Hysteroscopic metroplasty in DES-exposed and hypoplastic uterus

image of Septate-uterus
Septate uterus: partial (1 and 2), complete (3), complete with septate cervix (4), and complete with cervical and vaginal septation (5). JMIG.

Abstract

Hysteroscopic metroplasty for uterine enlargement: a treatment for diethylbestrol-exposed and hypoplastic uteri, Journal de gynécologie, obstétrique et biologie de la reproduction, NCBI PubMed PMID: 8901300, 1996. Full text: Hysteroscopic metroplasty in diethylbestrol-exposed and hypoplastic uterus: a report on 24 cases , Human reproduction (1998) 13 (10): 2751-2755, oxfordjournals, 1996.

OBJECTIVE
To determine the feasibility of correcting the uterine deformity in the diethylbestrol-exposed uterus and hypoplastic uterus.

DESIGN
Hysteroscopic metroplasty. Patients served as their own controls.

PATIENTS
Five patients referred for primary sterility (2 cases) or primo-secondary infertility with recurrent pregnancy loss or ectopic pregnancy (3 cases). Three of them had been exposed in utero to diethylbestrol. All of them have a hypoplastic uterus or uterine deformities as seen by hysterosalpingogram.

OUTCOME MEASURES
Postoperative hysterosalpingogram aspect. Ability to conceive and carry pregnancy to livebirth.

RESULTS
All the postoperative hysterosalpingograms appeared more normal than the preoperatively. Three patients have conceived since surgery.

CONCLUSION
Hysteroscopic metroplasty is feasible. It gives good anatomic results. This technique could be used in the patients with diethylbestrol-exposed or hypoplastic uteri, with severe infertility, recurrent pregnancy loss or implantations failures in a IVF program.

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Endometrial pattern in DES-exposed women undergoing IVF

undergoing-ivf
These 1996 study data suggested that endometrial pattern is one of the most significant variables for pregnancy outcome in DES-exposed women undergoing in-vitro fertilization.

Abstract

Endometrial pattern in diethylstilboestrol-exposed women undergoing in-vitro fertilization may be the most significant predictor of pregnancy outcome, Human reproduction (Oxford, England), NCBI PubMed PMID: 9021378, 1996 Dec. Full text: Human reproduction (1996) 11 (12): 2719-2723., oxfordjournals, 1996.

The objective of this study was to compare prospectively pregnancy outcome as it is related to ultrasonic endometrial echo pattern in women exposed to diethylstilboestrol (DES) in utero by their mother’s consumption with women not exposed to DES, all of whom were undergoing in-vitro fertilization (IVF).

Pregnancy outcome relative to endometrial thickness and pattern was evaluated in 540 cycles of IVF including DES (n = 50) and non-DES-exposed (n = 490) women. Endometrial patterns were designated as p1 = solid; p2 = ring; and p3 = intermediate.

  • DES patients exhibited p1 more often than the majority of the non-DES-exposed group.
  • There was no significant difference in endometrial thickness among the cycles where p1 was noted when comparing the DES (10.3 mm) with the non-DES-exposed (10.7 mm) groups.
  • Notably, within the group exhibiting p1, no pregnancies occurred in the 18 cycles of DES-exposed women compared with a 39.2% clinical pregnancy and 36.5% delivery rate in the non-DES-exposed controls (P < 0.0001 and P = 0.008 respectively).
  • Pregnancy rates were not significantly different in the cycles where the other endometrial patterns were found when comparing the two groups.

The impact of uterine shape on pregnancy outcome was also investigated.

  • A T-shaped uterine configuration was noted in 11 out of 18 (61.1%) cycles of DES-exposed women with pattern p1 compared with nine out of 23 (39.1%) with pattern p2.
  • Of cycles where a T-shaped uterus was demonstrated, none out of 11 (0%) with pattern p1 compared with four out of nine (44.4%) with pattern p2 resulted in pregnancy (P = 0.026).

These data suggest that endometrial pattern is one of the most significant variables for pregnancy outcome in DES-exposed women undergoing IVF.

It is our recommendation, based on the above results, that patients with a history of in-utero DES exposure who repeatedly demonstrate a solid endometrial pattern consider a gestational carrier as a possible means of achieving a biological offspring. Further investigation of both natural and hormone-replaced cycles in DES-exposed patients would address the potential for improvement of endometrial receptivity in these women. If improvement is possible, one could consider foregoing embryo replacement during the stimulated cycle with cryopreservation of the embryos for transfer at a later date. Perhaps midcycle endometnal sampling of DES-exposed women undergoing assisted reproductive technologies would help to define the endometrial variation.

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Vascular and morphological changes in uteri exposed to diethylstilbestrol in utero

Transvaginal-ultrasound
This 1996 study is particularly helpful in understanding the mechanisms of repeated miscarriage in the DES exposed because it suggests that vascular participation may be responsible. Sagittal image of the uterus showing some of the different measurements taken (day 5 of the menstrual cycle) Measurement 1 = maximum uterine length; measurement 2 = maximum uterine thickness; measurement 3 = maximum uterine cavity length.

Abstract

Transvaginal ultrasound studies of vascular and morphological changes in uteri exposed to diethylstilbestrol in utero, Human reproduction (Oxford, England), NCBI PubMed PMID: 8981149, 1996 Nov. Full text: Human Reproduction vol 11 no 11 pp 2531-2536, oxfordjournals, 1996.

The aim of this prospective study was to establish complementary data of uteri exposed to diethylstilbestrol (DES) in utero for transvaginal analysis and vascularity changes during the menstrual cycle.

A total of 28 women with DES-exposed uteri were compared with 60 non-exposed women. Transvaginal ultrasound and colour Doppler imaging were performed on days 5 and 22 of the menstrual cycle. Uteri were measured on sagittal and transverse scans. Uterine length, width, thickness and uterine cavity length and width were measured.

  • Uterine volume and uterine cavity area were calculated. DES-exposed uterine volume was equal to 31.84 +/- 3.37 cm3.
  • The cavity area of DES-exposed uterus was equal to 35.85 +/- 3.93 cm2.
  • Cervix length of DES-exposed uterus was significantly smaller than that of non-exposed uterus.
  • The uterine artery pulsatility index (PI) of DES-exposed uterus was significantly higher than that of normal uterus. Blood flow remained stable throughout the menstrual cycle.
  • The PI of DES-exposed uterus remained stable during the menstrual cycle, as in non-exposed uterus, and it decreased during the luteal phase. This lack of modification in vascularity of DES-exposed uterus may explain miscarriages and obstetric complications such as intrauterine growth retardation or pre-eclampsia.

The data may have implications for the assessment of reproductive status and the design of future studies on disorders of implantation in DES-exposed uterus. Based on these results, we now propose a study by Doppler transvaginal sonography and hysterography for all patients exposed in utero to DES Colour Doppler echography gives an appreciation of the implantation chances of DES patients. A high PI may in part explain repetitive miscarriages. We suggest low doses of aspirin for these patients from the beginning of pregnancy.

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Diethylstilbestrol effect on fetal development, gestation duration, number of offspring

Effect of diethylstilbestrol or zeranol on fetal development.

Abstract

Effect of diethylstilbestrol or zeranol on fetal development, gestation duration, and number of offspring in NMRI mice, “American journal of veterinary research, NCBI PubMed PMID: 8599523, 1995 Dec.

OBJECTIVE
To evaluate the effects of diethylstilbestrol (DES) or alpha-zearalanol (zeranol) on fetal development, gestation duration, and number of offspring.

DESIGN
Study effects of prenatal administration of DES or zeranol on various pre- and perinatal variables in an experimental group of mice, compared with effects in a control group.

ANIMALS
Pregnant NMRI mice.

PROCEDURE
Diethylstilbestrol or zeranol (150 mg/kg of body weight) or vehicle (controls) was administered SC to pregnant mice on days 9 and 10 of gestation. Fetuses from pregnant mice of each group were counted and weighed, and their size and head length were recorded. Additional pregnant mice delivered their fetuses naturally, and pups from each group were counted and their sex was determined. At the end of gestation, abortions were evaluated. All data were statistically analyzed.

RESULTS

  • Mean number of fetuses was significantly lower (P < 0.0001) in DES-treated (4.59 +/- 0.48) than in control mice (8.33 +/- 0.49).
  • Both estrogenic substances significantly reduced fetal size and weight (P < 0.0001), compared with control mice.
  • Diethylstilbestrol significantly increased abortion frequency (P < 0.0001) and gestation duration (P < 0.0001), compared with values for control mice.
  • A reduced number of live pups (P < 0.0001) from pregnant mice administered DES (5.48 +/- 0.38) or zeranol (5.97 +/- 0.49) was observed, compared with control mice (8.52 +/- 0.50), because of reduced number of male offspring (P < 0.0001).

CONCLUSIONS
Diethylstilbestrol or zeranol administered during mid-pregnancy leads to decreased fetal weight and size and lower numbers of male offspring at birth. Likewise, DES induced a significant increase in abortions and gestation duration.

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Pregnancy after transposition and repositioning of the ovaries in a DES-exposed patient

image of baby-sweat
This 1995 case was probably the first one with a pregnancy after repositioning of the ovaries in Europe and perhaps even in the world.

Abstract

Pregnancy after transposition and repositioning of the ovaries in a patient with clear-cell adenocarcinoma, Revue française de gynécologie et d’obstétrique, NCBI PubMed PMID: 8677407, 1995 Dec.

A young woman with a history of in utero exposure to distilbestrol was diagnosed with vaginal clear-cell adenocarcinoma. Management consisted of limited excision of the tumor followed by brachytherapy after transposition of the ovaries.

The patient had a successful pregnancy after reimplantation of the ovaries in their normal position and right adnexectomy for Chlamydia infection. The child was delivered by cesarean section.

This is probably the first case with a pregnancy after repositioning of the ovaries in Europe and perhaps even in the world.

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Refocusing on the gynecological and obstetrical consequences of intrauterine exposure to DES

image of hysterosalpingography
Full examination of the DES-exposed pregnant patients is advised, including colposcopy and hysterosalpingography.

Abstract

Refocusing on the gynecological and obstetrical consequences of intrauterine exposure to diethylstilbestrol (DES), Nederlands tijdschrift voor geneeskunde, NCBI PubMed PMID: 1996166, 1991 Jan.

The oncological and obstetrical follow-up is described of 321 patients who presented between 1981 and 1988 in the St Radboud Hospital with a history of intrauterine diethylstilbestrol (DES) exposure.

In 45 out of 321 cases cytological abnormalities were found including 20 cases of cervical intraepithelial neoplasia (CIN). No relation could be established between CIN and the extension of the cervical adenosis.

Twenty-two percent of 87 evaluable pregnancies terminated in spontaneous abortion, 13 percent of the patients delivered immaturely and 27 percent prematurely. These percentages were significantly higher than in the rest of the hospital population.

The consequences of intrauterine exposure to DES are discussed. Full examination of the patients is advised, including colposcopy and hysterosalpingography. If abnormalities are present it is advised to offer a timely cerclage in case of pregnancy.

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Cervical cerclage in early pregnancy

image of cervival-cerclage-suture
A cerclage in early pregnancy should be a strong consideration for some DES Daughters only ; routine cerclage placement is not recommended for all the DES affected.

Abstract

Cervical cerclage in early pregnancy, Journal of perinatology : official journal of the California Perinatal Association, NCBI PubMed PMID: 1919825, 1991 Sep.

A retrospective review of 33 patients who underwent transvaginal cervical cerclage for the treatment of an incompetent cervix from June 1984 through July 1987 was conducted. A total of 38 transvaginal cerclages were placed.

For the purposes of comparison, the patients were divided into three groups according to gestational age at the time of cerclage:

  1. group 1 less than or equal to 13 weeks;
  2. group 2 greater than 13 weeks, but less than 18 weeks;
  3. group 3 greater than or equal to 18 weeks.

There was no difference among groups in mean age, gravidity, history of diethylstilbestrol exposure (DES), prior pregnancy loss at or before 20 weeks, or prior dilation and curettage procedure. There were 24 modified McDonald and 14 modified Shrodkar procedures performed.

The mean gestational age of cerclage placement in group 1 was earlier than in group 2 and group 3 by 3.5 and 10.5 weeks, respectively. There were no major surgical complications in any of the three groups.

The overall incidence of preterm labor and preterm birth were 48.6% and 37.8%, respectively. Analysis of variance demonstrated a trend toward differences in the incidence of preterm labor, preterm birth, and estimated gestational age at delivery, with the earlier group favored. None of these, however, reached the level of statistical significance.

Estimated blood loss, obstetric complications, mean birthweight, and mean gestational age at delivery were not statistically different for the three study groups.

The above data are discussed and support given for the safety and efficacy of cervical cerclage placement in early pregnancy when compared with the more standard recommendations of placement at from 14 to 17 weeks’ gestational age.

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Are implantation and pregnancy outcome impaired in DES-exposed women after IVF and embryo transfer?

image of embryo-transfer
This 1990 study concluded that implantation and pregnancy outcome are impaired in DES-exposed women after Iin vitro fertilization.

Abstract

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.

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Ultrasound Surveillance of the Cervix during Pregnancy in DES Daughters

image of Ultrasound-surveillance
Knowledge of the ultrasound criteria for diagnosing cervical incompetency is required.

Abstract

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:

  1. the effect of DES exposure on reproductive performance,
  2. the efficacy of ultrasound selection of cerclage candidates,
  3. 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.

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Outcome of pregnancy in patients exposed in utero to diethylstilbestrol

CNGOF logo image
A comparison of the DES-exposed pregnancy experience in France and in the United States, by the CNGOF – Collège National des Gynécolgues et Obstétriens Français.

Abstract

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.

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