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仅通过双侧子宫卵巢显微吻合术对狒狒子宫血管体供应,实现活产和子宫胎盘功能不全。

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

机构信息

Department of Gynecology, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL33331, USA.

Mannheimer Foundation, 20255 SW 360th St., Homestead, FL 33034, USA.

出版信息

Hum Reprod. 2017 Sep 1;32(9):1819-1826. doi: 10.1093/humrep/dex242.

Abstract

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.

摘要

研究问题

使用显微吻合子宫-卵巢血管的血管形成体,并缺乏子宫动脉和静脉,能否使狒狒子宫支持妊娠至活产?

总结答案

我们的血管形成体模型允许健康的活产,尽管存在胎儿生长受限和死产的风险。

已知情况

子宫移植可以为人类提供活产,但需要活体供者进行长时间的剖腹术以进行子宫切除术。为了避免耗时的子宫静脉解剖,我们的小组之前已经表明,在结扎子宫静脉以及结扎子宫动脉和子宫静脉后,狒狒的子宫月经功能得以维持。

研究设计、大小和持续时间:在 19 个月的时间内,三只 nulligravid 雌性 Papio hamadryas 狒狒在繁殖群中进行了剖腹手术,以改变子宫灌注,并在自然交配后监测妊娠结局。

参与者/材料、设置、方法:三只繁殖群中的 nulligravid 雌性 Papio hamadryas 狒狒进行了剖腹手术,以结扎子宫动脉和静脉,并进行阴道切开术和宫颈阴道吻合术。在同一手术中,将子宫-卵巢动脉和静脉显微切开并重新吻合自身。术中器官灌注通过激光血管造影术确认。在恢复期后,通过月经血流和性皮肤循环监测月经周期,通过超声和宫颈活检监测子宫活力。每只狒狒都被释放到繁殖群中进行自然交配,并通过月经日历和早期超声进行妊娠日期记录。分娩结果在每个分娩中进行监测,包括新生儿体重和胎盘病理。如果发生死产,动物将被送回繁殖群进行重复交配尝试。在实现活产后,将母狒狒从研究中移除。

主要结果及其机会作用

试验中的每只狒狒都成功进行了手术,所有子宫均显示出活力,并在手术后 10 周内恢复了月经功能。繁殖群中的两次妊娠都发生在两个月经周期内。狒狒 1 和 2 最初出现阴道臀位死产,均表现出胎盘功能不全,其中 1 例伴有胎儿生长受限。狒狒 3 进行了计划剖宫产,导致正常生长的活产。狒狒 1 随后再次怀孕,通过剖宫产分娩。

局限性、谨慎的原因:在四个妊娠中的两个中发生死产,在四个妊娠中的一个中发生胎儿生长受限,这是我们灌注模型中最大的关注点。死产是否是由于胎盘功能不全还是臀位分娩造成的分娩创伤仍不确定。

研究结果的更广泛影响

两次活产的成功证明了进一步尝试改进我们提出的子宫血管形成体的一致性是合理的。这可能允许活体子宫供者进行侵入性更小和更短的供体子宫切除术。

研究资金/竞争利益:该研究没有外部赞助商,由克利夫兰诊所基金会提供支持。一些设备免费借给研究团队,包括 Novadaq Technologies, Inc.(加拿大米索瓜)提供的激光血管造影系统和 DB Surgical(美国佛罗里达州科勒尔斯普林斯)提供的手术显微镜。B.B.、K.A.、M.S.、K.R.、M.M.、P.F.E.、A.T. 和 T.F. 没有利益冲突。M.L.S. 和 S.Z. 报告作为 Medtronic-Covidien 的顾问的活动,S.Z. 还担任 Applied Medical 的顾问。

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