Duane E. Townsend

Fertility and Outcome of Pregnancy in Women Exposed in Utero to Diethylstilbestrol

Fertility and outcome of pregnancy were examined in women participating in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project. We compared 618 subjects who had prenatal exposure to DES with 618 control subjects. Fertility, measured in terms of pregnancies achieved, did not differ between the women exposed to DES and the controls. An increased risk of unfavorable outcome of pregnancy was associated with DES exposure (the relative risk of any unfavorable outcome of pregnancy was 1.69; P less than 0.001). Speculation on biologic mechanisms that might produce this difference is premature, since additional data about these subjects must be collected. Among DES-exposed women who became pregnant, 81 per cent had at least one full-term live birth.

An analysis of “long-term” follow-up results in patients with cervical intraepithelial neoplasia treated by cryotherapy

Two thousand eight hundred thirty-nine patients who had been treated by cryotherapy for cervical intraepithelial neoplasia (CIN) in nine different institutions were followed longitudinally after three negative Papanicolaou smears to ascertain the risk of recurrence. The cumulative risk of developing CIN after successful cryotherapeutic management of CIN was 0.41% at year 5, 0.44% at year 10, and 0.44% at year 14. There was no significant difference in risk between patients originally treated for CIN 1, CIN 2, or CIN 3.

Vaginal intraepithelial neoplasia: Biologic aspects and treatment with topical 5-fluorouracil and the carbon dioxide laser

A review of 41 evaluable patients was made in order to study vaginal intraepithelial neoplasia (VAIN) and to investigate new methods of treatment. Colposcopic examination of the vagina revealed white epithelium alone in 20 patients and white epithelium associated with vascular punctation in 15. No lesion had a vascular mosaic pattern. Most patients had multifocal disease located in the vaginal apex. Iodine staining was positive in six patients with negative colposcopic examinations. Twenty-four patients had severe dysplasia or carcinoma in situ, and 17 had minimal or moderate dyplasia. Associated genital disease occurred in 17 patients with antecedent cervical or vulvar squamous neoplasia, and six additional patients had coexistent lesions. The chronology of vaginal disease that appeared after treatment of cervical neoplasia suggests a persistent but decreasing likelihood of the development of VAIN with the passage of time. In patients followed without therapy, six had spontaneous remission of disease. Treatment was successful in 12 of 15 patients with topical 5-fluorouracil and in nine of 10 patients with the carbon dioxide laser. The advantage of these methods of treatment for patients with VAIN relative to surgical procedures and radiation therapy are considered.

Design and preliminary observations of National Cooperative Diethylstilbestrol Adenosis (DESAD) Project.

The National Cooperative Diethylstilbestrol Adenosis (DESAD) Project has completed the major portion of its enrollment phase with the examination of more than 3000 daughters of women taking synthetic nonsteroidal estrogens (denoted DES) during pregnancies occurring from the early 1940s to the mid-1960s. The aims of the Project are to fill urgent needs for information on the prevalence and incidence of structural and epithelial abnormalities or neoplastic changes and their complications in these young women. Participants are grouped by mode of entry as identified by prenatal record review (40.1%), documented as DES-exposed but walking in (25.1%), or referred (22.8%) to the DESAD Project for examination, and not documented as exposed but having gynecologic abnormalities typical of those associated with DES exposure (12.0%). This study cohort, in part having paired controls, will be examined annually for at least 5 years. Details of the design and selected preliminary findings are reported.

Dysplasia and cytologic findings in 4,589 young women enrolled in diethylstilbestrol-adenosis (DESAD) project.

Abstract This report presents the cytologic findings and the rates of dysplasia for 4,589 young women enrolled in the National Cooperative Diethylstilbestrol-Adenosis (DESAD) Project. Mucinous columnar cells and/or metaplastic squamous cells with or without mucinous droplets were encountered in 22% of vaginal scrape smears from all diethylstilbestrol (DES)-exposed participants identified by review of prenatal records and in 43% of women in whom vaginal epithelial changes (VEC) were observed by colposcopy or by iodine staining. The frequency of cellular findings in the vaginal scrape smears was closely related to the timing of the administration of the DES to the mother. With increasing age of the daughters, the overall frequencies of both the mucinous and metaplastic cells decreased; relative to each other, an increasing proportion was metaplastic squamous cells. These data suggest that, as the women grow older, vaginal adenosis regresses by the process of squamous metaplasia. Endometrial type cells were found in 2% of vaginal scrape smears. Their cyclical occurrence during the menstrual cycle and lack of correlation with the presence of VEC indicated an origin from the uterine corpus rather than the tuboendometrial type of adenosis. Squamous cell dysplasia of the vagina and cervix was detected by biopsy or scrape smear specimens in 1.8% of DES-exposed women in the record review group. The rate in unexposed women was twice as high. In general, the rates of dysplasia were higher in the cervix than vagina, and the more severe degrees of dysplasia were encountered only in those women who were referred to the DESAD Project or who themselves requested entry. Four patients who were referred or who themselves requested entry were found to have clear cell adenocarcinoma of the vagina. The vaginal smear provided the first clue to the presence of an abnormality in three of them.

Comparison of Histologic and Colposcopic Findings in Des-Exposed Females

A study was undertaken to evaluate the histologic alterations associated with two or the most abnormal colposcopic findings, mosaicism and punctation, that are commonly found in the vaginas and cervices of young women who have been exposed prenatally to diethylstilbestrol (DES). Four-fifths of 215 biopsy specimens from 171 exposed subjects with mosaicism or punctation disclosed metaplastic squamous epithelium, the presence of which is thought to reflect the repair of vaginal adenosis and cervical ectropion. Hyperkeratosis was observed in one-fifth of the specimens and was more frequent in lesions colposcopically graded I than II. Mild dysplasia was encountered in only one specimen. The findings indicate that the presence of squamous cell dysplasia cannot be predicted by the finding of Grade I or II mosaicism or punctation in the DES-exposed female despite the fact that these abnormal colposcopic patterns are associated with dysplasia in about 10% of cases when encountered in the cervix of the unexposed woman.

Vaginal epithelial changes in young women enrolled in the national cooperative diethylstilbestrol adenosis (Desad) project

Initial clinical findings arc reported for the 3339 young women enrolled in the Diethylstilbestrol Adenosis (DESAD) project. Changes in the vaginal nuicosa (VEC— vaginal epithelial changes), which were detected by colposcopy or iodine staining, occurred in 34% of 1275 participants identified by review of prenatal records, 59% of participants who themselves requested entry into the project, and 65% of participants referred by a physician. Analysis of data on the 298 women who were identified by record review and whose prenatal records contained complete information about drug exposure indicated that VEC is most closely associated with the timing of the onset of inlrauterine exposure to diethylstilbestrol (DES), total dose, and length of exposure. Frequency of VEC was also found to decrease with age. No instances of severe dysplasia, carcinoma in situ, invasive squamous cell adenocarcinoma, or clear cell carcinoma were observed among the women identified by record review.

Intraepithelial squamous lesions of the vulva: Biologic and histologic criteria for the distinction of condylomas from vulvar intraepithelial neoplasia

We reviewed 65 intraepithelial lesions of the vulva and distal vagina and compared the presence of koilocytosis, abnormal mitoses, and parabasal or basal nuclear enlargement with DNA microspectrophotometric distribution patterns and the presence of human papillomavirus antigen as determined by immunoperoxidase. Abnormal mitoses and cytologically atypical nuclear enlargement were specific predictors of aneuploidy and were reliable for distinguishing vulvar intraepithelial neoplasia (VIN) from condylomas. Koilocytosis was present in 100% of condylomas and 71% of aneuploid (VIN) lesions, but there were qualitative and quantitative differences in the distribution of koilocytic cells in the two classes of lesions. On the basis of these findings, criteria for distinguishing between VIN and condyloma are proposed.

Structural anomalies of the cervix and vagina in women enrolled in the Diethylstilbestrol Adenosis (DESAD) Project.

Among women exposed in utero to diethylstilbestrol (DES) and enrolled in the Diethylstilbestrol Adenosis (DESAD) Project, structural anomalies of the cervix or vagina were found in 25% of the 1,655 subjects identified by review of prenatal records, 43% of the 800 who themselves requested entry into the project, and 49% of the 1,089 referred by physicians but in only 2% of the 963 control subjects. Among the 367 cases found by record review to have complete information on the DES exposure, multivariate analysis indicated close association of the anomalies with the gestational week of first exposure and the total dose. Also, the prevalence rate of the anomalies was lower among subjects who had been pregnant and higher among those with later age at menarche.

A Randomized Study Comparing Endometrial Cryoablation and Rollerball Electroablation for Treatment of Dysfunctional Uterine Bleeding

STUDY OBJECTIVE To determine the effectiveness of endometrial cryoablation in comparison with rollerball electroablation. DESIGN Prospective, randomized study (Canadian Task Force classification I). SETTING Ten university and private medical centers in the United States. PATIENTS Two hundred seventy-nine women with menorrhagia due to benign causes. INTERVENTION Endometrial ablation using a Her Option cryoablation device in 193 women and rollerball electroablation in 86. MEASUREMENTS AND MAIN RESULTS Women treated by cryoablation received significantly less general anesthesia (46%) than those treated by electroablation (92%). Subjects maintained menstrual diaries for at least one cycle before and for 12 months after the procedure. Success was defined as reduction of menstrual bleeding to a score of 75 or less in the absence of retreatment. Success rates in the cryoablation and electroablation groups were 77.3% and 83.8%, respectively. Bleeding declined by 92% and 94%, respectively. Both procedures led to significant improvements in a broad range of symptoms including menses-related pain, mood, and overall improvement in quality of life. CONCLUSIONS Endometrial cryoablation is a safe and effective procedure in treatment of dysfunctional uterine bleeding. Its advantages include technical ease of performance, direct ultrasonographic view of depth of ablation, little anesthetic, and avoidance of potential complications related to distention media.