Reproductive performance of women with müllerian anomalies

uterinecongenitalanomalies
Classification of the anomalies of Müllerian duct developed by American Fertility Society (1988) and reproduced by Troiano and McCarthy.

Abstract

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.

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Infertility and upper genital tract changes in DES-exposed women

infertility-woman
In this 1986 study, more than 70% of the DES-exposed females showed abnormal hysterosalpingograms.

Abstract

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.

  • One hundred thirty-four (36%) of these women reported difficulties conceiving for a period of 1 or more years.
  • Seventy-three percent of these women had abnormal hysterosalpingograms.
  • The frequency of abnormal x-ray films in the women who did conceive within 1 year was essentially the same (74%). Furthermore, a similar number of women with normal x-ray films (37%) had difficulty conceiving as did women with abnormal x-ray films (36%).
  • When specific hysterosalpingographic abnormalities were related to the presence or absence of infertility, it was observed that the presence of a constriction of the upper uterine cavity resulted in a 2.26-times greater likelihood that a woman would not be able to conceive.
  • If a T-shaped uterus was found in association with constriction of the upper uterine cavity, the odds ratio for inability to conceive was found to be 2.63.
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Hysteroscopic metroplasty: term delivery rate after T-shaped uterus surgery

Term delivery rate after hysteroscopic metroplasty in patients with recurrent spontaneous abortion and T-shaped.

Abstract

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.

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Surgical correction of a T-shaped uterus and DES Daughters pregnancy outcome

image of 3D-T-shaped-uterus
Reconstruction in 3D-US of T-shaped uterus. 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.

Abstract

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.

Discussion

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.

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Outcome of IVF in DES-exposed daughters: experience in the 90s

image of ivf-treatment-post
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.

Click to download the full study.

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Beneficial effect of hysteroscopic metroplasty on the reproductive outcome in a T-shaped uterus

image of Hysterosonography-of-T-shape
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.

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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.

Click to download the full study.

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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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