Uterine anomalies – when to treat? , when to Circle?.

E. Shalev, MD

Department of Obstetrics and Gynecology, Haemek Medical Center, Afula. Faculty of Medicine, Technion - Israel Institute of Technology , Haifa, Israel.

Presented At The 2nd World Congress On Controversies In Obstetrics Gynecology & Infertility. Paris, France, September 6-9, 2001.

Reprints request; Prof’ E. Shalev Head, Department of Obstetrics and Gynecology, Haemek Medical Center, Afula Israel 18101

Tel: 972-4-6524031

Fax: 972-4-6524032

Introduction

Searching for anatomic factors is an obligatory step in the workup of patients presenting with infertility, history of recurrent pregnancy loss and unexplained preterm birth. When uterine anomaly is found in a woman with a history of recurrent pregnancy loss , proper surgical treatment should be considered . However, controversies still exist regarding the benefit of surgical uterine correction in patients suffering from primary infertility and the benefit of cervical cerclage in women with uterine anomaly. Furthermore, following incidental findings of uterine anomaly, regardless of insufficient data to support it, the question of “prophylactic” resection of uterine septa and/or cervical cerclage has been raised. In order to address the above-mentioned controversies we must first review the accepted classification of uterine anomalies, accuracy of diagnosis, prevalence of anomalies and the impact on reproduction with available treatment options.

Classification: Since the first description in 1675, various classification systems of mullerian anomalies have been designed. The current accepted system presented in Table 1. is the one adopted in 1988 by the American Society for Reproductive Medicine (1). This classification is a modification of Buttram and Gibbons classification described in 1979 (2). The classification is based on the degree of failure of normal development, grouping anomalies with similar clinical manifestation and treatment together with prognosis for pregnancy outcome.

Diagnosis: For many years HSG was the gold standard for diagnosis and investigation of uterine anomalies. The major advantage of this technique is the ability to assess concomitantly uterine cavity and tubal patency. However, HSG cannot reliably differentiate between a septate and a bicornuate uterus. Furthermore, HSG may miss minor uterine defects. Diagnostic hysteroscopy is superior to HSG in the evaluation of the uterine cavity. This, together with the possibility of simultaneous treatment has made the procedure the gold standard for investigating uterine anomalies. With concomitant guidance of transabdominal ultrasound (TAS), the procedure is ideal for surgical correction of even complex uterine anomalies (3). The rate of complications with the combined technique has been proved to be very low (4). The drawbacks of hysteroscopy are that it does not provide information on patency of the fallopian tubes nor on the external surface of the uterus. The simplest non-invasive imaging technique used for detecting uterine anomaly is ultrasonography. This technique can detect most uterine anomalies since it demonstrate external outline and the presence of two echogenic endometrial cavities (5). Transvaginal ultrasound (TVS) provides better mean for diagnosis and assessment of the septate uterus with sensitivity of 100% and specificity of 80% (6). Additional information concerning the uterine cavity and patency of the tubes can be obtained by instillation of liquid (saline) or contrast medium into the uterine cavity (hystero-sonography). Further improvement in the accuracy of assessing uterine anomalies has been observed using three-dimensional ultrasound with sensitivity and specificity of 100% compared to specificity of 95 % for TVS (7). Trans-abdominal sonography can also be used to guide complicated hysteroscopic procedures (8).

The availability of phased array coils and ultra-fast MR pulse sequences have increased the value of MR imaging in the evaluation of uterine anomalies. MRI can reliably characterize the nature of tissue separating uterine cavities and demonstrate the size and structure of each horn and cervix. Sensitivity and specificity of 100% was reported for MRI in the diagnosis of septate uterus (6). However, high cost and inaccessibility confined the technique to referral centers in research settings.

Laparoscopy provides the possibility of complete diagnostic workup and occasionally treatment of infertility. Laparoscopy can also be used for guidance of hysteroscopic metroplasty (9). The combination of laparoscopy and hysteroscopy permits correct classification and is still the gold standard for evaluating uterine anomalies.

Prevalence: the reported prevalenceof uterine anomalies varies enormously and ranges between 1 in 10 to 1 in 1600 women in different studies. This variation is due to the generally low prevalence of these anomalies, different rates in different populations groups, difficulties in diagnosis and the various techniques and classification systems. Based on Medline search (up to 1996) involving 22 studies, the prevalence of uterine anomalies in the general population was 0.5% (1 in 201). Anomalies were identified in 0.17% (1 in 594) of fertile women and in 3.5% (1 in 29) of infertile women (10). In a prospective study, ultrasound investigation was performed on 2065 women (girls and adults) for reason unrelated to uterine anomalies (11). The rate of uterine anomalies found in this apparently general population was 0.387% (1 in 259). These rates (0.4-0.5%) are 10 times less than the estimated 5% prevalence of uterine malformation in the general population, calculated from analyzing more recent studies (12). While prevalence of 0.5 % in general population seems to be an underestimation, probably due to under-diagnosis, the 5 % rate may be an overestimation due to patient selection. The true prevalence probably lies in between. The analysis of prevalence of uterine anomalies in fertile women in the two most recent reports varied from 0.17% (10) to 3 % (12). This wide range cannot be the result of true difference and must be a fault in study design. In a retrospective longitudinal study of a total of 3181 women (1289 fertile) the prevalence of uterine malformation in the fertile women was found to be 3.8% (13). Analyzing two studies with fair number of patients (>500) where the diagnosis of uterine anomalies was confirmed with endoscopic means (13,14) malformation was found in 3.1 % of women. For the purpose of evaluation the impact on fertility we will have to accept this number.

Distribution between different types : The reported distribution between the different types varied probably due to the different diagnostic modalities in different studies and the ambiguity in classification. In a recent review (15) the mean incidence of arcuate uterus was found to be 18.3% (range of 4-59.8%) , of septate uterus 34.9% (15-54.2%), of bicornuate uterus 26% (14.8-40%), of Unicornuate 9.6% (2.4-13.7%), of didelphys uterus 8.2% (0.8-26.8%) and of agenesis 2.9% (range of 2.9-9.3%). More than half of the patients had either septate or arcuate uteruses, both amenable to hysteroscopic treatment. In previous reviews the distribution was quit similar except for a higher rate of bicornuate uterus as opposed to lower rates of septate uterus (12) or arcuate uterus (10).

Implications and impact of treatment: The association of uterine anomalies with obstetrical complications has been long recognized. Early and late recurrent pregnancy loss, preterm labor and prematurity and abnormal fetal presentation are the major problems encountered. However, a large proportion of women with uterine malformation have no obstetrical problems. Since there is no large prospective study which follows the obstetrical outcome of these women, the only way to investigate this association is to compare the prevalence of malformation between a population with normal outcome to a population with various complications. In addition, the incidence of each complication should be compared between women with normal uterus to those with anomalous uterus. These, together with results of treatment, will give us an indirect idea of the implication of the various anomalies on various complications.

Infertility: The prevalenceof uterine malformation in infertile women ranges from 1 to 26 % with a mean of 3.4 % (15). This rate is not different from the rate in the fertile population (3.1%). It is quite difficult to assess the true prevalence of infertility in women with an anomalous uterus. Out of 176 patients with mullerian defects, infertility was reported in 34 (19.3%). In 10 of these 34, infertility could not be explained (29.4%). The rate of infertility is close to the observed 15% rate in the general population, however, the rate of unexplained infertility is higher than expected (16). Similarly, high prevalence (40%) of unexplained infertility was found in patients with secondary infertility but not in patients with primary infertility (17). In the later the rate was 19.6%, which is similar to that observed in the general population. The pregnancy rate in assisted reproduction in women with uterine anomalies was examined in 24 patients with acceptable results (18). The clinical pregnancy rate was 37.3% per embryo transfer and 70.8% per patient. In the septate uterus, the pregnancy rates per embryo transfer and per patient were 35.7% and 100 % respectively. It can be concluded that the presence of uterine anomaly per se does not reduce the chance of conception and thus conception rate cannot be significantly improved after metroplasty. The only rational to perform a prophylactic procedure would be in infertile elderly patients particularly prior to assisted reproduction not in order to increase fertility rates but to ensure successful pregnancy outcome.

Recurrent pregnancy loss: Uterine anomalies , particularly the septate uterus, has been associated with repeated pregnancy loss. Mean prevalence rate of 12.6% for uterine anomalies was calculated from 12 studies on 4506 women with recurrent abortions (15). The prevalence varied between studies from 1.8% to 37.6%. This rate is significantly higher than the one expected in the general population. The incidence of uterine malformation seems to be particularly high (43%) in women with late abortion and immature deliveries (12). In order to assess the prevalence of recurrent loss in women with uterine anomalies the result from untreated series have to be analyzed. The mean abortion rate calculated for each anomaly from series of untreated women, was the lowest (22.7%) in patients with arcuate uterus and the highest (44.3%) in patients with untreated septate uterus. The mean abortion rate for other anomalies was 32.2% in untreated didelphys uterus, 36% in bicornuate, and 36.5%, in unicornuate uterus (15). Regarding the time of miscarriage, it is interesting to note the findings of one study which reported 21.6% early pregnancy losses, suggesting the presence of defects that interrupt the normal early embryo development (13). It is quite clear now why most authors accept the notion that recurrent pregnancy loss is the most obvious indication for treatment of patients with uterine malformation. This notion has led to the question of whether or not to treat these patients from their first pregnancy (17). In order to assess the rate of pregnancy loss beginning with their first pregnancy, 176 patients were followed throughout their pregnancies (20). Similar abortion rates (31% and 36%) similar preterm delivery rates (24 and 18%) and same term delivery rates (45% and 44%) were observed in their first and consequent pregnancies. If hysteroscopic metroplasty can help to avoid pregnancy loss, these results will, at least theoretically, justify prophylactic treatment.

Result of metroplasty: Reviewing pregnancy outcome in 7 studies before and following metroplasty, the most significant change was in the rate of abortion (86.4% vs. 16.4), Term deliveries (3.3 vs. 76.2%) and livebirth (6.1% vs. 83.2%). The difference in preterm deliveries was less significant 9.8% before correction as opposed to 6.8% following the procedure (15). It seems that improvement in live births, which is the goal of treatment, was achieved by reducing pregnancy loss and not by decreasing preterm births. The low preterm births, before and obviously following metroplasty, is a challenge to the association of the anomalies with preterm births (21).

Preterm deliveries: Uterine anomalies have been found in 16% of patientsdelivering before 37 weeks (22). The preterm delivery rate in patients with uterine malformation varied from 7.5% in patients with arcuate uterus to 23% and 28% in the bicornuate and didelphys uterus respectively. The mean rates for the unicornuate and septate uterus were 16% and 22.4% respectively (15). From these numbers it is clear that patients with arcuate uterus will probably not benefit from surgical treatment. It seems that patients with septate uterus , bicornuate uterus and particularly didelphys uterus deserve special concern regarding risk of preterm delivery. However, management in high risk obstetric setting does not obviate the potential benefit of metroplasty for patients with septate uterus (23).

Cervical cerclage : Cervical incompetence was diagnosed by HSG in 23% to 41% of patients with uterine anomalies (21,24,25). At least in one study, improvement in pregnancy outcome was not observed following cerclage except with proven cervical incompetence (25). Others have observed a decrease in preterm births following cerclage regardless of cervical competency (21,24). Interestingly, in recent study, patients with uterine anomalies were randomly assigned to cerclage or conventional tocolytic therapy (26). The preterm birth rate was similar between patients with or without cerclage or with or without cervical incompetence. The only difference was a high rate of miscarriage (21%) in patients with uterine anomalies and cervical incompetence that were not treated. There is not enough data to justify cervical cerclage without history or diagnosis of cervical incompetence. These women may benefit from sonographic monitoring of cervical length (27).

Conclusions: Uterine anomalies are clearly associated with recurrent pregnancy loss and decrease live births. Pregnancy outcome is improved following hysteroscopic metroplasty. This procedure is recommended for patients with uterine anomalies amenable to the hysteroscopic procedure with a history of pregnancy loss and poor obstetric outcome. The procedure is not indicated for treatment of infertility but should be advised to women undergoing assisted reproduction in order to ensure pregnancy outcome. The procedure should be presented to women with septate uterus (not arcuate) prior to their first pregnancy as a prophylactic treatment. Patients in their first pregnancy, with incidental finding of anomalous uterus should be followed closely by monitoring cervical length. Cervical cerclage is indicated in patients with anomalous uterus and with history or diagnosis of cervical incompetence..

References

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Class I. hypoplasia/agenesis
  1. Vaginal
  2. Cervical
  3. Fundal
  4. Tubal
  5. Combined
/ Class II. Unicornuate:
  1. Isolated
  2. With rudimentary horn - communicating
  3. With rudimentary horn–non communicating with cavity
  4. With rudimentary horn – non communicating with no cavity

Class III. Uterus didelphys / Class IV. Bicornuate
  1. Complete (bicolis)
  2. Partial (unicolis)

Class V. Septate
  1. Complete
  2. Partial
/ Class VI. Arcuate
Class VII. Diethylstilbestrol related anomalies

Table 1. The American Fertility Society classification of mullerian anomalies (1).