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Keywords:

  • irradiation;
  • malignancy;
  • oophoropexy;
  • ovarian transposition

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Aim

To investigate the indications and effectiveness of ovarian transposition before pelvic irradiation.

Methods

This was a retrospective analysis of patients with malignancies who underwent ovarian transposition before pelvic irradiation. The collected data included age of patient, type and stage of cancer, details of irradiation treatment, and clinical and biochemical parameters of ovarian function during the period of follow-up.

Results

Fourteen adult and four pediatric patients with different types of cancers underwent ovarian transposition during the study period. The common tumor types for the adult patients were cervical cancer (n = 4), rectal cancer (n = 4) and medulloblastoma (n = 3), and for pediatric patients was medulloblastoma (n = 2). The mean age for adult patients was 31 years (range, 21–40) and for pediatric patients was 7 years (range, 4–10). Of the adult patients, 10 had adjuvant chemotherapy and four had neoadjuvant chemotherapy added to their radiotherapy program. All pediatric patients received adjuvant chemotherapy. Thirteen of 14 (92.85%) adult patients had normal serum level of follicle-stimulating hormone (FSH; ≤12 IU/L) and E2 (>50 pg/mL). Only one patient had premature menopause. All pediatric patients demonstrated a normal serum level of FSH (<12) and E2 for their age at 3 and 6 months after completion of their treatment. The mean follow-up was 42 months (range, 34–50).

Conclusion

Ovarian transposition is an effective procedure for the preservation of ovarian function. Young patients with non-hormone-dependent pelvic tumors should be offered a laparoscopic ovarian transposition before the start of pelvic radiotherapy.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Ovarian transposition (oophoropexy) is a surgical procedure to reposition the ovary out of the radiation field. If abdominal surgery is planned for tumor removal, oophoropexy can be concomitantly performed; alternatively, it may be performed as a separate, usually laparoscopic, procedure.

Ovarian preservation seems mandatory for young patients with non-hormone-dependent pelvic malignancies requiring pelvic irradiation to preserve ovarian function and to also preserve reproduction function in patients with non-gynecological cancers.

Oophoropexy is found useful in preserving ovarian function during the treatment of gynecological malignancies and hematological cancers such as Hodgkin's lymphomas. If oophoropexy is performed before radiation, ovarian function is maintained in most young women.[1-3] There have been suggestions that lateral transposition may be more protective than median transposition of the ovaries.[4, 5]

There are routine surgical risks, as well as possible unique complications, such as fallopian tube infarction, ovarian cyst formation, chronic pain, or migration of the ovaries back to their native position in the pelvis.[6]

We describe a retrospective series of 18 patients who underwent ovarian transposition before receiving pelvic irradiation as part of the treatment of different types of cancers. The aim of this study was to investigate the indications and effectiveness of ovarian transposition on the preservation of the ovarian function before pelvic irradiation for pelvic malignancies.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

A retrospective review of the medical records of all patients who underwent ovarian transposition at King Hussein Cancer Center in Jordan between January 2003 and December 2010 was conducted. The collected data included age of patient, type and stage of cancer, details of irradiation treatment, and clinical and biochemical parameters of ovarian function during the period of follow-up. All patients had oophoropexy to receive pelvic irradiation as part of their treatment. None of the patients had vasomotor symptoms and all of them had normal serum levels of follicle-stimulating hormone (FSH) before the procedure. The surgical procedure was performed by gynecological oncologist, general gynecologist and pediatric surgeon. The patients, and their parents if they were of pediatric age group, were informed of the risks and benefits, and the procedure was explained to them before an informed consent was obtained. Five patients had the ovarian transposition performed through laparotomy as a concomitant procedure when abdominal surgery was planned for tumor removal, and 13 patients had laparoscopic oophoropexy performed as a separate procedure.

Bilateral ovarian transposition to the paracolic gutter was performed in 17 patients and one had unilateral transposition. There was no radiological or clinical evidence of ovarian metastasis before the procedure. On follow-up, ovarian function was evaluated by the presence or absence of menopausal symptoms and the measurement of FSH and estrogen (E2) serum levels after completion of pelvic irradiation.

The collected data included patients' characteristics (age, marital status and menstrual cycle) in addition to their disease information (tumor type, stage, grade, cell type and treatment) and the serum level of FSH and E2.

Radiotherapy treatment was tailored to fit the tumor type. In patients with cervical cancer (n = 4), two patients received external irradiation (EBRT) only (54 Gy) and two patients received external pelvic irradiation (50.4 Gy) followed by high dose rate intravaginal brachytherapy (11 Gy/2 fractions). The daily fraction for patients who received external irradiation was 1.8 Gy. A 3-D conformal radiotherapy with multiple fields with 10 MV energy was used. Weekly concurrent cisplatin (50 mg/m2) with EBRT for 5 weeks was given to all patients.

Patients with medulloblastoma (n = 5; three adults and two pediatric) were of the average-risk category and had received a dose of 23.40 Gy/14 fractions of craniospinal therapy (CSRT) with a posterior fossa boost of 32.4 Gy (total dose, 55.8 Gy to posterior fossa) in fractions of 1.8 Gy/day, 5 days/week. The craniospinal irradiation was delivered in two opposing lateral fields to the brain and one direct spinal field using 6 MV energy. The boost to the posterior fossa was delivered via 3-D conformal radiotherapy using 6 MV.

The CSRT dose for the adult patients was 32.4 Gy. It was delivered in 18 fractions of 1.8 Gy/day, 5 fractions/week completed in 24 days with a boost of 19.8 Gy/11 fractions to the posterior fossa. Treatment for the craniospinal axis was completed in 244 days and the entire treatment was completed within 51 days. The spinal treatment volume extended laterally to cover the recesses of the entire vertebral bodies with at least a 1-cm margin at either side or inferiorly 1–2 cm below the termination of the thecal sac (S2–S3 level).

Patients who had rectal carcinoma, synovial sarcoma, osteosarcoma, ependymoma of the cauda equine and rhabdomyosarcoma, sacrococcygeal teratoma received external pelvic irradiation (45–60 Gy) using 3-D conformal radiotherapy with multiple fields with 10 MV energy. The upper border of the external pelvic field did not exceed the level of L5. All patients with rectal cancers received six courses of 5-fluorouracil on weekly regimen concomitantly with pelvic irradiation (45 Gy) as a neoadjuvant treatment.

After surgery, pediatric patients were treated with weekly vincristine during radiotherapy (1.5 mg/m2, maximum of eight doses), followed by eight cycles of chemotherapy, beginning 6 weeks after CSRT. At 3 and 6 months after completion of the planned treatment, serum level of FSH and E2 was obtained for all patients.

The statistical analysis was done using SAS ver. 9.1. Descriptive statistics were performed. The mean, minimum and maximum values for age, FSH and E2 levels were calculated.

Ethical approval was obtained from the institutional review board before commencing the study.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Fourteen adult and four pediatric patients with different types of cancers underwent ovarian transposition during the study period. For the adult age group, laparoscopic (n = 10) and open ovarian transposition (n = 4) had been performed before pelvic radiation therapy. No immediate intraoperative or postoperative complication was observed. Distribution of the tumor type in the adult and pediatric patients is presented in Table 1.

Table 1. Distribution of the tumor type in the adult and pediatric patients
Type of tumorn (%)
Adult patients 
Cervical cancer4(28.6)
Rectal cancer4(28.6)
Medulloblastoma3(21.4)
Ependymoma1(7.1)
Osteosarcoma(gluteal region)1(7.1)
Synovial sarcoma of right thigh1(7.1)
Total14(100.0)
Pediatric patients 
Medulloblastoma2(50.0)
Pelvic rhabdomyosarcoma1(25.0)
Sacrococcygeal teratoma1(25.0)
Total4(100.0)

The mean age was 31 years (range, 21–40). Twelve of 14 patients had regular menstrual cycles before the procedure. Ten women had adjuvant chemotherapy and four had neoadjuvant chemotherapy added to their radiotherapy program. Thirteen of 14 (92.85%) adult patients had normal serum level of FSH (≤12 IU/L) and E2 (>50 pg/mL).

Only one patient had menopausal symptoms in the form of hot flushes and anxiety and her FSH and E2 serum level were more than 45 IU/L and less than 40 pg/mL, respectively, at three consecutive measurements at 1, 3 and 6 months after the completion of pelvic radiation. This patient was 33 years old and was diagnosed with locally advanced low rectal cancer T3N1M0 (clinical). Before the neoadjuvant chemotherapy/radiotherapy treatment, the patient underwent laparoscopic oophoropexy of the left ovary while the right ovary was adherent to the tumor. A total dose of EBRT of 50.4 Gy in 28 fractions of 1.8 Gy/day, 5 days/week with concurrent chemotherapy of weekly 5-FU for six cycles was given.

The irradiation dose was 45 Gy, 18 Gy to the right and left ovary, respectively. The patient developed vasomotor menopausal symptoms immediately after the completion of radiotherapy. The irradiation dose to the ovary was calculated before treatment from the dose-volume histogram. A pinnacle planning system (computed tomography [CT] planner) was used to delineate the target and organ(s) at risk on each CT slice, and the data entered in the system to generate the dose distribution for the target and organ(s) at risk.

The patient then had a palliative colostomy because of progressive disease. In the last follow-up visit for the patient, that was 2 months before the data collection, she was alive with progressive disease.

In the pediatric group, laparoscopic (n = 3) and open oophoropexy (n = 1) had been performed. The mean age was 7 years(range, 4–10). The estimated radiation dose to the ovaries is presented in Table 2. All patients had adjuvant chemotherapy as follows: one patient received Carbotaxol, ifosfamide, Sodium 2-mercaptoethane sulfonate (MESNA); one patient received vincristine, lomustine and cisplatin; one patient received vincristine and cisplatin; and one patient received vincristine and cyclophosphamide. All patients demonstrated a normal serum level of FSH (<12) and E2 for their age at 3 and 6 months after completion of their treatment. The mean follow-up was 42 months (range, 34–50).

Table 2. Estimated irradiation dose to both ovaries after pelvic radiotherapy
Type of tumor (n)Mean dose
Medulloblastoma (5)1.3 Gy
Rectal cancer (4)2.1 Gy for three patients and 18 Gy for one patient
Cervical cancer (4)4.1 Gy
Pelvic rhabdomyosarcoma (1)2.65 Gy
Ependymoma (1)10.8 Gy
Other sarcomas (3)(6.4 Gy, 8.8 Gy 14.4 Gy)

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Ovarian transposition usually allows preservation of ovarian function by reducing the dose delivered to the ovaries.[2, 7] Oophoropexy is only justified when the risk of ovarian microscopic metastasis is very low. In this study, we are reporting on two groups of patients of different age (adult, n = 14; pediatric, n = 4).

The reported indications for ovarian transposition include a spectrum of pelvic and non-pelvic tumors: cervical cancer,[7-9] Hodgkin's disease,[9, 10] cauda equine ependymoma[9] and anorectal cancer.[11] This diversity was shown in our study, with the most common indications being medulloblastoma (n = 5), cervical cancer (n = 4), rectal cancer (n = 4) and musculoskeletal neoplastic disease (n = 4). None of our patients had ovarian transposition for Hodgkin's lymphoma because the majority were treated with systemic chemotherapy and pelvic irradiation therapy was not given.

Preservation of ovarian function is dependent on three factors: (i) the age of the patient; (ii) the dose of radiation delivered to the ovaries; and (iii) current use of chemotherapy (alkylating agents have the biggest negative impact on ovarian function).[9, 12, 13] A single dose of 8 Gy or fractionated doses of 15 Gy induce premature menopause in almost all females, while doses of less than 1.5 Gy do not have any effect on ovarian function; with doses between 1.5 and 8 Gy, the risk of menopause is mainly related to the patient's age.[14, 15] Craniospinal irradiation for medulloblastoma can impair fertility in girls, and 50–70% of patients who received radiotherapy to hypothalamic–pituitary axis developed oligomenorrhea and low estradiol level despite ovarian transposition. The published work indicates that an ovarian dose of 4 Gy causes permanent infertility in 30% of young females and that doses of less than 1.5 Gy over the whole treatment are desirable.

In the published work, the success of ovarian transposition in preserving the ovarian function is variable. Pahisa et al.[16] had a 72.7% success rate after a mean follow-up of 44 months. Morice et al.[12] achieved an ovarian preservation rate of 83% at a mean follow-up of 31 months. Al-badawi et al.[17] reported a 65% success rate after a mean follow-up of 33 months.

Stillman et al.,[18] in a series of 94 patients between the ages of 1 and 17 years, did not report any cases of menopause when the ovaries received less than 1.5 Gy, 14% of menopause when the dose was between 1 and 10 Gy, and 68% of patients developed menopause when the ovarian radiation dose was beyond 12 Gy.

Our series appears to confirm the figures of Stillman et al.[18] for the pediatric group and it exceeds the success rate of other reports[12, 16, 17] for the adult group. We observed no cases of menopause in the pediatric group and had 92.8% success rate of preservation of ovarian function in the adult group at a mean follow-up period of 42 months.

Although ovarian transposition does preserve ovarian function after pelvic irradiation, it may have a long-term affect on ovarian function. A greater likelihood of early or premature menopause has been reported.[19, 20] It is unresolved whether the surgery itself or the surgery type, such as laparotomy or laparoscopy, might have influenced ovarian function. Injuries to the ovarian vessels that often occur during surgical procedures may cause insufficient vascularization. The authors admit that the hormonal follow-up at 3 and 6 months after treatment completion is inadequate and this is a serious limitation for this study. The treating physicians relied mainly on clinical symptoms to assess the ovarian function during the follow-up period.

The patient who had lost her ovarian function was 33 years old and was diagnosed with locally advanced low rectal cancer T3N1M0 (clinical). She had a total dose of EBRT of 50.4 Gy and the ovarian irradiation dose was 18 Gy. The menopause may be attributable to irradiation dose.

The strength of this study is the diversity of the indications for oophoropexy and the age group analysis and reporting. The main limitations are the retrospective type and the small number of patients.

In conclusion, ovarian transposition is an effective procedure for the preservation of ovarian function. Young patients with non-hormone-dependent pelvic tumors should be offered a laparoscopic ovarian transposition before the start of pelvic radiotherapy.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
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