents. Am J Obstet Gynecol1971 ;109:135-9. 33. Neel JV. Update on the genetic effects of ionizing radiation: commentary. JAMA 1991 ;266:698-701. 34. Yoshimoto Y, Neel JV, Schull WJ, Kato H, Soda M, Eto R, Mabuchi K. Malignant tumors during the first 2 decades of life in the offspring of atomic bomb survivors. Am J Hum Genet 1990;46:1041-52. 35. Chambers SK, Chambers JT, Holm C, Peschel RE, Schwartz PE. Sequelae of lateral ovarian transposition in unirradiated cervical cancer patients. Gynecol Oncol 1990;39: 155-9.

20. Anderson B, LaPolla J, Turner D, Chapman G, Buller R. Ovarian transposition in cervical cancer. Gynecol Oncol 1993;49:206-14.

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