Deaths and Severe Adverse Events after the use of Mifepristone as an Abortifacient from September 2000 to February 2019.

OBJECTIVES: Primary: Analyze the Adverse Events (AEs) reported to the Food and Drug Administration (FDA) after use of mifepristone as an abortifacient. Secondary: Analyze maternal intent after ongoing pregnancy and investigate hemorrhage after mifepristone alone. METHODS: Adverse Event Reports (AERs) for mifepristone used as an abortifacient, submitted to the FDA from September 2000 to February 2019, were analyzed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAEv3). RESULTS: The FDA provided 6158 pages of AERs. Duplicates, non-US, or AERs previously published (Gary, 2006) were excluded. Of the remaining, there were 3197 unique, US-only AERs of which there were 537 (16.80%) with insufficient information to determine clinical severity, leaving 2660 (83.20%) Codable US AERs. (Figure 1). Of these, 20 were Deaths, 529 were Life-threatening, 1957 were Severe, 151 were Moderate, and 3 were Mild.The deaths included: 9 (45.00%) sepsis, 4 (20.00%) drug toxicity/overdose, 1 (5.00%) ruptured ectopic pregnancy, 1 (5.00%) hemorrhage, 3 (15.00%) possible homicides, 1 (5.00%) suicide, 1 (5.00%) unknown. (Table 1).Retained products of conception and hemorrhage caused most morbidity. There were 75 ectopic pregnancies, including 26 ruptured ectopics (includes one death).There were 2243 surgeries including 2146 (95.68%) D&Cs of which only 853 (39.75%) were performed by abortion providers.Of 452 patients with ongoing pregnancies, 102 (22.57%) chose to keep their baby, 148 (32.74%) had terminations, 1 (0.22%) miscarried, and 201 (44.47%) had unknown outcomes.Hemorrhage occurred more often in those who took mifepristone and misoprostol (51.44%) than in those who took mifepristone alone (22.41%). CONCLUSIONS: Significant morbidity and mortality have occurred following the use of mifepristone as an abortifacient. A pre-abortion ultrasound should be required to rule out ectopic pregnancy and confirm gestational age. The FDA AER system is inadequate and significantly underestimates the adverse events from mifepristone.A mandatory registry of ongoing pregnancies is essential considering the number of ongoing pregnancies especially considering the known teratogenicity of misoprostol.The decision to prevent the FDA from enforcing REMS during the COVID-19 pandemic needs to be reversed and REMS must be strengthened.

Laser Angiography to Assess the Vaginal Cuff During Robotic Hysterectomy.

BACKGROUND AND OBJECTIVES: Vaginal cuff dehiscence may be a vascular-mediated event, and reports show a higher incidence after robot-assisted total laparoscopic hysterectomy (RATLH), when compared with other surgical routes. This study was conducted to determine the feasibility of using laser angiography to assess vaginal cuff perfusion during RATLH. METHODS: This was a pilot feasibility trial incorporating 20 women who underwent RATLH for benign disease. Colpotomy was made with ultrasonic or monopolar instruments, whereas barbed or nonbarbed suture was used for cuff closure. Time of instrument activation during colpotomy was recorded. Images were captured of vaginal cuff perfusion before and after cuff closure. Reviewers evaluated these images and determined areas of adequate cuff perfusion. RESULTS: Indocyanine green (ICG) was visible at the vaginal cuff in all participants. Optimal dosage was determined to be 7.5 mg of ICG per intravenous dose. Mean time to appearance for ICG was 18.4 ± 7.3 s (mean ± SD) before closure and 19.0 ± 8.7 s after closure. No significant difference (P = .19) was noted in judged perfusion in open cuffs after colpotomy with a monopolar (48.9 ± 26.0%; mean ± SD) or ultrasonic (40.2 ± 14.1%) device. No difference was seen after cuff closure (P = .36) when a monopolar (70.9 ± 21.1%) or ultrasonic (70.5 ± 20.5%) device was used. The use of barbed (74.1 ± 20.1%) or nonbarbed (66.4 ± 20.9%) sutures did not significantly affect estimated closed cuff perfusion (P = .19). Decreased cuff perfusion was observed with longer instrument activation times in open cuffs (R2 = 0.3175). CONCLUSION: Laser angiography during RATLH allows visualization of vascular perfusion of the vaginal cuff. The technology remains limited by the lack of quantifiable fluorescence and knowledge of clinically significant levels of fluorescence.

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.

Laser Angiography with Indocyanine Green to Assess Vaginal Cuff Perfusion during Total Laparoscopic Hysterectomy: A Pilot Study.

STUDY OBJECTIVE: To determine feasibility of using laser angiography with indocyanine green (ICG) to assess vaginal cuff vascular perfusion during total laparoscopic hysterectomy (TLH). DESIGN: Pilot feasibility trial (Canadian Task Force classification II-2). SETTING: Academic-affiliated hospital. PATIENTS: Twenty women undergoing TLH for benign disease. INTERVENTIONS: Participants underwent 1:1 randomization of energy method used for colpotomy (ultrasonic vs monopolar) and vaginal cuff closure suture (barbed vs nonbarbed). After intravenous administration of ICG, laser angiography was used to capture images of the vaginal cuff before and after closure. Three reviewers analyzed fluorescent images of vaginal cuffs to determine percent of cuff perimeter with adequate perfusion when open and length of vaginal cuff adequately perfused when closed. MEASUREMENTS AND MAIN RESULTS: ICG fluorescence was visible at the vaginal cuff in all participants. Mean time to appearance of ICG in the pelvis after administration was 19.8 ± 6.8 seconds (mean ± SD) preclosure, and 26.0 ± 22.2 seconds postclosure. With ultrasonic energy 67.5% ± 17.4% of open cuff perimeter and 74.4% ± 20.5% of closed cuff length were adequately perfused, whereas with monopolar energy use 59.1% ± 17.4% of the open cuff perimeter and 66.3% ± 15.4% of closed cuff length were adequately perfused. Cuffs closed with barbed suture showed adequate perfusion along 71.5% ± 15.1% of the length, whereas those closed with nonbarbed suture showed 68.9% ± 20.9% adequate perfusion. When normalized to cervical cup circumference, ultrasonic energy required 1.0 ± .2 s/mm, whereas monopolar energy required .8 ± .3 s/mm (p = .162). Linear regression showed no association of normalized time of energy activation to percentage of perimeter of open cuff (R2 = .007) or length of closed cuff (R2 = .005) with adequate perfusion. No complications related to intravenous ICG administration occurred. CONCLUSION: Laser angiography with ICG allows evaluation of vascular perfusion at the vaginal cuff during TLH. This technique may facilitate future prospective studies examining causes for vaginal cuff dehiscence, a complication with potential for severe morbidity.