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Uterine transposition for fertility preservation in pelvic cancers
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  1. Reitan Ribeiro1,
  2. Glauco Baiocchi2,
  3. Andreas Obermair3,
  4. Caroline Nadai Costa4 and
  5. Mario Leitao5
  1. 1 Department of Gynecologic Oncology, Hospital Erasto Gaertner, Curitiba, Parana, Brazil
  2. 2 Department of Gynecologic Oncology, ACCamargo Cancer Center, Sao Paulo, São Paulo, Brazil
  3. 3 Queensland Centre for Gynaecological Cancer, Herston/Brisbane, Queensland, Australia
  4. 4 Department of Oncology, Parana Institute of Oncology, Curitiba, Brazil
  5. 5 Memorial Sloan-Kettering Cancer Center, New York, New York, USA
  1. Correspondence to Dr Reitan Ribeiro, Hospital Erasto Gaertner, Curitiba, Hospital, Brazil; reitanribeiro{at}hotmail.com

Abstract

Objective To review rates of uterine preservation and gonadal function, surgical outcomes, and pregnancy outcomes in patients undergoing surgical uterine transposition.

Methods A structured search and analysis of the published literature on uterine transposition was conducted. Information on study type, sample size, patient characteristics, clinical indications, details of the surgical technique, trans-operative and post-operative results, success rates in preserving reproductive organ function and fertility were extracted.

Results A total of 18 cases were reported to date. Patients’ median age was 29 (range 3–38) years. Rectal cancers accounted for 9 (50%) cases of published cases of uterine transposition, followed by 6 (33%) cervical squamous cell carcinomas, 1 (6%) vaginal squamous cell carcinoma, 1 (6%) sacral yolk sac tumor, and 1 (6%) pelvic liposarcoma. The median time for uterine transposition to the upper abdomen was 150 (range 80–360) min, and 90 (range 80–310) min for organ reimplantation in the pelvis. Cervical ischemia occurred in 5 (27.8%) cases, being the most commonly reported complication. The median follow-up time was 25 months, and three patients achieved spontaneous pregnancies resulting in successful gestations, out of five patients who were reported as having tried. One patient experienced recurrence and succumbed to the tumor during treatment.

Conclusions Uterine transposition is a feasible and safe surgical approach that offers patients undergoing pelvic radiotherapy an option to preserve gonadal and uterine function, with the potential for spontaneous pregnancy.

  • Cervical Cancer
  • Colorectal Neoplasms
  • Radiotherapy
  • Uterus
  • Postoperative complications

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INTRODUCTION

Patients with pelvic tumors often require radiation treatment with or without concurrent chemotherapy. However, pelvic radiotherapy will cause ovarian failure1 if no measures are taken to preserve ovarian function. The uterus is also negatively affected by pelvic radiation treatment, including the reduction of uterine volume, decreased distensibility due to myometrial fibrosis, uterine vascular damage, and endometrial injury.2–6 Thus, only in vitro fertilization techniques would be able to preserve the fertility of these patients, frequently with the need for uterine surrogacy.

First described in 2017,7 uterine transposition has emerged as a potential alternative that allows women who require radiation treatment to the pelvis to conceive spontaneously and carry a pregnancy to term, without the need for in vitro fertilization.8 This is achieved by transposing the uterus, ovaries, and fallopian tubes away and out of the radiation field, thus maintaining the anatomical integrity and continuity of these structures, thereby protecting the entire reproductive complex.

Uterine transposition may be indicated for patients requiring pelvic radiotherapy who desire pregnancy. The main indications include rectal cancer, pelvic sarcomas, anal canal cancers, vaginal cancers, and vulvar cancers.9 In highly selected cases, it may potentially be used for cervical cancer in the future.10 The objectives of this literature review are to review data on the feasibility and safety of preservation of the uterus and ovaries, surgical outcomes, and to characterize pregnancy outcomes in patients undergoing uterine transposition.

METHODS

We conducted comprehensive literature searches in recognized scientific databases such as PubMed, Scopus, Web of Science, and EMBASE. To overcome the lack of a specific MeSH term, we employed a broad search approach using the term ‘uterine transposition.’ This strategy was designed to capture all relevant articles regardless of their MeSH categorization. The inclusion criteria for the studies were defined as follows: (a) studies published in peer-reviewed scientific journals; (b) clinical studies, cohort studies, retrospective studies, and case reports addressing uterine transposition; (c) studies describing clinical indications, surgical techniques, outcomes, and oncological considerations of uterine transposition. After the initial search, the titles and abstracts of all identified studies were reviewed to determine their relevance. Studies that met the inclusion criteria were selected for full-text evaluation. Data were systematically extracted from the selected studies, including information on study type, sample size, patient characteristics, clinical indications, surgical technique details, pre-operative and post-operative outcomes, success rates in preserving reproductive organ function, and fertility. Oncological considerations were also assessed. We conducted a qualitative analysis of the results from the selected studies, highlighting relevant findings, exemplary clinical cases, and challenges encountered in the context of uterine transposition.

RESULTS

Initial searches identified 13 potentially relevant articles. Screening of abstracts excluded two articles that did not meet any of the inclusion criteria, as one was an editorial and the other a medical society consensus document. A meta-analysis for meaningful quantitative synthesis was not conducted due to the small overall sample size and heterogeneous inclusion and exclusion criteria. We identified eight case reports, two case series, and one surgical technique review. Three case reports11–13 had patients included in two other papers that published case series,8 10 and all five articles were used to extract information, thus avoiding duplication of cases. In the final dataset, 18 published cases were identified (table 1).

Table 1

Clinical characteristics of patients submitted to uterine transposition, in publication order

The mean age at the time of surgery was 29 (range 3–38) years. Adenocarcinomas of the rectum accounted for 9 cases (50%), followed by 6 (33%) cervical squamous cell carcinomas, 1 (6%) vaginal squamous cell carcinomas, 1 (6%) sacral yolk sac tumor, and 1 (6%) pelvic liposarcoma. The median follow-up time was 25 (range 1–51) months, and three patients achieved spontaneous pregnancies resulting in successful gestations, out of five patients who were reported as having tried. One patient developed peritoneal carcinomatosis from the rectal cancer during the follow-up.

Surgical Outcomes

Uterine transposition to the upper abdomen took a median surgical time of 140 (range 80–360) min, with a median blood loss of 60 (range 20–200) mL and a median length of hospital stay of 3 (range 1–3) days (table 2). The most commonly reported surgical complication was cervical ischemia, with a visually well-perfused uterine body, in 5 (28%) cases. Ten (56%) patients had their cervix placed trans-umbilically with menses through umbilicus. The other eight patients had the cervix left within the abdomen with the cervix at level of the umbilicus and uterine body above the umbilicus. These patients received concurrent medical treatment to suppress menstruation (except for the pediatric patient, whose uterine cervix remained in the lower abdominal position and did not require menstrual cycle suppression due to prepubescence).

Table 2

Surgical characteristics of the patients with pelvic cancers who were submitted to uterine transposition

Repositioning of the uterus into the pelvis took a median time of 130 (range 80–310) min, with a median hospitalization time of 3 (range 1–3) days. No repositioning-related complications were described.

Hormonal and Uterine Function

Ovarian hormonal function was determined in all but two patients. One patient was excluded from this analysis because she died before it was possible to evaluate the outcomes of this variable, and one patient was prepubertal at the time of her surgery. All other 16 patients were eligible and have shown normal hormonal function during post-operative follow-up. Normal uterine function was defined as the presence of normal menstrual cycles according to the patient’s pattern. A total of 14/16 patients (87.5%) preserved their uterine function. One patient experienced uterine/cervical necrosis and another patient requested a hysterectomy by the time the uterus was supposed to be reimplanted after radiation. The exact reason for the hysterectomy in this particular case is uncertain.

Pregnancy outcomes

Information regarding the number of patients who attempted to become pregnant during the follow-up period was not provided in most publications. However, out of the 15 patients who preserved the uterus and survived, we identified 5 (33%) patients who attempted to conceive. The papers mentioned two patients who attempted pregnancy without success, one of them even using IVF techniques. There were no reported cases of miscarriages.

Three (60%) of the 5 patients achieved a spontaneous pregnancy during the follow-up and carried their pregnancies until 36 weeks' estimated gestational age or later. The first baby born after uterine transposition13 was delivered by cesarean delivery without complications when the patient went into labor at 36 weeks and 2 days. Both (mother and baby) were discharged the day after with no complications. The second patient14 was admitted at 36 weeks of gestation due to ruptured membranes and the ultrasound found the fetus weight lower than the third percentile associated with oligohydramnios. A male newborn weighing 2500 g was delivered via cesarean delivery with Apgar scores of 8–9. Both mother and the child had an uncomplicated hospital stay and were discharged without any issues. The third baby was also delivered via a cesarian delivery at 38 weeks without a specific indication noted. Both mother and baby were discharged the day after without complications. All three babies were reported as having normal development in follow-up to date.

Oncological Outcomes

On average, patients commenced radiation treatment approximately 14 days (0 to 28 days) after uterine transposition. One patient with stage IB2 cervical cancer, who received neoadjuvant chemotherapy, had intra-operative 10 Gy radiotherapy administered to the vaginal apex according to the authors, followed by 46 Gy of external beam radiotherapy after surgery. The time interval between the completion of radiotherapy and uterine reimplantation was only mentioned for patients with cervical and vaginal cancer, with a median of 31.5 (range 5–90) days (Table 3).

Table 3

Treatment characteristics of patients with pelvic cancers and submitted to uterine transposition

One patient experienced a recurrence of rectal cancer and developed peritoneal carcinomatosis before her repositioning surgery could be completed. She died 4 months after the upper abdominal uterine transposition. No other cases of recurrence were described.

Discussion

Summary of main results

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.

Results in the Context of Published Literature

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.

Strengths and Limitations

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.

Implications for Practice and Future Research

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.

CONCLUSION

Uterine transposition is feasible and safe and offers the possibility of preserving gonadal and uterine function in patients undergoing pelvic radiotherapy, with the potential for spontaneous pregnancy without compromising oncological outcomes.

Ethics statements

Patient consent for publication

Ethics approval

Not applicable.

References

Footnotes

  • Twitter @glaucobaiocchi, @leitaomd

  • Contributors RR and CNC contributed to conceptualization, data collection, data analysis, writing the original draft of manuscript, and reviewing and editing the manuscript. RR, GB, AO, ML contributed to study planning, data analysis, reviewing, and final editing the manuscript. All authors had access to the data reported in the study and had final responsibility for the decision to submit the manuscript for publication.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.