Journal of a DES Daughter
Read all “T-shaped uterus” related posts published by Diethylstilbestrol “Journal of a DES Daughter”; a blog updated weekly about DES and its consequences.
What’s your diagnosis ?
32 year-old patient presents for an ultrasound scan at an infertility clinic. The patient has a 6 year history of infertility.
Transvaginal scan demonstrating a T-shaped uterine cavity commonly seen with maternal use of Diethylstilbestrol (DES).
A small T-shaped uterus with cavity constrictions is common in DES daughters
A rational systematic evaluation is essential to the management of a couple with repeated early pregnancy wastage. Psychologic support in the form of frequent discussions and sympathetic counseling are crucial to the successful evaluation and treatment of the anxious couple. A prompt and orderly evaluation will relieve anxiety. When no etiologic factor is identified, a 60% to 80% fetal salvage rate may be expected. Once a patient conceives, serial ultrasonography, beta-hCG determination, and estradiol determination may be useful in detecting the stage of the embryonic death if subsequent abortion occurs. A karyotypic analysis of the products of conception should be performed if fetal loss occurs.
PIP: This review of the current literature on the clinical management of repeated early pregnancy wastage focuses on several etiologic factors (i.e., genetic, medical, immunologic, endocrine, psychogenic, environmental, occupational, infectious, and uterine) which have been noted to result in repeated pregnancy wastage. Suggestions for further clinical study are outlined where appropriate, and a rational approach to clinical evaluation and management is provided, based on the interpretation of the state of the art. The frequency of clinically recognized spontaneous abortion in the general population has been estimated to range between 15-20%. The actual spontaneous abortion rate is difficult to determine due to the fact that some patients do not seek medical services and abort completely at home. Despite the present uncertainty concerning the actual risk of recurrent abortion, most clinicians agree that repeated early spontaneous pregnancy wastage (i.e., repeated pregnancy loss) is defined as the occurrence of 3 or more pregnancy losses prior to the 20th week of gestation. From cytogenetic studies of aborted products of conception, chromosomal abnormalities account for between 50-60% of spontaneous abortions in the 1st trimester of pregnancy. Most of the chromosomal aberrations involved in spontaneous abortions have been presumed to be due to random events that are not necessarily repetitious. Sporadic chromosomal errors account for approximately 30% of spontaneous pregnancy losses, and repeated pregnancy loss under these conditions would therefore occur as a matter of chance and would not be predictive of future pregnancy loss. Several medical diseases have been implicated in causing habitual abortion, and these include systemic lupus erythematosus, congenital cardiac disease, and renal disease. The severity of the disease correlates best with fetal wastage. An absence of blocking antibodies within the serum of women with repeated abortions was reported by Rocklin et al. A review of the literature shows that only an association exists between psychologic disturbances and habitual abortion. Intrauterine infection may result in early pregnancy wastage, and fetal death may result from an acute overwhelming infection. It has long been recognized that congenital anomalies of the uterus have been responsible in some instances for reproductive failure. The gynecologist must consider the time of initiation of an evaluation of a patient with reproductive loss. Any evaluation must include a complete history and a karyotypic analysis with fluorescent banding of both partners, a hysterogram, and a properly timed endometrial biopsy. In the authors’ experience, about 50% of patients with repeated pregnancy loss have no discernible etiologic factor. Subsequent early pregnancy should be carefully monitored in these patients. When no etiologic factor is identfied, a 60-80% fetal salvage rate may be expected.
Kaufman and associates performed hysterosalpingographic examinations of 267 women who had been exposed in utero to diethylstilbestrol (DES). One hundred
eighty-five (69%) of these women demonstrated an abnormality, and 82 women had normal findings. The pregnancy outcome among 93 women who conceived was significantly worse than that found in a control population of 87 women. Abnormalities on the hysterogram included a small T-shaped uterus with cavity constrictions.
The T-shaped uterus is the most commonly noted abnormality. Haney and Hammond recorded various uterine measurements, which revealed a reduced surface area of the endometrium of these patients, as compared with a suitable control population. Nevertheless, there was no increased incidence of pregnancy loss in patients enrolled in the National Cooperative Diethylstilbestrol Adenosis Project. Rosenfeld and Bronson noted that 3 of 25 DES-exposed women reported repeated abortion of three or more pregnancies. One of these patients conceived without therapy and carried to term. Thus, there is little evidence that the uterine defects associated with DES exposure in utero are associated with recurrent early pregnancy wastage.
Reproductive performance of women with müllerian anomalies, Current opinion in obstetrics & gynecology, NCBI PubMed PMID: 17495638, 2007 Jun.
PURPOSE OF REVIEW
This review discusses current diagnostic techniques for müllerian anomalies, reproductive outcome data, and management options in reproductive-age women.
RECENT FINDINGS
Multiple retrospective studies have investigated reproductive outcomes with müllerian anomalies, but few current prospective studies exist. Uterine anomalies are associated with normal and adverse reproductive outcomes such as recurrent pregnancy loss and preterm delivery, but not infertility. Furthermore, unicornuate, didelphic, bicornuate, septate, arcuate, and diethylstilbestrol-exposed uteri have their own reproductive implications and associated abnormalities. Common presentations of müllerian anomalies and current diagnostic techniques are reviewed. Surgical intervention for müllerian anomalies is indicated in women with pelvic pain, endometriosis, obstructive anomalies, recurrent pregnancy loss, and preterm delivery. Although surgery for most uterine anomalies is a major intervention, the uterine septum is preferentially managed with a hysteroscopic procedure. Several recent studies and review articles discuss management of the septate uterus in asymptomatic women, infertile women, and women with a history of poor reproductive outcomes. Current assessment of reproductive outcomes with uterine anomalies and management techniques is warranted.
SUMMARY
Müllerian anomalies, especially uterine anomalies, are associated with both normal and adverse reproductive outcomes, and management in infertile women remains controversial.
Upper genital tract changes and infertility in diethylstilbestrol-exposed women, American journal of obstetrics and gynecology, NCBI PubMed PMID 3717241, 1986 Jun.
A possible relationship of upper genital tract abnormalities in the diethylstilbestrol-exposed woman and infertility was studied.
Six hundred thirty-two women had roentgenography performed. Three hundred sixty-seven of these women were not using contraception and were actively trying to become pregnant.
Term delivery rate after hysteroscopic metroplasty in patients with recurrent spontaneous abortion and T-shaped, arcuate and septate uterus, Gynecologic and obstetric investigation, NCBI PubMed PMID: 21150155, 2011 Dec.
BACKGROUND
To evaluate the improvement of the term delivery rate after hysteroscopic metroplasty surgery in various uterine malformations.
METHODS
170 patients were eligible for the present retrospective case series study. Data were weighted for the number of pregnancies observed (n = 218) after surgical intervention, stratified to the number of previous abortions (at least 2) and type of malformation.
RESULTS
Before surgery, the overall term delivery rate was 5.5%. After surgery, the overall term delivery rate was 59% (absolute benefit increase, ABI, was 54.5) and correlated with the number of previous abortions (69.7% ABI = 64.2, 56.5% ABI = 51 and 26.3% ABI = 20.8 for 2, 3-4 and >4 abortions, respectively; p = 0.0008, log-rank test). Data stratified according to uterine malformations yielded the following term delivery rate: 66.7% for T-shaped uterus, 62.8% for septum/partial septum and 55.6% for arcuate uterus (NS, log-rank test). The number of previous abortions and maternal age also affected the term delivery rate. Their effect upon the term delivery rate, expressed as an odds ratio, was 1.73 (95% CI: 1.20-2.49) and 1.11 (95% CI: 1.05-1.18), respectively.
CONCLUSION
The term delivery rate was about 10-fold higher after surgery. T-shaped uterus surgery yielded the best term delivery rate.
Surgical approach to and reproductive outcome after surgical correction of a T-shaped uterus, Human reproduction (Oxford, England), NCBI PubMed PMID: 21398337, 2011 Jul.
Full text: Human Reproduction, Vol.0, No.0 pp. 1–5, 2011, doi: 10.1093/humrep/der056, March 11, 2011.
BACKGROUND
The aim of this study was to describe the surgical approach to, and evaluate the reproductive outcome of, a T-shaped uterus.
METHODS
The study included 97 women who were eligible for hysteroscopic surgery, by either monopolar or bipolar electrosurgical instruments. All had diagnostic hysteroscopy 2 months afterwards to assess the success of the procedure and determine whether any synechiae were present.
RESULTS
Forty-eight women (49.5%) became pregnant after metroplasty. The overall live birth rate per pregnancy before surgery was 0%; for these patients, it increased to 73%, and their miscarriage rate fell from 78 to 27% (P < 0.05). For all 57 pregnancies in 48 women, the ectopic pregnancy rate was 9% (n = 5), the miscarriage rate 28% (n = 16), the preterm delivery rate 14% (n = 8), the term delivery rate 49% (n = 28) and the live birth rate was 63% (n = 36).
CONCLUSIONS
Hysteroscopic metroplasty improves the live birth rate for women with a T-shaped uterus and a history of primary infertility, recurrent abortion or preterm delivery, although it is not a treatment of infertility.
A T-shaped uterus can be a primary or congenital malformation (related to DES exposure or other causes) or can be acquired due to marginal adhesions with a T-shaped appearance. The description of the surgical technique and the results of this series are important regardless of the cause of the anomaly.
Two-third of our cases had history of DES exposure, and the results of this series are encouraging for all malformations requiring modification of the cavity volume. The question of systematic cervical cerclage during pregnancy after metroplasty remains open.
Click to download the full study.
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.
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.
Click to download the full study.
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.
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.
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.
The impact of uterine shape on pregnancy outcome was also investigated.
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.
Click to download the full study.
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
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.