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Objective To study the risk factors leading to type II/III cesarean scar pregnancy and evaluate the efficacy of hysteroscopic treatment and subsequent reproductive outcomes. Design Retrospective study from 2013 to 2018. Setting Inpatient samples. Patient(s) A total of 439 patients with cesarean scar pregnancy received hysteroscopic treatment. They were grouped according to the type of surgery as hysteroscopy combined with dilation and curettage, systemic methotrexate followed by hysteroscopy combined with dilation and curettage, and uterine artery embolization or laparoscopic ligation of bilateral uterine arteries followed by hysteroscopy combined with dilation and curettage. Cesarean scar pregnancy was classified as types I, II, and III on the basis of the relationship between the gestational sac and myometrial thickness by ultrasound. Intervention(s) Not applicable. Main Outcome Measure(s) Risk factors leading to type II/III cesarean scar pregnancy. The success of hysteroscopic treatment as well as favorable reproductive outcomes. Result(s) The significant variables were multiple parity, prior cesarean section (CS), hysteroscopic therapy, and dilation and curettage after the last CS between type I and type II/III. There were significant differences among the three groups in symptoms, largest diameter of the gestational sac, presence of fetal heartbeat, myometrial thickness, type of cesarean scar pregnancy, blood loss, length of hospital stay, and expense. The rates of complications and success were 8.2% and 93.6%, respectively. Thirty-seven women conceived again, and 22 women completed a term pregnancy with no uterine rupture. The recurrence rate of cesarean scar pregnancy was 10.8%. Conclusions The type of cesarean scar pregnancy is related to the rates of multiple parity, cesarean deliveries, and dilation and curettage procedures after the last CS. Hysteroscopic therapy is a safe and effective surgical approach with a low risk of subsequent ectopic pregnancy.

A retroperitoneal ectopic pregnancy is an extremely rare type of ectopic pregnancy and is difficult to diagnose and treat. Owing to its occult onset, it is life-threatening and often associated with high mortality. A 28-year-old woman was admitted to the emergency department of our hospital owing to soreness of the left lower quadrant of the abdomen and amenorrhea for 60 days. Dilatation and curettage were performed at a local hospital to induce abortion, but no gestational sac was found. Elevated plasma human chorionic gonadotropin levels suggested an ectopic pregnancy. An ultrasound showed an approximately 4.0 cm × 3.0 cm mass in front of the middle and upper poles of the left kidney. The plasma beta–human chorionic gonadotropin level was 99 286.00 mIU/mL. Under laparoscopy, an ovoid mass measuring approximately 4.0 cm × 5.0 cm below the left renal vessels and the abdominal aorta was successfully resected. Methotrexate (50 mg/m2) was locally injected, and the retroperitoneum was sutured. Villi were observed in histopathologic sections. This case report highlights the importance of considering the possibility of a retroperitoneal ectopic pregnancy for patients with abdominal pain. Laparoscopic surgery by an experienced surgeon is the preferred method of treatment for this condition.

Introduction. Termination of pregnancy in a patient with huge uterine leiomyomata poses significant challenges to clinicians. In this study, we report the successful termination of pregnancy in a patient with large multiple uterine leiomyomata using a combined regimen of drugs for medical abortion. Case. A 42-year-old woman, 6 weeks pregnant, presented to the Family Planning Clinic with an unintended pregnancy. She had a large, irregular abdominal midline mass, equivalent in size to 30-32 weeks of pregnancy. Abdominal and transvaginal ultrasound examinations revealed a small intrauterine gestational sac with a yolk sac and multiple large uterine leiomyomata. Treatment with mifepristone (200 mg) was initiated at the clinic. In addition, she was instructed to sublingually take 800 μg of misoprostol after 24–48 h. Two weeks later, at the follow-up visit, the patient complained of continued light bleeding. A pelvic examination showed that her cervix was dilated by 1 cm. In addition, abdominal and transvaginal ultrasound revealed a thick, inhomogeneous endometrium. Owing to light bleeding and no anemia or infection, the patient received two additional doses of 800 μg misoprostol vaginally. Her bleeding subsided for 61 days, and she resumed her normal menstrual cycle. Conclusion. A first-trimester pregnancy with large multiple uterine leiomyomata can be safely terminated using a combination regimen of drugs for medical abortion. However, an additional dose of misoprostol is required for the successful termination of pregnancy.

Objective To study the relationship between postwash total motile sperm count (TMSC) and intrauterine insemination (IUI) outcomes. Design Retrospective review Setting Large fertility clinic Patient(s) A total of 92,471 insemination cycles from 37,553 patients were included in this study. Intervention(s) All stimulated clomiphene citrate, letrozole, and/or injectable gonadotropin IUI cycles performed at a single institution from 2002 through 2018 were reviewed. Generalized estimating equations (GEE) analysis was used to account for multiple cycles by individual patients and to adjust for female partner age, body mass index, and stimulation protocol. Main outcome measure(s) Successful clinical pregnancy was defined as ultrasound confirmation of an intrauterine gestational sac with fetal cardiac activity. Result(s) A total of 92,471 insemination cycles were available to evaluate the relationship between postwash TMSC and clinical pregnancy. Pregnancy rates were highest with TMSC of ≥9 × 106 and declined gradually as TMSC decreased. Complete data for the adjusted GEE analysis were available for 62,758 cycles. Adjusted GEE analysis among cycles with TMSC of ≥9 × 106 (n = 46,557) confirmed that TMSC in this range was unrelated to pregnancy. Conversely, TMSC was highly predictive of pregnancy (Wald χ2 = 39.85) in adjusted GEE analysis among cycles with TMSC of Conclusions IUI pregnancy is optimized with TMSC of ≥9 × 106, below which the rates gradually decline. Although rare, pregnancies were achieved with TMSC of

The objective of this study was to evaluate the impact of implantation outside the normal intra-uterine endometrium on development of the gestational sac.We reviewed and compared the ultrasound measurements and vascularity score around the gestational sac in 69 women diagnosed with a live tubal ectopic pregnancy (TEP) and 54 with a cesarean scar ectopic pregnancy (CSP) at 6-11 weeks of gestation who were certain of their last menstrual period.The rate of a fetus with a cardiac activity in the study population was significantly (P 0.001) higher in CSPs than in TEPs. The median maternal age, gravidity and parity were significantly (P =.005; P 0.001 and P 0.001, respectively) lower in the TEP than in the CSP group. The number of gestational sac size5th centile for gestational age was significantly (P 0.001) higher in the TEP than in the CSP group. There were no differences between the groups for the other ultrasound measurements. In cases matched for gestational age, the gestational sac size was significantly (P 0.001) smaller in the TEP compared to the CSP group. There was a significant (P 0.001) difference in the distribution of blood flow score with CSP presenting with higher incidence of moderate and high vascularity than TEP.Both TEP and CSP are associated with a higher rate of miscarriage than intrauterine pregnancies and the slow development of the gestation sac is more pronounced in TEPs probably as a consequence of a limited access to decidual gland secretions.

Introduction Despite the high prevalence of miscarriages, they are not systematically registered and few epidemiological studies have been done. As Finnish health registries are comprehensive and widely used in research, we validated the Finnish register data concerning diagnostics and treatment of miscarriage, and treatment-related adverse events. Material and methods We conducted a validation study regarding miscarriage-related codes of diagnoses and surgical procedures in a Finnish National Hospital Discharge Registry (NHDR) by comparing the information from the NHDR with that of the hospital records. We selected a random sample of 4 months during 1998-2016 from three hospitals, comprising 687 women aged 15-49 experiencing a first miscarriage during follow-up. Women with diagnoses unrelated to miscarriage, or proven to be other than miscarriage, were excluded. The final sample consisted of 643 women with confirmed miscarriage, which was used for analyses regarding the diagnosis, treatment and adverse events of miscarriage treatment. Results The majority of miscarriages registered in the NHDR were confirmed by the hospital records (positive predictive value [PPV] = 93.6% [95% confidence interval [CI] 91.8%-95.4%]). Different types of miscarriage were also reliably identified; spontaneous abortion with PPV = 85.6% (95% CI 80.9%-89.2%), missed abortion with PPV = 92.7% (95% CI 88.8%-95.3%) and blighted ovum with PPV = 91.1% (95% CI 84.3%-95.1%). The PPV of surgical treatment (62.2% [95% CI 55.7%-68.3%]) was lower than the PPV of non-surgical treatment (93.3% [95% CI 90.5%-95.3%]). The diagnoses regarding adverse events of miscarriage treatment could be reliably identified. The PPV for clinical infections was 76.0% (95% CI 56.6%-88.5%) and for retained products of conception or/and vaginal bleeding 96.8% (95% CI 83.8%-99.4%). Conclusions The coverage of the NHDR was good concerning identification of miscarriages, different types of miscarriages and non-surgical treatment. Nevertheless, there is a need for clearly defined procedural codes concerning to medical treatment of miscarriage. The register-based data are reliable and practicable for both clinical evaluation and research concerning miscarriage.

BACKGROUNDThe function of the gestational sac (GS) and the placenta in the closely related processes of embryogenesis and teratogenicity in the first trimester has been minimally described. The prevailing assumption is that direct teratogenic effects are mediated by the critical extraembryonic organ, the placenta, which either blocks or transfers exposures to the foetus. Placental transfer is a dominant mechanism, but there are other paradigms by which the placenta can mediate teratogenic effects. Knowledge of these paradigms and first trimester human developmental biology can be useful to the epidemiologist in the conduct of biomarker-based studies of both maternal and child health.OBJECTIVE AND RATIONALEOur aim is to provide a causal framework for modelling the teratogenic effects of first trimester exposures on child health outcomes mediated by the GS and placenta using biomarker data collected in the first trimester. We initially present first trimester human developmental biology for the sake of informing and strengthening epidemiologic approaches. We then propose analytic approaches of modelling placental mechanisms by way of causal diagrams using classical non-embryolethal teratogens (diethylstilboestrol [DES], folic acid deficiency and cytomegalovirus [CMV]) as illustrative examples. We extend this framework to two chronic exposures of particular current interest, phthalates and maternal adiposity.SEARCH METHODSInformation on teratogens was identified by a non-systematic, narrative review. For each teratogen, we included papers that answered the five following questions: (i) why were these exposures declared teratogens? (ii) is there a consensus on biologic mechanism? (iii) is there reported evidence of a placental mechanism? (iv) can we construct a theoretical model of a placental mechanism? and (v) can this knowledge inform future work on measurement and modelling of placental-foetal teratogenesis? We prioritized literature specific to human development, the organogenesis window in the first trimester and non-embryolethal mechanisms.OUTCOMESAs a result of our review of the literature on five exposures considered harmful in the first trimester, we developed four analytic strategies to address first trimester placental mechanisms in birth cohort studies: placental transfer and direct effects on the foetus (DES and maternal adiposity), indirect effects through targeted placental molecular pathways (DES and phthalates), pre-placental effects through disruptions in embryonic and extraembryonic tissue layer differentiation (folic acid deficiency), and multi-step mechanisms that involve maternal, placental and foetal immune function and inflammation (DES and CMV).WIDER IMPLICATIONSThe significance of this review is to offer a causal approach to classify the large number of potentially harmful exposures in pregnancy when the exposure occurs in the first trimester. Our review will facilitate future research by advancing knowledge of the first trimester mechanisms necessary for researchers to effectively associate environmental exposures with child health outcomes.

Splenic ectopic pregnancy is extremely rare but carries a high risk of uncontrollable life-threatening bleeding. Our aim is to try to diagnose those cases earlier and to include splenic preservation as good alternative for selected cases. Extensive review of the literature has been performed. Thirty-one case reports were identified, of which 4 have been excluded because they were not written in English. A 36-year-old woman presented to the Emergency Department with haemorrhagic shock. Despite the levonorgestrel intrauterine system (LNG-IUS) being in situ for 4 months, urinary and serum tests were both positive for pregnancy, and an ultrasound scan revealed haemoperitoneum suggestive of a ruptured ectopic pregnancy. An emergency Pfannenstiel laparotomy was performed and a diagnosis of spontaneous tubal abortion was made and the abdomen was subsequently closed. Following a period of cardiovascular instability on the Intensive Care Unit postoperatively, an urgent CT scan was performed which revealed bleeding from the spleen. A midline laparotomy was performed by the general surgeon, which involved resection of the gestational sac and splenorrhaphy. Twenty-seven cases were reviewed, and 73% of them presented as an emergency and 21 cases (81%) had been managed with splenectomy. CT scan had been used in eight of the previous case reports of splenic ectopic pregnancy with 100% diagnostic accuracy rate. Non-tubal ectopic pregnancies are very rare. Splenorrhaphy is a safe alternative to splenectomy in cases of splenic ectopic pregnancy. CT abdomen and pelvis with intravenous contrast can be very helpful in relatively stable patients with a vaginal ultrasound demonstrating an empty uterus, no clear adnexal masses or free fluid.

Objective: To demonstrate laparoscopic surgical management of parametrial ectopic pregnancy. Design: Video presentation of laparoscopic nerve-sparing treatment of parametrial pregnancy. Setting: Tertiary university center. Patient(s): A 33-year-old patient, nullipara at 8 weeks of gestation, with no comorbidity and no previous surgery, was admitted to a spoke hospital for acute abdominal pain. During hospitalization, a transvaginal gynecologic ultrasound revealed pregnancy with ectopic localization. Free pelvic fluid was detected, and a subsequent diagnostic laparoscopy was performed because of worsening symptoms. During the procedure, hemoperitoneum drainage was instituted and American Society of Reproductive Medicine stage III pelvic endometriosis was diagnosed. A round formation approximately 3 cm in diameter was found at the left posterior parametrium (Fig. 1). Due to the pregnancy position and β-human chorionic gonadotropic (β-hCG; 820 mUI /mL) values, conservative treatment was chosen. Thus, methotrexate at 50 mg/m2 body surface area was administered. A second dose of methotrexate was administered seven days after the first one, and the β-hCG increased to 1068 mUI. On day 14 after treatment, the β-hCG was 1053 mUI/mL. Therefore, surgical treatment was chosen, and the patient was transferred to our center. An ultrasound assessment confirmed the ectopic pregnancy with a live fetus in the left posterior parametrium. Intervention(s): The patient underwent operative laparoscopy to remove the ectopic pregnancy. Surgery was performed using a 3-dimensional optical system (TIPCAM 1, S D3-LINK; Karl Storz SE & Co., Tuttlingen, Germany). After drainage of the hemoperitoneum, the gestational sac was identified in the left posterior parametrium. The uterus, tubes, and ovaries showed normal morphology. Pelvic endometriosis was confirmed. After accessing the left pelvic retroperitoneum with the medial and lateral pararectal spaces’ opening and development, ipsilateral ureterolysis was necessary to isolate the parametrial pregnancy in close contact with it. Coagulation and sectioning of the deep uterine veins were essential to control hemostasis. Identification of the left hypogastric nerve, which was partially infiltrated by the chorionic villi, and the pelvic splanchnic nerves, was required to safeguard them (Fig. 2). Subsequently, the surgeon decided to place a ureteral stent to prevent urologic complications. Main Outcome Measure(s): The laparoscopic approach proved to be safe and feasible to manage parametrial pregnancy. Result(s): The pregnancy was removed entirely. The patient was discharged 72 hours after the procedure with an uneventful postoperative course. The histologic report confirmed the diagnosis of parametrial pregnancy on decidualized endometriotic tissue. The β-hCG serum level became negative in 20 days. Conclusion(s): Extrauterine pregnancies represent one of the leading causes of maternal death in the first trimester and constitute approximately 1%–2% of total pregnancies. Of these percentages, only 5%–8.3% are nontubal. Cases of abdominal pregnancy are even rarer, estimated at

PURPOSE: This study sought to identify the initiation of placental hormonal production as defined by the production of endogenous estradiol (E2) and progesterone (P4) in a cohort of patients undergoing programmed endometrial preparation cycles with single embryo transfers resulting in live-born singletons. METHODS: In this retrospective cohort study, patients undergoing either programmed frozen-thawed embryo transfer (FET) with autologous oocytes or donor egg recipient (DER) cycles with fresh embryos were screened for inclusion. Only patients who underwent a single embryo transfer, had a single gestational sac, and a resultant live-born singleton were included. All patients were treated with E2 patches and intramuscular progesterone injections. Main outcome measures were serial E2 and P4, with median values calculated for cycle days 28 (baseline), or 4w0d gestational age (GA), through 60, or 8w4d GA. The baseline cycle day (CD) 28 median value was compared to each daily median cycle day value using the Wilcoxon signed rank test. RESULTS: A total of 696 patients, 569 using autologous oocytes in programmed FET cycles and 127 using fresh donor oocytes, from 4/2013 to 4/2019 met inclusion criteria. Serum E2 and P4 levels stayed consistent initially and then began to increase daily. Compared to baseline CD 28 E2 (415 pg/mL), the serum E2 was significantly elevated at 542 pg/mL (P

Objective To present a confident tool for the diagnosis of interstitial ectopic pregnancy. 3-Dimensional US helps to reach a more proper diagnosis and enables to arrange therapeutic and surgical strategies. Case report A 36-year-old, gravida 4 para 2, woman was referred from the local medical department in the suspicion of ectopic pregnancy. Transabdominal ultrasound revealed an empty uterine cavity but an 8-week-old gestational sac located eccentrically on the right side of the uterine fundus. The Three-dimensional sonography (3D US) demonstrated a gestational sac (GS) over the right cornual region separated from the endometrial cavity. Interstitial pregnancy was impressed. Laparoscopic surgery was then arranged. After entering the pelvic cavity, a bulging mass was found over the utero-tubal junction, compatible with interstitial pregnancy. The wedge resection of interstitial ectopic pregnancy and right salpingectomy were undertaken. The patient was discharged within 2 days after the surgery. Conclusion The conventional sonography still remained the primary tool to diagnose the ectopic pregnancy, but 3D US played an indispensable role in demonstrating the precise location of GS. Interstitial ectopic pregnancy was symptomatically late in gestation and rupture of an interstitial pregnancy causes catastrophic consequence due to massive bleeding, so prompt and accurate diagnosis was definitely life-saving. Appropriate therapy or surgical intervention could be arranged.

OBJECTIVES To assess the diagnostic value and impact on management of visualizing on ultrasound an amniotic sac without a live embryo (amniotic sac sign). We also examined the potential effect on the number of follow-up visits in early pregnancy units of incorporating this sign into current diagnostic algorithms. METHODS This was a prospective cohort study of all pregnant women who attended a single specialist early pregnancy unit from July 2017 to November 2018 with symptoms of pain and/or bleeding, or with a history of ectopic pregnancy or miscarriage, at

Broad ligament pregnancies are rare and are often misdiagnosed, leading to serious consequences. In our hospital, we have treated six broad ligament pregnancies since 2000. They were diagnosed and operated on promptly, and treatment was successful. Ultrasound can detect early ectopic pregnancies promptly and effectively, avoiding advanced ectopic pregnancies. Early broad ligament pregnancies should be operated on promptly, and laparoscopic therapy is preferable. During the operation, attention must be paid to avoid massive bleeding and protect the ureter, because the ectopic gestational sac is located near the uterine artery and the ureter.

To develop a scoring system for the prediction of a successful pregnancy.Data were collected prospectively from women diagnosed with pregnancy from January 1, 2015, to December 31, 2018. Pregnant days, hormone levels, and gestational sac diameters were recorded. Relationships among the pregnancy days, hormones, and gestational sac were analyzed by Spearman correlation analysis. A scoring system was established and stratified by the 5th, 50th, and 95th percentile of hormone levels and gestational sac diameters on different pregnancy days. Pregnancy outcomes were predicted by the scores using quadratic polynomial regression analyses. A portable desktop analyzer was developed and the performance was evaluated by receiver operating characteristic (ROC) curve.In 273 successful pregnancy cases, the length of gestational days was significantly correlated to beta-human chorionic gonadotropin (β-hCG) (r = 0.74, p 0.001) and EWe successfully developed a scoring-based analyzer to evaluate the viability of embryos at different gestation stages and to predict the probability of a successful delivery, which would provide a reference for clinicians in postpregnancy management.

Background Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy, with a total of less than 32 cases reported in the English literature. Early diagnosis of REP is very difficult and all treatments entail a high risk of life-threatening complications. Case presentation A 29-year-old nulliparous woman presented a history of 50-day amenorrhea and 7-day upper abdominal pain without vaginal spotting. The serum beta-human chorionic gonadotropin (β-hCG) value was 65,004 m-international units per milliliter (mIU/mL), but no intrauterine gestational sac was found via transvaginal sonography (TVS). Then transabdominal ultrasonography (TAS) and abdominal contrast-enhanced computer tomography (CT) identified a retroperitoneal ectopic pregnancy (REP) tightly adjacent to the inferior vena cava and the abdominal aorta. After consultation from a multidisciplinary team, systemic methotrexate (MTX, intramuscular 20 mg daily for 5 consecutive days) combined with ultrasound-guided local potassium chloride solution injection into the gestational sac was scheduled firstly for the patient. However, serum β-hCG continued to increase and the patient experienced worsening abdominal pain. Laparotomy was performed jointly by a gynecologist and a vascular surgeon. During the operation, the gestational sac with fetal bud measuring about 4.5 × 4.0x3.0 cm, tightly adherent to the surface of inferior vena cava and the left side of abdominal aorta, was carefully dissociated out from the surrounding tissues and removed en bloc. Histopathology examination confirmed the diagnosis of REP. The patient recovered uneventfully and her serum β-hCG returned to normal range on the 23th postoperative day. Conclusions Considering the possibility of REP and combined radiological examinations, such as ultrasonography and CT, are crucial for the early diagnosis of this rare condition. A multidisciplinary team is necessary to treat REP.

Objective Intramural pregnancy (IMP) is a rare type of ectopic pregnancy and potentially fatal. Early diagnosis and management of IMP are important to preserve patient fertility. Here, we describe the use of minimally-invasive surgery for early IMP. Study design We retrospectively analyzed the clinical data of eight patients with IMP treated at our center (January 2010 to December 2018) and reviewed the literature describing minimally-invasive treatment of IMP. Results All eight patients had at least one risk factor for IMP. Two cases were confirmed by ultrasound, but ectopic pregnancy or gestational trophoblastic disease were initially suspected in the other cases. Surgery (laparoscopic in three patients, hysteroscopic in one patient, and laparoscopic combined with hysteroscopic in four patients) was successful in all cases, and all patients recovered well without complications. The literature review identified 14 articles describing 17 cases of IMP managed with minimally-invasive surgery. Laparoscopic surgery was used successfully as a sole treatment in 10 cases and after failure of hysteroscopic surgery in six cases. Only one case was treated with a combination of hysteroscopic surgery and methotrexate. Interestingly, one case at our center presented with a sinus connecting the gestational sac and uterine cavity and was treated successfully using hysteroscopic surgery during early pregnancy. Conclusions Laparoscopic surgery is a feasible management option for most cases of early IMP. Hysteroscopic surgery may be appropriate for cases where a sinus connects the gestational sac with the uterine cavity or when cornual ectopic pregnancy needs to be excluded.

Objective To investigate clinic-specific risk factors for monozygotic twinning (MZT) using a large, electronic database. Design Retrospective case-control study. Setting Infertility clinics. Patient(s) Using an electronic medical record system, viable clinical pregnancy (confirmation of a gestational sac(s) and presence of at least one fetal pole with a heartbeat on first trimester ultrasound), data were obtained from homologous in vitro fertilization (IVF) cycles after single ET from June 1, 2004, to December 31, 2016. Monozygotic twinning was defined as a pregnancy with two fetal heartbeats on ultrasound with sex concordance at birth. Intervention(s) None. Main Outcome Measure(s) Risk factors for MZT including cycle type, method of insemination, and method of cryopreservation. Result(s) Of the 28,265 IVF cycles that met inclusion criteria over the study period, 8,749 (31.0%) resulted in a viable intrauterine clinical pregnancy. There were 102 (2.7%) MZT in the fresh cycle cohort and 133 (2.7%) in the frozen cycle cohort. Neither cryopreservation nor the method of cryopreservation was a significant risk factor for MZT. However, the use of sequential media was an independent risk factor for MZT in fresh, but not frozen, ETs (odds ratio = 1.72, 95% confidence interval, 1.10–2.68). Significant differences were seen in the incidence of MZT between clinics, and this difference persisted after controlling for known risk factors (clinic 0, reference; clinic 2, odds ratio = 2.22; 95% confidence interval, 1.48–3.32; clinic 3, odds ratio = 1.93; 95% confidence interval, 1.30–2.87). Conclusion(s) Differences in MZT rates exist between individual IVF clinics, suggesting that variations in practice patterns may contribute to this event. The present study noted the use of sequential media was an independent risk factor for fresh but not frozen cycles.

Objective To evaluate the efficacy and safety of combined-therapy with ultrasound guided intrasacular injection of 50 mg of methotrexate (MTX) and a 50 mg/m2 dose of systemic MTX in uncomplicated ectopic pregnancies with ultrasonographic evidence of embryonic structures in the gestational sac. Study design We designed a retrospective study including 60 patients to assess the efficacy of combined MTX treatment and to determine which clinical or ultrasonographic variables could be associated with successful medical treatment. Failed medical treatment was defined when surgery was needed. For statistical analysis, we developed a descriptive analysis and a univariate logistic regression study. Results Medical approach was effective in 73.3 % of patients. MTX treatment was successful in 32 (68.1 %) out of 47 tubal pregnancies None of the 4 cervical or 2 abdominal pregnancies required surgery. Six (85.7 %) out of 7 cornual pregnancies were successfully treated. No statistically significant differences were found in the success rates according to clinical data, ultrasound or analytic characteristics of women. Conclusion Combined MTX therapy could be an effective and safe alternative in ectopic pregnancies with embryo in hemodynamically stable women. Clinical, ultrasound or analytic characteristics of patients should not entail a contraindication. In locations where surgery implies a technical difficulty, this option may decrease morbimortality rates frequently associated to a more invasive alternative.

PurposeTo identify predictors of complete miscarriage after expectant management or misoprostol treatment of non-viable early pregnancy in women with vaginal bleeding.MethodsThis 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-β-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.ResultsVariables 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.ConclusionsComplete 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.

To assess the safety and efficacy of local intra-gestational sac methotrexate injection followed by dilation and curettage (D&C) in treating cesarean scar pregnancies (CSP). Medical records of CSP patients treated with local intra-gestational sac methotrexate injection followed by dilation and curettage were analyzed at the Maternal and Child Hospital of Guangxi Zhuang Autonomous Region, China. Thirty-one patients were included in this study. The mean gestational age, sac diameter and thickness of the uterine scar were 49.6 ± 7.7 days, 1.8 ± 0.6 cm and 0.30 ± 0.15 cm, respectively. The median pretreatment serum β-human chorionic gonadotropin (β-HCG) level was 40,887 mIU/mL, with the 25th and 75th percentiles at 19,852 and 74,552, respectively. The median blood loss during D&C was 20 mL with the 25th and 75th percentiles at 10 mL and 50 mL. Following D&C, a Foley’s balloon catheter compression was implanted in 26 (83.9%) patients due to active uterine bleeding. All patients had a β-HCG regression time of ≤ 4 weeks after D&C. While 30 patients (96.8%) had a uterine recovery time of ≤ 4 weeks, and 29 patients (93.5%) had resumption of menstruation of less than 6 weeks. Three patients (9.7%) had complications. One of them suffered from massive vaginal bleeding and underwent s blood transfusion. There were no other complications, such as pelvic infection and uterine rupture during the procedures. And no patient was converted to surgical resection or uterine artery embolization. Overall, 30 patients (96.8%) were treated successfully. Local intra-gestational sac methotrexate injection followed by D&C with the aid of a Foley’s balloon catheter compression appears to be a safe and effective treatment for CSP. Further randomized controlled trials are suggested to confirm these findings.

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).

The aim of this study was to retrospectively evaluate the feasibility and safety of high-intensity focused ultrasound (HIFU) treatment as the preoperative management of cesarean scar pregnancy (CSP).225 patients with definite Type I CSP were treated with suction curettage under hysteroscopic guidance. Among them, 103 patients chose HIFU treatment before hysteroscopy (assign to the HIFU group), and the other 122 patients without any pretreatment before hysteroscopy to the control group. The successful rate, volume of intraoperative blood loss, time for serum β-human chorionic gonadotropin (β-hCG) level returned to normal, gestational sac disappeared, normal menstrual recovery, and adverse effects were collected and analyzed to compare the two approaches.The successful rate (98.06%) in the HIFU group was higher than that (91.80%) in the contrast group. The median ablation time was 39 min and the median HIFU sonication time was 106.6 s. The median volume of intraoperative blood loss in the HIFU group was lower than that in the contrast group (P 0.001), and the median time of gestational sac disappeared in the HIFU group was shorter than that in the contrast group. There were no statistically significant differences in the time of serum β-hCG returned to normal and days of menstrual recovery between the 2 groups.Based on our results, it appears that HIFU ablation is a safe and effective modality as pre-treatment before hysteroscopy in the management of CSP.

OBJECTIVE: To assess whether sonographic diagnosis of intrauterine hematoma (IUH) in the first trimester of pregnancy is associated with first-trimester miscarriage and antenatal, delivery and neonatal complications. METHODS: This was a prospective observational cohort study of women with an intrauterine singleton pregnancy between 5 and 14 weeks' gestation recruited at Queen Charlotte's and Chelsea Hospital, London, UK, between March 2014 and March 2016. Participants underwent serial ultrasound examinations in the first trimester, and the presence, location, size and persistence of any IUH was evaluated. First-trimester miscarriage was defined as pregnancy loss before 14 weeks' gestation. Clinical symptoms, including pelvic pain and vaginal bleeding, were recorded at each visit using validated symptom scores. Antenatal, delivery and neonatal outcomes were obtained from hospital records. Logistic regression analysis and the chi-square test were used to assess the association between the presence and features of IUH and the incidence of adverse pregnancy outcome. Odds ratios (OR) were first adjusted for maternal age (aOR) and then further adjusted for the presence of vaginal bleeding or pelvic pain in the first trimester. RESULTS: Of 1003 women recruited to the study, 946 were included in the final analysis and of these, 268 (28.3%) were diagnosed with an IUH in the first trimester. The presence of IUH was associated with the incidence of preterm birth (aOR, 1.94 (95% CI, 1.07-3.52)), but no other individual or overall antenatal, delivery or neonatal complications. No association was found between the presence of IUH in the first trimester and first-trimester miscarriage (aOR, 0.81 (95% CI, 0.44-1.50)). These findings were independent of the absolute size of the hematoma and the presence of vaginal bleeding or pelvic pain in the first trimester. When IUH was present in the first trimester, there was no association between its size, content or position in relation to the gestational sac and overall antenatal, delivery and neonatal complications. Diagnosis of a retroplacental IUH was associated with an increased risk of overall antenatal complications (P = 0.04). CONCLUSIONS: Our findings demonstrate that there is no association between the presence of IUH in the first trimester and first-trimester miscarriage. However, an association with preterm birth, independently of the presence of symptoms of pelvic pain and/or vaginal bleeding, is evident. Women diagnosed with IUH in the first trimester should be counseled about their increased risk of preterm birth and possibly be offered increased surveillance during the course of their pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. ispartof: ULTRASOUND IN OBSTETRICS & GYNECOLOGY vol:55 issue:4 pages:536-545 ispartof: location:England status: published

Objectives: To explore whether early first-trimester ultrasound can predict the third-trimester sonographic stage of placenta accreta spectrum (PAS) disorder and to elucidate whether combining first-trimester ultrasound findings with the sonographic stage of PAS disorder can stratify the risk of adverse surgical outcome in women at risk for PAS disorder. Methods: This was a retrospective analysis of prospectively collected data from women with placenta previa, and at least one previous Cesarean delivery (CD) or uterine surgery, for whom early first-trimester (5-7 weeks' gestation) ultrasound images could be retrieved. The relationship between the position of the gestational sac and the prior CD scar was assessed using three sonographic markers for first-trimester assessment of Cesarean scar (CS) pregnancy, reported by Cali et al. (crossover sign (COS)), Kaelin Agten et al. (implantation of the gestational sac on the scar vs in the niche of the CS) and Timor-Tritsch et al. (position of the center of the gestational sac below vs above the midline of the uterus), by two different examiners blinded to the final diagnosis and clinical outcome. The primary aim of the study was to explore the association between first-trimester ultrasound findings and the stage of PAS disorder on third-trimester ultrasound. Our secondary aim was to elucidate whether the combination of first-trimester ultrasound findings and sonographic stage of PAS disorder can predict surgical outcome. Logistic regression analysis and area under the receiver-operating-characteristics curve (AUC) were used to analyze the data. Results: One hundred and eighty-seven women with vasa previa were included. In this cohort, 79.6% (95% CI, 67.1-88.2%) of women classified as COS-1, 94.4% (95% CI, 84.9-98.1%) of those with gestational-sac implantation in the niche of the prior CS and 100% (95% CI, 93.4-100%) of those with gestational sac located below the uterine midline, on first-trimester ultrasound, were affected by the severest form of PAS disorder (PAS3) on third-trimester ultrasound. On multivariate logistic regression analysis, COS-1 (odds ratio (OR), 7.9 (95% CI, 4.0-15.5); P < 0.001), implantation of the gestational sac in the niche (OR, 29.1 (95% CI, 8.1-104); P < 0.001) and location of the gestational sac below the midline of the uterus (OR, 38.1 (95% CI, 12.0-121); P < 0.001) were associated independently with PAS3, whereas parity (P = 0.4) and the number of prior CDs (P = 0.5) were not. When translating these figures into diagnostic models, first-trimester diagnosis of COS-1 (AUC, 0.94 (95% CI, 0.91-0.97)), pregnancy implantation in the niche (AUC, 0.92 (95% CI, 0.89-0.96)) and gestational sac below the uterine midline (AUC, 0.92 (95% CI, 0.88-0.96)) had a high predictive accuracy for PAS3. There was an adverse surgical outcome in 22/187 pregnancies and it was more common in women with, compared to those without, COS-1 (P < 0.001), gestational-sac implantation in the niche (P < 0.001) and gestational-sac position below the uterine midline (P < 0.001). On multivariate logistic regression analysis, third-trimester ultrasound diagnosis of PAS3 (OR, 4.3 (95% CI, 2.1-17.3)) and first-trimester diagnosis of COS-1 (OR, 7.9 (95% CI, 4.0-15.5); P < 0.001), pregnancy implantation in the niche (OR, 29.1 (95% CI, 8.1-79.0); P < 0.001) and position of the sac below the uterine midline (OR, 6.6 (95% CI, 3.9-16.2); P < 0.001) were associated independently with adverse surgical outcome. When combining the sonographic coordinates of the three first-trimester imaging markers, we identified an area we call high-risk-for-PAS triangle, which may enable an easy visual perception and application of the three methods to prognosticate the risk for CS pregnancy and PAS disorder, although it requires validation in large prospective studies. Conclusions: Early first-trimester sonographic assessment of pregnancies with previous CD can predict reliably ultrasound stage of PAS disorder. Combination of findings on first-trimester ultrasound with second- and third-trimester ultrasound examination can stratify the surgical risk in women affected by a PAS disorder. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Objectives: To analyze the correlation between ultrasound typing and treatment modality of patients with an intrauterine ectopic pregnancy (cervical and cesarean scar). Material and methods: We retrospectively enrolled 65 patients diagnosed with cesarean scar pregnancy (CSP) or cervical pregnancy (CP) between February 2014 and May 2018. The cases were divided into two types according to the ultrasound presentation with a gestational sac (GS, type I) or a heterogeneous mass (HM, type II). Type I was further divided into type Ia (< 8 weeks) and type Ib (≥ 8 weeks); type II was defined as type IIa (with poor or no vascularity) and type IIb (with rich vascularity). Three treatment methods were applied in each group. Results: Of included cases, there were 53 CSP and 12 CP. There was no significant difference between Type I and Type II groups in any variable. The beta human chorionic gonadotropin (β-hCG) level and gestational age of type IIb were significantly higher compared to type IIa (p < 0.05). There was a positive correlation between ultrasound categories and treatment methods (rs = 0.723, p = 0.000). Analysis of CSP cases of initial treatment failure indicated success rate of initial dilation and curettage (D&C) was dependent upon ultrasonic types, mean sac diameter, gestational age, hCG level, and number of cesarean sections. Conclusions: The features of ultrasound imaging might provide an additional reference for the selection of clinical treatment methods.

Introduction: Cesarean scar pregnancy (CSP) is an uncommon entity, with high morbidity. Its diagnosis is difficult and delays in management are frequent. We report a series of cases of CSP and analysis of the differences in the outcomes depending on the moment of pregnancy in which they are treated.Case report: Twelve patients with a diagnosis of CSP. Seven of them were diagnosed and treated in the first trimester, often required more than one type of management, but were not transfused or presented complications. The five patients diagnosed lately in the pregnancy, always required cesarean section and emergency hysterectomy, with massive bleeding, transfusions, urinary or vascular complications.Discussion: CSP can be complicated by abnormal placental invasion when pregnancy continuity is allowed. The ideal management is the termination of pregnancy shortly after the diagnosis is made. Our series highlights the diagnostic difficulties that lead to late treatment with frequent complications.Conclusion: It is essential to perform routine analysis of the site of implantation of the gestational sac in the first-trimester ultrasonography and the CSP suspected cases should be handled by interdisciplinary teams in experienced centers.

Objectives: To investigate the risk factors of persistent cesarean scar pregnancy (PCSP) after dilation and curettage (D&C). Materials and methods: A retrospective, age-matched case–control study including 45 cases of PCSP patients after D&C was conducted between January 2013 and April 2018. For each case, 4 women who had been diagnosed with CSP and had the same age and same hospitalization period as the case group but no residual CSP tissue after D&C were selected as the controls (Control group, n = 180). Conditional logistic regression analysis was used to assess the risk factors of PCSP after D&C. Results: After conditional logistic regression, the 3 factors associated with PCSP after D&C were maximum diameter of CSP mass (or gestational sac) ≥4.5 cm (adjusted odds ratio [aOR] 6.51, 95% CI 1.39–30.47), myometrial thickness at the implantation site

OBJECTIVES To examine multiples of the median (MoM) values of serum free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a large series of pregnancies with a vanishing twin, determine the association of these values with the interval between embryonic death and blood sampling, and develop a model that would allow incorporation of these metabolites in first-trimester combined screening for trisomy. METHODS This was a retrospective study comparing maternal serum free β-hCG and PAPP-A levels at 11-13 weeks' gestation in 528 dichorionic pregnancies with a vanishing twin, including 194 (36.7%) with an empty gestational sac and 334 (63.3%) with a dead embryo, with those in 5280 normal singleton pregnancies matched for method of conception and date of examination. In vanishing-twin pregnancies with a dead embryo, marker levels were examined in relation to the estimated time between embryonic death and maternal blood sampling. RESULTS First, in pregnancies with a vanishing twin, median free β-hCG MoM was not significantly different from that in normal singleton pregnancies (1.000; 95% CI, 0.985-1.016 vs 0.995; 95% CI, 0.948-1.044; P = 0.849). Second, PAPP-A MoM was higher in vanishing-twin pregnancies than in normal singleton pregnancies (1.000; 95% CI, 0.985-1.015), both in the group with an empty gestational sac (1.165; 95% CI, 1.080-1.256; P = 0.0001) and in that with a dead embryo (1.175; 95% CI, 1.105-1.249; P < 0.0001). Third, in vanishing-twin pregnancies with a dead embryo, PAPP-A MoM was related inversely to the interval between estimated gestational age at embryonic demise and blood sampling (P < 0.0001). Fourth, in first-trimester screening for trisomy 21 in singleton pregnancies, the estimated detection rate, at a 5% false-positive rate, was 82% in screening by a combination of maternal age and fetal nuchal translucency thickness, and this increased to 86% with the addition of serum free β-hCG and to 91% with the addition of serum PAPP-A. Fifth, similar performance of screening can be achieved in pregnancies with a vanishing twin, provided the appropriate adjustments are made to the level of PAPP-A for the interval between estimated gestational age at embryonic demise and blood sampling. CONCLUSIONS First-trimester screening for trisomy in pregnancies with a vanishing twin should rely on a combination of maternal age, fetal nuchal translucency thickness and serum free β-hCG, as in singleton pregnancy, without the use of serum PAPP-A. Alternatively, PAPP-A can be included but only after appropriate adjustment for the interval between estimated gestational age at fetal demise and blood sampling. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound is essential in the evaluation and management of pregnancies of unknown location. Differential diagnoses include early pregnancy loss, pregnancy of unknown location, and ectopic pregnancies. Both transabdominal and transvaginal routes should be available, in addition to physical examination, for complete evaluation. Diagnostic criteria for early pregnancy loss have expanded in recent years to ensure false positive results do not lead to inappropriate evacuation of desired pregnancies.

It is well known that progesterone plays a major role in the maintenance of pregnancy, particularly during the early stages, as it is responsible for preparing the endometrium for implantation and maintenance of the gestational sac. The management of pregnant women at risk of a threatened or idiopathic recurrent miscarriage is complex and critical. Therefore, a group of obstetricians and gynecologists practicing in Saudi Arabia gathered to update the 2014 Saudi guidelines for threatened and recurrent miscarriage management. In preparation, a literature review was conducted to explore the role of oral, vaginal, and injectable progestogens: this was used as a basis to develop position statements to guide and standardize practice across Saudi Arabia.

Background Since the lockdown caused by the COVID-19 pandemic, restrictions on hospitals' activity forced healthcare practitioners to innovate in order to provide continuity of care to patients. The aim of this study was to evaluate the efficiency of a newly established protocol for medical abortion and to measure the level of satisfaction of the patients who experienced abortion at home. Methods This retrospective study compared all the patients who had an early medical abortion at up to 9 weeks of gestation during the two drastically different periods between December 2018 and March 2021 ("hospital" and "home" groups). We evaluated the expulsion of the gestational sac as a primary outcome. The rates of infection, hemorrhage, retained trophoblastic material and need for surgical management were also assessed. A survey was also used to measure the satisfaction and acceptability of the method. Results The rate of expulsion of pregnancy was not significantly different between the two groups: 92.9% in hospital versus 99% at home. Early retained trophoblastic material and surgical interventions were higher in the hospital group. No significant difference was observed for the remaining outcomes. Moreover, the level of acceptability was similar in both groups, though patients felt safer in the "hospital" group. Conclusion Switching an early medical abortion protocol from expulsion of pregnancy in hospital to expulsion of pregnancy at home is effective and acceptable to women, and may be associated with decreased rate of retained trophoblastic material. Further larger studies are needed to test the long-term result of this protocol.

Background In a pregnancy of unknown location, an intrauterine fluid collection may represent either the early gestational sac of an intrauterine pregnancy, or as reported in previous literature, the pseudogestational sac of an ectopic pregnancy. Various sonographic features have been used to distinguish these 2 entities, but the clinical relevance of the pseudogestational sac remains unclear. Objective To establish the incidence and relative rate of intrauterine fluid collection among ectopic and intrauterine pregnancies and to determine if the size of the collection differs between ectopic and intrauterine pregnancies Study Design We performed a retrospective cohort study of women with pregnancies of unknown location and pelvic or abdominal pain or bleeding. We calculated the incidences of intrauterine fluid collections among ectopic and intrauterine pregnancies, including both ongoing pregnancies and spontaneous abortions, given that that our focus was location and not viability. We calculated the relative risk of ectopic pregnancy if an intrauterine fluid collection was present, adjusting for age and vaginal bleeding. We compared the incidences of ectopic and intrauterine pregnancies among those with and without intrauterine fluid collections. Among those with collections, we compared the mean sac diameter between ectopic and intrauterine pregnancies in continuous and categorical fashions. Results We evaluated 1236 women presenting with a pregnancy of unknown location. The rates of ectopic and intrauterine pregnancies (including spontaneous abortions) were 13.1% and 63.9%, respectively, with the remainder lost to follow-up. On ultrasound, 452 women (36.6%) had an intrauterine fluid collection. Eight of 162 ectopic pregnancies (4.9%) had a collection, compared with 363 of 789 intrauterine pregnancies (46.0%) (P=.01). Of the ectopics with a fluid collection, 5 had an adnexal mass. The presence of intrauterine fluid collection decreased the risk of ectopic pregnancy (adjusted relative risk, 0.09; 95% confidence interval, 0.05–0.19) after adjusting for age and the presence of bleeding. Among those with an intrauterine fluid collection, the rate of ectopic pregnancy was 2.2%, and the rate of intrauterine pregnancy was 97.8%; among those without a collection, the rate of ectopic pregnancy was 26.7%, and the rate of intrauterine pregnancy was 73.3%. The mean sac diameter did not differ between ectopic and intrauterine pregnancies, whether analyzed continuously or categorically. Conclusion In the presence of an intrauterine fluid collection, the rate of ectopic pregnancy is very low. The size of the intrauterine fluid collection in a woman with a pregnancy of unknown location cannot be used to distinguish between a gestational sac and a pseudogestational sac. Pseudogestational sacs are uncommon and of little clinical consequence. In assessing pregnancies of unknown location, clinicians should incorporate the entire clinical picture, including other sonographic findings, to avoid incorrect or delayed diagnoses.

Background It is challenging to predict the outcome of the pregnancy when fetal heart activity is detected in early pregnancy. However, an accurate prediction is of importance for obstetricians as it helps to provide appropriate consultancy and determine the frequency of ultrasound examinations. The purpose of this study was to investigate the role of the convolutional neural network (CNN) in the prediction of spontaneous miscarriage risk through the analysis of early ultrasound gestational sac images. Methods A total of 2196 ultrasound images from 1098 women with early singleton pregnancies of gestational age between 6 and 8 weeks were used for training a CNN for the prediction of the miscarriage in the retrospective study. The patients who had positive fetal cardiac activity on their first ultrasound but then experienced a miscarriage were enrolled. The control group was randomly selected in the same database from the fetuses confirmed to be normal during follow-up. Diagnostic performance of the algorithm was validated and tested in two separate test sets of 136 patients with 272 images, respectively. Performance in prediction of the miscarriage was compared between the CNN and the manual measurement of ultrasound characteristics in the prospective study. Results The accuracy of the predictive model was 80.32% and 78.1% in the retrospective and prospective study, respectively. The area under the receiver operating characteristic curve (AUC) for classification was 0.857 (95% confidence interval [CI], 0.793–0.922) in the retrospective study and 0.885 (95%CI, 0.846–0.925) in the prospective study, respectively. Correspondingly, the predictive power of the CNN was higher compared with manual ultrasound characteristics, for which the AUCs of the crown-rump length combined with fetal heart rate was 0.687 (95%CI, 0.587–0.775). Conclusions The CNN model showed high accuracy for predicting miscarriage through the analysis of early pregnancy ultrasound images and achieved better performance than that of manual measurement.

Study question What are the ultrasonic characteristics of heterotopic intramural pregnancy (HIMP)? How to manage and what about the clinical outcomes of HIMP? Summary answer Expectant management may be a considerable choice for an non-viable intramural pregnancy (IMP). Most intrauteine pregnancies (IUPs) of HIMPs seems to have good outcomes. What is known already Heterotopic pregnancy (HP) post in vitro fertilization is very rare in infertility women, with a prevalence of 0.04%. HIMP is one of the rarest types of HP, where one gestational sac (GS) is embedded within the endometrial cavity and the other one GS is implanted in the myometriun. HIMP was firstly and only described by Jiangtao Lyu et al. in 2018. So far, little is known about its natural history and ultrasonic imaging characteristics. And there is no consensus regarding the ultrasound diagnosis and clinical management for HIMP due to few evidence-based medicine records. Study design, size, duration A retrospective observational study was conducted of 6 infertile women who obtained a HIMP through in vitro fertilization-embryo transfer (IVF-ET) between January 2009 and December 2019 at our reproductive centre. Participants/materials, setting, methods Six infertile women conceived a HIMP via IVF-ET were retrospectively retrieved between January 2009 and December 2019 at the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha City, China). The ultrasound diagnosis, clinical management and pregnancy outcome of these cases were analysed. The ultrasound findings, therapeutic methods and clinical outcomes were obtained from the hospital’s electronic medical records. This study was approved by the local ethics committee. Main results and the role of chance: Six women with HIMPs were retrospectively analysed. Among them, 5 cases were revealed by ultrasound scans; however, one case was misdiagnosed. The diagnostic accuracy was 83.3%. Five cases of HIMP were diagnosed at initial scan. The diagnostic time ranged from 22 to 38 days after ET (5 + 6 - 7 + 6 weeks). Among them, an intramural GS was observed in all 5 cases; embryonic cardiac activity (ECA) was detected in one case by the followed-up scans; there was a yolk sac only in one case; an empty GS was noted in 3 cases. An IUP was revealed in all 6 cases, and ECA was observed in 5 cases at the initial diagnosis or later. A GS with a yolk sac only was showed in one case. Among the 5 diagnostic women, one case with a live IMP was treated with laparoscopy at 8 + 1 weeks, 4 cases were managed expectantly. Of them, the IUPs of 4 cases delivered live infants and one case managed expectantly experienced miscarriage. In one case, IMP was misdiagnosed as interstitial pregnancy at day–28 scan. Exploratory laparoscopy and foetal reduction were performed at 8 + 2 weeks. Laparoscopy confirmed an IMP and the retained IUP delivered a live infant. Limitations, reasons for caution The case numbers are too few to draw any objective conclusions, because of the extreme rarity of HIMP. Thus, a further multi-centre larger prospective study will help to confidently illustrate the clinical significance, and effective and appropriate management method for women with a HIMP. Wider implications of the findings: Our study showed that HIMP may not be as rare as previously reported. Increased awareness of this condition, better comprehension of the diagnostic criteria and improved resolution of ultrasound equipment may result in more frequent and accurate detection of HIMP, which will be helpful for early management to preserve IUP. Trial registration number Not applicable.

Study question Can a scoring model based on morphokinetic data developed to predict pregnancy rates of day–5 blastocyst transfers (KIDSCORE™D5) predict pregnancy rates of day–6 blastocyst transfers? Summary answer KIDSCORE™D5 was able to predict the clinical pregnancy rates of embryo transfers done on day 6 with an area under the curve (AUC) of 0.72. What is known already KIDSCORE™D5 is a scoring model based on morphokinetic data developed to predict the pregnancy rates of day–5 blastocysts. In 2019, Regnier et al. reported that the AUC of KIDSCORE™D5 for predicting clinical pregnancy rates of day–5 blastocyst transfers was 0.6. However, as KIDSCORE™D5 is constructed based on morphological characteristics and developmental dynamics of day–5 blastocysts, it is unclear whether KIDSCORE™D5 can predict pregnancy rates of day–6 blastocyst transfers. Since there are many cases of day–6 blastocyst transfers, it is important to know if KIDSCORE™D5 can predict pregnancy rates of day–6 blastocyst transfers. Study design, size, duration This retrospective single-center study, which included 162 day–5 and 72 day–6 blastocyst transfers, respectively, was conducted at Takahashi Women’s clinic from January to December 2019. Blastocysts derived from 146 patients who underwent intracytoplasmic sperm injection. All blastocysts were cryopreserved and were transferred singly. Participants/materials, setting, methods We used EmbryoScope+™ (Vitrolife) for in-vitro culture and calculated KIDSCORE™D5 (ver.3) using Embryoviewer™ (Vitrolife). Blastocyst scoring was done from 1.0 to 9.9. Clinical pregnancy was defined as the presence of a gestational sac confirmed by transvaginal ultrasonography. Statistical analysis was performed with JMP Pro 15.00 (SAS). The relationship between KIDSCORE™D5 and clinical pregnancy was evaluated by the AUC using ROC curve analysis and multivariate analysis adjusted for patient age. Main results and the role of chance The mean KIDSCORE™D5 of day–5 and day–6 blastocysts was 7.1±1.7 and 3.7±1.5, respectively. KIDSCORE™D5 of day–6 blastocysts was significantly lower than that of day–5 blastocysts (p Limitations, reasons for caution This study had a small sample size, and it was a retrospective single-center study. In addition, the relationship between KIDSCORE™D5 and clinical pregnancy rates may vary among facilities. Therefore, a prospective multicenter validation is necessary. Wider implications of the findings: Our study results indicated that KIDSCORE™D5 predicted clinical pregnancy and that morphokinetic parameters related to clinical pregnancy were similar between day–5 and day–6 blastocysts. Hence, morphokinetic evaluation can serve as a criterion for deciding which of multiple day–6 blastocysts can be transferred. Trial registration number Not applicable

Study question Does ERICA’s prognosis ranking based on ploidy, predict early miscarriage following positive biochemical pregnancy test? Summary answer The lower ERICA grades embryos, the higher the likelihood of early miscarriage, irrespective of age group. What is known already The vast majority of early miscarriages are due to aneuploidy, but preimplantation genetic testing for aneuploidy (PGTA) is potentially invasive, expensive, time-consuming and usually necessitates cryopreservation. Current methods for embryo selection based on morphology and morphokinetics are poorly correlated with ploidy. ERICA is a deep-learning non-invasive tool for embryo ranking, trained to identify ploidy, and has previously been shown to be similar or better than experienced embryologists in assessing implantation potential. AI-based tools capable of embryo ranking and assessment could help save laboratory time and costs, avoiding risk to embryos from invasive techniques. Study design, size, duration Retrospective analysis of 599 blastocysts transferred over 12 months in which ERICA was used to assist embryologists during the embryo selection process. ERICA’s prognosis based on ploidy potential is presented as groups labelled as “optimal”, “good”, “fair”, or “poor”. Embryo transfers (ET) reaching biochemical pregnancy (beta-hCG ≥ 20iu) were considered for the study. Early pregnancy loss (EPL) was defined as a biochemical pregnancy failing to develop a gestational sac and/or failure to show heartbeat (FHR). Participants/materials, setting, methods ETs resulting in biochemical pregnancies at two IVF clinics were followed-up to FHR till 8 weeks gestation. EPLs were divided into groups according to the presence or absence of a pregnancy sac. ERICA’s suggested prognosis during the embryo selection process was tested against pregnancy outcomes. Further analysis of pregnancy outcomes and their relation to ERICA’s labels was also performed based on age groups. Z-test for two proportions was used to assess statistical significance. Main results and the role of chance 506 ETs were performed for 599 embryos (mean 1.2 embryos), from which 285 resulted in positive pregnancy tests (56.3%). Thirty-one (10.9%) EPLs happened before the identification of a gestational sac (GS). Ten pregnancies failed to develop FHR after initial GS identification (3.9%), for an overall EPL of 14.4%. The average age in this group was 35.4 years. When evaluated using ERICA’s labels “optimal”, “good”, “fair, and “poor”, chances of miscarriage before GS were 8.9% (8/89); 14.1% (11/78); 18.5% (5/27); and 18.7% (9/48) respectively, where denominator represents total number within a label (i.e. EPL/n). When including all EPLs, chances of miscarriage according to the same labels were 11.2%; 17.9%; 22.2%; and 22.9% respectively. ERICA’s performance to anticipate the risk of EPL showed statistical significance when the optimal label was compared against all other labels (Z -1.786, p Limitations, reasons for caution The retrospective nature of this study along with its sample-size might limit the reach of our conclusions, in particular for older patients. The results we present must still be confirmed prospectively, and on a larger dataset. Wider implications of the findings Most EPLs are attributed to genetic factors, hence ERICA’s training for embryo ranking was based on ploidy. We conclude that ERICA’s AI is able to identify embryos at a higher risk of EPL non-invasively. Cytogenetic studies from products of miscarriage would help to confirm the hypothesis. Trial registration number Not applicable

Study question How informative is the score grade of KIDScore version 3 for day 5 blastocyst for clinical pregnancy in biopsied and non-biopsied embryos? Summary answer Potential clinical pregnancy is predicable according to score grades (above 7.0), regardless the use of PGT-A, in blastocysts on day 5. What is known already Time-lapse technology has promoted, along with the use of artificial intelligence (A.I.), a new spectrum of tools to improve embryo selection. Several software and algorithms have been launched in ART field in the last years, with the perspective of providing a substantial boost in IVF outcomes. KIDScore is one of these new tools, developed based on morphology and morphokinetics of embryo development with known clinical outcome and validated with transfer of blastocyst on day 3 or 5. Yet, it is highly recommended an in-house validation of any A.I. tool before it started to be apply in clinical decisions. Study design, size, duration Retrospective cohort study in a single private IVF center. Positive or negative clinical pregnancy (fetal heartbeat and gestational sac presence/absence) record of patient’s autologous and donated cycles using fresh and frozen oocytes, with or without PGT-A embryos transfers using the Embryocope® Plus incubator, that underwent single embryo transfers (total sET, n = 415; euploid = 228, non-biopsied = 187) of blastocysts developed on day 5 were included. Biochemical pregnancy and miscarriage were excluded of this analysis. Participants/materials, setting, methods Negative and positive clinical pregnancy KIDScoreTMDay 5’s were stratified in three subgroups, according to V3 score intervals: subgroup 1: range between 1.0-3.9 (n = 29), subgroup 2: 4.0-6.9 (n = 154) and subgroup 3: 7.0-9.9 (n = 232). sET of euploid embryos (n = 228) were also analyzed in the described subgroups (subgroup 1: n = 17; subgroup 2: n = 93 and subgroup 3: n = 118, respectively). For the analysis, Mann-Whitney, Chi-square and Fisher tests were used for statistical analysis, values of p Main results and the role of chance Maternal age between overall positive and negative pregnancies were similar (38,48±3,86 versus 38,75±3,83,p = 0,3573). When comparing score subgroups, overall positive clinical pregnancy rates were significant different [subgroup 1: 20.7% (6/29); subgroup 2: 43.5% (67/154); subgroup 3: 63.8% (148/232),p < 0.0001]. When analyzing subgroup 1 versus subgroup 2 there was also a difference in positive clinical pregnancy (p = 0.023) and subgroup 3 also showed a higher rate in clinical pregnancy when compared to subgroup 1 and 2 together (scores from 1.0 to 6.9,p < 0.0001). Analyzing only euploid embryos, the results on positive clinical pregnancy were also significant different between subgroups [subgroup 1: 35.3% (6/17); subgroup 2: 45.2% (42/93); subgroup 3: 61.0% (72/118),p = 0,024, and subgroup 1 + 2 versus subgroup 3,p = 0,0115]. Maternal age between positive and negative clinical pregnancies in PGT-A cycles were similar (37,81±1,61 versus 38,38±3,25,p = 0,069). Analyzing only non-biopsied embryos, the results on positive clinical pregnancy were also significant different between subgroups [subgroup 1: 0.0% (0/12); subgroup 2: 41.0% (25/61); subgroup 3: 66.7% (76/114),p = 0,0343, and subgroup 1 + 2 versus subgroup 3,p < 0.0001]. Maternal age between positive and negative clinical pregnancies in non-biopsied cycles were also similar (39,40±4,75 versus 39,22±4,43,p = 0,7816). Positive clinical pregnancy in subgroup 3 were similar in biopsied and non-biopsied subgroups (61% versus 66.7%,p = 0.4133). Limitations, reasons for caution The retrospective nature and low data of subgroup 1 (1.0-3.9 score), since they naturally are the last option to be chosen for transfer. Wider implications of the findings Differences on positive clinical pregnancy between subgroups (mainly scores greater than 7.0) reinforce the use of A.I. as a complementary tool for embryo selection. Interestingly, positive clinical pregnancy in 7.0-9.9 subgroup were similar in euploid and non-biopsied embryos, strengthening another potential application of A.I. in transposing embryo aneuploidy barrier. Trial registration number Not Applicable

Background Pregnancy in a rudimentary horn is an extremely rare type of ectopic pregnancy. A rudimentary uterine horn pregnancy is associated with a risk of spontaneous rupture and bleeding during surgery due to the increased uterine blood flow. Recent advances in imaging modalities have enabled laparoscopic surgery to be performed in cases without rupture in the early stages of pregnancy. However, there are few reports of successful pregnancies and deliveries after treatment of rudimentary horn pregnancies. We report the successful management of a case of non-communicating rudimentary horn pregnancy by local injection of methotrexate followed by complete laparoscopic excision along with a review of the literature. Case presentation The patient was a 29-year-old Japanese woman, gravida 2, nullipara. She was diagnosed with a left unicornuate uterus with a right non-communicating rudimentary horn on hysterosalpingography and magnetic resonance imaging. A gestational sac with a heartbeat was observed in the right rudimentary uterine horn at 6 weeks of gestation. A diagnosis of ectopic pregnancy in a non-communicating rudimentary horn was made. Color Doppler detected multiple blood flow signals around the gestational sac, which were clearly increased compared to the left unicornuate uterus. Her serum human chorionic gonadotropin level was 104,619 mIU/ml. A 100 mg methotrexate injection into the gestational sac was administered, and laparoscopic surgery was performed on day 48 after the methotrexate treatment. The right rudimentary horn and fallopian tube were successfully excised with minimal bleeding. A spontaneous normal pregnancy was established 6 months after the surgery. The pregnancy was uneventful, and a baby girl was born by elective cesarean section at 38w0d. Conclusion Combined local methotrexate injection and laparoscopic surgery are safe treatment options for patients with a unicornuate uterus with a non-communicating rudimentary horn pregnancy.

Objective To demonstrate the laparoscopic excision technique of a juvenile cystic adenomyoma and show how the decidualization of ectopic endometrial tissue can lead to the misdiagnosis of a focus of ectopic pregnancy. Design Description and step-by-step demonstration of the surgical procedure using a video recording (Canadian Task Force Classification 3). Setting Teaching and research hospital. Patient(s) A 27-year-old gravida 2 parity 1 patient with one previous caesarean delivery presented to the emergency department with symptoms of pelvic pain and delayed menses. Her beta-human chorionic gonadotropin level was 2,161 mIU/mL. On transvaginal ultrasonography the uterine cavity appeared empty without any signs of a gestational sac, and a 42×45 mm heterogeneous mass was observed on the right cornual area. An 18×21 mm cystic area was observed within the mass. A diagnosis of cornual pregnancy was made and two doses of systemic methotrexate treatment were administered. On the 12th day following medical treatment, the patient reported increasing abdominal pain and free fluid was observed in the pouch of Douglas on ultrasonography. The decision to perform laparoscopic cornual excision was made. Main Outcomes and Measure(s) On laparoscopic exploration a tubal ectopic pregnancy was observed within the left fallopian tube. The presence of two simultaneous ectopic pregnancies, located in the left fallopian tube and the right cornual area, was suspected. However, upon careful inspection, the right fallopian tube appeared normal and the mass initially thought to be a right cornual pregnancy appeared more like a degenerated fibroid. A left salpingectomy was performed and the excision of the mass in the right cornual area was planned. An incision was made over the mass and the cystic inner area containing chocolate-brown colored fluid was drained. As there was no pseudo capsule surrounding the mass, the diagnosis of focal adenomyosis instead of degenerated fibroid was made. No endometriotic foci were observed within the pelvis. Different from the enucleation of a fibroid, the mass was dissected from the middle into two halves until healthy myometrium was reached on the floor of the mass. The two halves of the mass were resected totally by dissecting the adenomyotic tissue from the myometrium starting from the caudal end towards the cranial end. The first layer of the remaining myometrial defect was sutured extracorporeally with No.1 polyglactan sutures. The second and third layers were sutured intracorporeally with V-loc sutures. The resected left fallopian tube containing the ectopic pregnancy and the adenomyotic mass were externalized through a posterior colpotomy incision. Result(s) The patient was discharged 24 hours postoperatively without any complications. A diagnosis of juvenile cystic adenoma was made upon histopathological examination. The patient reported subsiding of her dysmenorrhea on the postoperative third month. Conclusion(s) Juvenile cystic adenomyosis (JCA), is a rare form of focal adenomyosis which is usually located in close proximity to the uterine insertion of the round ligament, contains a cystic inner area larger than 1 cm and is encountered before the age of 30 years. Some authors reported JCA to be an accessory and cavitated uterine mass (ACUM) anomaly developing as a result of gubernaculum dysfunction. The only difference between the two conditions is reported to be the presence of a denser area of adenomyosis surrounding the cystic area lined with endometrium in JCA than in ACUM. This case has shown that decidual changes observed in ectopic endometrial tissue within an adenomyotic area may be misdiagnosed as a focus of ectopic pregnancy. Atypical endometriomas demonstrating decidual changes may also be misdiagnosed as ovarian malignancies. In non-emergency situations, waiting for the decidualization effect of ectopic endometrium to subside can help in the definitive diagnosis of such cases. Our technique for JCA excision is different from enucleation of a fibroid and may aid in the total resection and dissection of the adenomyotic tissue from healthy myometrium.

Aim To describe our first clinical pregnancy following a uterus transplant from a brain-dead donor and to discuss current issues with deceased donor uterus transplantation as they relate to obstetrical success. Methods In August 2016, a 26-year-old woman with Mayer-Rokitansky-Kuster-Hauser syndrome was the fourth person worldwide to receive a uterine transplant from a deceased donor and was the second in our trial. in vitro fertilization treatments using the long gonadotropin-releasing hormone agonist protocol preceded the transplantation procedure. Frozen embryo transfers were performed in months 12, 13, 16, 19 and 23 after transplant. Results Recovery of the uterus of a 24-year-old brain-dead nulliparous donor and the transplant procedure itself was uncomplicated. No abnormalities were revealed on Pap smears, which were performed every 6 months during the post-transplant period, and cervical biopsies showed no epithelial dysplasia. The fifth frozen embryo transfer resulted in a clinical pregnancy. Three weeks after embryo transfer, an intrauterine gestational sac containing an embryo with a heartbeat was detected. One week later, signs of a missed abortion were revealed by ultrasound. Two weeks later, spontaneous bleeding occurred, and an ultrasound examination performed a week later confirmed an empty uterine cavity. Conclusion In light of present research, both deceased donor uterine procurement and transplantation surgeries are technically feasible; however, more experience is needed to determine the pregnancy success rate associated with this method. Thus, additional trials of deceased donor uterine transplantation should be performed in the future to continue research related to this promising concept for the treatment of absolute uterine factor infertility.

Objective To determine the value of yolk sac size and shape for prediction of pregnancy outcome in the first trimester. Material and methods 500 pregnant women between 6+0 and 9+6 weeks of gestation underwent transvaginal ultrasound and yolk sac diameter (YSD), gestational sac diameter (GSD) were measured, presence/absence of yolk sac (YS) and shape of the yolk sac were noted. Follow up ultrasound was done to confirm fetal well-being between 11+0 and 12+6 weeks and was the cutoff point of success of pregnancy. Results Out of 500 cases, 8 were lost to follow up, YS was absent in 14, of which 8 were anembryonic pregnancies. Thus, 478 out of 492 followed up cases were analyzed for YS shape and size and association with the pregnancy outcome. In our study, abnormal yolk sac shape had a sensitivity and specificity (87.06% & 86.5% respectively, positive predictive value (PPV) of 58.2%, negative predictive value (NPV) of 96.8% in predicting a poor pregnancy outcome as compared to yolk sac diameter (sensitivity and specificity 62.3% & 64.1% respectively and PPV and NPV of 27.3% and 88.7% respectively). The degree of association for both the variables was significant to the level of p Conclusion The presence or absence of yolk sac has a strong predictive value for poor pregnancy outcome. Yolk sac shape was a better predictor of poor pregnancy outcome in terms of higher specificity and negative predictive value as compared to yolk sac diameter.

Objective: To demonstrate the efficacy of management for cesarean scar ectopic pregnancies up to 8 weeks' gestation using ultrasound-guided Foley balloon catheter placement combined with dilation and curettage (D and C) at TuDu Hospital. Subjects and Methods: A quasi-experimental study was conducted from March 2015 to March 2016. Patients with imaging-confirmed cesarean ectopic pregnancies were admitted to an inpatient unit at Tu Du Hospital. A Foley balloon catheter was placed inside the uterus under ultrasound guidance and was left in place for 24 h. Afterward, the patient underwent ultrasound-guided D and C. Follow-up to confirm success included serial blood draws to measure beta-human chorionic gonadotropin (β-hCG) levels until a value of 0, and routine ultrasounds to confirm absence of a gestational sac and no evidence of vascularity at the site of the cesarean section scar. Results: A total of 311 patients were enrolled over 3 months. Overall, 90.7% (95% confidence interval [CI]: 86.8%–93.9%) patients were successfully treated with this regimen. Several factors that were significantly associated with successful management included gestational age

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 (β-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 β-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 β-hCG level was reduced by 50% within 3 days and decreased to

Myomectomy scar pregnancy is a rare intramural pregnancy in which gestational sac is implanted in the myometrium, in the previous myomectomy scar separate from endometrial cavity and fallopian tubes. Heterotopic pregnancy is presence of simultaneous gestation at two or more implantation sites. Our patient presented at 7 weeks, in-vitro fertilization (IVF) conception with previous four IVF failures and myomectomy 3 months prior. Transvaginal sonography revealed twin live pregnancies, one intrauterine and another in the posterior wall of the uterus distinctly separate from the endometrial cavity. Laparoscopy revealed a ruptured intramural pregnancy, another unruptured tubal pregnancy which was initially missed by USG. After laparoscopic management, intrauterine pregnancy continued resulting in live birth at 35 weeks. This case adds to the literature and highlights the importance of early diagnosis and timely intervention of a rare form of an ectopic gestation. This is the only reported case in literature with a heterotopic gestation and a coexistent myomectomy scar pregnancy and the only one resulting in successful live birth after laparoscopic management of a ruptured myomectomy scar pregnancy in a heterotopic gestation. Early diagnosis is important for salvaging the intrauterine gestation and one should actively look for them at viability scan especially in assisted reproductive technology (ART) conception and scarred uterus.

Background An increased incidence of monozygotic twinning after a blastocyst transfer has been previously reported in assisted reproductive technology treatment. It is uncertain whether this phenomenon is due to the extended culture time, culture medium, or inherent blastocyst parameters. Objective This study aimed to investigate the association between blastocyst parameters (in vitro culture time, blastocyst stage, and inner cell mass and trophectoderm grading) and the incidence of monozygotic twinning after assisted reproductive technology. Study Design This was a retrospective cohort study employing data from a multicenter, large, electronic database from 4 academic hospitals. All clinical pregnancies after a single blastocyst transfer between January 2014 and February 2020 were included. Blastocyst morphology was evaluated based on the Gardner grading system, considering the blastocyst stage, and inner cell mass and trophectoderm grading (grades A, B, and C). Monozygotic twinning was defined as ≥2 fetal heartbeats in a single gestational sac or 2 gestational sacs with sex concordance at birth. The multivariable predicted marginal proportions from logistic regression models were used to compute adjusted relative risks for the association between blastocyst parameters and the incidence of monozygotic twinning. Results The overall monozygotic twinning rate was 1.53% (402 of 26,254 cases). The monozygotic twinning was not associated with the culture time in vitro (day 5 vs day 6) or blastocyst stage (early, blastocyst, expanded, hatching, and hatched). Alternatively, monozygotic twinning was associated with lower inner cell mass grading (B vs A: adjusted relative risk, 1.67 [95 % confidence interval, 1.28–2.25]; C vs A: adjusted relative risk, 1.98 [95% confidence interval, 1.18–3.11]) and higher trophectoderm grading (B vs C: adjusted relative risk, 1.38 [95% confidence interval, 1.03–1.92]; A vs C: adjusted relative risk, 2.14 [95% confidence interval, 1.45–3.20]). The incidence of monozygotic twinning was the lowest in blastocysts with grade A inner cell mass and grade B or C trophectoderm (0.82%, as the reference) and the highest in blastocysts with grade B or C inner cell mass and grade A trophectoderm (2.40%; adjusted relative risk, 2.62; 95% confidence interval, 1.60–4.43). The incidence of monozygotic twinning in blastocysts with consistent inner cell mass or trophectoderm grading was somewhere in between (both A: 1.58%; adjusted relative risk, 1.86 [95% confidence interval, 1.23–3.04]; both B or C: 1.59%; adjusted relative risk, 1.84 [95% confidence interval, 1.29–2.90]). Conclusion Higher risk of monozygotic twinning was associated with blastocyst morphology specific to those blastocysts with loosely arranged inner cell mass cells combined with tightly packed trophectoderm cells.

To provide reference for the diagnosis and treatment of retroperitoneal ectopic pregnancy (REP), we conducted a review on all of the reported cases in English by summarizing their clinical manifestation, diagnosis, management and prognosis. A total of 25 literatures including 26 REP cases were collected from PubMed database. 40 % (10/25) of the patients had a history of tubal pregnancy, 65.4 % (17/26) was spontaneous pregnancy, and the average period of amenorrhea was 56.7 days. Abdominal pain is the most common (53.8 %, 14/26) symptom of REP. Ultrasound is the main method of diagnosing REP. Only 30.8 % (8/26) were diagnosed as REP at the initial visit, and 55.6 % (10/18) of those who were misdiagnosed received unnecessary invasive treatment. The pregnancy sites of REP are complex, and it can be simply divided into pelvic REP and abdominal REP. Due to preoperative misdiagnosis, 46.2 % (9/26) of REP experienced two or more treatments. Except for 2 patients who received local methotrexate (MTX) injection in the gestational sac, the other 24 patients underwent surgical treatment, and all patients had a good prognosis. Due to insufficient knowledge, the rate of misdiagnosis and mistreatment of REP is high. The key to diagnosing REP is to consider the possibility of REP and the scanning field during examination can cover the site of pregnancy. Local MTX injection and surgical resection are both effective methods for the treatment of REP.

In this study, we intend to evaluate pregnancy outcomes in women who undergo artificial frozen embryo transfer (FET) and stop estradiol (E2) after vaginal ultrasound observation of a gestational sac and heartbeat. In this randomized phase III clinical trial, we recruited 291 patients who underwent FET. We randomly assigned 64 pregnant women to a study or a control group after observation of a gestational sac and heartbeat at 6-week gestational age. E2 administration continued until week 12 of gestational age for the control group, but was discontinued for the study group. Progesterone-in-oil administration continued until week 12 of gestational age for both groups. Serum levels for E2 and progesterone were measured on the initial progesterone and embryo transfer (ET) days, and at weeks 6 and 12 of pregnancy in both groups. The miscarriage rate was 1/32 (3.13%) in the study group and 6/32 (18.75%) in the control group after the intervention and confirmation of a fetal heartbeat. This difference was statistically significant. All patients who remained under intervention, which included 29 in the study group and 24 in the control group, had live births. Although the mean serum E2 and progesterone levels steadily increased from the initial day of progesterone administration to week 12 of gestational age, they were not significantly different between the two groups. Maternal complications were significantly more common in the control group. Earlier discontinuation of E2 for luteal phase support of FET cycles may be taken into consideration. Additional clinical studies should be conducted to determine an accurate estimation of the time when E2 should be discontinued during FET luteal phase support. NCT04013438, registered 9 July 2019—Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04013438?cond=NCT04013438&draw=2&rank=1.

AIM To compare the effect of pituitrin local injection (PIT) and uterine artery embolization (UAE) as pretreatment before surgery during the management of cesarean scar pregnancy (CSP). METHODS Forty-nine CSP patients diagnosed in our department of Suzhou Ninth People's Hospital from October 2017 to October 2019. All patients underwent hysteroscopy and negative pressure aspiration (for type I CSP) or laparoscopic wedge-resection (for type II and III CSP) following one of the preoperative treatments: PIT group (n = 26) and UAE group (n = 23). The baseline clinical data, intraoperative blood loss, blood transfusion rate, postoperative hospital stay, hospitalization expenses, postoperative pain, postoperative fever, postoperative serum β-human chorionic gonadotropin (β-hCG) level, and pregnancy outcome were reviewed and analyzed. RESULTS There was no significant difference (p ≥ 0.05) between two groups in baseline characteristics including age, gravidity, previous cesarean section times, interval since last cesarean delivery, menolipsis time, maximum diameter of gestational sac or mass under ultrasound, fetal cardiac activity and preoperative β-hCG level. There was no significant difference in blood loss, transfusion rate, and postoperative β-hCG reduction percentage (p ≥ 0.05) either. The postoperative hospital stay, hospitalization expenses, postoperative pain, and postoperative fever rate in PIT group were significantly lower than those in UAE group (p

Heterotopic pregnancy (HP) is a dizygotic twin pregnancy in which one gestational sac is intrauterine and the other is extrauterine. The prevalence of HP is unknown in Cameroon where the diagnosis is difficult and usually fortuitous like in other resource-poor settings. We herein depict pitfalls and delays in the diagnosis and management of a ruptured heterotopic pregnancy at the Yaounde University Teaching Hospital. After a wrong diagnosis and inadequate treatment, our patient presented at our emergency unit with severe pelvic pain and clinical signs of hemoperitoneum with shock. She underwent a total left salpingectomy through laparotomy. She had a complete spontaneous abortion five days after the surgery. Given that sonography is not routinely available in emergency departments in resource-poor settings, it may be relevant for practitioners to always bear HP in mind when facing ruptured ectopic pregnancies.

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. β-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.