A Phase I Assessment of Utero-ovarian Transposition (UOT) for Fertility Preservation in Patients With Pelvic Malignancies Undergoing Whole Pelvic Radiotherapy (WPXRT)

Summary

This study is designed as a Phase I clinical trial enrolling female patients aged 18-40 years who have been diagnosed with pelvic malignancies requiring whole pelvic external radiation therapy (WPXRT) and who express interest in preserving fertility and ovarian function. The trial's primary objective is to assess the feasibility and safety of uterine and ovarian transposition (UOT). Premenopausal women under the age of 40 will undergo UOT using a novel minimally invasive approach. Feasibility and safety will be evaluated through standardized postoperative assessments, including: (A) success in mobilizing and repositioning the uterus, ovaries, and fallopian tubes while maintaining vascular integrity; (B) documentation of surgical complications; (C) monitoring the timeliness and adherence to planned WPXRT. To enhance safety and optimize outcomes, intraoperative imaging with indocyanine green fluorescence and Doppler ultrasonography will be employed. Short-term success will be defined by technical success in repositioning the uterus and ovaries with preserved vascular integrity, absence of major surgical complications, and timely initiation and completion of WPXRT. Long-term success will be evaluated by the preservation of fertility. The study's primary objective is also to evaluate surgical, reproductive, and quality-of-life outcomes following UOT. This objective will determine the procedure's efficacy in preserving ovarian and menstrual function and its potential to support future pregnancies. Endpoints include: (A) maintenance of normal premenopausal levels of FSH, LH, AMH, and estradiol at defined postoperative intervals; (B) assessment of menstrual timing, regularity, and characteristics to document return of ovulatory cycles; (C) evaluation of uterine integrity and reproductive potential using pelvic ultrasonography; (D) comprehensive evaluation of patient quality of life encompassing physical, emotional, sexual, and reproductive well-being. These measures will inform optimization of surgical techniques and provide a foundation for scaling the procedure to a broader population in future studies.

Detailed description

This is a phase I study aimed to evaluate feasibility and safety of utero-ovarian transposition (UOT) in young women undergoing whole pelvic radiation therapy (WPXRT) for treatment of a colorectal or other cancers localized to the pelvis. By comprehensively evaluating real-world outcomes for women undergoing this procedure, the proposed work will lay the groundwork necessary to establish UOT as a viable option for fertility preservation and survivorship for this unique patient population. Rigorous inclusion and exclusion criteria will ensure the selection of appropriate candidates, who will undergo a minimally invasive transposition of their cervix, uterus, tube and ovaries outside the planned radiation fields, thus sparing transposed organs from radiation exposure. Following a brief recovery, the radiation oncology team will proceed with WPXRT to treat each patient's cancer. If chemotherapy is indicated, it will be completed at this time, prior to the second procedure. After completing radiation therapy and/or chemotherapy, the uterus and adnexa will be surgically returned to their normal anatomical position. This study will assess surgical outcomes for enrolled subjects undergoing this care plan, assess quality of life and the preservation of fertility and uterine receptivity by multiple objective measures. Throughout the study, patients will be closely monitored for perioperative outcomes, including surgical complications, hospital stay, and quality of life. Patterns of menstruation, as well as levels of key hormones routinely used to assess fertility (FSH, LH, AMH, and estradiol) will be measured at key time points. Successful UOT will be defined as the ability to complete the procedure and successfully restore a viable uterus and adnexa capable of supporting normal menstruation and fertility post-radiation therapy. The resumption of menstrual cycles for six months following the procedure will be evaluated. Quality of life will be evaluated at multiple steps as women undergo the proposed procedures as well as throughout the planned 6 months follow up window. Data generated by this pilot study will provide critical insights into the feasibility, safety, and potential benefits of UOT as a fertility-preserving and ovarian function-conserving option for patients with pelvic malignancies undergoing WPXRT. Moving forward, data from this study will be used not only to build out the programmatic and clinical infrastructure needed to further evaluate the efficacy of UOT, but also to overcome roadblocks to its successful clinical implementation in the future.

Arms & interventions

• ProcedureUteroovarian transposition

  Uteroovarian transposition involves temporarily relocating the uterus, both ovaries and fallopian tubes outside the planned radiation field. Once WPXRT is complete, a second surgery is performed to return these organs to their natural position in the patient's pelvis.

Outcome measures

Eligibility criteria