Utero-ovarian Transposition in Patients With Pelvic Malignancies Undergoing Whole Pelvic Radiotherapy

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.

Eligibility

Inclusion Criteria:

1. Age: Women 18 - 40 years of age who wish to preserve their fertility.
2. Malignancy: Diagnosis of pelvic malignancies that require radiotherapy, including:

   1. Colon and rectal cancer with tumors.
   2. Anal cancer.
   3. Other pelvic malignancies that require administration of WPXRT.
3. Desire for Fertility Preservation: The patient expresses a clear desire to preserve fertility and the ability to carry a pregnancy in the future.
4. Preoperative Ovarian Function: The patient must have normal ovarian function, demonstrated by specific hormonal values, including:

   1. Follicle-Stimulating Hormone (FSH): \<10 IU/L
   2. Luteinizing Hormone (LH): within normal reference range for reproductive age (typically 1.5-8 IU/L in the early follicular phase).
   3. Anti-Müllerian Hormone (AMH): \>1 ng/mL
   4. Estradiol (E2): within the normal range for the follicular phase (usually 30-120 pg/mL).
5. No Distant Metastasis: Absence of metastatic disease confirmed by imaging (CT, MRI, or PET scans).
6. Body Mass Index (BMI) \< 35.
7. Signed Informed Consent.

Exclusion Criteria:

1. Advanced Cancer Stage: Patients with locally advanced or metastatic disease.
2. Significant Uterine Pathology: Presence of large uterine fibroids, adenomyosis, or other intrauterine pathologies that would complicate the procedure or future pregnancy.
3. Poor General Health or Comorbidities: Severe medical conditions that contraindicate surgical intervention, that include but not limited to:

   * Cardiovascular Disease:

     1. Recent (within 6 months) myocardial infarction (MI).
     2. Ejection fraction (EF): EF \<30%.
     3. Uncontrolled hypertension: Systolic BP \>180 mmHg or Diastolic BP \>110 mmHg prior to surgery.
     4. Severe aortic stenosis: Valve area \<1 cm² with symptomatic status.
   * Uncontrolled Diabetes Mellitus:

     1. Hemoglobin A1c (HbA1c) \> 9%
     2. Persistent fasting glucose \>250 mg/dL preoperatively despite optimization.
   * Severe Respiratory Diseases:

     1. Forced expiratory volume (FEV1): \<50%.
     2. Oxygen saturation: Resting SpO₂ \<88% on room air without supplemental oxygen.
     3. CO2 retention: PaCO₂ \>50 mmHg.
   * Connective Tissue Disorders:

     1. Severe systemic lupus erythematosus (SLE): Active lupus nephritis with GFR \<30 mL/min.
     2. Scleroderma with severe pulmonary hypertension or FVC \<50% predicted.
     3. Rheumatoid arthritis with severe cervical spine instability (atlantoaxial subluxation).
   * Severe Inflammatory Bowel Disease (IBD):

     1. Severe Crohn's or ulcerative colitis flares with C-reactive protein (CRP) \>10 mg/L and hypoalbuminemia (Albumin \<2.5 g/dL).
     2. Severe malnutrition: BMI \<18.5 kg/m² or Prealbumin \<10 mg/dL
   * Steroid dependency:

     1. Chronic steroid use (\>20 mg prednisone daily) with no feasible taper pre-surgery.
4. Prior Pelvic Radiotherapy.
5. Prior history of systemic chemotherapy and immunotherapy that resulted in significant toxicity and residual deficit.
6. Pregnancy: Patients who are currently pregnant are excluded from consideration for uterine transposition.
7. Unsuitable for Ovarian Function Preservation: Women with signs of poor ovarian reserve, including:

   * FSH: \>10 IU/L
   * AMH: \<1 ng/mL
   * Estradiol: outside normal range.
8. Non-Candidate for Fertility: Patients with contraindications to future pregnancy, such as severe uterine abnormalities or significant risk for pregnancy-related complications.
9. Body Mass Index (BMI) ≥35.
10. Absence of One of the Gonadal Vessels.
11. Other unlisted conditions or diagnoses that, in the opinion of the primary investigator, render the patient an unsuitable candidate for uteroovarian transposition.

Conditions4

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