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Embryonic death in early pregnancy: a new look at the first trimester

Goldstein SR
OBJECTIVE: To examine the frequency of pregnancy loss following successful development of anatomical embryonic landmarks identified with endovaginal ultrasound. METHODS: Two hundred thirty-two women with positive urinary pregnancy tests and no antecedent history of vaginal bleeding had endovaginal sonography performed at the initial visit and at subsequent visits as indicated clinically. The presence of anatomical and embryonic structures (gestational sac, yolk sac, embryo) and cardiac activity was recorded. Patients were followed until delivery unless sonographic evidence of nonviability was seen or spontaneous loss occurred. RESULTS: Twenty-seven losses occurred during the embryonic period, four losses occurred in the fetal period, and there were 201 live births. If a gestational sac developed, subsequent loss of viability in the embryonic period occurred in 11.5%; loss rates were 8.5% with a yolk sac, 7.2% for an embryo up to 5 mm, 3.3% for an embryo of 6-10 mm, and 0.5% for an embryo larger than 10 mm. No pregnancies were lost between 8.5 and 14 menstrual weeks. The fetal loss rate after 14 weeks was 2.0%. CONCLUSIONS: The rate of early pregnancy loss decreases successively with gestational age and is virtually complete by the end of the embryonic period (70 days after onset of the last menstrual period). Subsequent pregnancy losses in the fetal period occur between 14 and 20 weeks. This pattern of early pregnancy death suggests a period of embryonic loss distinct from one of fetal loss. Based on these data, the physiologic significance of the traditional boundary of the first trimester as an appropriate dividing time line for early pregnancy may be questioned
PMID: 8041550
ISSN: 0029-7844
CID: 12927

Postmenopausal endometrial fluid collections revisited: look at the doughnut rather than the hole

Goldstein SR
OBJECTIVE: To report 30 postmenopausal women and the thickness of the tissue surrounding an endometrial fluid collection seen on vaginal probe ultrasound. METHODS: During routine ultrasound-enhanced bimanual examination, nine postmenopausal women with unremarkable palpatory findings and no history of bleeding were found to have endometrial fluid collections. The patients were 9-24 years postmenopausal. All underwent prompt endometrial sampling. Each woman had some degree of cervical stenosis as judged by the operator. At curettage, all had scant tissue, which was reported by the pathologist as 'inactive endometrium.' RESULTS: Ultrasound scans on each patient were rereviewed, and it was found that the endometrium surrounding the fluid was uniformly 3 mm thick or less. Subsequently, 21 additional patients with small endometrial fluid collections have been seen. Eighteen of these had thin endometrium peripherally and were followed conservatively for 6-26 months. Six cases resolved and 12 remained unchanged. Three patients had a thickened heterogeneous endometrium peripheral to the fluid collection. In one, D&C was unsuccessful in two attempts because of cervical stenosis, and hysterectomy was performed. A 15-mm endometrial polyp was found. Two other patients with thickened endometrium surrounding the fluid had D&C, and hysteroscopy revealed simple hyperplasia without atypia. CONCLUSIONS. Normal atrophic postmenopausal endometrium in association with cervical stenosis can produce endometrial fluid collections, seen easily on vaginal probe ultrasound. If the endometrial tissue surrounding the fluid is thin (3 mm or less), the endometrium is invariably inactive and sampling is not necessary. If the peripheral endometrium is thicker than 3 mm, sampling is mandatory because the tissue cannot be expected to be invariably inactive and sampling is not necessary. If the peripheral endometrium is thicker than 3 mm, sampling is mandatory because the tissue cannot be expected to be inactive. Thus, the presence or amount of fluid is not as important as the thickness and character of the surrounding tissue
PMID: 8164935
ISSN: 0029-7844
CID: 12969

Use of ultrasonohysterography for triage of perimenopausal patients with unexplained uterine bleeding

Goldstein SR
OBJECTIVE: Concerns about pathologic anatomy in perimenopausal women with irregular vaginal bleeding have made invasive diagnostic procedures commonplace. This study evaluated the use of fluid instillation to enhance vaginal probe ultrasonographic examination of the endometrium in such patients. STUDY DESIGN: This was a prospective study of 21 women between 40 and 52 years old with irregular vaginal bleeding. On day 4 to 6 of the menstrual cycle a 5.3F Soules intrauterine insemination catheter (Cook ObGyn, Spencer, Ind.) was inserted, and under direct ultrasonographic examination sterile saline solution was slowly infused. If present, any polyp or submucous myoma was noted and the endometrial thickness surrounding the fluid was measured. Invasive endometrial sampling was then carried out. RESULTS: Of the 21 patients, 8 had obvious polypoid lesions and underwent triage for operative hysteroscopic removal. The pathology report confirmed benign polyps in all 8. Three patients had submucous myomas. Two had wire loop resectoscopic excision. The third, with a submucous myoma that extended to the serosal edge of the uterus, received expectant management. Nine patients had no obvious anatomic lesion and endometrial thickness of < or = 4 mm. Biopsy in all 9 of these patients revealed early proliferative endometrium. One patient had endometrial thickness of 8 mm; fractional curettage with hysterectomy revealed simple hyperplasia without atypia. CONCLUSIONS: Endometrial fluid instillation to enhance vaginal ultrasonography in perimenopausal women can reliably distinguish between patients with minimal tissue whose bleeding may be of anovulatory origin and best treated with hormonal therapy and those patients with significant amounts and type of tissue in need of formal curettage. Furthermore, polyps may be distinguished from submucous myomas, which allows appropriate preoperative triage for operative hysteroscopy when indicated and eliminates the need for diagnostic hysteroscopy
PMID: 8116714
ISSN: 0002-9378
CID: 12998

Unusual ultrasonographic appearance of the uterus in patients receiving tamoxifen [see comments] [Comment]

Goldstein SR
Tamoxifen is widely used as adjunctive therapy for patients with breast cancer and has been suggested as protection against the development of breast cancer in women at risk on the basis of heredity. It is a nonsteroidal estrogen antagonist, but like all antagonists it has some agonistic properties. Its administration should result in atrophic changes in the endometrium, but paradoxically some reports have found hyperplasia and even carcinomas developing prospectively in patients on tamoxifen therapy. Increasingly, endovaginal ultrasonography is being used for endometrial assessment in a wide variety of patients. This report is the first description of an unusual ultrasonographic finding in the uteri of some patients receiving tamoxifen. Initially believed to be endometrial in location, when viewed after fluid instillation (sonohysterogram) the heterogenous bizarre ultrasonographic appearance was actually found to represent small subendometrial sonolucencies in the proximal myometrium. Because none of these patients were clinically bleeding and all had inactive endometria on biopsy, it seems prudent not to overinterpret ultrasonography findings in patients receiving tamoxifen who have not had fluid-enhanced assessment
PMID: 8116695
ISSN: 0002-9378
CID: 12999

An updated protocol for abortion surveillance with ultrasound and immediate pathology [see comments] [Comment]

Goldstein SR; Danon M; Watson C
OBJECTIVE: To modify and improve a protocol for surveillance of patients presenting for routine elective abortion services. METHODS: Six hundred seventy-four women presenting for routine elective first-trimester abortions were studied. All were 84 or fewer days after the last menstrual period, had no history of bleeding, and had positive urine pregnancy tests. Each woman was scanned initially with an empty-bladder transabdominal technique. If no sac was seen, endovaginal ultrasonography was performed. All terminations had modified gross examination of tissue (3x magnification) as well as staining for microscopic analysis. RESULTS: Six hundred twelve patients (90.8%) demonstrated intrauterine gestations on transabdominal ultrasound, 595 of which were 12 or fewer weeks. Suction and sharp curettage and examination of tissue revealed products of conception in all. Seventeen subjects (2.5%) were found to be 13 or more weeks despite bimanual examinations and last menstrual period suggesting 12 or fewer weeks. Sixty-two patients had no sac seen on transabdominal ultrasound, 34 of whom had definitive intrauterine gestations on endovaginal ultrasound. Curettage revealed chorionic villi in all. Two had unruptured definitive ectopic pregnancies seen on endovaginal ultrasound. Twenty-one women with no sac seen on endovaginal ultrasound underwent curettage as the next step in triage; chorionic villi proved an intrauterine gestation in 17. The additional four had decidua only on pathology. Rising hCG levels in two of these four led to a diagnosis of ectopic pregnancy, whereas falling hCG levels in the other two led to a presumptive diagnosis of complete abortion, possibly tubal pregnancy in light of the lack of vaginal bleeding. CONCLUSION: Pre-abortion sonography eliminates inadvertent second-trimester cases, and immediate postoperative examination of curettage material expedites the diagnosis of ectopic pregnancy when present
PMID: 8272309
ISSN: 0029-7844
CID: 13014

Endovaginal ultrasonographic measurement of early embryonic size as a means of assessing gestational age [see comments] [Comment]

Goldstein SR; Wolfson R
Crown-rump length has consistently been found to be the most accurate method of determining gestational age in the first trimester. The original regression curve established by Robinson in 1973 with static arm scanners remains the one most widely employed. New endovaginal ultrasonographic probes afford a degree of detail that allows embryonic structures to be seen as soon as they are distinct from the yolk sac. Previously, measurements of very early embryonic structures have mistakenly been labeled crown-rump lengths. There has been widespread use of nomograms constructed from regression curves, where the bulk of the data were derived from small fetuses and then such curves extrapolated back to embryos of very small size. The purpose of this study was to establish a nomogram for gestational age assessment by measuring early embryos prior to the development of a 'crown' or 'rump.' This present study consisted of 143 patients. To be included they had to have had no history of any prior bleeding, and all were delivered of singleton infants within 2 weeks of their estimated delivery date by last menstrual period. All had a single early embryonic size measurement between 1 and 25 mm using high-frequency endovaginal probes. Regression analysis revealed a linear equation of Gestational age (days) = early embryonic size (mm) + 42 with a correlation coefficient r = 0.87; 95% confidence limit = +/- 3 days. We conclude that using high-frequency vaginal ultrasonographic probes and having a better understanding of embryonic anatomic stages allow for the construction of a nomogram of gestational age derived from measurements of early embryonic size prior to development of a crown-rump length
PMID: 7636950
ISSN: 0278-4297
CID: 13042

Thyrotropin-releasing hormone stimulation tests in infants

Rapaport, R; Sills, I; Patel, U; Oppenheimer, E; Skuza, K; Horlick, M; Goldstein, S; Dimartino, J; Saenger, P
The TSH response to TRH administration (7 micrograms/kg) was measured in 68 infants (22 premature) who had abnormal thyroid screening tests by the filter paper method and whose serum thyroid function tests were only mildly abnormal. Twenty-eight infants (12 premature) had peak TSH values of 35 mU/L or less and were considered normal (group I). Forty infants (10 premature) had peak TSH values above 35 mU/L and were considered hyperresponsive (group II). The mean age at testing, screening T4, TSH levels that prompted the testing, as well as baseline T4, T3, and free T4 at the time of TRH testing were not different between the groups. The mean (+/- SD) baseline TSH value was greater in group II (6.8 +/- 2.3 mU/L) than in group I (4.4 +/- 2.2 mU/L; P < 0.001). However, there was a great deal of overlap in the individual TSH values (group I, 0.9-10 mU/L; group II, 1.9-10.6 mU/L). Mean peak TSH levels were significantly different in the two groups (group I, 24 +/- 7.7 mU/L; group II, 60.3 +/- 26.1 mU/L; P < 0.001). During long term follow-up, all 25 group I infants available for evaluation have been confirmed as clinically and biochemically normal. No infant diagnosed as normal was later found to have evidence of hypothyroidism. Fourteen infants in group II have had evidence of thyroid dysfunction. We conclude that the TSH response to TRH stimulation is a useful tool for the evaluation of infants suspected of having primary hypothyroidism. Whether hyperresponsiveness to TRH represents a form of neonatal hypothyroidism requiring treatment remains to be determined.
PMID: 8408462
ISSN: 0021-972x
CID: 3697322

Conservative management of small postmenopausal cystic masses

Goldstein SR
PMID: 8513633
ISSN: 0009-9201
CID: 13137

Significance of cardiac activity on endovaginal ultrasound in very early embryos

Goldstein SR
OBJECTIVE: To evaluate the significance of cardiac activity on endovaginal ultrasound in embryos up to 10 mm in size. METHODS: Ninety-six women with positive urinary pregnancy tests had vaginal probe ultrasound examinations at the first clinical visit. All had discernible embryos between 1-10 mm in greatest length. The presence or absence of discernible cardiac activity was recorded. None of the subjects had any antecedent bleeding. All were available for follow-up until delivery or completion of a failed pregnancy. RESULTS: Seventy-four women had cardiac activity present at the initial study and 22 did not. Eighty-one delivered healthy newborns and 15 had early pregnancy failure. All embryos that ultimately proved normal showed cardiac activity by the time they were 4 mm in size. However, absence of detectable cardiac activity in embryos of 3 mm or less was still associated with a 41% continuation rate. CONCLUSIONS: Cardiac activity is present in normal embryos before it can be detected on ultrasound. There are variations in the type and frequency of ultrasound equipment, maternal anatomical characteristics (obesity, coexisting fibroids, uterine version), and in the visual acuity of observers. Nevertheless, we conclude that in our hands, the absence of cardiac activity in embryos measuring 4 mm or more is reliably associated with embryonic death. In contrast, the lack of cardiac activity in embryos of 3 mm or less is nondiagnostic and may warrant follow-up study in 3-5 days
PMID: 1407892
ISSN: 0029-7844
CID: 13418

Use of endovaginal ultrasound in the overall gynecologic examination

Goldstein SR
Endovaginal ultrasound scanning is not merely a subset of conventional ultrasonography as practiced today. It should not be reserved for the imaging specialist. Its unique characteristics allow its incorporation into the overall routine gynecologic examination
PMID: 1803301
ISSN: 0889-8545
CID: 13822