Benjamin D. Beran

Uterine viability in the baboon after ligation of uterine vasculature: a pilot study to assess alternative perfusion and venous return for uterine transplantation

OBJECTIVE To assess, in two separate groups of baboons, uterine viability after ligation of the uterine veins and uterine viability after ligation of both the uterine arteries and veins, respectively. DESIGN Prospective, observational study. SETTING Baboon breeding colony. ANIMAL(S) Six naïve female Papio hamadryas baboons with indicators of normal reproductive function. INTERVENTION(S) Three baboons underwent surgical interruption of the uterine veins bilaterally, and three baboons underwent surgical interruption of the uterine arteries and the uterine veins bilaterally. All baboons also underwent colpotomy, cervico-vaginal reanastomosis, and intraoperative near-infrared fluorescence imaging after vessel ligation. In the postoperative period, transabdominal sonography, vaginoscopy, and endocervical biopsy were performed on all animals. MAIN OUTCOME MEASURE(S) Postoperative uterine and ovarian viability. RESULT(S) Near-infrared imaging confirmed intraoperative perfusion of the uterus and cervico-vaginal anastomosis in all cases. In all subjects, sonography revealed normal uteri, and vaginoscopy revealed well-healed anastomoses. Endocervical biopsies (five of six) demonstrated pathologically normal endocervical tissue without evidence of necrosis. Cyclical sex skin turgescence and menstruation were unanimously observed. CONCLUSION(S) Disruption of bilateral uterine vessels does not affect uterine or ovarian viability in the baboon. Bilateral uterine artery and vein ligation furthers development of a minimally invasive approach to donor hysterectomy.

Livebirth and utero-placental insufficiency in Papio hamadryas baboons with uterus angiosome perfused by bilateral utero-ovarian microsurgical anastomoses alone

STUDY QUESTION Can the baboon uterus support a gestation to livebirth with an angiosome using microsurgically anastomosed utero-ovarian vessels and lacking uterine arteries and veins? SUMMARY ANSWER Our angiosome model allows healthy livebirth albeit with risk of fetal growth restriction and stillbirth. WHAT IS KNOWN ALREADY Uterine transplant can provide livebirth in humans, but requires a living donor to undergo a prolonged laparotomy for hysterectomy. In an attempt to avoid the time-consuming dissection of the uterine vein, our group has previously shown maintenance of baboon uterine menstrual function after ligation of the uterine vein and after ligation of both the uterine artery and uterine vein. STUDY DESIGN, SIZE, DURATION In a 19-month timespan, three baboons underwent laparotomy to surgically alter uterine perfusion, and pregnancy outcomes were monitored after spontaneous mating in a breeding colony. PARTICIPANTS/MATERIALS, SETTING, METHODS Three nulligravid female Papio hamadryas baboons in a breeding colony underwent laparotomy to ligate uterine arteries and veins along with colpotomy and cervico-vaginal anastomosis. During the same surgery, the utero-ovarian arteries and veins were microsurgically transected and re-anastomosed to themselves. Intraoperative organ perfusion was confirmed with laser angiography. After a recovery period, monitoring of menstrual cycling via menstrual blood flow and sex-skin cycling occurred, as well as uterine viability via sonography and cervical biopsy. Each baboon was released to the breeding colony for spontaneous mating and pregnancies dated by menstrual calendar and compared with early ultrasound. Delivery outcomes were monitored in each including neonate weight and placental pathology. In the event of a stillbirth, the animal was returned to the breeding colony for repeat mating attempts. After achieving a livebirth, the maternal baboon was removed from the study. MAIN RESULTS AND THE ROLE OF CHANCE Each baboon in the trial underwent successful surgery with all uteri demonstrating viability and return of menstrual function within 10 weeks of surgery. Pregnancies occurred within two menstrual cycles in breeding colony. Baboons one and two initially had vaginal breech stillbirths, both with appearance of placental insufficiency, and one with fetal growth restriction. Baboon three underwent scheduled cesarean delivery resulting in a normally grown livebirth. Baboon one had a subsequent pregnancy resulting in a livebirth via cesarean delivery. LIMITATIONS, REASONS FOR CAUTION Stillbirth in two of four gestations, and fetal growth restriction in one of four, are the largest concerns in our perfusion model. It remains uncertain whether the stillbirths resulted from placental insufficiency, or birth trauma from breech deliveries. WIDER IMPLICATIONS OF THE FINDINGS The success of two livebirths warrants further attempts at improving consistency of our proposed uterine angiosome. This may allow living uterine donors to undergo less-invasive and shorter donor hysterectomy procedures. STUDY FUNDING/COMPETING INTEREST(S) The study had no external sponsors, and was supported by the Cleveland Clinic Foundation. Some equipment was loaned without cost to the research team including a laser angiography system courtesy of Novadaq Technologies, Inc. (Missaugua, ON, Canada) and a surgical microscope courtesy of DB Surgical (Coral Springs, FL, USA). B.B., K.A., M.S., K.R., M.M., P.F.E., A.T. and T.F. have no conflicts of interest. M.L.S. and S.Z. report activity as consultants for Medtronic-Covidien, and S.Z. also is a consultant to Applied Medical.

Anatomy of the Internal Iliac Vein: Implications for Uterine Transplant

STUDY OBJECTIVE Uterine transplantation has proven feasible since the first live birth reported in 2014. To enable attachment of the uterus in the recipient, long vascular pedicles of the uterine and internal iliac vessels were obtained during donor hysterectomy, which required a prolonged laparotomy to the living donors. To assist further attempts at uterine transplantation, our video serves to review literature reports of internal iliac vein anatomy and demonstrate a laparoscopic dissection of cadaver pelvic vascular anatomy. DESIGN Observational (Canadian Task Force Classification III). SETTING Academic anatomic laboratory. Institutional Review Board ruled that approval was not required for this study. INTERVENTION Literature review and laparoscopic dissection of cadaveric pelvic vasculature, focusing on the internal iliac vein. MEASUREMENTS AND MAIN RESULTS Although the internal iliac artery tends to have minimal anatomic variation, its counterpart, the internal iliac vein, shows much variation in published studies [1,2]. Relative to the internal iliac artery, the vein can lie medially or laterally. Normal anatomy is defined as some by meeting 2 criteria: bilateral common iliac vein formed by ipsilateral external and internal iliac vein at a low position and bilateral common iliac vein joining to form a right-sided inferior vena cava [2]. Reports show 79.1% of people have normal internal iliac vein anatomy by these criteria [2]. The cadaver dissection revealed internal iliac vein anatomy meeting criteria for normal anatomy. CONCLUSION Understanding the complexity and variations of internal iliac vein anatomy can assist future trials of uterine transplantation.