DES-exposed patients must be observed closely for ectopic pregnancy, spontaneous abortion, and PTD
1999 Study Abstract
To review the effects of in utero exposure to diethylstilbestrol (DES) on müllerian development and subsequent reproductive function.
The literature on DES and reproductive function was reviewed and summary data are presented. The studies were identified through the computerized MEDLINE database and a manual search of relevant bibliographies.
An understanding of the reproductive performance of women who were exposed to DES in utero is useful for counseling these patients regarding their risks and treatment options.
1999 Study Summary
In the wake of the DES and thalidomide tragedies, the effect of new pharmaceuticals on pregnancy is now considered and medications are used more judiciously during pregnancy. The anatomic changes associated with exposure to DES in utero are well known even though the pathogenic mechanisms are not. Although new cases of vaginal clear cell adenocarcinoma resulting from exposure to DES in utero are not expected at this point, an unknown number of exposed women are still facing several reproductive hazards in their quest for a viable live birth. These patients must be observed closely for ectopic pregnancy, spontaneous abortion, and PTD. In spite of their poor obstetric histories, they can be reassured that approximately 80% ultimately will be successful. Surgical correction of the structural abnormalities in an attempt to improve their reproductive performance is not advised. The use of prophylactic cervical cerclage may be beneficial, but a consensus is lacking.
Effect of diethylstilbestrol on reproductive function, Goldberg JM1, Falcone T., Fertil Steril. 1999 Jul;72(1):1-7., NCBI PMID: 10428139.
DES-exposed women have a higher risk of infertility
2001 Study Abstract
Although it is well established that women exposed to diethylstilbestrol in utero have an increased risk of spontaneous abortion, ectopic pregnancy, and preterm delivery, it is not known whether they also have an increased risk of infertility. The authors assessed this question in data from a collaborative follow-up study of the offspring of women who took diethylstilbestrol during pregnancy. In 1994, 1,753 diethylstilbestrol-exposed and 1,050 unexposed women from an ongoing cohort study (National Cooperative Diethylstilbestrol Adenosis Study and Dieckmann cohorts) provided data on difficulties in conceiving and reasons for the difficulty. Age-adjusted relative risks were computed for the association of diethylstilbestrol exposure with specific types of infertility. A greater proportion of exposed than unexposed women were nulligravid (relative risk (RR) = 1.3, 95% confidence interval (CI): 1.1, 1.5), and a greater proportion had tried to become pregnant for at least 12 months without success (RR = 1.8, 95% CI: 1.6, 2.1). Diethylstilbestrol exposure was significantly associated with infertility due to uterine and tubal problems, with relative risks of 7.7 (95% CI: 2.3, 25) and 2.4 (95% CI: 1.2, 4.6), respectively. The present findings indicate that diethylstilbestrol-exposed women have a higher risk of infertility than do unexposed women and that the increased risk of infertility is primarily due to uterine or tubal problems.
Sadly for many DES daughters having their own children is not possible! Many of us who have experienced miscarriages, want to have kids but are struggling or unable to…
Infertility among women exposed prenatally to diethylstilbestrol,NCBI, PMID: 11495854, 2001 Aug 15;154(4):316-21. Full text: Oxford Journals Medicine & Health International Journal of Epidemiology link.
In this 1980 study, the difference in pregnancy outcomes between the DES daughters and the unexposed is highly significant
Reproductive histories were compared for 226 diethylstilbestrol-exposed daughters and 203 DES-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.
Pregnancy outcomes in DES-exposed women are worse than those in unexposed women
2000 Study Abstract
To evaluate long-term pregnancy experiences of women exposed to diethylstilbestrol (DES) in utero compared with unexposed women.
This study was based on diethylstilbestrol-exposed daughters, the National Collaborative Diethylstylbistrol Adenosis cohort and the Chicago cohort, and their respective nonexposed comparison groups. Subjects who could be traced were sent a detailed questionnaire in 1994 that contained questions on health history, including information on pregnancies and their outcomes. We reviewed 3373 questionnaires from exposed daughters and 1036 questionnaires from unexposed women.
The response rate was 88% among exposed and unexposed women. Diethylstilbestrol-exposed women were less likely than unexposed women to have had full-term live births and more likely to have had premature births, spontaneous pregnancy losses, or ectopic pregnancies. Full-term infants were delivered in the first pregnancies of 84.5% of unexposed women compared with 64. 1% of exposed women identified by record review (relative risk [RR] 0.76, confidence interval [CI] 0.72, 0.80). Preterm delivery of first births occurred in 4.1% of unexposed compared with 11.5% of exposed women, and ectopic pregnancies in 0.77% of unexposed compared with 4.2% of exposed women. Spontaneous abortion was reported in 19.2% of DES-exposed women compared with 10.3% in control women (RR 2.00, CI 1.54, 2.60). According to complete pregnancy histories (many women had more than one pregnancy), preterm births were more common in DES-exposed women (19.4% exposed versus 7.5% unexposed (RR 2.93 CI 2.23, 3.86). Second-trimester spontaneous pregnancy losses were more common in DES-exposed women (6.3% versus 1.6%; RR 4.25, CI 2.36, 7.66). More first-trimester spontaneous abortions occurred in DES-exposed women than in controls (RR 1.31, CI 1.13, 1.53), and DES-exposed women had at least one ectopic pregnancy more often than unexposed women (RR 3.84, CI 2.26, 6.54).
Pregnancy outcomes in DES-exposed women were worse than those in unexposed women.
Higher infertility rate and abnormalities found in the DES Daughters
Infertility was examined among 343 diethylstilbestrol-exposed and 303 unexposed daughters whose mothers participated in an evaluation of diethylstilbestrol use during pregnancy 35 years ago. Of the married individuals who were not using contraception and who were actively trying to conceive, a greater proportion of diethylstilbestrol-exposed women than unexposed subjects experienced primary infertility (33% versus 14%, p less than 0.001). Among those with primary infertility, abnormal hysterosalpingograms were observed in 46% of the diethylstilbestrol-exposed group and in none of the unexposed group (p less than 0.02), while tubal abnormalities were found in 42% of the exposed and in none of the unexposed (p = 0.02). First pregnancies were achieved by 40 (58%) women exposed to diethylstilbestrol and 18 (64%) unexposed subjects. Twenty-four (60%) of the exposed women and 15 (83%) of the unexposed individuals who conceived had a live-born infant who survived. The estimated cumulative rate of first pregnancy was 16% for the exposed group and 36% for the unexposed group at 12 months after the diagnosis of primary infertility (p less than 0.05).
American journal of obstetrics and gynecology, 1981
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%.
In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes
2011 Study Abstract:
Before 1971, several million women were exposed in utero to Diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood.
We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero.
Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows:
for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75)
spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88)
preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86)
loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54)
ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38)
preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89)
stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54)
early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31)
grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27)
breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18).
For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes.
CONCLUSIONS: In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. (Funded by the National Cancer Institute).
Read: Adverse health outcomes in women exposed in utero to diethylstilbestrol, NCBI, PMID: 21991952, 2011 Oct 6;365(14):1304-14. doi: 10.1056/NEJMoa1013961.
Ectopic pregnancy and miscarriage: diagnosis and initial management
The National Institute for Health and Clinical Excellence believes doctors do not give enough information or support to women at risk of miscarriages or ectopic pregnancies. NICE says that the NHS should consider setting up dedicated services for pregnant women who may have an ectopic pregnancy or who experience pain or bleeding in their first trimester. This is according to their December 2012 guideline on the diagnosis and management of ectopic pregnancy and miscarriage in early pregnancy.
These scans examine a woman’s reproductive organs, including the uterus, ovaries, cervix and vagina
” Ectopic pregnancy, in which the fertilized egg grows in the fallopian tubes or other spots outside the uterus, typically leads to miscarriage and can even prove fatal. Now, a review of the data finds that taking a patient’s history along with a clinical exam is not enough to diagnose the condition in women with abdominal pain or vaginal bleeding during early pregnancy.
Instead, the researchers concluded that transvaginal ultrasound is the single best way to evaluate suspected ectopic pregnancy. These scans examine a woman’s reproductive organs, including the uterus, ovaries, cervix and vagina. ” DES Daughters are at a higher risk for ectopic/tubal pregnancies.