In the current review of the literature, uterine transposition was shown to be feasible and safe in a total of 18 reported cases worldwide to date. It successfully preserved hormonal ovarian function in all patients who underwent the surgery. The procedure effectively preserved the uterus and its menstrual function in 14 of 16 patients. Although it is not possible to provide an exact fertility rate due to insufficiently documented data, it can be asserted that the procedure offers the potential for patients to achieve spontaneous pregnancies and carry them to term, resulting in healthy babies.

To date, no pelvic radiotherapy technique has been able to preserve patient fertility. For these patients, the only options are cryopreservation of oocytes and/or embryos for having a child with their own genetic material and ovarian transposition to maintain ovarian hormone production, as recommended by American Society of Clinical Oncology (ASCO).15 16 Cryopreservation and ovarian tissue transplantation are alternative options, but data are still lacking. However, these techniques do not allow women to safely carry a pregnancy to term, and requires a surrogate uterus. Additionally, these treatments may not be practical options due to religious, legal, social, and/or economic constraints.

Evaluating the rate of preservation of hormone function, uterine transposition appears to be at least as efficient as ovarian transposition alone. A recent meta-analysis17 showed that 66.6% of patients with rectal and anal cancer who underwent ovarian transposition preserved their hormonal function. The factor that appears most important for preserving function is the distance of the ovary from the radiation field, as observed by Hwang et al,18 where ovary location more than 1.5 cm above the iliac crest was related to a greater chance of preserving gonadal function in patients with cervical cancer undergoing radiation therapy. Sioulas et al19 reported 90% of ovarian function preservation in patients with non-gynecological cancers aged younger than 40 years placing the ovaries above the level of L5–S1, corresponding to the superior aspect of the pelvic radiation field. Probably, the high success rate in preserving hormonal function observed in our review is due to the technical rigor of the surgery, which requires positioning of the ovaries well outside of the radiation field. The actual radiation dose was 0.46 Gy for the right ovary, 0.15 Gy for the left ovary, and 0.46 Gy for the uterus in the patient who had the first live birth from the technique,13 with the uterus positioned in the hypochondrium. In the pediatric patient,20 the maximum uterine and ovarian doses were 20 and 13 Gy, respectively, but in addition to being a small patient, her uterus was positioned in the lower abdomen. This difference in dose underscores the need to maintain technical rigor in distancing the uterus and adnexa from the radiation field.

Another factor that might have been crucial for the positive result of hormonal preservation was the additional care that surgeons take in uterine transpositions to avoid any ischemia that could result in the loss of the patients' uterus.9 It should be noted that there was limited follow-up in the studies reported here, and ovarian failure could have develop in later years beyond the current available follow-up.1

Considering the group of patients in whom the preservation of menstrual cycles could be evaluated (excluding the prepubertal patient and the patient who died before uterine repositioning) the vast majority of patients (14 of 16 patients) had preserved uterine function (normal menstrual cycles). There is no study in the literature citing the rate of normal cycles in patients submitted to ovarian transposition, or if they can get pregnant. There are anecdotal cases of pregnancy in these conditions, often involving in vitro fertilization with high doses of hormone therapy to increase the chances of implantation and sometimes with catastrophic outcomes for the mother and/or fetus.21–26 Thus, it is considered that the chance of a patient having regular menstrual cycles after pelvic radiotherapy, even with ovarian transposition, is virtually zero, which greatly favors the results obtained with uterine transposition.

Assessing the pregnancy rate in patients undergoing uterine transposition is challenging. It is common for patients undergoing fertility-preserving treatments not even to attempt to become pregnant. A prospective study27 with 212 patients undergoing radical vaginal trachelectomy showed that only 35.8% attempted to become pregnant after the procedure. The relatively short follow-up observed in the current review does not allow us to conclude how many patients undergoing uterine transposition will actually seek pregnancy. However, the demonstrated three cases of spontaneous pregnancies suggest that the procedure can achieve its main objective.

Probably the greatest merit of the technique is its accessibility. The possibility of pregnancy without the use of in vitro fertilization techniques makes it viable in resource-limited areas, making it a promising alternative for these specific areas.28 Religious issues are also relevant, as some patients may not accept assisted fertilization.29

Although mothers and newborns had a good postpartum outcome, two patients went into labor at 36 weeks. Therefore, the importance of rigorous prenatal monitoring for these patients should be emphasized. Patients should also be thoroughly informed about the risk of pre-term labor and its potential consequences.

Among all complications, cervical ischemia was the most common. The surgeons should be aware of preserving the descending vessels along the cervix to avoid ischemia. It is also important avoid the cervical exteriorization in the umbilicus to protect the cervix from abdominal wall constriction. This complication was described only in patients who had had the cervix anastomosed to the umbilicus. In the group of patients with the cervix not attached to the umbilicus, a small cervical ischemia would probably go clinically undetected with no major consequences, because the cervix is not visible. The fact that patients with the cervix left within the abdomen did not experience problems with this suggests that permanent adoption of this strategy should be considered. Uterine necrosis, on the other hand, remains one of the greatest concerns of the procedure, although to date only one case has been published in this series of 18 patients.

The time of approximately 2 weeks for the start of radiotherapy after surgery seems to be adequate. However, the reader of this article needs to know that this time period does not include the time between the initial consultation and surgery. When compared with the standard method available—the harvest of oocytes for subsequent in vitro fertilization, where the delay between the start of ovulation induction and egg collection is longer than 2 weeks29—uterine transposition would not be a disadvantage. Additionally, after an induction cycle due to ovarian enlargement, it may be necessary to wait about 2 weeks for them to return to normal size to allow for proper planning and the start of radiotherapy.30 Furthermore, in an ideal scenario, this patient should also undergo ovarian transposition surgery, thus adding to the overall duration of both procedures. It is worth noting that patients can also be offered ovarian transposition without prior egg collection since the eggs can be collected later.25

The published studies do not have sufficient power to determine the efficacy of the procedure for oncologic outcomes. However, as only one patient developed a recurrence in a group of patients with relatively advanced tumors, the outcomes can be interpreted as at least encouraging. An important issue related to uterine transposition is the risk of recurrence in the cervix. Patients with indications for adjuvant radiotherapy typically have the residual cervix radiated, but in patients undergoing transposition, the residual cervix is placed outside the radiation field. Mangler et al31 reported 7 (2.2%) cervical recurrences in 320 patients undergoing radical vaginal trachelectomies combined with laparoscopic pelvic lymph node removal, with a mean follow-up of 48 months. Notably, 80% of cervical recurrences occurred in patients with tumors larger than 2 cm. Thus, we recommend limiting uterine transposition in cervical cancer to selected cases only. It is imperative to monitor these patients closely to further reduce morbidity in cases of recurrence, preferably every 3 months as suggested by Mangler et al.31 It is also extremely important that these cases be conducted within research protocols to avoid subjecting patients to unreasonable risks.

One of the strengths of this study is that the study design is most applicable to the rarity of the condition. Case series can be one of the only ways to collect information and evidence since randomized clinical trials are not feasible due to the low incidence of the surgical procedure. More than likely, a randomized controlled clinical trial would be infeasible in this patient cohort. Although due to the limited number of cases, it is not possible to define a new medical practice, the study allows identification of patterns that will lead to further in-depth research. Another strength of this study is the inclusion of patients from different countries, especially developing countries, which shows that the procedure can be reproduced outside of academic institutions.

We acknowledge the limitations of this review, including the absence of a specific MeSH term for uterine transposition and the possibility of selection bias due to the inclusion of only studies published in scientific journals. A possible weakness of this literature review is that certain data were not available owing to the retrospective nature of the data collection. Another (publication) bias could be that unsuccessful surgical procedures and uterine transposition procedures with unwanted outcomes might be more likely to remain unreported, leading to a bias in favor of positive results.

In summary, the uterine transposition procedure is feasible and safe in tertiary reference centers, and its promising results justify its continued assessment for reproducibility and oncological outcomes within research protocols. We recommend that all women being considered for uterine transposition are informed about the novelty and experimental nature of this technique and the limitations of our current knowledge. Prospective cases should be discussed with experienced colleagues to ensure they are truly appropriate candidates for this procedure.

All patients should be offered standard methods of fertility preservation, even if they accept uterine transposition. We recommend embryo and/or oocyte cryopreservation, as this can serve as an alternative if uterine preservation does not work and assist patients in becoming pregnant if uterine preservation is successful but the patient cannot conceive spontaneously.

Conducting further studies that determine radiation doses scattered to the uterus and adnexae, as well as determining obstetric outcomes, would be of utmost importance. Given the low incidence of cases of uterine transposition, ideally, a prospective multicenter database dedicated to these procedures should be established. This database would aim to systematically collect relevant data, allowing for a more comprehensive and precise analysis. Such an initiative would be essential to assist clinical decisions related to uterine transposition, as well as to provide valuable insights and clarify the issues surrounding this procedure, contributing to the advancement of medical practice and fertility preservation in patients with pelvic cancer.