Imaging in gynecological disease (25): clinical and ultrasound characteristics of intramural pregnancy.

OBJECTIVE: To describe the clinical and sonographic characteristics of intramural pregnancy, as well as the available management options and treatment outcomes. METHODS: This was a retrospective single-center study of consecutive patients with a sonographic diagnosis of intramural pregnancy between November 2008 and November 2022. An intramural pregnancy was diagnosed on ultrasound when a pregnancy was implanted within the uterine corpus, above the level of the internal cervical os and separate from the interstitial section of the Fallopian tube, and extended beyond the decidual-myometrial junction. Clinical, ultrasound, relevant surgical and histological information and outcomes were retrieved from each patient's record and analyzed. RESULTS: Eighteen patients were diagnosed with an intramural pregnancy during the study period. Their median age was 35 (range, 28-43) years and the median gestational age at diagnosis was 8 + 1 (range, 5 + 5 to 12 + 0) weeks. Vaginal bleeding with or without abdominal pain was the most common presenting symptom, recorded in eight patients. Nine (50%) patients had a partial and nine (50%) had a complete intramural pregnancy. Embryonic cardiac activity was present in eight (44%) pregnancies. The majority of pregnancies (n = 10 (56%)) were initially managed conservatively, including expectant management in eight (44%) cases, local injection of methotrexate in one (6%) and embryocide in one (6%). Conservative management was successful in nine of the 10 (90%) pregnancies, with a median time to serum human chorionic gonadotropin resolution of 71 (range, 35-143) days. One patient with an ongoing live pregnancy had an emergency hysterectomy for a major vaginal bleed at 20 weeks' gestation. No other patient managed conservatively experienced any significant complication. The remaining eight (44%) patients had primary surgical treatment, comprising transcervical suction curettage in seven (88%) of these cases, while one patient presented with uterine rupture and underwent emergency laparoscopy and repair. CONCLUSIONS: We describe the ultrasound features of partial and complete intramural pregnancy, demonstrating key diagnostic features. Our series suggests that, when intramural pregnancy is diagnosed before 12 weeks' gestation, it can be managed either conservatively or by surgery, with preservation of reproductive function in most women. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A novel method for office aspiration curettage in cases of retained products of conception: A randomized controlled trial.

INTRODUCTION: Missed abortion can be treated with medication or aspiration curettage. A Karman aspiration cannula is another option. We evaluated its success in evacuating retained products of conception (RPOC) based on symptoms, endometrial thickness, endometrial irregularity, and blood flow seen on Doppler ultrasound (indicative of placenta). MATERIAL AND METHODS: This prospective, randomized, nonblinded trial was conducted in a university-affiliated medical center. It included 40 women diagnosed with missed abortion and two failed courses of 600 µg buccal misoprostol, one  week apart, randomly assigned to treatment or controls. One week after the second misoprostol course, immediately after evaluating endometrial thickness, endometrial irregularity using Doppler ultrasound, and with blood flow indicative of RPOC, women in the aspiration group underwent endometrial suction with a Karman aspiration cannula. The 5-6 mm cannula attached to a 60 mL syringe was inserted into the uterus under ultrasound guidance. The contents were aspirated until the uterus was empty. Control group patients did not receive additional treatment. All were scheduled for ambulatory, operative hysteroscopy under anesthesia 1 month later (departmental protocol). On that day, all women with RPOC on Doppler ultrasound underwent hysteroscopy. Bleeding days, days with pain, pain according to visual analog scale, length of hospitalization, and infection rate were recorded. NIH clinical trial registration number NCT02917785. RESULTS: In the study group, 90% did not need hysteroscopy, compared with 50% of controls (p = 0.014). No complications were noted. At all visits, we used Doppler ultrasound to exclude or confirm RPOC. Pathology revealed RPOC in all women who underwent aspiration. Average visual analog scale score for office aspiration (n = 20) was 4.9 ± 3.6. vs. 6.3 ± 3.4 for the first (p = 0.157) and 4.7 ± 3.3 for the second (p = 0.836) misoprostol treatment cycle. The treatment group experienced 6.1 days of bleeding and the control group experienced 1.4 days (p = .006). CONCLUSIONS: Based on our criteria of diagnosing RPOC according to symptoms, endometrial thickness, endometrial irregularity, and blood flow indicative of placental tissue seen on Doppler ultrasound and histo-pathological confirmation, aspiration using Karman cannula can be an effective therapeutic approach. It may be a safe alternative for women with RPOC after misoprostol failure.

Conservative cesarean scar pregnancy treatment: local methotrexate injection followed by hysteroscopic removal with hysteroscopic tissue removal system.

OBJECTIVE: To describe a conservative cesarean scar pregnancy (CSP) treatment in a patient with the desire for future pregnancy. To date, there is no gold standard for the management of a viable CSP. There is a wide range of treatment options that include major surgery and minimally invasive procedures. Moreover, after a minimally invasive treatment, the gestational sac may be visible at ultrasound for >6 months. The described technique may be useful to avoid complications related to the use of energy with a large reduction in operative times. DESIGN: Description of the technique with narrated video footage. SETTING: Academic tertiary hospital. PATIENT(S): A 31-year-old woman with a previous cesarean section was referred to our clinic with lower abdominal pain. Transvaginal ultrasound revealed a gestational sac with a viable embryo located in the anterior isthmic region, suggestive of CSP at 9 weeks of gestation. Appropriate counseling describing the two diametrically opposite clinical management options was performed, and the patient decided to terminate the pregnancy. Informed consent was obtained from the patient. INTERVENTION(S): Hysteroscopy was performed under local anesthesia in an outpatient setting, using a 2.9-mm Hopkins II Forward-Oblique Telescope 30° endoscope (Karl Storz, Tuttlingen, Germany) with a 4.3-mm inner sheath and 5F instruments. A 3.7F needle (Deflux metal needle; Oceana Therapeutics, Edison, NJ) was pushed into the myometrial tissue surrounding the implantation site of the gestational sac at four different points. Six additional injections were performed into the gestational sac, and 50-mg methotrexate was injected. The appropriate follow-up was performed to determine the success of the procedure. ß-Human chorionic gonadotropin was dosed weekly until negative. After 6 weeks, to remove the avascular trophoblastic remnants found at ultrasound evaluation, the patient underwent hysteroscopic removal with a 6-mm TruClear hysteroscopic tissue removal system (Medtronic Parkway, Minneapolis, MN). A contemporary transabdominal ultrasound was performed to minimize surgical risks. MAIN OUTCOME MEASURE(S): Complete and conservative CSP treatment with the absence of surgical complications. RESULT(S): Conservative cesarean scar pregnancy treatment was performed successfully with primary local methotrexate injection followed, after 6 weeks, by hysteroscopic removal of the CSP remnants with the TruClear hysteroscopic tissue removal system. The first procedure lasted 6 minutes, whereas hysteroscopic removal of the CSP lasted 5 minutes. Both procedures were performed in an outpatient setting, and no complications were detected during and after the treatments. The patient reported good health at the 1-month follow-up visit, and the ultrasound showed an empty isthmocele (Fig. 1). CONCLUSION(S): Primary local methotrexate injection followed by hysteroscopic removal of the CSP remnants with the hysteroscopic tissue removal system may be a valuable treatment for women who desire pregnancy in the near future. This combined technique may avoid potential complications, such as thermal-induced myometrial injuries or uterine perforation. Moreover, the operator has the possibility to perform an under-vision procedure with a lower incidence of intraoperative and postoperative bleeding. Because it does not reduce fertility/pregnancy rate, this technique should be a valid option in patients who desire future pregnancy.

Evaluation of adherence rates following ectopic pregnancy to inform management decisions in a public hospital system.

INTRODUCTION: Adherence to follow-up is an important consideration when treating non-emergent ectopic pregnancy. Our aim was to evaluate the management of ectopic pregnancy among patients in a public hospital system and to identify factors related to adherence of medical management in this population. MATERIAL AND METHODS: A retrospective review to evaluate the management of ectopic pregnancy among women in a public hospital system, including all women undergoing treatment for ectopic pregnancy from 2012 to 2017. Data were abstracted from the medical record. Women who were adherent to follow-up were compared to those who were non-adherent. Log-binomial regression was used to identify factors associated with management type and adherence to follow-up of medical management. RESULTS: Of 283 women diagnosed with an ectopic pregnancy, 182 (64.3%) were managed surgically and 101 (35.7%) were managed with methotrexate. Among non-emergent cases, presence of fetal cardiac activity, human chorionic gonadotropin (HCG) level ≥5000mIU/mL, ectopic size ≥3.5 cm, and multigravid status was associated with surgical management. Among patients receiving methotrexate, 66 (65.3%) adhered to required lab draws 4 and 7 days following methotrexate administration (+/-1 day). Among those receiving methotrexate 45.5% (n = 46) were lost to follow-up. Lower prevalence of adherence to follow-up (i.e. lab draws completed until pregnancy levels were negative) was observed among non-Hispanic African American (RR=0.64, 95%CI 0.45-0.94) compared to white women and women with multigravid status (RR=0.67, 95%CI 0.48-0.95) after adjustment. CONCLUSIONS: Nearly half of those treated with methotrexate failed to complete follow-up. African-American women and multigravida women were at higher risk of being lost to follow up.

A pharmacologically-based approach to high dose methotrexate administration to investigate nephrotoxicity and acute kidney injury biomarkers in children and adolescents with newly diagnosed osteosarcoma.

PURPOSE: High dose methotrexate (HDMTX) acute kidney injury (AKI) results in prolonged hospitalization and treatment delays. Using a pharmacologically-based approach, HDMTX was administered with standard combination therapy to patients with osteosarcoma; nephrotoxicity was assessed. METHODS: Patients were randomized by cycle to 4 h or 12 h HDMTX (12 g/m2) infusions administered with hydration, alkalization and leucovorin rescue. Urinalysis, AKI biomarkers, and estimated glomerular filtration rate using serum creatinine or cystatin C (GFRCr or GFRcysC) were obtained. Serum and urine methotrexate concentrations [MTX] were measured. RESULTS: Patients (n = 12), median (range) age 12.4 (5.7-19.2) years were enrolled; 73 MTX infusions were analyzed. Median (95% Confidence Interval) serum and urine [MTX] were 1309 (1190, 1400) µM and 16.4 (14.7, 19.4) mM at the end of 4 h infusion and 557 (493, 586) µM and 11.1 (9.9, 21.1) mM at the end of 12 h infusion. Time to serum [MTX] < 0.1 µM was 83 (80.7, 90.7) h and 87 (82.8, 92.4) h for 4 and 12 h infusions. GFRCr was highly variable, increased after cisplatin, and exceeded 150 ml/min/1.73 m2. GFRcysC was less variable and decreased at the end of therapy. AKI biomarkers were elevated indicating acute tubular dysfunction, however, did not differ between 4 and 12 h infusions. Radiographic and histological response were similar for patients receiving 4 h or 12 h infusions; the median percent tumor necrosis was > 95%. CONCLUSIONS: Reducing peak serum and urine MTX concentration by prolonging the infusion duration did not alter risk of acute kidney injury. GFRcysC was decreased at the end of therapy. Proteinuria and elevations in AKI biomarkers indicate that direct tubular damage contributes to HDMTX nephrotoxicity. CLINICAL TRIAL: NCT01848457.

Ectopic pregnancy management by V-NOTES technique.

Ectopic pregnancy is a frequent and life-threatening risk of childbearing. Its management represents a mainstay of emergency gynecological surgery, and laparoscopy is the surgical gold standard technique. The technique of transvaginal natural orifice transluminal endoscopic surgery (V-NOTES) for the management of ectopic pregnancy is presented herein. The procedure is illustrated by an instructive video article that standardizes the essential steps to make the technique ergonomic and easy to perform (step-by-step explanations). This surgical technique allows to consider vaginal salpingectomy using a combined cœlio-vaginal approach. After a posterior colpotomy, an Alexis retractor was inserted in the pouch of Douglas followed by the placement of a dedicated platform on which three trocars were fixed. Pneumoperitoneum was then achieved. Once the diagnosis of ruptured tubal ectopic pregnancy was established, a salpingectomy was performed. As a minimally invasive approach, this procedure has high patient acceptance and seems to improve favorable clinical outcomes.

Cesarean scar pregnancy: Two case report and therapeutic management algorithm.

OBJECTIVE: We aimed to present two cases of cesarean scar pregnancy (CSP) and a literature review to discuss their management. CASES: We reported two cases of cesarean scar pregnancy (CSP) treated in Strasbourg's University Hospital between 2016 and 2018 and carried out an updated literature review concerning their treatment. RESULTS: The first case is a superficial implantation CSP managed by methotrexate (MTX) then ligation of the uterine arteries and echo-guided aspiration. The second case is a deep implantation CSP managed by MTX and then laparoscopic excision with clamping of the uterine arteries. In the literature, the most commonly used treatments are: MTX, echo-guided aspiration, and the combination of uterine artery embolization followed by echo-guided aspiration. CONCLUSION: We established an algorithm in which CSP treatment by MTX can be considered alone if criteria are met. If not, surgery, chosen according to the depth of implantation, will be associated with MTX with a preventive hemostasis procedure by embolization or ligation of the uterine arteries.

Use of haemostatic gel in the management of cervical pregnancy: a case report.

PURPOSE: This case report aimed to describe haemostatic agents with systemic methotrexate (MTX) as an effective management for cervical pregnancy with bleeding. CASE PRESENTATION: A 34-year-old nulligravida patient was referred due to vaginal spotting and lower abdominal discomfort, and was diagnosed with a cervical pregnancy at 6 weeks of gestation. The patient was treated with a multi-dose MTX regimen, and the bleeding was successfully controlled with haemostatic agents, which were applied at the bleeding site of the cervix. After completion of MTX treatment, beta human chorionic gonadotropin (ß-hCG) decreased to undetectable range. Furthermore, patients could preserve her uterus and maintain fertility. CONCLUSION: Haemostatic agents can be regarded as an effective option for vaginal bleeding due to cervical pregnancy.

Microcrystalline Cellulose and Crospovidone Identified in Placentas With Vaginal Misoprostol Use.

Misoprostol is a prostaglandin analog commonly used to induce termination of pregnancy. Clandestine home terminations complicate forensic fetal autopsy when a history of misoprostol use is withheld and the gross and histologic findings are sparse, as is often the case. One hundred thirty-two placentas with no vaginal misoprostol use, low-dose misoprostol use, and high-dose misoprostol use were reviewed for the presence, volume, and locations of microcrystalline cellulose and crospovidone, common tablet fillers in misoprostol tablets. Microcrystalline cellulose and/or crospovidone was identified in 0 (0%) of 88 cases with no vaginal administration or low-dose vaginal administration and 29 (66%) of 44 placentas with high-dose vaginal administration. When identified, microcrystalline cellulose and/or crospovidone is most commonly present on the maternal surfaces of the extraplacental membranes. The presence of microcrystalline cellulose and/or crospovidone was associated with smaller placental weight (Mann-Whitney U, P = 0.019). These fillers have a reasonable sensitivity for high-dose vaginal tablet use and are very specific. Although they are not diagnostic for misoprostol administration, they provide a finding that may prompt additional investigation into the nature of the vaginal tablet administered and the circumstances surrounding birth.

Interventions for non-tubal ectopic pregnancy.

BACKGROUND: Non-tubal ectopic pregnancy is the implantation of an embryo at a site lying outside the uterine cavity or fallopian tubes. Sites include a caesarean scar, the cornua uteri, the ovary, the cervix, and the abdomen. There has been an increasing trend in the occurrence of these rare conditions, especially caesarean scar pregnancy (CSP). OBJECTIVES: To evaluate the clinical effectiveness and safety of surgery, medical treatment, and expectant management of non-tubal ectopic pregnancy in terms of fertility outcomes and complications. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) search portal and nine other databases to 12 December 2019. We handsearched reference lists of articles retrieved and contacted experts in the field to obtain additional data. SELECTION CRITERIA: We included randomized controlled trials (RCTs) published in all languages that examined the effects and safety of surgery, medical treatment, and expectant management of non-tubal ectopic pregnancy. DATA COLLECTION AND ANALYSIS: We used Cochrane standard methodological procedures. Primary outcomes were treatment success and complications. MAIN RESULTS: We included five RCTs with 303 women, all reporting Caesarean scar pregnancy. Two compared uterine arterial embolization (UAE) or uterine arterial chemoembolization (UACE) plus methotrexate (MTX) versus systemic MTX and subsequent dilation and suction curettage; one compared UACE plus MTX versus ultrasonography-guided local MTX injection; and two compared suction curettage under hysteroscopy versus suction curettage under ultrasonography after UAE/UACE. The quality of evidence ranged from moderate to very low. The main limitations were imprecision (small sample sizes and very wide confidence intervals (CI) for most analyses), multiple comparisons with a small number of trials, and insufficient data available to assess heterogeneity. UAE/UACE versus systemic MTX prior to suction curettage Two studies reported this comparison. One compared UAE with systemic MTX and one compared UACE plus MTX versus systemic MTX, in both cases followed by a suction curettage. We are uncertain whether UAE/UACE improved success rates after initial treatment (UAE: risk ratio (RR) 1.00, 95% CI 0.90 to 1.12; 1 RCT, 72 women; low-quality evidence; UACE: RR 0.87, 95% CI 0.54 to 1.38; 1 RCT, 28 women; low-quality evidence). We are uncertain whether UAE/UACE reduced rates of complications (UAE: RR 0.47, 95% CI 0.13 to 1.75; 1 RCT, 72 women; low-quality evidence; UACE: RR 0.62, 95% CI 0.26 to 1.48; 1 RCT, 28 women; low-quality evidence). We are uncertain whether UAE/UACE reduced adverse effects (UAE: RR 1.58, 95% CI 0.41 to 6.11; 1 RCT, 72 women; low-quality evidence; UACE: RR 1.16, 95% CI 0.32 to 4.24; 1 RCT, 28 women; low-quality evidence), and it was not obvious that the types of events had similar values to participants (e.g. fever versus vomiting). Blood loss was lower in UAE/UACE groups than systemic MTX groups (UAE: mean difference (MD) -378.70 mL, 95% CI -401.43 to -355.97; 1 RCT, 72 women; moderate-quality evidence; UACE: MD -879.00 mL, 95% CI -1135.23 to -622.77; 1 RCT, 28 women; moderate-quality evidence). Data were not available on time to normalize ß-human chorionic gonadotropin (ß-hCG). UACE plus MTX versus ultrasonography-guided local MTX injection We are uncertain whether UACE improved success rates after initial treatment (RR 0.95, 95% CI 0.56 to 1.60; 1 RCT, 45 women; very low-quality evidence). Adverse effects: the study reported the same number of failed treatments in each arm (RR 0.88, 95% CI 0.40 to 1.92; 1 RCT, 45 women). We are uncertain whether UACE shortened the time to normalize ß-hCG (MD 1.50 days, 95% CI -3.16 to 6.16; 1 RCT, 45 women; very low-quality evidence). Data were not available for complications. Suction curettage under hysteroscopy versus under ultrasonography after UAE/UACE. Two studies reported this comparison. One compared suction curettage under hysteroscopy versus under ultrasonography after UAE, and one compared these interventions after UACE. We are uncertain whether suction curettage under hysteroscopy improved success rates after initial treatment (UAE: RR 0.91, 95% CI 0.81 to 1.03; 1 RCT, 66 women; very low-quality evidence; UACE: RR 1.02, 95% CI 0.96 to 1.09; 1 RCT, 92 women; low-quality evidence). We are uncertain whether suction curettage under hysteroscopy reduced rates of complications (UAE: RR 4.00, 95% CI 0.47 to 33.91; 1 RCT, 66 women; very low-quality evidence; UACE: RR 0.18, 95% CI 0.01 to 3.72; 1 RCT, 92 women; low-quality evidence). We are uncertain whether suction curettage under hysteroscopy reduced adverse effects (UAE: RR 3.09, 95% CI 0.12 to 78.70; 1 RCT, 66 women; very low-quality evidence; UACE: not estimable; 1 RCT, 92 women; very low-quality evidence). We are uncertain whether suction curettage under hysteroscopy shortened the time to normalize ß-hCG (UAE: MD 4.03 days, 95% CI -1.79 to 9.85; 1 RCT, 66 women; very low-quality evidence; UACE: MD 0.84 days, 95% CI -1.90 to 3.58; 1 RCT, 92 women; low-quality evidence). Non-tubal ectopic pregnancy other than CSP No studies reported on non-tubal ectopic pregnancies in locations other than on a caesarean scar. AUTHORS' CONCLUSIONS: For Caesarean scar pregnancies (CSP) it is uncertain whether there is a difference in success rates, complications, or adverse events between UAE/UACE and administration of systemic MTX before suction curettage (low-quality evidence). Blood loss was lower if suction curettage is conducted after UAE/UACE than after administration of systemic MTX (moderate-quality evidence). It is uncertain whether there is a difference in treatment success rates, complications, adverse effects or time to normalize ß-hCG between suction curettage under hysteroscopy and under ultrasonography (very low-quality evidence). There are no studies of non-tubal ectopic pregnancy other than CSP and RCTs for these types of pregnancy are unlikely.

Predictors of complete miscarriage after expectant management or misoprostol treatment of non-viable early pregnancy in women with vaginal bleeding.

PURPOSE: To identify predictors of complete miscarriage after expectant management or misoprostol treatment of non-viable early pregnancy in women with vaginal bleeding. METHODS: This was a planned secondary analysis of data from a published randomized controlled trial comparing expectant management with vaginal single dose of 800 µg misoprostol treatment of women with embryonic or anembryonic miscarriage. Predefined variables-serum-progesterone, serum-ß-human chorionic gonadotropin, parity, previous vaginal deliveries, gestational age, clinical symptoms (bleeding and pain), mean diameter and shape of the gestational sac, crown-rump-length, type of miscarriage, and presence of blood flow in the intervillous space-were tested as predictors of treatment success (no gestational sac in the uterine cavity and maximum anterior-posterior intracavitary diameter was ≤ 15 mm as measured with transvaginal ultrasound on a sagittal view) in univariable and multivariable logistic regression. RESULTS: Variables from 174 women (83 expectant management versus 91 misoprostol) were analyzed for prediction of complete miscarriage at ≤ 17 days. In patients managed expectantly, the rate of complete miscarriage was 62.7% (32/51) in embryonic miscarriages versus 37.5% (12/32) in anembryonic miscarriages (P = 0.02). In multivariable logistic regression, the likelihood of success increased with increasing gestational age, increasing crown-rump-length and decreasing gestational sac diameter. Misoprostol treatment was successful in 80.0% (73/91). No variable predicted success of misoprostol treatment. CONCLUSIONS: Complete miscarriage after expectant management is significantly more likely in embryonic miscarriage than in anembryonic miscarriage. Gestational age, crown-rump-length, and gestational sac diameter are independent predictors of success of expectant management. Predictors of treatment success may help counselling women with early miscarriage.

Outcome of cesarean scar pregnancy treated with local methotrexate injection.

Local injection of methotrexate (MTX) has been widely used for caesarean scar pregnancy (CSP), but the optimal candidate remains undetermined. The aim of this study is to determine the risk factors associated with treatment failure among patients who received a single dose of local MTX. This is a retrospective cohort study. Clinical information was compared between treatment success vs. failure groups. Risk factors related to treatment failure were also investigated with multivariate analysis. Of 47 patients diagnosed with CSP, 30 received local MTX injection. The initial serum ß- human chorionic gonadotropin (hCG) level in the failure group was significantly higher than in the success group (p = 0.048), and the cut-off value was 47,000 mIU/ml. The rate of type 2 position of the gestational sac in the failure group was significantly higher than in the treatment success group (p = 0.031). A high initial serum ß-hCG level (≥ 47,000 mIU/ml) was identified as the independent risk factor for treatment failure (adjusted odds ratio = 21.9; 95% confidence interval = 1.3-383.1). Type 2 gestational sac position and a higher level of ß-hCG at diagnosis appear to be associated with poor outcomes after local injection of a single dose of MTX.

Luteal blood flow as a predictive factor for methotrexate treatment outcomes in women with unruptured tubal pregnancy.

BACKGROUND: Blood flow in the corpus luteum is associated with luteal function. However, the impact of luteal blood flow on methotrexate (MTX) treatment in women with unruptured tubal pregnancy has not been reported. The aim of the present study was to observe the impact of luteal blood flow on the therapeutic effect of MTX in women with unruptured tubal pregnancy. METHODS: A prospective observational study recruited 129 women with unruptured tubal pregnancy in the First Affiliated Hospital of Xi'an Jiaotong University from September 2016 to June 2018. One hundred and fifteen women were treated successfully with MTX, and women were divided into 2 groups according to luteal blood flow: the poor luteal blood flow group and the abundant luteal blood flow group. The therapeutic effects were compared between the two groups. RESULTS: Women in the abundant luteal blood flow group had a significantly higher serum ß-human chorionic gonadotropin (ß-hCG) level 4 days, 1 week and 2 weeks after MTX treatment compared with women in the poor luteal blood flow group (P < 0.05). The average diameter of the ectopic mass 1 week, 2 weeks and 3 weeks after MTX treatment in women with abundant luteal blood flow was significantly larger (P < 0.05), and the time of serum ß-hCG clearance and ectopic mass disappearance were significantly longer compared with those in women in the poor luteal blood flow group (P < 0.05). CONCLUSIONS: Luteal blood flow might be a predictive factor for MTX treatment outcomes in women with unruptured tubal pregnancy, and those with abundant luteal blood flow need a longer recovery time.

Effect of treatment of phantom cows with a progesterone-based synchrony programme.

Aim: To determine the effect of a progesterone-based synchrony programme on the daily hazard of conception and the probability of being pregnant at the end of the seasonal mating period in cows not observed in oestrus within 35-49 days of insemination and that were diagnosed non-pregnant (phantom cows) on seasonally calving New Zealand dairy farms. Secondary aims were to determine the prevalence of phantom cows and estimate the proportion of phantom cows with a functional corpus luteum (CL) at enrolment. Methods: Phantom cows from 14 New Zealand commercial dairy farms were enrolled in a randomised, controlled trial. Cows that were artificially inseminated ≤14 days after mating start date and were not subsequently detected in oestrus, were presented for pregnancy diagnosis approximately 49 days after mating start date. Non-pregnant cows were diagnosed as phantom cows and randomly allocated to treatment and control groups. A milk sample was collected for progesterone assay to determine the presence of a functional CL. Treatment consisted of an injection of buserelin and insertion of an intravaginal device containing progesterone on Day 0, injections of dinoprost and equine chorionic gonadotrophin, and removal of the intravaginal device on Day 7, injection of buserelin on Day 9, and fixed time artificial insemination on Day 10. Treatment group cows were then mixed with bulls for the remainder of the seasonal mating period. Cows allocated to the control group were mated naturally by bulls. Statistical models were constructed to determine the effect of treatment on the daily hazard of conception and the probability of being pregnant at the end of the seasonal mating period. Results: A total of 378/4,214 (9.0%) cows presented for pregnancy diagnosis were diagnosed as phantom cows. A functional CL was diagnosed in 257/362 (71.0%) phantom cows. Median predicted enrolment to conception intervals were 33 (95% CI = 30-45) and 30 (95% CI = 28-33) days, for cows in the control and treatment groups, respectively. The odds of being pregnant at the end of mating were 1.70 (95% CI = 1.34-2.17) times greater for treated phantom cows than untreated phantom cows. Estimated marginal mean proportion pregnant at mating end date were 59.5 (95% CI = 47.9-70.1)% and 71.5 (95% CI = 62.6-79.0)% for control and treatment group cows, respectively. Conclusions: Treatment with a progesterone-based synchrony programme significantly increased the probability of phantom cows being pregnant at the end of the seasonal mating period.

Prognostic accuracy of a novel methotrexate protocol for the resolution of tubal ectopic pregnancies.

OBJECTIVE: To evaluate if a decreasing human chorionic gonadotropin (hCG) between day (D) 1 and D7 is an equal or better predictor of tubal ectopic pregnancy (EP) resolution following methotrexate (MTX) treatment than the current standard of care. STUDY DESIGN: This was a retrospective cohort prognostic accuracy study of women with a transvaginal ultrasound (TVS)-confirmed tubal EP (November 2006-December 2015). After single-dose MTX treatment, D4/7 hCG ratios were compared with that of D1/D7 in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) to predict EP resolution. RESULTS: Tubal EP was diagnosed in 301/7350 (4.1%) women who underwent TVS for early pregnancy-related complaints. The patients were managed accordingly: expectant, 84/301 (27.9%); MTX, 65/301 (21.6%); surgery, 152/301 (50.5%). A D1/D7 hCG ratio ≤0.85 predicted successful resolution of tubal EPs (P < 0.001) treated with MTX with sensitivity 0.84 [95% confidence interval (CI), 0.69-0.94]), specificity 0.71 [95%CI, 0.48-0.89], PPV 0.84 [95%CI, 0.69-0.94], NPV 0.84 [95%CI, 0.69-0.94], which is comparable to the prognostic performance of the D4/7 protocol. CONCLUSION: In patients with tubal EP carefully selected for and treated with MTX, it may be reasonable to eliminate the D4 hCG in the follow-up algorithm.

Society for Maternal-Fetal Medicine (SMFM) Consult Series #49: Cesarean scar pregnancy.

Cesarean scar pregnancy is a complication in which an early pregnancy implants in the scar from a prior cesarean delivery. This condition presents a substantial risk for severe maternal morbidity because of challenges in securing a prompt diagnosis, as well as uncertainty regarding optimal treatment once identified. Ultrasound is the primary imaging modality for cesarean scar pregnancy diagnosis, although a correct and timely determination can be difficult. Surgical, medical, and minimally invasive therapies have been described for cesarean scar pregnancy management, but the optimal treatment is not known. Women who decline treatment of a cesarean scar pregnancy should be counseled regarding the risk for severe morbidity. The following are Society for Maternal-Fetal Medicine recommendations: We recommend against expectant management of cesarean scar pregnancy (GRADE 1B); we suggest operative resection (with transvaginal or laparoscopic approaches when possible) or ultrasound-guided vacuum aspiration be considered for surgical management of cesarean scar pregnancy and that sharp curettage alone be avoided (GRADE 2C); we suggest intragestational methotrexate for medical treatment of cesarean scar pregnancy, with or without other treatment modalities (GRADE 2C); we recommend that systemic methotrexate alone not be used to treat cesarean scar pregnancy (GRADE 1C); in women who choose expectant management and continuation of a cesarean scar pregnancy, we recommend repeat cesarean delivery between 34 0/7 and 35 6/7 weeks of gestation (GRADE 1C); we recommend that women with a cesarean scar pregnancy be advised of the risks of another pregnancy and counseled regarding effective contraceptive methods, including long-acting reversible contraception and permanent contraception (GRADE 1C).

Reconceptualizing safe abortion and abortion services in the age of abortion pills: A discussion paper.

At the conference "Developing an Advocacy Agenda for Abortion in the 21st Century and Making Change Happen" held on 5-7 September 2018, Lisbon, Portugal, organized by the International Campaign for Women's Right to Safe Abortion, it was argued that abortion services not only need to be treated as a bona fide form of health care but also completely reconceptualized, particularly because of the influence of medical abortion pills. It emerged, however, that there is no consensus on how this reconceptualization should be configured. Indeed, substantial differences arose, or so it appeared, complicated not only by different exigencies in national settings but also reflecting differing perspectives, specifically, those held primarily by health professionals compared to those held by advocates who felt they spoke for women needing abortions. In the course of these discussions, questions emerged on how much women should be able to do on their own, whether and why services were necessary in every case, where services should be located, what they should offer, who should provide them, and who should be in charge of the process. The biggest discussion was over the extent to which women can safely self-manage use of medical abortion pills for abortion in both the first and second trimester, and to what extent health professional control should be relinquished. Regardless of these arguments, however, since 1988 with the discovery in Brazil that misoprostol is an abortifacient, over-the-counter access to medical abortion (MA) pills began to put self-management of abortion on the map. Today, self-management is happening in almost every country, and we have no idea how many abortions are taking place anymore. Moreover, because of the work of safe abortion information hotlines, there is a growing body of evidence that self-management of abortion by women is safe - or at least far less unsafe than what prevailed in the past. Looking beyond the abortion rights movement, the crux of the issue is whether the state should continue to control abortion, with power over individual decisions delegated to the medical profession - or whether, as has been happening at a snail's pace for the last half century, and as with contraception and emergency contraception too - control can and should be more and more in women's hands. This paper examines these perspectives and attempts to describe what a consensus might look like. It concludes that convincing governments and conservative health professionals to accept a large dose of self-management will not be easy.

Direct Methotrexate Injection into the Gestational Sac for Nontubal Ectopic Pregnancy: A Review of Efficacy and Outcomes from a Single Institution.

STUDY OBJECTIVE: To evaluate the efficacy of nontubal ectopic pregnancy (NTEP) management with direct methotrexate (MTX) injection into the gestational sac. DESIGN: A retrospective chart review. SETTING: A tertiary academic and teaching hospital. PATIENTS: All cases of confirmed NTEP were retrospectively identified from 2012 to 2017. INTERVENTIONS: Ultrasound-guided direct injection of MTX into the fetal pole and surrounding gestational sac and a single dose of systemic MTX with or without fetal intracardiac injection of potassium chloride. MEASUREMENTS AND MAIN RESULTS: Treatment failure, complications from treatment, operating time, and days to negative serum human chorionic gonadotropin (hCG) after treatment were measured. Fourteen women (age 34 ± 5.2 years) with NTEP underwent direct MTX injection (cesarean scar, n = 4; interstitial, n = 6; cervical, n = 4). The mean estimated gestational age was 49 ± 11, CI (43, 56 days). One patient required laparoscopic intervention with a failure rate of 1 of 14 (a double interstitial, heterotopic pregnancy). There were no other major complications. The time in the operating room was similar for all NTEP types. The average time to negative serum hCG was not different for cesarean scar (84.5 ± 36 days), cervical pregnancies (70.5 ± 19 days), or interstitial pregnancies (45.3 ± 38 days, p = .15). CONCLUSION: Direct MTX injection into the gestational sac for NTEP treatment is safe and effective. The failure rate of 7% is considerably lower than what was previously reported for a failure of systemic MTX in similar cases (25%). Resolution of serum hCG after treatment can be quite prolonged even in uncomplicated cases.

Day 1 change in maternal serum ß-HCG levels as an early predictor of successful medical therapy in ectopic pregnancies.

Objective: To evaluate the role of ß-HCG level changes between days 0 and 1 as an early predictor of methotrexate success in cases of tubal ectopic pregnancy.Methods: A retrospective study included 86 tubal ectopic pregnancies treated with a single-dose methotrexate protocol of 50 mg/m2 of body surface. ß-HCG measurements were taken on days 0, 1, 4 and 7 where day 0 is the day of methotrexate injection. Day 0 ß-HCG and the percentage change in ß-HCG level between days 0 and 1 (HCG index) were calculated and compared between patients who were successfully or unsuccessfully treated. Receiver operator characteristics (ROC) curves were plotted to identify the best cutoff levels.Results: The average level of ß-HCG (1416.8 versus 2502.5 IU/L, p=.001) and its increment after 24 hours (12.9 versus 27.1%, p=.001) were significantly lower in the successful treatment group. ROC curves for ß-HCG level and its relative increment revealed that cutoff values of ≤1550 IU/L and ≤13% increment showed a sensitivity of 90 and 70% respectively for successful methotrexate treatment.Conclusion: Day 0 ß-HCG level ≤1550 IU/L and an increment of ≤13% after 24 hours are early predictors of successful methotrexate treatment for tubal ectopic pregnancy.