Uterine cervical cancer is still the

Transcription

1 ORIGINAL ARTICLES: FERTILITY PRESERVATION Association between the location of transposed ovary and ovarian function in patients with uterine cervical cancer treated with (postoperative or primary) pelvic radiotherapy Jong Ha Hwang, M.D., Ph.D., Heon Jong Yoo, M.D., Sae Hyun Park, M.D., Myong Cheol Lim, M.D., Ph.D., Sang-Soo Seo, M.D., Ph.D., Sokbom Kang, M.D., Ph.D., Joo-Young Kim, M.D., Ph.D., and Sang-Yoon Park, M.D., Ph.D. Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea Objective: To evaluate the effectiveness of ovarian transposition procedures in preserving ovarian function in relation to the location of the transposed ovaries in patients who underwent surgery with or without pelvic radiotherapy. Design: Retrospective. Setting: Uterine cancer center. Patient(s): A total of 53 patients with cervical cancer who underwent ovarian transposition between November 2002 and November Intervention(s): Ovarian transposition to the paracolic gutters with or without radical hysterectomy and lymph node dissection. Main Outcome Measure(s): Preservation of ovarian function, which was assessed by patient's symptoms and serum FSH level. Result(s): Lateral ovarian transposition was performed in 53 patients. Based on receiver operator characteristic curve analysis, optimum cutoff value of location more than 1.5 cm above the iliac crest was significantly associated with preservation of ovarian function after treatment (area under receiver operator characteristic curve: 0.757, 95% confidence interval [CI]: ). In univariate analysis, higher location of transposed ovary more than 1.5 cm from the iliac crest was the only independent factor for intact ovarian function (odds ratio 9.91, 95% CI: ). Multivariate analysis confirmed that the location of transposed ovary (odds ratio 11.72, 95% CI ) was the most important factor for intact ovarian function. Conclusion(s): Location of transposed ovary higher than 1.5 cm above the iliac crest is recommended to avoid ovarian failure after lateral ovarian transposition after primary or adjuvant pelvic radiotherapy in cervical cancer. (Fertil Steril Ò 2012;97: Ó2012 by American Society for Reproductive Medicine.) Key Words: Ovarian transposition, cervical cancer, radiotherapy Uterine cervical cancer is still the second most frequent cancer among women worldwide (1). About half of the patients are younger than 35 years of age (2). Although radiation therapy plays an important role in the management of cervical cancer, it can induce ovarian damage and longterm hormone replacement therapy is Received January 5, 2012; revised February 9, 2012; accepted February 29, 2012; published online March 30, J.H.H. has nothing to disclose. H.J.Y. has nothing to disclose. S.H.P. has nothing to disclose. M.C.L. has nothing to disclose. S.-S.S. has nothing to disclose. S.K. has nothing to disclose. J.-Y.K. has nothing to disclose. S.-Y.P. has nothing to disclose. Reprint requests: Sang-Yoon Park, M.D., Ph.D., Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, 323 Illsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do , South Korea ( parksang@ncc.re.kr). Fertility and Sterility Vol. 97, No. 6, June /$36.00 Copyright 2012 American Society for Reproductive Medicine, Published by Elsevier Inc. doi: /j.fertnstert indicated for young women. Early menopause is associated with osteoporosis and cardiovascular disease in addition to climacteric symptoms such as hot flushing, urogenital atropy, and sexual dysfunction. Long-term hormone replacement therapy to manage early menopause results in low compliance and adverse effects such as increasing of cardiovascular events in older women, breast cancer, and dementia. To minimize this side effect, it is necessary to relocate the ovaries away from the radiation field when treating young women with cervical cancer. Ovarian transposition was described by McCall et al. (3) in 1958 as an effective method to protect ovaries from radiation for the patients with uterine cervical cancer treated with radiotherapy. Ovarian transposition can be done by laparotomy or laparoscopy (4). The preservation of ovarian function does not influence the course of cervical cancer with small cervical mass. Many gynecologic oncologists performed lateral ovarian conservation VOL. 97 NO. 6 / JUNE

2 ORIGINAL ARTICLE: FERTILITY PRESERVATION in patients with uterine cervical cancer who would be undergoing adjuvant radiotherapy to preserve their ovarian function and for use for possible future oocyte. Therefore, ovarian preservation could be beneficial in premenopausal women because postoperative radiotherapy is sometimes required. However, not all transposition procedures result in preservation of ovarian function. It is necessary to know the risk factors affecting ovarian function in a transposed ovary to minimize the rate of ovarian failure. The aims of this study were to evaluate the effectiveness of lateral ovary transposition in maintaining ovarian function after pelvic radiotherapy and whether the location of the transposed ovary is predictive of the preservation of normal ovary function in patients with cervical cancer who undergo ovarian transposition followed by radiotherapy. FIGURE 1 MATERIALS AND METHODS Study Population The electronic medical records of 53 patients with cervical cancer who underwent ovarian transposition at National Cancer Center between November 2002 and November 2010 were reviewed. This study was approved by the Institutional Review Board of the National Cancer Institute. Laparoscopic ovarian transposition was performed in 19 patients and open ovarian transposition in 34 patients. Fourteen patients with para-aortic LN metastasis or no FSH follow-up were excluded. Of 53 patients, 17 ovarian transpositions were performed as part of surgical lymph node staging procedures after which primary chemoradiotherapy was planned. In 33 patients, radical hysterectomy and lymph node dissection was performed with 23 patients receiving postoperative adjuvant radiotherapy. Ovarian transposition only was performed in three patients (Supplemental Fig. 1, available online). Adjuvant radiotherapy was indicated in patients who had a high risk factor, such as positive node, parametrial involvement, and involvement of resection margin, or at least two intermediate risk factors, such as bulky tumor more than 4 cm in diameter, deep stromal invasion, and lymphovascular space invasion. For three patients, laparoscopic ovarian transposition was performed as the only surgical procedure before chemoradiotherapy. Ovarian Transposition Procedure Ovarian transposition was performed when the ovaries looked macroscopically normal. Both ovaries were mobilized and grasped. The ureters were identified through the peritoneum. The broad ligament leaflets were bluntly separated and the posterior broad ligament peritoneum was incised along the infundibulopelvic ligaments up to the level of the aortic bifurcation. The infundibulopelvic ligament including ovarian vessels was sufficiently mobilized to reserve sufficient length of the neurovascular pedicle to transpose each ovary as high as possible with the least possible tension. The utero-ovarian ligament was cut off and divided at its uterine origin. The ovaries were transposed bilaterally to the paracolic gutters after ensuring that the vascular supply was not hampered by The roentgenogram of a patient who underwent ovarian transposition that shows the metallic clips in kidneys, ureters, and bladder. The perpendicular distance (bidirectional arrow) between the clip (white arrow) of the lower border of the ovary and the horizontal line (white line) of iliac crest was used to evaluate the cutoff point for preserving normal function of the transposed ovary. kinking or direct injuries of the pedicle. Two surgical clips were applied to the upper and lower borders of each transposed ovary, therefore the position of the transposed ovaries could be identified by a subsequent roentgenogram (Fig. 1). Each ovary was inspected to confirm hemostasis. The perpendicular distance between the clip of the lower border of the higher-located ovary of two transposed ovaries and the horizontal line to the iliac crest was measured and compared to the FSH level. The mean of two independently measured values was used. Radiotherapy Radiotherapy consisted of whole pelvic external beam radiotherapy and high-dose-rate brachytherapy. External beam radiation therapy was administered to the whole pelvis, including the entire uterus, paracervical, parametrial, and uterosacral regions, and external iliac, hypogastric, and obturator lymph nodes using the box technique. The superior, lateral, and inferior borders of the anteroposterior and posteroanterior fields were the L4-L5 interspace 1 cm away from the pelvic rim and the midobturator foramen. However, radiation fields were modified according to the individual anatomy and the extent of disease as noted by pelvic magnetic resonance imaging. A total of 5,040 cgy was delivered 1388 VOL. 97 NO. 6 / JUNE 2012

3 Fertility and Sterility in 28 fractions of 180 cgy, five times a week, using 15 MV photons for postoperative radiotherapy. Concurrent chemotherapy with weekly cisplatin (40 mg/m 2 ) was administrated during external bean radiation to the patients with positive lymphadenopathies on pathologic report. For the patients who underwent primary radiotherapy, high-dose-rate brachytherapy using iridium-192 sources was administered at the end of external beam radiotherapy with fractional doses of cgy and five to six fractions twice a week. Evaluation of Ovarian Function Ovarian function was evaluated with serum FSH levels using RIA to assess ovarian function. Serum FSH was measured 6 months after the ovarian transposition and the yearly afterward. This was repeated at shorter intervals when menopausal symptoms, such as hot flushes, were reported. Ovarian function was considered to be preserved when the last follow-up FSH level without hormone replacement therapy was <30 miu/ml and patients displayed no menopausal symptoms. The patients were categorized into three groups. Group 1 comprised patients who received radiotherapy and had normal ovarian function. Group 2 comprised patients who received radiotherapy and did not have normal ovarian function. Group 3 comprised patients who did not receive radiotherapy. Patients with para-aortic LN metastasis received extended external radiation; these patients were excluded in this study (Supplemental Fig. 2, available online). Statistical Analysis Kruskal-Wallis test and Mann-Whitney U test were used to compare values between groups. Nominal variables were analyzed by the c 2 test. P<.05 was considered to be statistically significant. Receiver operator characteristic (ROC) analysis and 95% confidence interval (CI) were used to analyze location of transposed ovary and to determine the optimum cutoff point for preserving ovarian function. Ovarian function was analyzed by age, radiation dose, location of transposed ovary, and body mass index (BMI). A logistic regression model was used to analyze the relationship between covariates and normal ovarian function after lateral ovarian transposition followed by radiotherapy. Data were analyzed using Stata software version 10.0 (StataCorp). RESULTS From November 2002 to November 2010, 414 patients with uterine cervical cancer underwent radical hysterectomy and lymph node dissection (N ¼ 318) or staging operation (N ¼ 96) at the National Cancer Center, Republic of Korea. Fiftythree of 414 patients underwent ovarian transposition. Ten of the 53 patients did not receive adjuvant radiotherapy after ovarian transposition. Bilateral ovarian transposition was achieved in 48 (90.6%) patients and unilateral ovarian transposition in 5 patients (9.4%). No intraoperative or postoperative morbidities related to the ovarian transposition procedure were evident. Fourteen patients were excluded from the evaluation of ovarian function due to follow-up loss or lack of information on serum FSH level. The median age of the patients who received radiotherapy and had normal ovarian function (group 1) was 31.5 years (range years), which was younger than the median age of 39.9 years (range years) of the patients who received radiotherapy and were in a menopausal state (group 2) or the median age of 38.3 years (range years) of the patients who did not receive radiotherapy (group 3) (P¼.014). All women in group 1 except one were <40 years of age. In 39 patients, 14 patients had less than stage IB2 disease, 9 had clinical stage IB2 disease, 2 had stage IIA disease, and 14 had stage IIB disease. Twenty-seven patients (69.2%) had squamous cell carcinoma, eight (20.5%) had adenocarcinoma, and two (5.1%) had adenosquamous carcinoma. One verrucous carcinoma and one small cell carcinoma were included. All eight patients who did not receive adjuvant radiation displayed normal ovarian function. Ten (32.3%) of 31 patients who received adjuvant radiotherapy had normal ovarian function. The patients were categorized according to the presence of radiotherapy and level of FSH (Supplemental Fig. 2). Patient characteristics are summarized in Table 1. Seven (16.7%) of 42 patients who received adjuvant radiotherapy after ovarian transposition had recurrent disease, which comprised liver metastasis (N ¼ 2), pelvic wall mass (N ¼ 2), seeding pattern (N ¼ 1), pelvic/para-aortic lymph node and sigmoid colon (N ¼ 1), and supraclavicular lymph node (N ¼ 1). Five of seven patients underwent open ovarian transposition with radical hysterectomy and two patients (lymph node recurrence and pelvic wall recurrence, respectively) underwent laparoscopic ovarian transposition with staging operation. Two of seven patients died. No patient presented with an ovarian metastasis or symptomatic ovarian cyst. In seven patients with recurrent disease, four patients had IB disease (IB1, N ¼ 2; IB2, N ¼ 2) and two patients had IIB disease. One IIA disease was included. There was no significant difference in BMI among the groups (P¼.167). Median duration of follow-up (from operative date to last FSH value) was 39.8 months (range months) in group 1. The FSH value in group 2 was higher than group 1 and group 3 (P<.05). There was no significant difference in FSH value between group 1 and group 3; the median FSH of each group was 3.4 miu/ml (range miu/ml) and 5.9 miu/ml (range miu/ml), respectively (Table 1). The ROC curves were constructed, and the area under the curve with a 95% CI was calculated to determine the optimum cutoff point of the vertical distance of the transposed ovaries from the iliac crest to preserve normal ovarian function after radiotherapy (Fig. 2). Based on analysis of the ROC-area under the curve value (0.757, 95% CI: ), the minimum cutoff level of the lower portion in the higher located ovary was 1.5 cm above the iliac crest (P¼.02). In univariate analysis, location of transposed ovary higher than 1.5 cm above the iliac crest (P¼.01, odds ratio [OR] 9.91, 95% CI ) was an independent factor for ovary function in patients with lateral ovarian transposition. Age <40 years showed borderline significance (P¼.065, OR 0.818, 95% CI ). However, age was significantly correlated with ovarian failure (OR 9.92, P¼.01, 95% CI ) when age was analyzed with a cutoff value of 32 years of age instead of 40 years of age, based on the VOL. 97 NO. 6 / JUNE

4 ORIGINAL ARTICLE: FERTILITY PRESERVATION TABLE 1 Characteristics of patients who underwent ovarian transposition (N [ 39). Group 1 (N [ 10) Group 2 (N [ 21) Group 3 (N [ 8) Total (N [ 39) Age (y) > % Tumor stage (FIGO) %IB IB IIA IIB Histology Squamous cell carcinoma Adenocarcinoma Adenosquamous cell carcinoma Other BMI (kg/m 2 ) 19.3 ( ) 21.6 ( ) 20.3 ( ) 20.9 ( ) Hormone FSH 3.4 ( ) 95.3 ( ) 5.9 ( ) 45.3 ( ) E ( ) 13.9 ( ) 46.4 ( ) 69.4 ( ) Note: Group 1, adjuvant radiotherapy plus FSH <30; group 2, adjuvant radiotherapy plus FSH >30; group 3, no adjuvant radiotherapy. BMI ¼ body mass index; FIGO ¼ International Federation of Gynecology and Obstetrics. ROC curve. The BMI and external radiation dose did not influence ovary function significantly. The high-dose-rate brachytherapy was excluded. Multivariate analysis was performed including factors that were found to be significant or of borderline significance in the univariate analysis. In the multivariate analysis, location of transposed ovary higher than 1.5 cm above the iliac crest (P¼.014, OR 11.72, 95% CI ) was a factor for normal ovarian function after lateral ovarian transposition followed by radiotherapy, and age <40 years (P¼.071, OR 10.18, 95% CI ), which showed borderline significance (Table 2). However, age was significantly correlated with ovarian failure (OR 15.85, P¼.02, 95% CI ) when age was analyzed with a cutoff value of 32 years of age. DISCUSSION Eight of 10 patients who did not receive adjuvant radiotherapy had normal ovarian function when at least one of the ovaries is saved. The FSH level was not followed up in two patients who had no climacteric symptoms. However, when postoperative radiotherapy is considered to be possibly given, FIGURE 2 The receiver operator characteristic (ROC) curve and location of the transposed ovary in the 31 patients who received primary or adjuvant radiotherapy. (A) ROC and ROC area under the curve values were (95% confidence interval ). The best cutoff value was 1.5 cm above the iliac crest (P<.022). (B) Distribution of the lower clip in the higher located ovary. The solid line denotes the level of the iliac crest and the dashed line indicates 1.5 cm above the iliac crest VOL. 97 NO. 6 / JUNE 2012

5 Fertility and Sterility TABLE 2 Multivariate analysis of factor associated with normal ovarian function after lateral ovarian transposition after adjuvant radiation (N [ 31). Characteristics No. of patients, N (%) Univariate analysis Multivariate analysis P value OR (95% CI) P value Age (y) <40 20 (65.5) ( ).071 R40 11 (35.5) Location a Upper b 11 (35.5) ( ).014 Lower b 20 (65.5) Radiation dose c %5,040 cgy 20 (65.5).25 >5,040 cgy 11 (35.5) BMI (m/kg 2 ) <185 5 (16.1).248 R18.5, <23 18 (58.1) R23 8 (25.8) a The clip's location at the lower border in the higher located ovary. b Upper ¼ more than 1.5 cm above iliac crest; lower ¼ less than 1.5 cm above iliac crest. c The dose of external radiation. The dose HDR brachytherapy was excluded. ovarian transposition is needed to protect ovaries from radiation as oocytes are very sensitive to radiation-induced damages. Radiation dose affects the menopausal age (5). Ovarian failure can occur after single dose of 400 cgy or a fractionated regimen of 1,500 cgy during 10 days. The radiation dose inducing ovarian failure after treatment decreases with increasing age (6). A study reported that ovarian function was preserved in 64% of patients with bilateral ovarian transposition who received a radiation dose of <500 cgy (7). Typically, within 4 8 weeks after radiation, serum E 2 levels decline, whereas FSH levels progressively increase and menopausal symptoms, such as hot flushing, become evident. The possibility of cancer metastasis to the transposed ovaries could be a major concern. Although the chance of ovarian metastasis have been thought to be rare and negligible (8, 9), ovarian metastasis on transposed ovary in patients treated for squamous cell carcinoma of the uterine cervix has been reported (10). In another study, ovarian metastasis was found in 1 of 103 patients (11). We experienced seven recurrent cases during follow-up, none of which had ovarian metastasis. However, we recently experienced a case of ovarian metastasis that was diagnosed at 2.5 months after laparoscopic lateral ovarian transposition after primary radiotherapy in a patient with adenocarcinoma of the uterine cervix, who was not included in this study. Regarding the association of tumor histology and ovarian metastasis, Tabata et al. (12) noted that ovarian metastasis is frequently found in patients with adenocarcinoma. Other investigators have reported that the rate of ovarian metastasis was not related with histologic type (11, 13, 14). The risk of ovarian metastasis in transposed ovary increases in patients with a bulky tumor (12, 13). Morice et al. (11) recommended that bilateral ovarian transposition should be reserved for patients with small cervical mass (<3 cm) to decrease the risk of ovarian metastasis. An oophorectomy could rarely facilitate the early detection of occult metastasis from primary tumor in advanced cervical cancer. The transposed ovary can also induce complications such as torsion of ovarian pedicle, bleeding, and symptomatic ovarian cyst (15, 16). In this study, right salpingooophorectomy was performed in one patient (because of a 20-cm endometriotic cyst) who underwent laparoscopic bilateral ovarian transposition 6.2 years ago. Therefore, the risks of complications including ovarian cyst, endometriosis, and the risk of ovarian metastasis, as well as benefits of ovarian transposition such as preservation of hormone function should be explained to the patient before surgery. In our institution, lateral ovarian transposition is not a standard procedure in young patients with uterine cancer and it depends on the surgeon's preference and patient's request. The ovaries can be transposed medially behind the uterus, laterally outside the radiation field, or to any distant site (15). There is no consensus concerning the location of transposed ovaries, although the general agreement appears to be as high and as lateral as possible from the original sites to be away from the pelvic radiotherapy field. The approach to transpose ovaries to a high anterolateral position at least 3 4 cm above the umbilical line, and not the paracolic gutter, has been reported (17). The merit of this approach would be that it is not only good for the standard pelvic radiation field but also can be used in the situations where an extended abdominopelvic radiation field needs to be used. A greater likelihood of early menopause when the ovaries are transposed has been reported (15, 18, 19). The effectiveness of lateral ovarian transposition for ovarian preservation after adjuvant radiation has been studied. In three studies, the rate of ovarian failure after adjuvant radiation in patients after lateral ovarian transposition varied widely from 17.0% 88.6% (9, 14, 15). Another study reported that 57% of patients experienced ovarian failure after transposition of ovary more than 3 cm above the umbilical line (17). Although the distance of the transposed ovaries from the radiation field is considered important, VOL. 97 NO. 6 / JUNE

6 ORIGINAL ARTICLE: FERTILITY PRESERVATION injuries to the ovarian vessels that often occur in surgical procedures and insufficient vascularization need to be considered at the same time. In our series, all 10 women (31%) who underwent radical hysterectomy and lymph node dissection plus bilateral ovarian transposition without adjuvant radiotherapy had FSH level <30 or no menopausal symptoms, suggesting that ovarian function was not impaired from our ovarian transposition procedure. Half of the patients who experienced ovarian failure in our study were older than 40 years and six patients in group 2 was more than 45 years when follow-up FSH level was checked, which might explain the relatively high rate of ovarian failure in our study population. Premenopausal hysterectomy accelerates ovarian failure. Moorman et al. (20) reported that the risk for earlier ovarian failure was increased in patients who underwent hysterectomy due to benign disease such as leiomyoma and endometriosis. We suggest a cutoff value of the location of a transposed ovary as 1.5 cm above the iliac crest with 63.6% (95% CI 30.8% 89.1%) sensitivity of 85% (95% CI 62.1% 96.8%) specificity of 70% (95% CI 34.8% 93.3%) positive predictive value, and an 81% (95% CI 58.1% 94.6%) negative predictive value. Age is also known to be an important factor determining the success of ovarian transposition for candidate patients (11, 19, 21). It has been reported that the rate of menopause after hysterectomy is fairly high in patients who undergo hysterectomy with an ovarian transposition procedure when the patients'a age is more than 40 years (17). Lateral ovarian transposition is generally recommended in patients who are <40 years of age (7 9, 11, 19). In this study, age (<40 years) showed borderline significance. However, age was significantly correlated with ovarian failure when age was analyzed with a cutoff value of 32 years instead of 40 years, based on the ROC curve. Therefore, bilateral ovarian transposition is strongly recommended in patients who are <32 years of age. The relationship between body weight and the age at menopause have been examined (22, 23). The BMI affects age of natural menopause and a greater BMI contributes to later age of menopause (22). Increased peripheral conversion of plasma androstenedione (A) to estrone (E 1 ) resulting from obesity is related to the delay in menopausal age (24). In our study, BMI did not influence the preservation of ovarian function, which might be explained because Korean women generally have a lower rate of overweight and obesity compared with Western women. Our study has several limitations. First, it does not provide the highest level of evidence because the study design is retrospective. Missing data of FSH level might reduce the quality. Second, there is a potential difference in preserving ovarian function between unilateral ovarian transposition and bilateral ovarian transposition. We did not stratify ovary function by the number of transposed ovary. Last, although it is unresolved whether surgery itself is the cause of earlier ovarian failure, surgery type, such as laparotomy or laparoscopy, might have influenced ovarian function. In summary, lateral ovarian transposition is a safe method. The selection of young patients and adequate location of the transposed ovary is required to maintain ovarian function effectively after adjuvant radiotherapy. Larger studies are needed to confirm the risk factors predicting ovarian failure after radiation in patients who undergo lateral ovarian transposition. REFERENCES 1. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in Intern J Cancer/J Intern Cancer 1993;54: Waggoner SE. Cervical cancer. Lancet 2003;361: McCall CM, Keaty EC, Thompson JD. Conservation of ovarian tissue in the treatment of carcinoma of the cervix with radical surgery. Am J Obstet Gynecol 1958;75: [discussion: 600 5]. 4. Pahisa J, Martinez-Roman S, Martinez-Zamora MA, Torne A, Caparros X, Sanjuan A, et al. Laparoscopic ovarian transposition in patients with early cervical cancer. Intern J Gynecol Cancer 2008;18: Sakata R, Shimizu Y, Soda M, Yamada M, Hsu WL, Hayashi M, et al. Effect of radiation on age at menopause among atomic bomb survivors. Radiation Res Husseinzadeh N, van Aken ML, Aron B. Ovarian transposition in young patients with invasive cervical cancer receiving radiation therapy. Intern J Gynecol Cancer 1994;4: Wallace WH, Thomson AB, Saran F, Kelsey TW. Predicting age of ovarian failure after radiation to a field that includes the ovaries. Int J Radiat Oncol Biol Phys 2005;62: Clough KB, Goffinet F, Labib A, Renolleau C, Campana F, de la Rochefordiere A, et al. Laparoscopic unilateral ovarian transposition prior to irradiation: prospective study of 20 cases. Cancer 1996;77: Bisharah M, Tulandi T. Laparoscopic preservation of ovarian function: an underused procedure. Am J Obstet Gynecol 2003;188: Morice P, Haie-Meder C, Pautier P, Lhomme C, Castaigne D. Ovarian metastasis on transposed ovary in patients treated for squamous cell carcinoma of the uterine cervix: report of two cases and surgical implications. Gynecol Oncol 2001;83: Morice P, Juncker L, Rey A, El-Hassan J, Haie-Meder C, Castaigne D. Ovarian transposition for patients with cervical carcinoma treated by radiosurgical combination. Fertil Steril 2000;74: Tabata M, Ichinoe K, Sakuragi N, Shiina Y, Yamaguchi T, Mabuchi Y. Incidence of ovarian metastasis in patients with cancer of the uterine cervix. Gynecol Oncol 1987;28: Sutton GP, Bundy BN, Delgado G, Sevin BU, Creasman WT, Major FJ, et al. Ovarian metastases in stage IB carcinoma of the cervix: a Gynecologic Oncology Group study. Am J Obstet Gynecol 1992;166(1 Pt 1): Owens S, Roberts WS, Fiorica JV, Hoffman MS, LaPolla JP, Cavanagh D. Ovarian management at the time of radical hysterectomy for cancer of the cervix. Gynecol Oncol 1989;35: Anderson B, LaPolla J, Turner D, Chapman G, Buller R. Ovarian transposition in cervical cancer. Gynecol Oncol 1993;49: Husseinzadeh N, Nahhas WA, Velkley DE, Whitney CW, Mortel R. The preservation of ovarian function in young women undergoing pelvic radiation therapy. Gynecol Oncol 1984;18: Huang KG, Lee CL, Tsai CS, Han CM, Hwang LL. A new approach for laparoscopic ovarian transposition before pelvic irradiation. Gynecol Oncol 2007;105: Ranney B, Abu-Ghazaleh S. The future function and fortune of ovarian tissue which is retained in vivo during hysterectomy. Am J Obstet Gynecol 1977; 128: Feeney DD, Moore DH, Look KY, Stehman FB, Sutton GP. The fate of the ovaries after radical hysterectomy and ovarian transposition. Gynecol Oncol 1995;56: Moorman PG, Myers ER, Schildkraut JM, Iversen ES, Wang F, Warren N. The effect of hysterectomy with ovarian preservation on ovarian function. Obstet Gynecol 2011;118: VOL. 97 NO. 6 / JUNE 2012

7 Fertility and Sterility 21. Haie-Meder C, Mlika-Cabanne N, Michel G, Briot E, Gerbaulet A, Lhomme C, et al. Radiotherapy after ovarian transposition: ovarian function and fertility preservation. Intern J Radiation Oncol Biol Phys 1993;25: Akahoshi M, Soda M, Nakashima E, Tominaga T, Ichimaru S, Seto S, et al. The effects of body mass index on age at menopause. Intern J Obesity Relat Met Dis 2002;26: Neslihan Carda S, Bilge SA, Ozturk TN, Oya G, Ece O, Hamiyet B. The menopausal age, related factors and climacteric symptoms in Turkish women. Maturitas 1998;30: MacDonald PC, Edman CD, Hemsell DL, Porter JC, Siiteri PK. Effect of obesity on conversion of plasma androstenedione to estrone in postmenopausal women with and without endometrial cancer. Am J Obstet Gynecol 1978; 130: VOL. 97 NO. 6 / JUNE

8 ORIGINAL ARTICLE: FERTILITY PRESERVATION SUPPLEMENTAL FIGURE 1 Classification according to the type of operation in the patients who underwent ovarian transposition (N ¼ 53). RT ¼ radiotherapy e1 VOL. 97 NO. 6 / JUNE 2012

9 Fertility and Sterility SUPPLEMENTAL FIGURE 2 Classification according to adjuvant radiotherapy and presence of ovarian function in the patients who underwent ovarian transposition (N ¼ 53). Group 1, patients who received adjuvant radiotherapy and normal ovarian function; group 2, patients who received adjuvant radiotherapy and were in menopausal state; group 3, patients who did not receive adjuvant radiotherapy. VOL. 97 NO. 6 / JUNE e2