Efficacy of transvaginal ultrasound-guided local injections of absolute ethanol for ectopic pregnancies with intrauterine implantation sites.

BACKGROUND: Cervical pregnancies, interstitial tubal pregnancies, and cesarean scar pregnancies, which are ectopic pregnancies with intrauterine implantation sites exhibit increasing trends with the recent widespread use of assisted reproductive technologies and increased rate of cesarean deliveries. The development of high-sensitivity human chorionic gonadotropin testing reagents and the increased precision of transvaginal ultrasonic tomography have made early diagnosis possible and have enabled treatment. Removal of ectopic pregnancies using methotrexate therapy and/or uterine artery embolization has been reported. However, delayed resumption of infertility treatments after methotrexate therapy is indicated, and negative effects on the next pregnancy after uterine artery embolization have been reported. AIM: To examine the efficacy and safety of ultrasound-guided topical absolute ethanol injection in ectopic pregnancies with an intrauterine implantation site. METHODS: In this study, we retrospectively examined the medical records of 21 patients who were diagnosed with an ectopic pregnancy with an intrauterine implantation site at our hospital, between April 2010 and December 2018, and underwent transvaginal ultrasound-guided local injections of absolute ethanol to determine the treatment outcomes. We evaluated the treatment methods, treatment outcomes, presence of bleeding requiring hemostasis measures and blood transfusion, complications, and treatment periods. Successful treatment was defined as the completion of treatment using transvaginal ultrasound-guided local injections of absolute ethanol alone. RESULTS: There were 21 total cases comprising 10 cervical pregnancies, 10 interstitial tubal pregnancies, and 1 cesarean scar pregnancy. All patients completed treatment with this method. No massive hemorrhaging or serious adverse reactions were observed during treatment. The mean gestation ages at the time of diagnosis were 5.9 wk (SD, ± 0.9 wk) for cervical and 6.9 wk (SD, ± 2.1 wk) for interstitial tubal pregnancies. The total ethanol doses were 4.8 mL (SD, ± 2.2 mL) for cervical pregnancies and 3.3 mL (SD, ± 2.2 mL) for interstitial pregnancies. The treatment period was 28.5 days (SD, ± 11.7 d) for cervical pregnancies and 30.0 ± 8.1 d for interstitial pregnancies. Positive correlations were observed between the blood ß- human chorionic gonadotropin level at the beginning of treatment and the total ethanol dose (r = 0.75; P = 0.00008), as well as between the total ethanol dose and treatment period (r = 0.48; P = 0.026). CONCLUSION: Transvaginal ultrasound-guided local injections of absolute ethanol could become a new option for intrauterine ectopic pregnancies when fertility preservation is desired.

Ultrasound-guided local ethanol injection for fertility-preserving cervical pregnancy accompanied by fetal heartbeat: Two case reports.

BACKGROUND: The incidence of cervical pregnancy is increasing due to the recent widespread application of assisted reproductive technology. Although hysterectomy has been a treatment option, high-sensitivity human chorionic gonadotropin testing and improved accuracy of transvaginal ultrasound imaging have increased possibility of uterine preservation. Dilation and curettage with methotrexate therapy and uterine artery embolization have been reported as treatments with fertility preservation; however, certain disadvantages limit their use. CASE SUMMARY: In our two reported cases, we avoided massive bleeding and immediately resumed infertility treatment using ultrasound-guided local ethanol injection for cervical pregnancies with fetal heartbeats. CONCLUSION: This treatment may be a new fertility-preserving option for cervical pregnancy.

Successful Conservative Treatment of Cesarean Scar Ectopic Pregnancy with Local Injections of Absolute Ethanol.

Cesarean scar ectopic pregnancy (CSEP) is becoming more common worldwide. Here, we report a case of cesarean scar pregnancy successfully treated using transvaginal ethanol injection. A 31-year-old female (gravida 3, para 2) with two prior cesarean sections presented at 9 weeks and 3 days of pregnancy. Her serum human chorionic gonadotropin level was 91,798 mIU/mL. CSEP was confirmed by transvaginal ultrasonography, pelvic magnetic resonance imaging, and color Doppler ultrasonography. Transvaginal absolute ethanol local injection under transvaginal ultrasound guidance was performed. She was discharged 7 days after treatment with no complications and resumed normal menses 1 month after treatment. We describe a safe and successful treatment option for CSEP.

Retrospective outcome in women aged 45 years and older undergoing natural cycle IVF treatment.

RESEARCH QUESTION: Is natural cycle IVF treatment beneficial to middle-aged women with poor ovarian response? DESIGN: Retrospective investigation of outcomes in women aged 45 years and older, who underwent natural cycle IVF treatment between 2009 and 2018 in a single assisted reproduction clinic with the aim of reporting several successful outcomes. RESULTS: In total, 2408 IVF retrievals in women aged 45 years and older were included in this study. Mean serum FSH level on day 3 was 21.4 ± 12.5 (range: 0.3-93.7) IU/ml. One fresh cleavage-stage embryo was transferred in 37.4% (900/2408) of the initiated cycles. The overall clinical pregnancy rate and live birth rate per fresh embryo transfer were 2.8% (25/900) and 0.8% (7/900), respectively. Natural cycle IVF treatment led to seven successful deliveries during the period. All seven women who successfully delivered were poor ovarian responders who met the diagnostic Bologna criteria and, among them, three had elevated serum FSH levels on day 3 (range: 39.0-47.1 mIU/ml). All seven had full-term delivery, and no congenital abnormalities were observed in their infants. No significant difference was found in serum FSH level on day 3 between those with and without positive beta-HCG test results. CONCLUSIONS: These findings suggest that natural cycle IVF treatment could be an option for older poor responders in countries that do not permit egg donation. Careful counselling is required, however, because of the low probability of live births after IVF in middle-aged women.

Managing Ectopic Pregnancies by Targeting Chorionic Villi with a Transvaginal Injection of Ethanol into the Lacunar Space.

Methotrexate has been the main mode of non-surgical treatment for ectopic pregnancies. However, we have developed an easier, repeatable method that can be applied even to patients with a high beta-human chorionic gonadotropin (ß-hCG) level and/or positive fetal heartbeat, by targeting chorionic villi with a transvaginal injection of absolute ethanol (AE) into the lacunar space (intervillous space). The efficacy and safety of this method were examined in 242 cases of ectopic pregnancy, including 103 with positive fetal heartbeat. Serum ß-hCG level was measured at frequent intervals, and transvaginal ultrasonography was performed to observe the gestational sac and hyperechoic inner ring. Of the 242 patients, 222 (91.7%) were successfully treated. The average number of AE injection(s) required was 1.6 (range: 1-5), and the average dose was 3.2 mL. After the treatment, many of the patients tried to conceive again, and 63 of the traceable 145 patients (43.4%), who had fallopian tube pregnancy, and 7 of the traceable 12 patients (58.3%), who had cervical or cesarean scar pregnancies, successfully conceived and delivered babies with no observed side effects. Therefore, this method could be an effective treatment for ectopic pregnancy with the potential to replace conventional surgical interventions and medical treatment using methotrexate.

A Novel Treatment for Cervical and Cesarean Section Scar Pregnancies by Transvaginal Injection of Absolute Ethanol to Trophoblasts: Efficacy in 19 Cases.

STUDY OBJECTIVE: To evaluate the efficacy of a nonsurgical treatment for cervical pregnancy (CP) and cesarean section scar pregnancy (CSP). DESIGN: Retrospective clinical study (Canadian Task Force classification III). SETTING: Private assisted reproductive technology practice. PATIENTS: Nineteen women with CP (n = 16) or CSP (n = 3), including 6 patients with positive fetal heartbeat. INTERVENTION: Transvaginal local injection of absolute ethanol (AE) into the hyperechoic ring (lacunar space) around the gestational sac under ultrasound guidance. MEASUREMENTS AND MAIN RESULTS: Serum beta-human chorionic gonadotropin (ß-hCG) was measured at frequent intervals, and ultrasound and/or magnetic resonance imaging was used to observe the gestational sac. In 9 patients, the serum ß-hCG level was effectively reduced with a single AE injection at 2 hours. In the remaining 10 patients, the level decreased but then increased in 4 and slowly decreased in the other 6; all of these 10 patients required 2 to 5 repeat AE injections. In all patients, serum ß-hCG level was reduced by 50% within 3 days and decreased to <10% of the initial level within 14 days. In 18 patients (95%), the level was decreased to 1.0 mIU/mL within 40 days. Seven patients were treated on an outpatient basis. Twelve patients received no anesthesia. Five patients subsequently became pregnant, and each had a live birth. There was no recurrent CP or CSP. The procedure was successful in all 19 patients. CONCLUSION: This procedure is an effective treatment for CP or CSP that could be used in place of conventional surgical interventions and medical treatment using MTX.

A microwell culture system that allows group culture and is compatible with human single media.

PURPOSE: A microwell culture system that facilitates group culture, such as well-of-the-well (WOW), improves embryonic development in an individual culture. We examined the effect of WOW on embryonic development in vitro with commercially available human single culture media. METHODS: Using four different commercial human single culture media, in vitro development and imprinted gene expression of bovine embryos cultured in WOW were compared to droplet culture (one zygote per drop). To determine the effects of microwell and group culture on embryonic development, different numbers of embryos were cultured in droplet or WOW. Diffusion simulation of accumulating metabolites was conducted using the finite volume method. RESULTS: WOW had a positive effect on bovine embryonic development, regardless of the type of single culture media. Imprinted gene expression was not different between droplet- and WOW-derived blastocysts. The microwell and group cultures in WOW showed a significant positive effect on the rate of total blastocysts and the rate of development to the expanded and hatching blastocyst stages. The assumed cumulative metabolite concentration of WOW with one embryo was 1.47 times higher than that of droplet culture with one embryo. Furthermore, the concentration of WOW with three embryos was 1.54 times higher than that of WOW with one embryo. CONCLUSIONS: In using human single culture media, a microwell culture system that allows group culture could be a powerful clinical tool for improving the success of assisted reproductive technologies.

[Analysis of the relevance of the mutations of the precore and basic core promoter in HBV genome with the DNA amount of HBV viremia].

In the course of hepatitis B, serum concentrations of the virus usually fall following sero-conversion, characterized by the loss of HBe antigen and appearance of detectable anti-HBe. However, hepatitis B viremia may persist even after sero-conversion. We assessed the association of continuous viremia with the precore (PC) (G1896A) mutation, basic core promoter (BCP) (A1762T, G1764A) mutations, the viral genotype and the quantity of viral DNA. Neither PC nor BCP mutations were detected in the viral DNA isolated from cases in which HBV became negative during the course of infection. The virus quantity increased after sero-conversion in all of the cases of persistent viremia with HBV genotype C harboring BCP mutations, indicating that the BCP mutation in genotype C is a determinant of continuous viremia. This feature was not evident in infections with HBV genotype B. Although the PC mutation was detected in the viral DNA from both genotypes B and C in continuous viremia, the mutation was not relevant to the quantity of virus. Our data suggest that HBV genotype C has a predisposition to acquire BCP mutations and these mutations activate virus replication after sero-conversion. This mechanism may be a cause of the poor prognosis of hepatitis with HBV genotype C. In conclusion, analyses of HBV genotype and BCP mutations are imperative to determine the prognosis of hepatitis B.

Natural IVF cycles may be desirable for women with repeated failures by stimulated IVF cycles.

PURPOSE: Although many reports support stimulated in vitro fertilization, several patients do not respond to it well. Furthermore, stimulated treatment could be associated with reduced ovarian response. We describe three successful cases involving patients of advanced age from whom dominant follicles were retrieved during the natural cycle. MATERIALS AND METHODS: All patients had failed to bear children through stimulated in vitro fertilization. In case 1, a follicle was retrieved after a gonadotropin-releasing hormone agonist was used to induce luteinizing hormone surge. In cases 2 and 3, pregnancy was achieved via completely natural cycles. RESULTS: One embryo was transferred every 16 cycles. Ongoing pregnancy--defined as pregnancy progressing beyond gestation week 9--was established in three cycles. The patients successfully delivered and had uneventful neonatal courses. CONCLUSION: Mature oocyte retrieval followed by natural rather than stimulated in vitro fertilization might be a potential treatment for patients of advanced age when stimulated in vitro fertilization has been repeatedly unsuccessful.

The efficacy and safety of managing ectopic pregnancies with transvaginal ultrasound-guided local injections of absolute ethanol.

PURPOSE: To describe the efficacy and safety of managing ectopic pregnancies (EP) with ultrasound-guided local injections of absolute ethanol (AE). METHODS: 69 cases of EP following IVF performed in our clinic were treated with a local injection of 0.3 ml AE with a 23-gauge needle under transvaginal ultrasonic guidance. The efficacy was evaluated comparing serum beta-human chorionic gonadotropin (beta-hCG) levels before and after the injection. RESULTS: In the 60 successful cases (87%), the serum beta-hCG level decreased by 10-30% in two hours postinjection. Of these, 46 were effective with a single injection and the half-life of beta-hCG was achieved within 4 days in 45 cases. In 56 cases (including repetitive administration) serum beta-hCG levels decreased to 20 mIU/mL within 20 days. The treatment showed no side effects and could be given on an outpatient basis without anesthesia. CONCLUSIONS: This method was shown to be a safe, effective new approach to treating EP.