Ovarian transposition before pelvic radiation

INTRODUCTION — Oocytes are uniquely sensitive to radiation injury. A mathematical model predicted 16 gray (Gy) of radiation would deplete the ovarian oocyte pool at age 20 years and 10 Gy of radiation would deplete the ovarian oocyte pool at age 45 years [1]. One method of protecting the ovaries from radiation injury is to transpose them out of the radiation field (ie, ovarian transposition, also known as ovarian suspension, oophoropexy, or ovariopexy) [2,3]. The vascular pedicle remains intact in ovarian transposition, which distinguishes this procedure from ovarian transplantation.

Historically, the ovaries were relocated medially by suturing them to the posterior uterus, and protected during radiation therapy with a lead shield placed centrally on the abdomen. However, medially placed ovaries still absorb radiation from scatter and some transmission through the shield, reducing the efficacy of the procedure. In one report of medial ovarian transposition by positioning the ovaries behind the uterus in 11 girls with Hodgkin lymphoma, the authors reported 14 pregnancies approximately 15 years later [4]. Contemporary procedures transpose the ovaries above the pelvic brim and as lateral as possible, which minimizes the ovarian dose of radiation and improves efficacy compared with medial approaches. Various lateral locations have been used, including the base of the round ligament, the level of lower kidney pole, and the paracolic gutters [5,6].

Related topics are discussed in detail separately, including:

●Pelvic radiation and toxicity (see "Treatment-related toxicity from the use of radiation therapy for gynecologic malignancies")

●Ovarian failure following radiation therapy (see "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery")

PATIENT SELECTION — Ovarian transposition is performed to preserve fertility or prevent early menopause in reproductive-age patients who are undergoing pelvic or low abdominal radiation therapy and who will be treated with chemotherapy with low probability of gonadotoxicity (table 1). In our institution, the most common cancers in adults treated with low abdominal radiation are rectal and anal. These cancers are usually also treated with fluorouracil (FU) or mitomycin, which are not gonadotoxic, thus these patients are candidates for ovarian transposition. In children, Hodgkin or non-Hodgkin lymphoma, vaginal or uterine tumors, pelvic Ewing's sarcoma, and spinal tumors are more common reasons for referral for the procedure [7,8].

The decision to perform ovarian transposition depends on a combination of factors including the patient’s age, ovarian reserve, desire for future pregnancy, personal preferences (eg, willingness to take hormone therapy for premature menopause), medical condition, and prognosis. The patient’s medical team (medical and radiation oncologists, reproductive endocrinologist, and surgeon who will perform the transposition) should help the patient weigh the risks and benefits of ovarian transposition based on the specific clinical situation.

The potential benefit of the procedure is lower in older patients and those at increased risk of ovarian metastases:

●Menopausal patients are not candidates for ovarian transposition, as the benefits of protecting postmenopausal ovarian function are minimal.

●Patients over 40 years old are not good candidates for transposition because they generally have reduced fertilization potential and are a high risk for ovarian failure even with the procedure [9].

●Patients with cancers at moderate or high risk for ovarian metastasis may not be good candidates for ovarian preservation and, in turn, ovarian transposition. Cancers at high risk of ovarian metastasis include leukemia, neuroblastoma, and Burkitt lymphoma; moderate risk cancers include adenocarcinoma/adenosquamous carcinoma of the cervix, squamous cell cervical cancer >3 cm in diameter or >stage Ib1 [10], colon cancer, stage IV breast cancer, and/or infiltrative lobular breast cancer [11]. The incidence of ovarian metastasis among patients with cervical cancer undergoing ovarian transposition is 0.4 percent [12].

PREOPERATIVE EVALUATION AND COUNSELING — Patients whose primary objective is fertility preservation should be referred to a reproductive endocrinologist/reproductive surgeon to assess ovarian reserve and discuss their options for fertility preservation. Embryo cryopreservation is the most effective method of fertility preservation; mature oocyte cryopreservation is also effective and is a good option if no sperm are available for fertilization prior to cryopreservation. These procedures can be performed in addition to, or instead of, ovarian transposition, depending on the time and resources available before the start of cancer therapy. Retrieval of immature oocytes followed by in vitro maturation and vitrification is a good method of obtaining oocytes when it is not advisable for the patient to undergo ovulation induction [13]. Ovarian tissue cryopreservation is another option, but it is an investigational procedure. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery".)

For patients over 35 years of age and younger patients with risk factors for premature ovarian failure, ovarian reserve should be evaluated. However, no test is highly reliable in predicting fertility potential. The author measures basal serum follicle-stimulating hormone (FSH) (on cycle day 3 if possible) and anti-müllerian hormone (AMH) levels and antral follicle count (AFC). AMH is most useful when time is limited because it can be measured anytime during the menstrual cycle. A menopausal level of FSH (>40 mIU/L) strongly suggests that the procedure will be futile for preserving fertility. High FSH (>10 to 25 mIU/mL on cycle day 3, the cut-off is highly laboratory dependent), low AMH (<0.5 ng/mL), and low AFC (4 to 10 antral follicles usually measured between days 2 and 4 of a regular menstrual cycle) indicate poor ovarian reserve, suggesting poor fertility potential. (See "Female infertility: Evaluation", section on 'Assessment of ovarian reserve'.)

PROCEDURE — Good communication is crucial among the treatment team (medical and radiation oncologists, reproductive endocrinologist, and surgeon performing the transposition). Before surgery, the radiation oncologist should outline the field of radiation on the abdominal wall so the surgeon can determine the best location of transposition.

Ovarian transposition can be performed by laparotomy or laparoscopy; outcomes are similar for both approaches [14]. For patients who are not already undergoing laparotomy for primary treatment of their disease (eg, open radical hysterectomy for cervical cancer), laparoscopy is the preferred approach. The minimally invasive procedure has fewer complications and a shorter healing time than laparotomy, allowing earlier initiation of radiation therapy. Radiation can be started within a day or two following laparoscopy.

We retrieve immature oocytes under transvaginal ultrasound guidance, as well as at laparoscopy before ovarian transposition. In young girls, immature oocytes can only be harvested at laparoscopy.

The key steps of the procedure are:

●The primary trocar is inserted cephalad from the upper margin of the radiation field usually 2 to 3 cm above the umbilicus. This facilitates relocation of the ovaries as high as possible.

●Two secondary trocars are placed at the same level or slightly lower. A third trocar is inserted higher, if needed.

●The abdominal cavity is thoroughly examined, including the liver and diaphragm. We perform peritoneal lavage for cytologic examination, although there is no evidence supporting its use routinely.

●If oocyte retrieval is planned for oocyte or embryo cryopreservation, an oocyte retrieval needle is used to aspirate all visible follicles. If ovarian cryopreservation is planned, we perform a unilateral ovarian wedge resection or occasionally a unilateral oophorectomy. The decision is based on the patient’s preference. Appropriate personnel and laboratory facilities must be available to process these specimens. Before processing the ovarian wedge specimen, the embryologist makes another attempt to retrieve oocytes from all visible follicles in the ovarian tissue.

●The course of each ureter is identified.

●The ovarian ligament and vessels on each side are divided and the mesovarium on each side is opened (figure 1).

●The remaining mesovarium is incised to the infundibulopelvic ligament, leaving the vascular pedicle inside the ligament intact.

●The ovaries are mobilized to a level cephalad to the anterior superior iliac spine without tension [15]. In one report, the authors recommended transposing the ovaries at least 1.12 cm higher than the iliac crest plane [16]. To provide sufficient mobilization, the peritoneum along the infundibulopelvic ligament is incised above the ureter and as far as the aortic bifurcation or paracolic gutter. If mobilization remains inadequate, the fallopian tubes are transected (picture 1); however, in most cases, they can be left intact, facilitating future spontaneous conception [14].

●After ensuring that the ovarian blood supply is not kinked or compromised, the transposed ovaries are sutured securely to the peritoneum lateral to the lower paracolic gutters, close to the lateral aspect of the colon near the level of the iliac fossa, using non-absorbable sutures.

●The lateral opening in the broad ligament caudal to the newly located ovaries is closed with a few sutures to prevent herniation. Alternatively, the transposed ovary can be first inserted into a peritoneal opening retroperitoneally from the infundibulopelvic ligament until it is in the desired new location [17].

●Surgical hemoclips are applied to the border of each ovary to help the radiation oncologist identify the site of the transposed ovaries.

COMPLICATIONS — Complications of ovarian transposition are rare and include reports of injury and torsion of the ovarian blood vessels resulting in vascular ovarian injury, abdominal pain, and infarction of the fallopian tube. Small bowel obstruction related to postsurgical adhesions has also been reported [12].

While ovarian cyst formation is common (and has been reported in up to 95 percent of patients [12]), it may be unrelated to the ovarian transposition procedure.

OUTCOMES

Ovarian function — The purpose of ovarian transposition is to protect the ovaries from radiation and thus preserve endocrine function and fertility. Most of the data on reproductive function after ovarian transposition are based on case reports or small case series.

In a systematic review including almost 700 patients with cervical cancer undergoing ovarian transposition and radiotherapy, ovarian function was preserved in 62 percent of patients; when stratified according to treatment type, preservation of ovarian function was more common after vaginal brachytherapy (86 percent) than those undergoing external radiation therapy plus vaginal brachytherapy (55 percent) [9,12]. Even after chemotherapy, preservation of ovarian function was achieved in 51.1 percent of patients. Ovarian function was considered normally preserved when the follicle-stimulating hormone (FSH) level was <10 mIU/mL, E2 was >50 pg/mL, and when follicles were present on the ultrasound scan.

Younger patient age is an important factor for success. In a small retrospective study of 27 patients with cervical cancer treated with ovarian transposition before pelvic radiation and 29 controls who underwent hysterectomy/trachelectomy without transposition before pelvic radiation, those aged 25 to 30 years, 31 to 35 years, and 35 to 40 years who underwent transposition had five-year ovarian survival rates of 87.5, 62.5, and 42.9 percent, respectively, compared with 0 percent in the nontransposed control group [18]. In a previous review of the literature, laparoscopic ovarian transposition in patients younger than 40 years was associated with preservation of ovarian function in 39 of 44 patients (88.6 percent) [14].

In another retrospective study including 26 females aged 18 and younger with brain tumors treated with spinal irradiation in whom follow-up data were available, those who underwent pretreatment laparoscopic oophoropexy (58 percent of patients) compared with those who did not had a trend towards lower rates of ovarian dysfunction (defined as an elevated FSH level or persistent amenorrhea; 13 versus 45 percent); however, this was not statistically significant [19]. The lack of difference could have been due to the small sample size.

With advances in radiotherapy, including intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc radiation therapy (VMAT), radiation exposure to the ovaries may be further minimized.

The uterus is less sensitive to radiation therapy than the ovaries, but may be affected. (See "Overview of infertility and pregnancy outcome in cancer survivors".)

Pregnancy — Pregnancy rates depend on many factors, including age, type of cancer treatment, and underlying infertility factors. The following studies are examples of the available data:

●A study of 11 girls with Hodgkin lymphoma who underwent bilateral medial ovarian transposition at a median age of 13 years reported 14 pregnancies (12 live births [1 twin] and 3 miscarriages) [4].

●In a series of 37 consecutive patients who underwent ovarian transposition with uterine conservation and pelvic irradiation therapy for pelvic cancer, the overall pregnancy rate was 12/37 (32 percent); a total of 18 pregnancies were achieved among the 12 patients [20]. When the results were analyzed by diagnosis (group 1:27 patients with clear cell adenocarcinoma of the vagina and/or the cervix; group 2: 9 patients with ovarian dysgerminoma and 1 patient with uterine sarcoma), the pregnancy rate was lower in group 1 (15 versus 80 percent). The authors hypothesized the low pregnancy rate in group 1 may be related to diethylstilbestrol-related anomalies of the reproductive tract in addition to brachytherapy [10]. However, there were other differences between groups; for example, more patients in group 1 received brachytherapy (27/27 versus 0/10).

In patients who undergo hysterectomy, gestational carrier pregnancy is possible using oocytes retrieved from the transposed ovaries; several successful cases have been reported [21,22]. (See "Gestational carrier pregnancy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gynecologic surgery".)

SUMMARY AND RECOMMENDATIONS

●Patient selection

•Ovarian transposition is performed to preserve fertility or prevent early menopause in reproductive-age patients who are undergoing pelvic or low abdominal radiation therapy and who will not be treated with gonadotoxic chemotherapy (table 1). (See 'Patient selection' above.)

•Menopausal patients are not candidates for ovarian transposition.(See 'Patient selection' above.)

•Patients over 40 years old with poor ovarian reserve and patients with cancers at moderate or high risk for ovarian metastasis in whom ovarian preservation is contraindicated are also not good candidates for the procedure. (See 'Patient selection' above.)

●Preoperative counseling – Patients should be referred to a reproductive endocrinologist/reproductive surgeon to assess ovarian reserve and discuss their options for fertility preservation. Embryo cryopreservation is the most effective method of fertility preservation; mature oocyte cryopreservation is also effective and is a good option if no sperm are available for fertilization prior to cryopreservation. These procedures can be performed in addition to, or instead of, ovarian transposition, depending on the time and resources available before the start of cancer therapy. (See 'Preoperative evaluation and counseling' above.)

●Procedure

•In patients who are not already undergoing laparotomy for primary treatment of their disease, laparoscopy is the preferred approach and allows early initiation of radiation therapy. (See 'Procedure' above.)

•If oocyte or embryo cryopreservation is planned, all visible follicles are aspirated at the time of the procedure. If ovarian cryopreservation is planned, we perform a unilateral ovarian wedge resection or occasionally unilateral oophorectomy. (See 'Procedure' above.)

•The ovarian ligament and vessels on each side are divided and the mesovarium on each side is opened (figure 1). If mobilization remains inadequate, the fallopian tubes are transected (picture 1); however, in most cases, they can be left intact. (See 'Procedure' above.)

●Outcomes – Laparoscopic ovarian transposition has low complication rates and ovarian function is preserved in most patients. In patients who also undergo hysterectomy, gestational carrier pregnancy is possible using oocytes retrieved from the transposed ovaries. (See 'Outcomes' above.)