Aust N Z J Obstet Gynaecol 2020; 60: 574–578

DOI: 10.1111/ajo.13182

ORIGINAL MANUSCRIPT

Asherman syndrome: Audit of a single-operator cohort

of 423 cases

Thierry Vancaillie1,2 , Karen Chan1,3, Jinzhu Liu1,2, Rebecca Deans1,3,4,5 and

Elizabeth Howard2

1
Department of Women’s and
Children, University of New Background: The diagnosis of Asherman syndrome, or ‘intra-uterine adhe-
South Wales, Sydney, New South sions’ is often overlooked when the symptoms of amenorrhea and hematometra
Wales, Australia
2
are missing.
Women’s Health and Research
Institute of Australia, Sydney, New Aims: This audit reviews the clinical data of a large cohort of patients treated by a
South Wales, Australia single operator.
3
Department of Gynaecology, Royal
Materials and Methods: From July 1998 till the end of December 2017, 423 pa-
Hospital for Women, Sydney,
New South Wales, Australia tients with intra-uterine adhesions were treated by a single operator. Clinical infor-
4
Sydney Children’s Hospital, Sydney, mation was obtained by review of the medical files and phone interviews.
New South Wales, Australia
5
Results: Amenorrhea was recorded in 163/423 patients (38.5%), 225/423 (53.2%)
Genea, Sydney, New South
Wales, Australia patients did not have amenorrhea and for 35/423 (8.3%) patients the informa-
tion was missing. A hematometra was documented in 19/423 (4.5%) patients.
Correspondence: Prof Thierry
Vancaillie, 97-99 Bathurst Street, level Pregnancy was achieved in 215/246 (87.4%). Patients with stage II disease did best
12, Sydney, NSW 2000, Australia. with a pregnancy rate of 94.5% (P = 0.029).
Email: [email protected]
Conclusion: Asherman syndrome should be considered in any woman with a his-
Conflicts of Interest: The authors
report no conflicts of interest.
tory of miscarriage or postpartum curettage who then fails to conceive again.

Received: 29 May 2019;

KEYWORDS
Accepted: 27 April 2020
Asherman syndrome, infertility, intra-uterine adhesion

INTRODUCTION MATERIALS AND METHODS

Asherman described a syndrome of traumatic amenorrhea. From July 1998 until the end of December 2017, 423 patients
However, amenorrhea is not a necessary element. The term ‘in- with intra-uterine adhesions were treated by a single operator
tra-uterine adhesions’ has been put forward as an alternative and (TV). Ethics approval to contact the patients for completion of
is widely used in the fertility community. their records was obtained (SEHS LHD Ethics committee approval
The aim of this retrospective audit is to present the near-20- number 07/207 24). All patients presented with infertility, with
year experience of a single operator in treating Asherman syn- the majority experiencing secondary infertility with at least one
drome and intra-uterine scarring. Issues about obstetric outcome previous pregnancy. Twenty-one out of 423 (5.0%) patients were
were addressed in collaboration with other colleagues from the nulliparous with surgical trauma or an infectious process as the
department and are published elsewhere.1 presumed cause for the intra-uterine scarring.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited.
© 2020 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal
Australian and New Zealand College of Obstetricians and Gynaecologists

574wileyonlinelibrary.com/journal/anzjog
 1479828x, 2020, 4, Downloaded from https://obgyn.onlinelibrary.wiley.com/doi/10.1111/ajo.13182 by Cochrane Peru, Wiley Online Library on [02/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
T. Vancaillie et al. 575

For longitudinal analysis of the data, patients were empirically

grouped into five-year blocks. The first block up to the end of 2004
also includes the few patients from before the turn of the century
and the last block is only two years long (2016 + 2017). A minimum
of one-year follow-up is available.
For staging of the condition, a system is used, adapted from
the one originally described by Dr. Wamsteker.2,3 His method of
staging is based on evaluation of the proportion of the cavity af-
fected by scarring using hysterosalpingography: stage I = <25%
of the cervical canal and cavity affected; stage II = <50% of the
cervical canal and cavity affected; stage III = <75% of the cervical
canal and cavity affected; and stage IV = more than 75% of the
cervical canal and cavity affected. One exception to this classifi-
cation based on affected surface area is that when the internal
cervical os is fully closed with or without extension into the cer-
vical canal or the isthmus, the patient is classified as having at
least stage II.
The surgical technique for treatment of the condition has been
previously published.4,5 Briefly, both X-ray and trans-abdominal
sonography are used for guidance of the surgical procedure
which consists of resection of scar tissue using hysteroscopic mi-
cro-instruments (Karl Storz, Tuttlingen, Germany).
From July 2008 a hyaluronic acid emulsion was used to fill the
cavity at the end of the procedure in an attempt to promote nor-
mal healing.6,7 In October 2015, platelet-rich plasma introduced
into the uterus at the end of the procedure in patients 38 years
or older with stage III or IV, was added to the treatment algorithm
with the same intention.8
Patients with stage I or II were allowed to attempt concep-
tion immediately after treatment. Those with stage III or IV
F I G U R E 1 Xray images of a patient with stage III Asherman
were scheduled for a sonohysterogram if the procedure was
at the start (A) and the end (B) of the first of three procedures
deemed complete, or a repeat synechiolysis if the treatment required to treat the condition.
was deemed incomplete. Some patients with stage III or IV
underwent sequential procedures before being allowed to at- pregnancy outcome (SPSS, version 25, IBM, Armonk, NY, USA
tempt conception.9 The number of procedures varied from two 2018, and R, version 3.6.2, r-project.org, 2019).
to five. Figure 1A shows the hysterosalpingogram of a patient
with stage III disease during the early stages of the synechioly-
RESULTS
sis and Figure 1B shows the same patient at the end of the
first procedure. A follow-up procedure was scheduled in this
Age distribution
particular patient.
Medical management consisted of doxycycline 100 mg daily Figure 2 shows a bar graph of the age distribution of patients
for a total of seven days, starting two days prior to the planned within each time period.
surgery. In some cases, the patient’s menstrual cycle was manipu- The average age of the first block of patients (n = 38) was 33.9,
lated to accommodate scheduling, using a standard combination the average age of the last block (n = 133) was 36.7 (P = 0.008;
oral contraceptive pill continuously until seven days prior to the t-test). Correlation between age and staging of the condition did
scheduled procedure. All patients would take 2 mg of oestradiol not show any statistically significant trend (P = 0.238; one-way
orally starting on day two of menses and continue until ten days ANOVA). There were no patients under the age of 28 in the stage
after intervention. IV group.
Pregnancy was defined as an ultrasound demonstrating a
pregnancy regardless of location or viability.
Clinical presentation
Analyses were performed by descriptive statistics for clini-
cal presentation and patient demographics and by analysis of The amenorrhea, dysmenorrhoea and hematometra rates are
variance (ANOVA), t-test, χ2 tests and multivariate analysis for listed in Table 1
 1479828x, 2020, 4, Downloaded from https://obgyn.onlinelibrary.wiley.com/doi/10.1111/ajo.13182 by Cochrane Peru, Wiley Online Library on [02/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
576 Audit of 423 Asherman cases

TABLE 2 Trigger events

n %

Miscarriage 210 49.6

Postpartum intervention 102 24.1
Hysteroscopic surgery 27 6.4
Laparotomy + myomectomy 5 1.2
B Lynch suture (or similar) 4 0.9
Other (eg uterine embolisation) 7 1.7
Multiple triggers 31 7.3
Missing data 37 8.8
Total 423 100

Prevalence of events thought to be responsible for scar formation. In

some cases, the trigger event was not clear or there were several po-
tential candidate incidents. These cases were grouped in the category
of multiple triggers.
FIGURE 2 Age distribution of patients over time.

TABLE 3 Pregnancy† rate per block of time

Initiating event
n %
Information on a potential trigger for adhesion formation is avail-
2004 22/27 81.5
able in 386 of the 423 (91.3%) patients (Table 2).
2005–2009 44/55 80.0
The average delay between the initiating event and the pre-
2010–2014 80/84 95.2**
sentation for management of 226/423 cases with available infor-
2015–2017 56/66 84.8
mation, was 16.1 months. Patients with stage IV had a longer delay
of 31.2 months (P < 0.01; t-test). Patients who had been surgically There are 14 files with inadequate information on the date of concep-
treated elsewhere, unsuccessfully, prior to referral, had an aver- tion post-treatment. The total number of patients available for analy-
sis is therefore 232.
age of ten months longer delay prior to treatment (23.0 months vs
†Pregnancy is defined as an ultrasound demonstrating a pregnancy
13.3 months; P < 0.001; t-test). regardless of location or viability.
**
P = 0.037 (χ2 test).

Pregnancy rate
A generalised mixed effects regression model was used to de-
Conception outcome is available for 246 of the 424 (58.0%) cases. termine the odds ratio of pregnancy for each of the Asherman
Pregnancy was achieved in 215 of these 246 women, representing syndrome stages after adjusting for maternal age and the num-
an overall success rate of 87.4%. If all missing data are assumed to ber of corrective interventions, keeping participant ID as a
represent failures, the success rate was 50.8%. The pregnancy rate random effect.
over time (Table 3) increased from 81.5% in 2004 and 80.0% in 2009, The estimates of odds ratios are relative to women with stage
to 95.2% in 2014 (P = 0.037; χ2 test). The pregnancy rate for the last I Asherman syndrome. Women with stage II Asherman syndrome
cohort is 84.8%, but there is a shorter observation time for them. had an increased odds of becoming pregnant of 2.07 (95% CI:
Those successful in achieving conception presented with 1.11–3.84) times that of women with stage I; stage III patients had
an average age of 34.73 years old vs 36.99 for those who were an increased odds of becoming pregnant of 1.79 times that of
unsuccessful (P = 0.011; t-test). Patients with stage II Asherman stage I; however, this was not statistically significant (95% CI: 0.93–
experienced the best outcome with a conception rate of 94.5% 3.46). There was a statistically significant association between ma-
2
(P = 0.039; χ test) (Table 4). ternal age and the odds of becoming pregnant, which decreased

TABLE 1 Clinical presentation

Amenorrhea % Dysmenorrhoea % Hematometra %

Present 163 38.5 101 23.8 19 4.5

Absent 225 53.2 261 61.8 273 64.5
Missing data 35 8.3 61 14.4 131 31.0
Total 423 100 423 100 423 100

The incidence of amenorrhea, dysmenorrhoea (increased or de novo) and hematometra within the entire cohort. The relatively high number of
missing data for the presence of hematometra is due to the fact that sonography is not routinely performed prior to treatment.
 1479828x, 2020, 4, Downloaded from https://obgyn.onlinelibrary.wiley.com/doi/10.1111/ajo.13182 by Cochrane Peru, Wiley Online Library on [02/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
T. Vancaillie et al. 577

TABLE 4 Pregnancy† rate per stage of disease randomised controlled trials. Results and discussions should be
accordingly interpreted.
Stage n %
Patients with stage II Asherman achieve the best result (94.5%),
1 46/54 85.2
surpassing the outcome of treatment of stage I (85.2%). The im-
2 86/91 94.5**
pact of intra-uterine scarring on fertility is more complex than our
3 61/71 85.9 current understanding. Stage II Asherman cases represent those
4 20/27 74.1 patients with 50% of surface affected or less, but also those pa-
Total 213/243 87.7 tients with occluded internal os, yet when the total affected area
The staging of the condition was unclear from the notes in three cases. is <25%. The presence of scar tissue within the isthmus, even if
The total number of patients with available staging of the condition the internal os is not completely closed, will induce amenorrhea
therefore is 243. in most cases without the development of a hematometra. The
†Pregnancy is defined as an ultrasound demonstrating a pregnancy
presence of a hematometra is uncommon (4.5%). It is therefore
regardless of locations or viability.
**
P = 0.039 (Pearson’s χ2 test comparing stage II to the three hypothesised that the presence of intra-uterine scar tissue im-
other stages). pedes normal endometrial function.
It is likely that women with intra-uterine scarring, but with
by a multiple of 0.92 (95% CI: 0.87–0.98) per year of age. There preserved endometrial function are fertile and may achieve con-
was no clinical or significant association between the number of ception. However, the question remains whether a pregnancy
interventions and the odds of a woman with Asherman syndrome conceived under those circumstances is at a higher risk for mis-
becoming pregnant (1.01; 95% CI: 0.87–1.18). carriage.10 The stage I group likely includes patients in whom the
The conception rate for those patients who developed presence of minimal scar tissue is mostly an incidental finding and
intra-uterine adhesions secondary to triggers, unrelated to infertility is due to other factors.
pregnancy (32/386 patients with documented trigger event), The low conception rate (43.8%) in patients who developed in-
is only 43.8%. tra-uterine scarring secondary to a trigger unrelated to pregnancy
is in line with other publications.11
Surgical management of intra-uterine scarring requires exper-
DISCUSSION tise. In the interest of improved patient outcomes, an argument
should be made for pooling of cases into dedicated treatment
This retrospective audit has significant limitations due to the dif- centres. An intra-uterine contraceptive device or a custom-made
ficulty in collecting follow-up data. However, the focus of this audit balloon are traditionally inserted12–14 as a mechanical barrier at
has been the clinical presentation and its evolution over time. completion of a synechiolysis.15 We choose not to use a true phys-
The data from this cohort show there is no typical presen- ical barrier. Our treatment philosophy is simple: (i) identify the
tation of Asherman syndrome. Amenorrhea despite ovulation, scar tissue; (ii) remove the scar tissue; and (iii) promote normal
was present in less than half the patients. Too often this leads healing. Figure 3 shows the hysterosalpingography of a patient
to a delay in diagnosis. The average delay in this cohort is 16
months, part of which can be explained by breastfeeding-induced
physiologic amenorrhea.
The increasing age of the Asherman patients reflects the
general trend of delaying pregnancy in Australia. However, the
ageing Asherman population does not present with a more
advanced stage of the condition. On the other hand, younger
patients are more likely to be successful in achieving preg-
nancy after treatment. Therefore, age is an important factor in
attaining success.
Patients developing intra-uterine scarring after a miscarriage
(first and second trimester) vs within the postpartum, have the
same chance of achieving success after treatment. However, it is
our impression that scarring more likely will involve the corpus
after a postpartum trigger, whereas the isthmus is the more likely
location after a miscarriage. Dealing with isthmic synechiae is
technically less challenging.
F I G U R E 3 Xray image showing the imprint of a
The surgical technique with hysteroscopic micro-instru-
levonorgestrel intra-uterine device, which had been placed
ments, the use of X-ray, the addition of hyaluronic acid or after synecholysis at a different institution, several weeks after
platelet-rich plasma, have not been tested via prospective removal of the device.
 1479828x, 2020, 4, Downloaded from https://obgyn.onlinelibrary.wiley.com/doi/10.1111/ajo.13182 by Cochrane Peru, Wiley Online Library on [02/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
578 Audit of 423 Asherman cases

treated elsewhere for removal of intra-uterine adhesions in whom 4. Broome JD, Vancaillie TG. Fluoroscopically guided hysteroscopic
a levonorgestrel containing device was inserted. The X-ray was division of adhesions in severe Asherman syndrome. Obstet
Gynecol 1999; 93: 1041–1043.
taken several weeks after the device was removed, at the start of
5. Thomson AJ, Abbott JA, Kingston A et al. Fluoroscopically guided
the first of three procedures this patient required to restore the synechiolysis for patients with Asherman's syndrome: menstrual
uterine cavity. The phantom outline of the device is clearly identi- and fertility outcomes. Fertil Steril 2007; 87: 405–410.
fiable with near complete obliteration of the surrounding uterine 6. De Angelis B, D’Autilio MFLM, Orlandi F et al. Wound healing: in
vitro and in vivo evaluation of a bio-functionalized scaffold based
cavity. It is clear that insertion of the device did not achieve its
on hyaluronic acid and platelet-rich plasma in chronic ulcers. J
intended goal. Clin Med 2019; 8: 1486.
The addition of hyaluronic acid emulsion was intended to im- 7. Nyman E, Henricson J, Ghafouri B et al. Hyaluronic acid acceler-
prove the outcome of patients, especially those with stages III and ates re-epithelialization and alters protein expression in a human
wound model. Plast Reconstr Surg Glob Open 2019; 7(5): e2221.
IV. However, a significant improvement was not achieved.
8. Aghajanova L, Houshdaran S, Balayan S et al. In vitro evidence
In conclusion, intra-uterine adhesions are not always asso- that platelet-rich plasma stimulates cellular processes involved
ciated with clinical symptoms. However, their presence should in endometrial regeneration. J Assist Reprod Genet 2018; 35:
be considered in any woman presenting with infertility after 757–770.
9. Hanstede MM, van der Meij E, Goedemans L, Emanuel MH.
a miscarriage or postpartum curettage. Treatment should be
Results of centralized Asherman surgery, 2003–2013. Fertil Steril
performed by experienced operators in dedicated centres. The
2015; 104: 1561–1568.e1.
surgical method used, namely endoscopic mechanical micro-in- 10. Hooker AB, Lemmers M, Thurkow AL et al. Systematic review and
struments under direct vision as well as sonographic and image meta-analysis of intrauterine adhesions after miscarriage: prev-
intensifier control, yields good results. alence, risk factors and long-term reproductive outcome. Hum
Reprod Update 2014; 20(2): 262–278.
11. Song D, Liu Y, Xiao Y et al. A matched cohort study comparing the
outcome of intrauterine adhesiolysis for Asherman's syndrome
ACKNO WL EDGM EN TS
after uterine artery embolization or surgical trauma. J Minim
The authors wish to acknowledge the contribution of Paul Invasive Gynecol 2014; 21: 1022–1028.
12. Orhue AA, Aziken ME, Igbefoh JO. A comparison of two adjunc-
Stevenson in reviewing the statistical calculations of this audit.
tive treatments for intrauterine adhesions following lysis. Int J
Gynaecol Obstet 2003; 82(1): 49–56.
13. Shi X, Saravelos SH, Zhou Q et al. Prevention of postoperative ad-
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