The current study showed that OT could effectively preserve ovarian function in patients treated with adjuvant RT, and EBRT and VB were significant prognostic factors affecting OFFS. Moreover, the preservation of both ovaries resulted in a significant increase in OFFS in the group without RT.
OT is a surgery to transpose the ovaries out of the field of radiation to protect them from radiation damage [12]. Hoekman et al. [11] noted that the 5-year ovarian survival rate was 60.3% in patients who underwent OT before RT, whereas all patients who received RT without OT had ovarian failure, which is similar to our study. The degree of ovarian damage and ovarian failure is affected by the radiation dose of ovaries [13, 14]. Several studies reported that the OT before pelvic RT reduces the ovarian dose received to approximately 5–10% of that in the untransposed ovaries [6, 15, 16]. Winarto et al. demonstrated that the lateral transposed ovaries receives about 0.45–4.5 Gy, corresponding to 1–10% of the total RT dose of 45 Gy [16]. Our study showed that the rate of OFFS at 2 years was 61.4% for patients with OT before pelvic RT, whereas all patients who received adjuvant RT without OT had ovarian failure. Therefore, OT before pelvic RT could be helpful for preserving ovarian function for candidates for adjuvant RT or CCRT.
Our results showed that in groups 1 and 2, 78% (18/23) of the patients received EBRT alone, and 22% (5/23) had an additional VB in addition to EBRT. The rates of ovarian preservation at 2 years after RT were 54.5% in EBRT alone and 0% in patients with EBRT plus VB. Morice et al. [17] reported that the ovarian survival was 100% (11/11) after OT, 90% (53/59) after OT and VB, and 60% (15/25) after OT, VB and EBRT. Clough et al. [18] reported that the mean dose of transposed ovary was 2 Gy, whereas the untransposed ovary was 32.2 Gy on pelvic dosimetry of patients who received 65 Gy with VB alone. Although the number of patients with VB in our study was small, additional VB was a significant prognostic factor in ovarian survival.
Several studies reported that location of transposed ovary was associated with ovarian survival, and the distance between the edge of the RT field and the transposed ovaries affects the successful preservation of ovarian function. Winarto et al. suggested the above iliac crest as the suboptimal placement of the ovary [16]. Yoon et al [10] also noted that location of transposed ovaries may be associated with ovarian failure after RT. They suggested that young women with early-stage cervical cancer who might be a candidate for postoperative RT should be transposed to the ovaries as highly as possible during radical hysterectomy to avoid ovarian failure. Hwang et al [19] suggested that location of transposed ovary more than 1.5 cm above the iliac crest was recommended to preserve ovarian function after pelvic RT in uterine cervical cancer. In addition, even if the ovaries are sufficiently outside the RT field, ovarian damage can also occur as a result of scattered radiation doses. Van et al. [20] reported that patients experienced ovarian failure if the scatter radiation dose to the transposed ovaries was more than 300 cGy. The current study showed that in group 1, all four patients treated with EBRT plus VB had transposed ovary below the iliac crest (median − 1.9 cm, range − 5.1-[-0.5]), and all experienced early ovarian failure. The location of the transposed ovary was associated with OFFS in univariate analysis. Thus, the ovaries should be transposed as high and laterally as possible from the pelvic brim, especially in candidates who received definitive CCRT with EBRT and brachytherapy.
The degree of ovarian damage is dependent on the patient’s age as well as the irradiated ovarian dose and type of gonadotoxic agent used [6, 14, 21, 22]. OT has been generally suggested for patients aged under 40 years because the patient’s age is also known to be a crucial factor to determine the success of OT for candidate patients [4, 14, 17, 18]. Morice et al. [17] reported the limited value of OT in patients over 40 years because they have an intrinsically decreased fertilization possibility as well as a much higher risk for ovarian failure despite OT. They noted that the rate of menopause after hysterectomy is clearly too high to recommend OT to patients tagged 40 years and older treated for cervical cancer. It has been reported that for patients who undergo hysterectomy with OT procedure, ovarian failure occurred in 14.3% (1/7) of patients under 40 years of age, compared with 85.7% (6/70) in patients over 40 years of age [23]. In contrast to previous studies, our study demonstrated that older age (≥ 40 years) did not affect the ovarian failure in the groups with RT (groups 1 and 2) or without RT (groups 3 and 4). Moreover, OT procedure itself did not affect ovarian failure in patients without RT. The median age at menopause among Korean women is approximately 50 years [24]. The age of menopause ranged from 33 to 61 years, with 88.2% between 45–55 years, 9.4% under 44 years, and 2.4% over 56 years. Considering that ovarian failure can affect the quality of life as well as lead to hot flashes, vaginal dryness, and cardiovascular disease, OT could be sufficiently considered even in Korean women aged over 40 years.
The sequelae of OT such as ovarian cysts, ovarian torsion, ovarian metastasis and bowel obstruction is considered when performing OT [25]. Morice et al. [17] reported that for patients undergoing radical hysterectomy and OT, the development of benign ovarian cyst was reported in 23% (22/95) patients, three of whom required surgical intervention. The rates of ovarian cysts were 18% (2/11) in the radical hysterectomy alone group, 34% (20/59) in the group that underwent radical hysterectomy and VB, and 0% (0/29) in patients who underwent radical hysterectomy, EBRT and VB (p = 0.01) in their study. Chambers et al. [26] reported that the incidence of symptomatic ovarian cysts was 7.4% in patients who underwent radical hysterectomy alone and 7% in patients who also received RT as compared to 24% in those who underwent OT, and most ovarian cysts required surgical intervention. Gomez-Hidalgo et al. reported two cases of ovarian torsion after OT [27]. The current study showed that OT did not affect the ovarian failure in the group without RT. Although OT did not affect ovarian failure, consideration should be given to the surgical morbidity mentioned in previous studies.
The number of remaining ovaries can affect ovarian failure. In a previous study, Buekers et al. [3] noted that ovarian failure was significantly different between patients of unilateral oophorectomy and contralateral OT and those with ovaries preserved and transposed (4 months vs 43 months, p = 0.003). All patients with unilateral oophorectomy had ovarian failure by 1 year after treatment, but 41% patients with both ovaries retained maintained ovarian function after one year in their study. Our result showed that in the group without RT, the number of remaining ovaries was an independent factor for ovarian failure, which is similar to previous study. However, unilateral oophorectomy also showed favorable outcome with 75.8% of 2-year OFFS in patients without RT in the current study.
The current study had several limitations. First, this study was retrospective; therefore, serum FSH levels were not collected regularly during the follow-up period. Second, the number of patients included in this study was small. The number of patients in group 1, 2, and 3 was less than 30, making it difficult to divide into subgroups for analysis. Third, this study did not address the dosimetry effects of the transposed ovary on ovarian failure. Since ovarian dose is associated with ovarian function preservation, analysis on the dosimetric impact of pelvic irradiation received by the transposed ovary is required in the future.