Hystero-embryoscopy: evaluation and evacuation of spontaneous missed abortions.

OBJECTIVE: To demonstrate the steps for hystero-embryoscopic evaluation of a 7-week spontaneous missed abortion and evacuation of the products of conception. Illustrate the surgical technique and highlight its advantages in improving the evaluation of spontaneous missed abortions. DESIGN: Video case presentation and demonstration of surgical technique. SETTING: Tertiary referral center. PATIENT(S): The patient provided consent for the video and its publication. INTERVENTION(S): Following vaginoscopy, the cervix was approached without prior blind cervical dilation. Navigation from the endocervix to the endometrial cavity was performed using a 2.9-mm diameter hysteroscope. The endometrial cavity was thoroughly inspected revealing an intact gestational sac and submucosal fibroids. An operative grasper was introduced, the chorion and amnion were penetrated, and embryoscopy was performed. In-flow was reduced for external morphological inspection of the embryo, which was then grasped and retrieved. The procedure was continued by introducing of a 26-french bipolar resectoscope, after which the products of conception were excised without electricity and sent for histologic and genetic analyses. MAIN OUTCOME MEASURE(S): This procedure allowed for proper embryonic evaluation and hysteroscopic evacuation of products of conception was successfully performed. RESULT(S): Cytogenic analysis of this case revealed a female embryo with trisomy 15. No maternal and fetal cell admixture was noted in the analysis, allowing a precise diagnosis. CONCLUSION(S): Hystero-embryoscopy is a valuable diagnostic and therapeutic procedure for cases of missed abortion. It may reveal embryonic morphological abnormalities, expand the diagnostic spectrum in the evaluation of pregnancy loss, and avoid potential complications from blind curettage.

Missed abortion with negative biomarkers.

BACKGROUND: First-trimester bleeding and pregnancy loss are common reasons for presentation to emergency departments. Women of childbearing age frequently receive urine and serum pregnancy tests, which are thought to be reliable markers of pregnancy. CASE PRESENTATION: We report a case of a 34-year-old woman who presented to an emergency department with vaginal bleeding and abdominal pain and was found to have negative urine and serum markers of pregnancy. A transvaginal ultrasound detected non-viable fetal tissue and the patient underwent an uncomplicated spontaneous abortion. CONCLUSIONS: Physicians should consider the use of ultrasonography to assess for pregnancy or retained fetal products in the appropriate patient, even with negative serum or urine markers of pregnancy.

The impact of pre-evacuation ultrasound examination in histologically confirmed hydatidiform mole in missed abortion.

BACKGROUND: Early detecting hydatidiform mole in missed abortion is challenge. In this retrospective observational study, we analysed the sensitivity of detecting hydatidiform mole by pre-evacuation ultrasound examination or naked eye after surgical uterine evacuation in missed abortion. METHODS: Data on 577 cases with histologically confirmed hydatidiform mole were collected over a 10-year period and analysed. Data included serum ß-hCG level before surgical evacuation, the ultrasound examination findings, histology findings and naked eye findings. In addition, serum ß-hCG level on 2398 cases without hydatidiform mole was also collected. RESULTS: The median maternal age was 29 (range, 17-53) years and the range of gestational age was 6 to 12 weeks. The sensitivity of detecting hydatidiform mole by ultrasound examination or by naked eye was 25% or 60% respectively. This sensitivity was not increased by the combination of ultrasound and naked eye. There was no difference in the sensitivity of detecting subtypes of hydatidiform mole. The higher ß-hCG level was seen in cases with hydatidiform mole, compared to cases without hydatidiform mole. However, there was a lot of overlap in the distributions of ß-hCG between the two groups. CONCLUSIONS: In this study, we found lower sensitivity of detecting hydatidiform mole by ultrasound in missed abortion. ß-hCG level was higher in hydatidiform mole than in non- hydatidiform mole in missed abortion. Although higher sensitivity of detecting hydatidiform mole is seen by naked eye (60%), in order to minimise missed opportunity of detecting hydatidiform mole, our study suggests that routine histopathological examination is necessary in missed abortion.

Neural Tube Defects in Embryonic Life: Lessons Learned From 340 Early Pregnancy Failures.

OBJECTIVES: The aim of this study was to evaluate the feasibility of sonographic assessment of the embryonic/fetal neural tube in nonviable pregnancies and to determine the defect incidence. METHODS: Prospective analysis of transvaginally acquired 3-dimensional (3D) multiplanar and 3D surface-rendered volume sets of 340 cases of missed abortion between March 2010 and September 2015 was performed. Data regarding karyotype and postmortem examination as well as demographic features and the outcomes of subsequent pregnancies were evaluated. RESULTS: In 223 cases, an embryo/fetus was detected and considered suitable for further evaluation: in 37 of 223 (16.6%) embryos/fetuses, a neural tube defect was present: 27 of 37 cephaloceles, 5 of 37 anencephalies/exencepahlies, 3 of 37 spina bifidas, 1 of 37 caudal regression syndrome, and 1 of 37 iniencephaly. Additional alterations were not observed. In 7 of 37 cases karyotyping was carried out and showed no aneuploidy. Eight subsequent pregnancies had a favorable outcome, with 1 ending in an intrauterine fetal death during the 22nd week of gestation. Maternal folic acid supplementation was provided for all subsequent pregnancies. No neural tube defects occurred. CONCLUSIONS: Sonographic 3D evaluation of complete neural tube closure in embryonic/fetal demise is technically feasible and can be achieved in embryos with a crown-rump length greater than 8 mm. In 26 of 37 cases a defective closure site could be allocated to high-risk areas known for early embryonic demise. Regardless of the etiology of different neural tube defects, high-dose folic acid prophylaxis must be recommended in all cases. Sonographic evaluation of the neural tube, including 3D surface-rendered images, should be offered to every woman with a missed abortion because of the impact on subsequent pregnancies.

Association between uterine position and transvaginal misoprostol treatment for early pregnancy failure.

AIM: We aimed to determine the importance of uterine position as a predicting factor of success rate in medically treated early pregnancy failure (EPF). METHODS: We carried out a retrospective cohort study at the Obstetrics and Gynecology Department of a tertiary medical center between January 2011 and June 2012. We included women diagnosed with EPF, which we defined as women diagnosed with missed abortion up to 13 gestational weeks. Patients were treated with one or two doses of 800 µg of misoprostol vaginally in accordance with the department's protocol. Demographic, clinical, and treatment success data were collected from patient electronic records. RESULTS: A total of 255 women were included in our study. The success rate after treatment with misoprostol for the anterior uterine group was 78.7% as compared to the non-anterior uterine group, which achieved a success rate of 88.1%. This difference was not statistically significant (P = 0.180). In a multivariate analysis comparing patients for whom treatment with misoprostol was successful as opposed to patients for whom treatment failed, only embryonic sac size showed a statistically significant difference, measuring shorter in the success group. CONCLUSION: Uterine position has no effect on success rate of misoprostol treatment for EPF.

Utility of ßhCG monitoring in the follow-up of medical management of miscarriage.

OBJECTIVE: To evaluate the percentage change in total ßeta-unit human chorionic gonadotropin (ßhCG) levels (%ΔßhCG) in the prediction of treatment outcomes following intravaginal misoprostol for missed miscarriage before 13 weeks. METHODS: A secondary analysis of a randomised controlled study of medical management of miscarriage was performed. Total ßhCG levels were collected before misoprostol (baseline) and after a planned seven day interval (follow-up), when a transvaginal ultrasound (TVUS) reported a gestational sac as present or not. If no sac at TVUS, surgery was indicated on clinical criteria. %ΔßhCG ((baseline ßhCG - follow-up ßhCG)/baseline ßhCG × 100) was evaluated in the prediction of a sac at TVUS and surgery on clinical criteria. RESULTS: %ΔßhCG was calculated for cases with ßhCG levels within two days of misoprostol and TVUS; calculation interval determined case number. The median %ΔßhCG for 24 cases with a persistent sac (6-9 day interval) was significantly lower than for 145 with no sac (58.75% (interquartile range (IQR): 37.59-76.69; maximum 86.54) vs 97.65% (IQR: 95.44-98.43); P < 0.0001). The median %ΔßhCG for eight cases needing surgery on clinical criteria (5-9 day interval) was significantly lower than for 140 cases with no sac not needing surgery (79.68% (IQR: 64.63-91.15; maximum 94.06) vs 97.68% (IQR: 95.61-98.50); P < 0.0001). The area under the receiver-operator curve was 0.975 for prediction of a persistent sac and 0.944 for prediction of surgery on clinical criteria, respectively. %ΔßhCG > 87% predicted no sac at TVUS. %ΔßhCG > 94.5% predicted no surgery on clinical criteria. CONCLUSION: %ΔßhCG calculation over one week reliably predicted treatment outcomes after medical management of missed miscarriage.

Ultrasound Evaluation of First Trimester Complications of Pregnancy.

OBJECTIVE: OUTCOMES:: EVIDENCE: A MEDLINE search and review of bibliographies identified articles was conducted. VALUES: The evidence collected was reviewed by the Diagnostic Imaging Committee of the Society of Obstetricians and Gynaecologists of Canada. The recommendations were made according to the guidelines developed by The Canadian Task Force on Preventive Health Care (Table 1). BENEFITS, HARMS, AND COSTS: Women presenting with first trimester bleeding may be incorrectly diagnosed with a missed abortion, may have an ectopic pregnancy overlooked, or may be inappropriately reassured about viability. Improvement in the identification of the sonographic landmarks of normal embryonic development and awareness of the sonographic risk factors of pregnancy failure may lead to more case-specific management strategies. Diagnosis of suspected ectopic pregnancy often involves an assessment of both hormonal markers and sonographic features. Maternal morbidity and mortality can be reduced with an early diagnosis of ectopic pregnancy.

Recurrent vomiting in a woman due to miscarriage: think out of the box.

A 25-year-old gravida 2 para 1 with 12-week amenorrhoea presented a second time for recurrent vomiting in pregnancy. She was diagnosed to have a missed miscarriage following absent fetal heart seen in an early scan. She opted for conservative management. However, on the third presentation, her vomiting continued. Repeated transvaginal ultrasound scan showed a fetus with a crown rump length of 19 mm, which is equivalent to 8 weeks and 4 days, with absence of fetal heart pulsation. Thyroid function tests and ß human chorionic gonadotropin were then requested. Results showed that the patient's serum ß human chorionic gonadotropin level was markedly raised to 147,000. A molar pregnancy was suspected. Her thyroid function tests came back normal. Suction curettage was performed and histopathology confirmed a partial molar pregnancy. On follow-up, the ß human chorionic gonadotropin level was normal by 7 weeks after the curettage.

Use of cell-free DNA in the investigation of intrauterine fetal demise and miscarriage.

OBJECTIVE: To estimate whether cell-free DNA is present in nonviable pregnancies and thus can be used in diagnostic evaluation in this setting. METHODS: We conducted a prospective cohort study of 50 participants at MedStar Washington Hospital Center, Washington, DC, between June 2013 and January 2014. Included were women with pregnancies complicated by missed abortion or fetal demise. All gestational ages were considered for study participation. Participants with fetal demise were offered the standard workup for fetal death per the American College of Obstetricians and Gynecologists. Maternal blood samples were processed to determine the presence of cell-free DNA, the corresponding fetal fractions, and genetic abnormalities. RESULTS: Fifty samples from nonviable pregnancies were analyzed. The average clinical gestational age was 16.9 weeks (standard deviation 9.2). The mean maternal body mass index was 30.3 (standard deviation 9.1). Seventy-six percent (38/50) of samples yielded cell-free DNA results, that is, had fetal fractions within the detectable range of 3.7-65%. Among the 38, 76% (29) were classified as euploid, 21% (8) as trisomies, and 3% (1) as microdeletion. A cell-free DNA result was obtained more frequently at ultrasonographic gestational ages of 8 weeks or greater compared with less than 8 weeks (87.9% [n=29/33, 95% confidence interval (CI) 72.7-95.2; and 52.9%, n=9/17, 95% CI 31.0-73.8] of the time, respectively, P=.012). Time from demise was not associated with obtaining a result. CONCLUSION: Among nonviable pregnancies, cell-free DNA is present in the maternal plasma with fetal fractions greater than 3.7% in more than three fourths of cases after an ultrasonographic gestational age of 8 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01916928. LEVEL OF EVIDENCE: III.

Novel insights into early embryonic demise via 3D surface rendered imaging in 107 cases.

PURPOSE: Sonographic imaging techniques including 3 D volumetry were evaluated in women with missed abortion. Special emphasis was put on the impact of additional information regarding the etiology of the demise and improved visualization of embryonic and fetal anomalies due to the application of the latest imaging tools, e. g. HD live™. Parental acceptance of a more realistic display of the embryo/fetus in missed abortion was analyzed. MATERIALS AND METHODS: Between 09/2009 and 09/2012, 107 pregnancies with a missed abortion in the first trimester were included in this prospective survey. Using a transvaginal approach, all 2 D and 3 D studies were carried out with high-resolution 5 - 9 and 6 - 12 MHz probes. RESULTS: The mean gestational age was 70.3 days (49 - 110 days). The difference between estimated gestational age and sonographic age at evaluation for missed abortion was 13.5 days (-13 - 40 days). Additional information via three-dimensional volume acquisition, like craniofacial deformities, clefts, neural tube defects, abdominal wall defects and caudal regression syndrome, could be documented in 23/107 cases (21.5 %). In 2/107 cases the parents disapproved of the 3 D visualization due to the more realistic presentation. CONCLUSION: 3 D ultrasound in cases of missed abortion can provide additional information regarding the presence of structural anomalies. It may give further details regarding the timing of embryonic/fetal demise in early pregnancy. Sufficient informational value is regularly obtained in cases having a CRL > 8 mm. In counseling parents, 3 D ultrasound is a useful tool and is generally well accepted.

Early embryonic morphology sonographically assessed and its correlation with yolk sac in missed abortion.

PURPOSE: To provide additional information about embryo morphology sonographic assessment and its correlation with yolk sac. METHODS: A systematic study in 200 consecutive cases of missed abortion <10 weeks diagnosed by transvaginal ultrasound. RESULTS: In 104 gestations of embryos with morphological abnormalities, 88 (84.6 %) were at least 1 week smaller than expected for gestational age and 16 (15.4 %) were the expected size. From 32 normal morphologic embryos, 7 (21.9 %) were at least 1 week smaller than expected for gestational age, and 25 (78.1 %) were the expected size (p < 0.005). Normal morphologic embryos are linked more frequently with normal yolk sac (62.5 %). Findings in anembryonic gestations (GD1) included an absent yolk sac (46.9 %) and a cystic yolk sac (25 %). Likewise, findings in GD2-3 embryos included more frequently a cystic yolk sac (42.9 %) and an absent yolk sac (32.5 %). GD4 embryos are associated with an echogenic yolk sac (40 %), a relatively small-hypoplastic- (40 %) and a relatively large-cystic- (20 %). In DI embryos, yolk sac appears cystic (62.5 %) or echogenic (37.5 %). CONCLUSIONS: Our study proves the correlation between morphology of conceptuses and yolk sac appearance in cases of missed abortion.

Association between increased yolk sac diameter and abnormal karyotypes.

AIMS: To investigate the association between increased yolk sac diameter and abnormal karyotype. METHODS: Retrospective analysis of 42 patients with no history of diabetes between 6 and 12 weeks of gestation with increased yolk sac diameter measuring ≥6 mm was evaluated by transvaginal ultrasound. Sonographic findings were correlated with karyotype. The Fisher's exact test and exact conditional logistic regression analysis were used for statistical analysis. RESULTS: Chromosome abnormalities were found in 76.2% of chorionic villi samples. A statistically significant relationship between karyotype and missed abortion was detected (P=0.001). None of the patients with a yolk size diameter ≥8 mm and viable pregnancy had a normal karyotype. Trisomy 15 or 16 was strongly associated with missed abortion (unadjusted odds ratio=14.97, P=0.01). Nine patients with viable pregnancy had a yolk sac ≥6 mm (six patients with normal karyotype, one patient with monosomy X, one patient with trisomy 16, and one patient with trisomy 21). CONCLUSION: Our data indicate that enlarged yolk sac may also be visualized in viable pregnancies. Patients with an enlarged yolk sac and normal karyotype require detailed ultrasound evaluation in the second and third trimester.

The p53-HDM2 gene-gene polymorphism interaction is associated with the development of missed abortion.

BACKGROUND: The interaction between p53 and human double minute 2 (HDM2) plays an important role in apoptosis; therefore, functional polymorphisms in these genes might have adverse effects in early pregnancy. In this study, we investigated whether p53 codon 72 and HDM2 promoter (SNP309) polymorphisms were associated with the development of missed abortion. METHODS: Women with missed abortions (n= 60) and healthy controls (n= 64) were included in the study. Genotyping of the p53 codon 72 and HDM2 SNP309 (T > G) polymorphisms was performed by PCR with sequence-specific primers and PCR-restriction fragment length polymorphism analysis, respectively, using villous samples. The mRNA and protein levels for p53 and HDM2 were measured by real-time PCR and semi-quantitative immunohistochemistry, respectively. RESULTS: For the p53 codon 72 polymorphism, no difference in genotype or allele frequencies was observed in women with missed abortion versus controls. However, for the HDM2 SNP309 (T > G) polymorphism, G/G genotype was associated with a higher risk of missed abortion compared with the T/T+ T/G genotypes (P= 0.043). Women carrying the HDM2 G/G genotype or p53 Pro/Pro genotype had higher HDM2 mRNA (P= 0.04 and P= 0.013, respectively) and protein (P= 0.001 and P= 0.037, respectively) levels than women with other HDM2 SNP309 and p53 codon 72 genotypes. CONCLUSIONS: The genotypes HDM2 SNP309 G/G and p53 codon 72 Pro/Pro can induce high levels of HDM2, which may be associated with missed abortion.

A Swedish study of midwives' and nurses' experiences when women are diagnosed with a missed miscarriage during a routine ultrasound scan.

OBJECTIVES: The aim was to describe midwives' and nurses' experiences when women are diagnosed with a missed miscarriage during a routine ultrasound scan in pregnancy weeks 18-20. STUDY DESIGNS: A qualitative content analysis with an inductive approach and 13 semi-structured interviews were used for data collection from these three domains: midwives at an ultrasound department, midwives at a maternity clinic and nurses at a gynecological ward. Content analysis resulted in six codes, four categories and one primary theme. MAIN OUTCOME MEASURES: The four categories identified were: the interviewees' experiences of women's reactions, support from the midwife and nurse, the interviewees' experiences of men's reactions and communication between care providers and women. The main theme focused on the interviewees' noting that women had a premonition that something was wrong with their pregnancy. This could for example have been in the form of minor bleeding or the fact that pregnancy symptoms had receded and there were no movements by the fetus. The midwives carried out a follow-up with assessment. CONCLUSIONS: Women need confirmation of their premonitions of a missed miscarriage so that a diagnosis can be made as early as possible in their pregnancy. Women and their partners who have suffered a missed miscarriage need extended support on an individual basis in addition to follow-up assistance as assessed by the midwives.

Early pregnancy failure: factors affecting successful medical treatment.

BACKGROUND: The results of medical treatment for early pregnancy failure are conflicting. OBJECTIVES: To determine whether gestational sac volume measurement as well as other variables can predict the success rate of medical treatment for early pregnancy failure. METHODS: The study group comprised 81 women diagnosed with missed abortion or anembryonic pregnancy who consented to medical treatment. Demographic data were collected and beta-human chorionic gonadotropin level was documented. Crown-rump length and the sac volume were measured using transvaginal ultrasound. TVU was performed 12-24 hours after intravaginal administration of 800 micro g misoprostol. If the thickness of the uterine cavity was less than 30 mm, the women were discharged. If the sac was still intact or the thickness of the uterine cavity exceeded 30 mm, they were offered an additional dosage of intravaginal misoprostol or surgical uterine evacuation. RESULTS: Medical treatment successfully terminated 32 pregnancies (39.5%), 30 after one dose of misoprostol and 2 after two doses (group A); 49 underwent surgical evacuation (group B), 47 following one dose of misoprostol and 2 following two doses. There were no significant differences between the groups in age and gestational week. Gestational sac volume did not differ between groups A and B (10.03 and 11.98 ml respectively, P = 0.283). Parity (0.87 and 1.43, P = 0.015), previous pregnancies (2.38 and 2.88, P = 0.037), and betahCG concentration (6961 and 28,748 mlU, P = 0.013) differed significantly between the groups. CONCLUSIONS: Gestational sac volume is not a predictor of successful medical treatment for early pregnancy failure. Previous pregnancies and deliveries and higher betahCG concentration negatively affect the success rate of medical treatment.

Gestational sac volume in missed abortion and anembryonic pregnancy compared to normal pregnancy.

PURPOSE: To compare gestational sac (GS) volume (GSV) between normal pregnancies and missed abortions and anembryonic pregnancies and to determine at what gestational age differences in GS volume become evident. METHODS.: GSV in missed abortion and anembryonic pregnancy were measured using three-dimensional ultrasound and the results were compared with GSV in normal pregnancies. Pregnancies between 6 and 12(+6) gestational weeks of age according to last menstrual period were included in normal pregnancies, missed abortions, and anembryonic pregnancies. RESULTS: There were 141 normal pregnancies and 82 missed or anembryonic abortions. GSV was significantly larger in normal pregnancies than in missed or anembryonic abortion: 27.51 + or - 25.25 cm(3) and 8.04 + or - 10.54 cm(3), respectively (p < 0.001). When stratified by weeks, statistically significant differences were found beginning at 7 weeks, while GSV measurements were not significantly different between the normal and abnormal pregnancies from 6 to 6(+6) weeks. CONCLUSION: GSV in missed abortion and anembryonic pregnancies is significantly smaller than in normal pregnancies, starting at 7 weeks of gestational age. This finding may be helpful in the diagnosis of missed abortion or anembryonic pregnancies in selected cases.