Pregnancy after gamete intrafallopian transfer in a DES Daughter with primary infertility

Gamete-Intrafallopian-Tube-transfer image
This GIFT reproductive technique, tested here in 1988, may prove to be an effective treatment for some of the DES-exposed women.

Abstract

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.

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Management of the diethylstilbestrol-exposed pregnant patient

image of pregnant
This 1987 study said that the placement of a cerclage early in pregnancy should be a strong consideration for DES Daughters. Pregnant Wife.

Abstract

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.

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Experience with DES-exposed infertile women in a program of IVF

image of in-vitro-fertilization
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.

Abstract

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.
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Complications of pregnancy in mice exposed prenatally to DES

image of lab-mouse
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.

Abstract

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.

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Exposure to diethylstilbestrol during intrauterine life

image of T-shape-uterus
Pregnancy complications seem to have a predilection for DES-exposed women who have abnormal cervices or who have a T-shaped hypoplastic uterus found on hysterosalpingography.

Abstract

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,
  • spontaneous abortions,
  • 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.

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Structure and function of the fallopian tubes following exposure to diethylstilbestrol during gestation

Fuzzy-womb-for-E
DES Daughters were found to have unique tubal morphologic features consisting of a foreshortened, convoluted tube with “withered” fimbria with a pinpoint os at laparoscopy. Fuzzy womb for E.

Abstract

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.

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Reproductive and gynecologic surgical experience in diethylstilbestrol-exposed daughters

trying-to-rest
Spontaneous abortion, ectopic pregnancy, incompetent cervix, and premature labor occurred significantly more often in the DES-exposed population than in the normal controls. trying to rest.

Abstract

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%.
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Pregnancy outcome in women exposed to DES in utero, their mothers, and unexposed siblings

Pregnancy Outcome in 98 Women Exposed to Diethylstilbestrol In Utero.

Abstract

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:

  1. 167 age-matched, normal women,
  2. 20 siblings not exposed to DES who had achieved pregnancy,
  3. 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%).

Click to download the full study.

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Pregnancy outcome in women exposed to diethylstilbestrol in utero

image of pregnant-woman
The outcomes of the pregnancies of DES-exposed women registered in the Stilbestrol Clinic at the Stanford University Medical Center were examined in 1981. Pregnant Woman.

Abstract

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.

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Reproductive performance of DES-exposed female progeny

image of empty-couffin
This 1981 study showed that fetal wastage is high in DES Daughters.

Abstract

Obstetrics and gynecology, Volume 58 – Issue 1, July 1981.

The reproductive performance of 106 patients exposed in utero to diethylstilbestrol by maternal ingestion is described.

Fetal wastage is high, apparently because of spontaneous abortion during the first and second trimesters.

Recommendations – see image below – are made for preconception counseling of exposed progeny to increase fetal salvage.

Obstetrics and gynecology, Volume 58 – Issue 1, July 1981.

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