Mean position of the tape in the cervix. Sagittal view.
Abstract
Early prophylactic cervical cerclage for hypoplastic cervix following exposure to DES in utero, Journal de gynécologie, obstétrique et biologie de la reproduction, NCBI PubMed PMID: 16208200, 2005 Oct. Full text: Service de Gynécologie-Obstétrique DOI: 10.1016/S0368-2315(05)82882-0, OCTOBER 2005.
AIM Presentation of a prophylactic cerclage technique, placed in the beginning of second trimester of the pregnancy, derived from McDonald cerclage and adapted to hypoplastic cervix following exposure to DES in utero.
MATERIALS AND METHODS Prospective study including 20 pregnant patients exposed to DES in utero and presenting a hypoplastic cervix. Study of the location of the cerclage tape in the cervix and of changes in cervical length (before and after cerclage) assessed by physical examination of the cervix and by transvaginal ultrasonography.
RESULTS The cervix was longer after cerclage as shown by physical examination and by ultrasound. The tape was localized near the internal cervical os, its posterior portion nearer the internal cervical os than its anterior portion.
CONCLUSION This easy-to-perform technique of cerclage of hypoplastic cervix allows the tape to be localized near the internal cervical os without colpotomy and without use of the transabdominal approach, while allowing vaginal delivery.
Among women with Mullerian anomalies, those with DES exposure in utero demonstrated the poorest outcome.
Abstract
Effects of Mullerian anomalies on in vitro fertilization outcome, Journal of assisted reproduction and genetics, NCBI PubMed PMID: 11699126, 2001 Oct. Full text: Journal of Assisted Reproduction and Genetics, Vol. 18, No. 10, 2001 PMC3455312, May 7, 2001.
PURPOSE To assess the effect of Mullerian anomalies on pregnancy rates in women undergoing in vitro fertilization (IVF).
METHODS The records of 37 patients with and 819 patients without Mullerian anomalies undergoing a first cycle of IVF between December 1995 and July 1998 were included in this retrospective study. Outcome variables included maximal estradiol level, number of days of stimulation, number of follicles, number of oocytes, fertilization rate, and ongoing/livebirth pregnancy rate.
RESULTS Patients with Mullerian anomalies had a significantly lower ongoing pregnancy rate (8.3%) than did controls (24.8%). No patients with diethylstilbestrol (DES)-related anomalies had an ongoing pregnancy.
CONCLUSIONS Among women with Mullerian anomalies, those with DES exposure in utero demonstrated the poorest outcome, with no ongoing pregnancies in 22 cycles. Physicians should use this information in counseling such patients about reproductive choices.
It is important for obstetrician-gynecologists to be aware of the consequences of DES exposure in utero on pregnancy outcome.
Abstract
Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring, Obstetrics and gynecology, NCBI PubMed PMID: 11004345, 2000 Oct. Full text: The American College of Obstetricians and Gynecologists, VOL. 96, NO. 4, OCTOBER 2000 pregnancyoutcomesdes2000, October 2000.
OBJECTIVE To evaluate long-term pregnancy experiences of women exposed to diethylstilbestrol (DES) in utero compared with unexposed women.
METHODS This study was based on diethylstilbestrol-exposed daughters, the National Collaborative Diethylstilbestrol 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.
RESULTS 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). (64.5 percent of women with in utero DES exposure had full-term infants, compared with 84.5 percent of matched women who had not been exposed to DES).
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. The DES-exposed women had higher rates of ectopic pregnancy (4.2 percent versus 0.77 percent).
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). The DES-exposed women had higher rates of preterm delivery (19.4 percent versus 7.5 percent)
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). The DES-exposed women had higher rates of second-trimester spontaneous abortion (6.3 percent versus 1.6 percent).
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).
CONCLUSION This comprehensive review confirmed that pregnancy outcomes for DES-exposed women are significantly worse than those of unexposed women.
Among DES-exposed women identified by record review, 74.5% became pregnant (5.6% fewer than unexposed controls), and among those women 85% delivered at least one live full-term infant. Although pregnancy outcomes in DES-exposed women were significantly worse than those of unexposed women, many of the exposed women were able to conceive and deliver a live full-term infant.
Even if it is assumed that DES was no longer used in pregnancy after 1971 in the United States (which is not actually the case), there are still many DES-exposed women of reproductive age. Thus, it is important for obstetrician-gynecologists to be aware of the consequences of DES exposure in utero on pregnancy outcome. Consequently, high-risk obstetric care may be indicated for pregnant women who were exposed to DES in utero.
Rates of term delivery and live birth in DES-exposed patients versus controls. 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.
Abstract
Effect of diethylstilbestrol on reproductive function, Fertility and sterility, NCBI PubMed PMID: 10428139, 1999 Jul. Full text: FERTILITY AND STERILITY, Volume 72, Issue 1, Pages 1–7 S0015-0282(99)00153-3, July 1999.
OBJECTIVE To review the effects of in utero exposure to diethylstilbestrol (DES) on müllerian development and subsequent reproductive function.
DESIGN 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.
RESULT(S) In utero exposure to DES resulted in
reduced fertility
and increased rates of ectopic pregnancy,
spontaneous abortion,
and preterm delivery.
CONCLUSION(S) 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.
Infertile patients with a history of in utero exposure to DES exhibit a significantly impaired implantation rate following Iin vitro fertilization, and the outcome of assisted reproductive technology remains poor.
Abstract
Outcome of IVF in DES-exposed daughters: experience in the 90s, Journal of assisted reproduction and genetics, NCBI PubMed PMID: 9401869, 1997 Oct. Full text: Journal of Assisted Reproduction and Genetics, Vol. 14, No. 9, 1997, NCBI PubMed PMC3454843, 1997 Oct.
Purpose The outcome of in vitro fertilization (IVF) in a group of infertile women with a history of in utero exposure to diethylstilbestrol (DES) was analyzed. Records from an academic IVF program were retrospectively reviewed.
Methods Seventeen infertile women with a self-reported history of exposure to DES in utero, attending the IVF unit at Massachusetts General Hospital (MGH) for assisted reproductive technology (ART), underwent 27 IVF cycles. Analysis of the outcome of IVF including implantation and ongoing pregnancy rates was performed. The data were compared with results from a group of 20 infertile patients with idiopathic infertility undergoing 27 IVF cycles at MGH during the same period. The patients in the two groups were matched for age, basal day 3 levels of follicle stimulating hormone and serum estradiol, and the number and quality of embryos transferred.
Results The response to controlled ovarian hyperstimulation was comparable in the two groups. Significantly lower implantation and ongoing pregnancy rates following IVF and embryo transfer were seen in the utero DES-exposed group compared to the control patients.
This study confirms a poor outcome of IVF in infertile women with a history of in utero exposure to DES. The significantly impaired implantation rate (2%) following IVF in this category of infertile women is striking and concordant with earlier reported data.
The risk of ectopic pregnancy is quoted to be eight times greater in women with a history of exposure to DES and appears to be the leading factor contributing to a poor reproductive performance in this group.
No prognostic implication could be attributed to the presence of a T-shaped uterine cavity in terms of ability to conceive and carry a pregnancy to term. Of the two successful IVF cycles in the DES-exposed group, one of the patients had a T-shaped uterine abnormality, while in the second patient the uterine cavity was hypoplastic.
Conclusions This study determined impaired implantation to be a major factor contributing to infertility in women undergoing IVF with a history of in utero exposure to DES. The ovarian response to controlled hyperstimulation, the fertilization and cleavage rates, and the embryo quality remain unaffected in these patients. The mechanism for implantation failure remains obscure and the prognosis for ART is guarded for patients exposed to DES in utero.
Hysterosonography of T-shaped uterus. DES-exposed women with a T-shaped uterus who want to improve their reproductive function should be encouraged to undergo hysteroscopic metroplasty.
Abstract
Beneficial effect of hysteroscopic metroplasty on the reproductive outcome in a ‘T-shaped’ uterus, Gynecologic and obstetric investigation, NCBI PubMed PMID: 8821883, 1996.
Eight women (aged 27-43) with reproductive dysfunction who were diagnosed by hysterosalpingogram and hysteroscopy as having a ‘T-shaped‘ uterus were operated on using fiberoptic hysteroscopic guidance; the uterine side walls were incised until a normal uterine cavity was achieved.
The women’s gynecologic and obstetric records were compared before and after the operation.
In all the 8 women the operation was without complications and resulted in a satisfactory uterine cavity.
Before the operative procedure, the women had had 10 spontaneous abortions and 1 ectopic pregnancy.
The postoperative performance available for 7 of the 8 women showed 4 term pregnancies in 3 women, 1 ectopic pregnancy, and no abortions.
Our study suggests that hysteroscopic metroplasty in women with a T-shaped uterus improves the reproductive outcome, mainly in women with repeated abortions. We conclude that women with a T-shaped uterus who want to improve their reproductive function should be encouraged to undergo hysteroscopic metroplasty.
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.
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.
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.
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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