Are implantation and pregnancy outcome impaired in diethylstilbestrol-exposed women after in vitro fertilization and embryo transfer? Fertility and sterility, NCBI PubMed PMID: 2379627, 1990 Aug.
Forty-six infertile women with a history of diethylstilbestrol (DES) exposure in utero underwent 149 stimulation attempts for in vitro fertilization (IVF). The mean (+/- SE) number of preovulatory oocytes harvested at retrieval and transferred was 3.9 +/- 3.3 (536/138) and 2.6 +/- 1.4 (328/124).
When compared with patients with tubal factor infertility and less than or equal to 4 pre-embryos transferred, the clinical pregnancy rate (15.3% versus 22%) was not statistically different. However, the term/ongoing pregnancy rate was significantly lower in the study group (8% versus 16%). Comparison of the IVF outcome with different uterine anomalies as detected by hysterosalpingogram (n = 29) showed a trend for a worse prognosis in women with constrictions and a combination of T-shape and constrictions.
It is concluded that implantation and pregnancy outcome are impaired in DES-exposed women after IVF.
Ultrasound surveillance of the cervix during pregnancy in diethylstilbestrol-exposed offspring, Obstetrics and gynecology, NCBI PubMed PMID: 2643065, 1989 Feb.
Twenty-three diethylstilbestrol (DES)-exposed patients were evaluated through 27 pregnancies to determine their eligibility for admission to a prospective protocol that combined serial ultrasound surveillance of the lower uterine segment-cervical complex with periodic pelvic examinations to diagnose cervical incompetency.
Of these, 21 pregnant women, including seven vaginectomy patients, were matched to 84 low-risk controls to determine the following:
the effect of DES exposure on reproductive performance,
the efficacy of ultrasound selection of cerclage candidates,
and the influence of previous partial vaginectomy on reproductive outcome.
Five DES-exposed patients were diagnosed as having cervical incompetency and had cerclages placed. There were no missed diagnoses of cervical incompetency.
The DES-exposed patients delivered statistically earlier in gestation than did controls (268 +/- 13 versus 276 +/- 10 days). It was not evident that this difference was important clinically, as there were no neonatal deaths, very low birth weight infants, second-trimester losses, or deliveries before 252 days (36 weeks) among the study patients.
Previous vaginectomy did not affect the frequency of the diagnosis of cervical failure or the neonatal outcome. After ultrasound surveillance and treatment for incompetent cervix, a majority of our patients delivered at term without cerclage placement. Therefore, routine cerclage placement is not recommended.
Knowledge of the ultrasound criteria for diagnosing cervical incompetency is required.
Outcome of pregnancy in patients exposed in utero to diethylstilbestrol. Survey by the National College of French Gynecologists and Obstetricians, Journal de gynécologie, obstétrique et biologie de la reproduction, NCBI PubMed PMID: 3294279, 1988.
This study analyses the outcome of 110 pregnancies that occurred in 57 patients who were exposed to DES (DiEthylStilboestrol) during their fetal life.
The quantities of Distilbene that were received in the first trimester of the pregnancy were the same in France and in the United States.
The obstetrical complications of exposure in utero to DES were identically the same in France and in the United States.
Of particular note is the high level of extra-uterine pregnancies (15%)
and of 1st and 2nd trimester miscarriages (42%).
Only 41% of the population exposed to DES delivered a live baby.
It is estimated that 80,000 women were exposed to it in France. Exposure in utero to DES has given rise to a public health problem.
Adverse outcomes of pregnancy in women exposed to diethylstilbestrol in utero, The Journal of reproductive medicine, NCBI PubMed PMID: 3351803, 1988 Jan.
We analyzed data collected by interview and medical record review for 200 women exposed to diethylstilbestrol (DES) and 12,240 unexposed women to evaluate the relation between maternal DES exposure and outcomes of pregnancy.
Low birth weight, short gestation, bleeding in the first trimester, toxemia, breech presentation and premature rupture of the membranes occurred more often among the exposed women.
These relationships remained statistically significant after the use of linear regression and logistic regression analyses to control for multiple confounding factors.
Both exposed women and their physicians should be aware of the possible relationship between maternal exposure to DES and late adverse outcomes of pregnancy. Close medical supervision of these women throughout pregnancy and delivery is recommended.
Pregnancy after gamete intrafallopian transfer in a woman with primary infertility and in utero exposure to diethylstilbestrol. A case report, The Journal of reproductive medicine, NCBI PubMed PMID: 3290479, 1988 May.
In utero exposure to diethylstilbestrol (DES) has an adverse effect on reproductive performance and may be associated with infertility.
Gamete intrafallopian transfer (GIFT) is a new reproductive technique that has been advocated as an alternative to in vitro fertilization in women with at least one normally functioning fallopian tube. The process involves the translaparoscopic placement of oocytes and sperm into the fallopian tube. The technique has been successful in treating infertility due to endometriosis, male factors and immunologic factors as well as unexplained infertility.
We accomplished the first successful GIFT procedure in a woman with significant uterine effects from prenatal DES exposure. This technique may prove to be an effective treatment for infertile women with DES exposure who have no adequate explanation for their infertility.
Management of the diethylstilbestrol-exposed pregnant patient: a prospective study, American journal of obstetrics and gynecology, NCBI PubMed PMID: 3631167, 1987 Sep.
Over a 5-year period we have managed 63 diethylstilbestrol-exposed pregnant patients with a standardized protocol requiring weekly cervical examination and decreased physical activity of the patient.
Twenty-six patients (42%) underwent a prophylactic cerclage for a history of second-trimester loss or a hypoplastic cervix on initial clinical examination (group I).
Thirty-six patients (58%) were followed expectantly (group II).
Sixteen patients (44%) in group II demonstrated cervical change and required an emergency cerclage.
Twenty-one patients were managed expectantly with no cerclage.
The gestational age at delivery for group I was 37.7 +/- 2.80 versus 34.5 +/- 6.9 weeks for patients without a cerclage (p = 0.04).
There were no perinatal deaths if a cerclage was performed, whereas there were five deaths (24%) in the group without cerclage.
The five deaths occurred at a mean gestational age of 24.40 +/- 4.0 weeks and a mean birth weight of 614.00 +/- 441.73 gm.
Patients with a hypoplastic cervix or prior reproductive loss had a better outcome with early cerclage than patients with a normal cervix followed expectantly.
We presently lack a reliable method to detect the diethylstilbestrol-exposed patient at greatest risk for perinatal loss. Based on our experience we believe that placement of a cerclage early in pregnancy should be a strong consideration.
Experience with diethylstilbestrol-exposed infertile women in a program of in vitro fertilization, Fertility and sterility, NCBI PubMed PMID: 6724012, 1984 Jul.
Twenty infertile women with a history of diethylstilbestrol exposure in utero were seen in Norfolk for the purpose of in vitro fertilization.
Seventeen patients had undergone 25 stimulated cycles with harvest of oocytes by laparoscopy. The serum estradiol response to stimulation in these patients and the number and quality of oocytes retrieved did not differ significantly from those of patients with infertility due to blocked fallopian tubes.
There were four pregnancies in 17 patients after 21 cycles of embryo transfers, for a pregnancy rate of 23.5% per patient, or 19% per embryo transfer.
Two of the pregnant patients have had a term delivery,
one has had a preclinical abortion,
and one has a single intrauterine gestation in progress.
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.