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 abovementioned 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 prevalence of 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 prevalence of 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
untreated women, was
abortion rate calculated for
each anomaly from series of
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 patients delivering
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..
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Table 1. The American Fertility Society classification of mullerian anomalies (1).
Class I. hypoplasia/agenesis
a. Vagina
l
Class II. Unicornuate:
a. Isolated
b. With
b. Cervic
al
with cavity
d. With
rudimentary
horn
communicating with no cavity
ned
Class IV. Bicornuate
a. Complete (bicolis)
b. Partial (unicolis)
Class V. Septate
-
c. With rudimentary horn–non communicating
e. Combi
Class III. Uterus didelphys
horn
communicating
c. Fundal
d. Tubal
rudimentary
Class VI. Arcuate
a. Complete
b. Partial
Class VII. Diethylstilbestrol related anomalies
–
non