Complications of pregnancy in mice exposed prenatally to DES, Teratology, NCBI PubMed PMID: 6845221, 1983 Feb.
Women exposed prenatally to diethylstilbestrol (DES) develop a variety of reproductive tract anomalies. Most of these anomalies have been replicated in strain CD-1 mice after similar DES exposure.
Recently, impaired reproductive performance in DES-exposed women has been reported. To see whether the mouse model also replicates this defect, a study of reproduction was performed. Pregnant CD-1 mice were injected with DES and their female offspring were raised to breeding age. The latter were then exposed continuously to untreated males for a maximum of 4 months.
Among 74 mated mice,
34 became pregnant
and 11 of these pregnancies ended in abortion or stillbirth.
Other anomalies encountered were:
two fetuses with compressed heads,
one of which seemed blocked from delivery by a vaginal adenocarcinoma;
two uterine tumors,
one of which was a teratocarcinoma;
two teratomas located in uterine lumina;
and two uteri containing placentas without embryos.
Since the frequency of successful pregnancies in the DES-exposed mice was reduced below control levels to a degree similar to that reported for DES-exposed women, the validity of the mouse model has been confirmed for this characteristic.
Exposure to diethylstilbestrol during intrauterine life. Signs that should suggest this. Therapeutic implications, Journal de gynécologie, obstétrique et biologie de la reproduction, NCBI PubMed PMID: 6655208, 1983.
From now on it is general knowledge that there is marked increase in the frequency of clear cell cancers of the cervix and of the vagina in daughters whose mothers were given diethylstilboestrol (DES) during their pregnancies. Equally well known is the high fréquency of vaginal adenosis in these patients.
Since 1977, moreover, several North American writers have commented on the lowering in reproductive capacity of these women. It seems that women who were exposed to DES in utero had
a greater frequency of extra-uterine pregnancies,
and perinatal mortality of their offspring as compared with carefully selected control series.
These complications seem to have a predilection for women who have abnormal cervices or who have a T-shaped hypoplastic uterus found on hysterosalpingography.
Recently it has been found that there is a higher level of female sterility as compared with male sterility in these patients.
Reviewing the literature and describing the principal abnormalities has made it possible for us to produce a hypothesis. This should explain how the action of DES on the mesonephric canals of Wolff causes changes in the shape of the uterus.
Structure and function of the fallopian tubes following exposure to diethylstilbestrol (DES) during gestation, Fertility and sterility, NCBI PubMed PMID: 7308519, 1981 Dec.
The association between the use of diethylstilbestrol (DES) and vaginal and cervical adenocarcinoma and adenosis in the progeny was first reported by Herbst et al. in 1971. This progeny will reach a peak as far as reproduction is concerned in this decade. It is estimated that 2 million women may be involved to varying degrees.
Changes in uterine and cervical contour and structure have been detailed. Thus DES exposure and anatomic changes in the Müllerian system have been documented.
In this report 16 women in the reproductive age group who were exposed to DES in utero and presented with infertility are discussed. On workup for infertility they were found to have unique tubal morphologic features consisting of a foreshortened, convoluted tube with “withered” fimbria with a pinpoint os at laparoscopy.
The diagnosis could not be made at the time of hysterosalpingogram. Three patients had surgery in an attempt to correct this condition; and in all cases the surgery was unsuccessful.
No statistical data is offered as to epidemiologic factors or incidence rates, but the suspected increase in infertility and ectopic pregnancy rates in patients with DES exposure may corroborate these findings.
Reproductive and gynecologic surgical experience in diethylstilbestrol-exposed daughters, American journal of obstetrics and gynecology, NCBI PubMed PMID: 7315913, 1981 Dec.
Information on reproductive history, gynecologic operations, and examinations was analyzed for 338 diethylstilbestrol (DES)-exposed and 298 unexposed women whose mothers participated in an evaluation of DES use in pregnancy 28 years ago.
A history of infrequent menses (less often than every 36 days) was reported more commonly by the exposed women (32%) than by the unexposed women (15%) and the mean duration of menstrual flow was also less.
A greater number of exposed women than unexposed women experienced primary infertility (53 versus 19). The reasons for these differences are not currently known.
Comparison of the outcomes of first pregnancies showed a higher proportion of premature births, spontaneous abortions, and ectopic pregnancies in the exposed women (P less than 0.001).
The difference in the occurrence of ectopic pregnancies was statistically significant (8 versus 0; P less than 0.005).
An adverse pregnancy outcome was more likely in DES-exposed women with cervicovaginal ridges.
However, when the outcome of all pregnancies were considered, 81% of the exposed women had at least one living child.
More exposed women than unexposed women had gynecologic surgical procedures, which may, in part, be due to the increased medical surveillance of the exposed group.
The spectrum of diseases at operation in both groups was similar.
Adnexal masses and pelvic inflammatory disease were more commonly reported among the exposed women while the occurrence of endometriosis in both groups was similar.
For the exposed women who had been examined at the Chicago Lying-In Hospital over a 4-year period, epithelial changes in the vagina had disappeared in 32% and cervicovaginal ridges had disappeared in 57%.
Pregnancy Outcome in 98 Women Exposed to Diethylstilbestrol In Utero, Their Mothers, and Unexposed Siblings, Obstetrics and gynecology, Volume 59 – Issue 3, July 1981.
The reproductive capability and labor complications of 98 women exposed to diethylstilbestrol (DES) in utero were compared with those of three separate control groups. The controls consisted of:
167 age-matched, normal women,
20 siblings not exposed to DES who had achieved pregnancy,
and their mothers.
Spontaneous abortion, ectopic pregnancy, incompetent cervix, and premature labor occurred significantly more often in the DES-exposed population than in the normal controls.
The controls also achieved a higher percentage of desired pregnancies overall; this was statistically significant (89.6 versus 75.0%, P less than .001).
When compared with their mothers, however, the DES-exposed population achieved a greater percentage of desired, viable pregnancies (75.6 versus 67.0%, P less than .001).
The unexposed siblings of the DES women achieved a higher percentage of desired, viable pregnancies than did their exposed sisters (86.9 versus 73.6%, P = .274), but less than the normal population (86.9 versus 89.6%).
American journal of obstetrics and gynecology, NCBI PubMed PMID:7234915, 1981 May.
The presence of anomalies in vagina, cervix, and uterine body of women exposed to diethylstilbestrol in utero has provoked interest and concern regarding the reproductive potential of these women. To expand and to evaluate better better the current knowledge in this matter, the outcomes of the pregnancies of exposed women registered in the Stilbestrol Clinic at the Stanford University Medical Center were examined.
The results were combined with the published results of similar examinations of other institutions and a summation of all available data is presented.
Although it is evident that the majority (79%) of exposed women who have become pregnant and not regularly sought abortion have obtained at least one living infant, the incidence of spontaneous abortion and preterm delivery has consistently been found to be greater in exposed women than in unexposed control women.
One of every 30 pregnancies reported in exposed patients has been ectopically located.
Additionally, there is suggestive evidence that exposed women with teratologic changes have a higher incidence of pregnancy loss than those without such changes.
However, few of these observations can boast statistical validity and statistical validation of the same observation by separate investigators has not been obtained. Moreover, none of the teratologic changes in exposed patients has been seen to preclude normal pregnancy and term delivery.
Diethylstilbestrol DES exposure in utero produces histologic and gross anatomic abnormalities in the lower and upper female genital tract. The authors investigated the reproductive history of 71 DES-exposed women by comparing their questionnaire data with those of 69 demographically matched non-DES-exposed control subjects.
The study group’s menstrual indices were comparable with those of the control group except in menstrual flow, which was significantly shorter in duration (P < .001), and in dysmenorrhea, which was reported more often (P<.05).
Fertility, as indicated by incidence of pregnancy, mean gravidity, and frequency of infertility problems, did not differ between groups.
The incidence of early (less than 20 weeks) pregnancy complications, ectopic pregnancy, and spontaneous abortion was comparable between groups. However, the incidence of late (after 20 weeks) pregnancy complications, premature delivery (40%, P<.001), and perinatal death (25%, P<.05) was significantly increased in the study group. Among DES-exposed subjects with gross cervicovaginal changes, premature delivery was even more frequent (71.4%, P<.0005), and consequently it was associated with a higher perinatal mortality (43%, P<.001).
The authors conclude that DES exposure in utero in this study group was not associated with increased difficulty in conceiving or early pregnancy complications. However, among pregnancies that progressed beyond 20 weeks’ gestation, the incidence of premature delivery was significantly increased and associated with an increased perinatal mortality. The mechanism(s) for these premature deliveries remains to be elucidated.
A comparison of pregnancy experience in DES-exposed and DES-unexposed daughters
The Journal of reproductive medicine, NCBI PubMed, PMID:7359503, 1980 Feb.
Reproductive histories were compared for 226 DES-exposed and 203 -unexposed daughters whose mothers participated in a double-blind evaluation 27 years before.
Irregular menstruation was slightly more common among the exposed (10%) than among the unexposed (4%).
Nineteen of the exposed and only four of the unexposed had primary infertility.
Among those at risk, 86% of the unexposed and 67% of the exposed had become pregnant. The reasons for these differences are not known.
Comparison of evaluable first pregnancy outcome revealed full-term live birth to be more common among the unexposed (85%) than the exposed (47%).
Premature live birth was experienced by 22% of the exposed but only 7% of the unexposed.
Nonviable outcomes of stillbirth, neonatal death, miscarriage and ectopic pregnancy occurred in 31% of the exposed and 8% of the unexposed.
The difference in pregnancy outcomes between the groups is highly significant. The DES-exposed with transverse cervicovaginal ridges were more likely to experience a nonviable outcome. Overall 82% of the exposed and 93% of the unexposed had at least one live offspring.