The primary purpose of this paper is to assess the efficacy of the use of the intrauterine device (IUD) as an adjunctive treatment modality, for intrauterine adhesions (IUAs). All eligible literatures were identified by electronic databases including PubMed, Scopus, and Web of Science. Additional relevant articles were identified from citations in these publications. There were 28 studies included for a systematic review. Of these, 5 studies were eligible for meta-analysis and 23 for qualitative assessment only. Twenty-eight studies related to the use of IUDs as ancillary treatment following adhesiolysis were identified. Of these studies, 25 studies at least one of the following methods were carried out as ancillary treatment: Foley catheter, hyaluronic acid gel, hormonal therapy, or amnion graft in addition to the IUD. There was one study that used IUD therapy as a single ancillary treatment. In 2 studies, no adjunctive therapy was used after adhesiolysis. There was a wide range of reported menstrual and fertility outcomes which were associated with the use of IUD combined with other ancillary treatments. At present, the IUD is beneficial in patients with IUA, regardless of stage of adhesions. However, IUD needs to be combined with other ancillary treatments to obtain maximal outcomes, in particular in patients with moderate to severe IUA.
Intrauterine adhesions (IUAs) or Asherman’s syndrome has been reported and studied for more than a century. This disease occurs mainly as a result of the trauma of dilatation and curettage, postabortal infection, hypoestrogenism, genital tuberculosis, and previous uterine surgery, producing partial or complete obliteration in the uterine cavity and/or the cervical canal, resulting in conditions such as amenorrhea, hypomenorrhea, infertility, or recurrent pregnancy loss [
This systematic review and meta-analysis was conducted in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines.
All eligible studies were identified on computerized databases (PubMed, Scopus, and Web of Science), using the keywords “Asherman syndrome,” “Asherman’s syndrome,” “Fritsch syndrome,” “gynatresia,” “intrauterine adhesions,” “intrauterine synechiae,” “synechia uteri,” and “uterine synechiae.” The search included studies from the earliest publication date to February 2014 in English publications but some IUD use in Chinese patent that translated to English. Additional relevant articles were identified from citations within these publications.
Because of the lack of randomized control trials (RCT), observational studies (prospective/retrospective cohort and case-control studies) were included for review. Reviews and case reports were excluded from this systematic review. Studies were selected by electronic databases including PubMed, Scopus, and Web of Science. First, eligibility was assessed based on the title and abstract. Full manuscripts were obtained for all studies that were selected. In the second step, examination of the full manuscript was carried out to study the eligibility of the study. Most of the studies used multiple ancillary treatment methods to prevent readhesions in the treatment of IUAs. There was no single study that was solely focused on comparing the efficacy of IUD as an adjunctive therapy in patients with IUAs following the adhesiolysis procedure. Therefore, we evaluated and examined the outcomes of all included studies that used the following various techniques of the adhesiolysis procedure such as Foley catheter, hyaluronic acid gel, hormonal therapy, or amnion graft in addition to the IUD.
The primary outcomes measure of the IUDs as ancillary treatment following adhesiolysis was identified with the management of IUAs. Secondary meta-analyses were performed to estimate the association between outcomes of IUA with relation of classification of IUA, type of IUD, and duration course of IUD. Subsequently in the second analysis for menstruation, pregnancy, and live birth rates.
From each study, the following data was extracted: first author, year of publication, type of study, classification of IUA, the number of participants, mean age, stage of adhesion, surgical techniques of adhesiolysis, type of IUD, duration course of IUD, ancillary treatment used (hormone therapy, Foley catheter, hyaluronic acid gel, and amnion graft), and complications. The primary outcomes of interest included clinical outcomes (normal or improvement in menstrual flow, pregnancy, and live birth rates). Studies were eligible for meta-analysis if the methods of follow-up were adequate for the outcome and necessary statistics could be retrieved.
Statistical analyses were performed by using the Review Manager (RevMan) version 5.0 software (The Cochrane Collaboration, Copenhagen, Denmark) and SAS 9.3 (SAS Institute, Cary, NC, USA). The Mantel-Haenszel method was conducted for pooling of dichotomous data and presented as odds ratio (OR) with 95% confidence interval (CI). The presence of statistical heterogeneity was calculated using the
Searches identified 1314 publications. The search strategy yielded 605 from PubMed, 310 from Scopus, and 399 from Web of Science citations including 750 duplicates. A flow chart showing search results appeared in Figure
Flow chart showing search results.
Characteristics of the included studies are given (Table
Characteristics of included studies.
Source, year | Study type | Number of |
Classification | Adhesion stage | Surgical technique | IUD | HT | FC | Normal/improved |
Conception rate |
Live birth rate |
---|---|---|---|---|---|---|---|---|---|---|---|
Caspi and Perpinial, 1975 [ |
NR | 80 (74 followed up) |
NR | NR | Vaginal approach (long curved scissors) | Yes | Yes | No | NR | 62/74 (83.7) | 40/62 (64.5) |
|
|||||||||||
March and Israel, 1976 [ |
NR | 10 |
NR | NR | Hysteroscopic miniature scissors | Yes | Yes | Yes | 10/10 (100) |
1/1 (100) | 1/1 (100) |
|
|||||||||||
March and Israel, 1981 [ |
NR | 38 |
NR | Mild ( |
Hysteroscopy with miniature scissors | Yes (35) | Yes | Yes | NR | (87.2) | (87.2) |
|
|||||||||||
Ismajovich et al., 1985 [ |
NR | 51 |
NR | Mild ( |
Hysteroscopic scissors, uterine dilator | Yes | No | No | 46/51 (90) |
46/51 (90) | 40/46 (85) |
|
|||||||||||
Fedele et al., 1986 [ |
Retrospective | 31 |
NR | Mild ( |
Hysteroscopic scissors | Yes | Yes | No | 21/31 (67.7) |
13/27 (40.7) | 13/27 (40.7) |
|
|||||||||||
Valle and Sciarra, 1988 [ |
Retrospective | 187 |
AFS | Mild ( |
Hysteroscopy and sharp dissection with hysteroscopic scissors (hysterosalpingography guided) | Yes (151) | Yes | No | 134/151 (88.2) |
143/187 (76.4) | 114/143 (79.2) |
|
|||||||||||
Bellingham, 1996 [ |
NR | 17 (16 followed up) |
NR | NR | Hysteroscopic division under US guidance | Yes | Yes | No | 11/13 (84.6) |
8/10 (80) | 8/10 (80) |
|
|||||||||||
Roge et al., 1997 [ |
Retrospective | 54 (52 followed up) (NR) | AFS | Mild ( |
Hysteroresectoscopy with resection electrode needle (under US guidance) | Yes | Yes | Yes | NR | 34/52 (65.3) | 24/34 (70.5) |
|
|||||||||||
Chen et al., 1997 [ |
NR | 7 |
March | Severe | Hysteroresectoscopy with resection electrode needle | Yes | Yes | No | 7/7 (100) |
3/4 (75) | 2/3 (66.6) |
|
|||||||||||
Feng et al., 1999 [ |
Retrospective cohort study | 365 |
Sugimoto | NR | Hysteroscopy with microscissors and biopsy forceps | Yes | Yes | No | 294/351 (83.7) |
156/186 (83.8) | NR |
|
|||||||||||
Ozumba and Ezegwui, 2002 [ |
NR | 50 (44 followed up) | NR | NR | Uterine sound and occasionally uterine dilators | Yes | Yes | No | 34/44 (77.2) |
4/44 (9) | NR |
|
|||||||||||
Orhue et al., 2003 [ |
NR | 110 |
NR | NR | Blind adhesiolysis under US guidance | Yes |
Yes | Yes |
32/51 (32.7) |
14/51 (27.5) | 6/14 (42.8) |
|
|||||||||||
Alborzi et al., 2003 [ |
Prospective | 30 |
ASRM | Stage I ( |
Hysteroscopy scissors (under vision of laparoscopy) | Yes | Yes | No | 30/30 (100) |
19/30 (63.3) | 15/30 (50) |
|
|||||||||||
Zikopoulos et al., 2004 [ |
NR | 46 |
AFS | Stage I ( |
Resection using electrode needle ( |
Yes | Yes | No | 13/14 (92.85) |
35/46 (76.1) | 20/46 (43.5) |
|
|||||||||||
Efetie, 2006 [ |
Retrospective | 71 |
NR | NR | Hysteroscopy, uterine sound | Yes | Yes | Yes | 34/71 (47.9) |
8/71 (11.3) | NR |
|
|||||||||||
Fumino et al., 2007 [ |
NR | 47 |
AFS | I ( |
Pushing via tip of hysteroscopy ( |
No | No | No | NR | 20/47 (42.5) | NR |
|
|||||||||||
Shokeir et al., 2008 [ |
Retrospective | 61 |
AFS | Stage II ( |
Hysteroscopy with electrode needle | Yes |
Yes | No | NR | 10/40 (40) | 2/10 (20) |
|
|||||||||||
Yasmin et al., 2007 [ |
Descriptive study | 20 (19 followed up) (26.1) | NR | Mild ( |
Blunt and resectoscopic dissection | Yes | Yes | Yes | 18/19 (94.7) |
2/19 (10.5) | 1/2 (50) |
|
|||||||||||
Yu et al., 2008 [ |
Retrospective | 85 |
ESH |
Mild ( |
Hysteroscopy using electrode needle or loop | Yes | Yes | No | 46/62 (74.2) |
39/85 (45.88) | 25/39 (64.1) |
|
|||||||||||
Pabuccu et al., 2008 [ |
Prospective, randomized trial | 71 |
AFS | Stage III | Sharp hysteroscopic division under US guidance | Yes | Yes | No | NR | Group 1: 17/36 |
Group 1: 10/36 |
|
|||||||||||
Roy et al., 2010 [ |
Retrospective | 96 (89 followed up) |
ESH, |
I ( |
Hysteroscopic monopolar with Collin’s knife | Yes | Yes | No | 53/75 (70.67) |
36/89 (44.4) | 31/36 (86.1) |
|
|||||||||||
Salma et al., 2011 [ |
NR | 60 (59 followed up) |
AFS | Severe | Hysteroscopy using scissors or electrode needle under direct vision | Yes | Yes | Yes | 56/59 (94.9) |
NR | NR |
|
|||||||||||
Myers and Hurst, 2012 [ |
Retrospective | 12 |
AFS | Severe | Hysteroscopy scissors | Yes | Yes | Yes | 12/12 (100) |
6/8 (75) | 4/6 (66.6) |
|
|||||||||||
Fernandez et al., 2012 [ |
Retrospective | 23 (22 followed up) |
ESHRE |
IV, severe | Hysteroscopy and bipolar electrosurgery system | No | No | No | 1/24 (4.3%) (after |
9/22 (40.9) | 6/22 (27.2) |
|
|||||||||||
Mohamed et al., 2012 [ |
Retrospective | 363 (130 followed up) |
ESGE | Grade I ( |
Hysteroscopy with unipolar and bipolar electrosurgery | Yes | Yes | Yes | 3/4 (75%) |
40 (31.5%) | 36/40 (90) |
|
|||||||||||
Yamamoto and Takeuchi, 2013 [ |
Retrospective | 27 |
AFS | Mild ( |
Hysteroscopic loop monopolar knife, Hegar’s dilators (under US guidance) | Yes | Yes | No | 27/27 (100) improved | 14/27 (52.9 ) | 3/27 (11) |
|
|||||||||||
Lin et al., 2013 [ |
Retrospective cohort study | 107 |
AFS | Mild ( |
Hysteroscopic scissors | Yes (28) | Yes | Yes | 18/28 (64.2) |
NR | NR |
|
|||||||||||
Şendağ et al., 2013 [ |
NR | 24 |
ESH | Grade 1 ( |
Hysteroscopy with sharp scissors | Yes (11) | Yes | Yes | 24/24 (100) |
4/14 (28.5) | 3/4 (75) |
HT = hormonal therapy; IUD = intrauterine device; FC = Foley catheter; NR = not reported. “Yes” = studies that used IUD; “No” = studies that didn’t used IUD.
The classification systems of included studies.
American Fertility Society (AFS), 1988 | Stage I, stage II, stage III |
---|---|
European Society of Hysteroscopy (ESH), 1989 | Stage I, stage II, IIa, or III, stage IIIa, IIIb, or IV |
European Society of Gynecological Endoscopy (ESGE), 1995 | Stage I, stage II, IIa, or III stage IV, Va, or Vb |
March, 1978 | Mild, moderate, severe |
The meta-analysis results are summarized in Figure
Summary of meta-analysis presenting odds ratio (OR) with 95% confidence interval (CI) for menstruation rates number (a), fertility rates number (b), and live birth rates number (c) of postoperative use of Lippes loop IUD with 3-month follow-up for the management of IUAs. IUAs: intrauterine adhesions and IUD: intrauterine device.
In five studies, there were 188 cases of IUAs among 266 women with secondary infertility compared after use of IUD with 98 cases of IUA among 188 women with secondary infertility (Figure
In three studies, there were 84 cases of IUAs among 145 women with abortion compared after use of IUD with 26 cases of IUA among 84 women with abortion (Figure
Postoperative use of the intrauterine device (IUD) as an adjunctive treatment modality, for intrauterine adhesions (IUAs). IUD needs to be combined with other ancillary treatments to obtain maximal clinical outcome (improvement in menstrual flow) and fertility (pregnancy and live birth rates), in particular in patients with moderate to severe IUA. Because of the high rate of reformation of intrauterine adhesions (3.1% to 23.5%), especially severe adhesions (20% to 62.5%), preventing of reformation of adhesions after surgery is essential to successful treatment [
Hysteroscopic adhesiolysis [
Uterine-shaped IUD [
Summary of previously published studies that used various techniques of IUD therapy and ancillary treatment in patients with intrauterine adhesions.
Source, year | Type of IUD | Duration of IUD used | Hormone therapy | Foley |
Hyaluronic acid | Amnion graft |
---|---|---|---|---|---|---|
Caspi and Perpinial, 1975 [ |
Lippes loop | 3 cycles | Yes | No | No | No |
March and Israel, 1976 [ |
Lippes loop | 2 months | Yes | Yes | No | No |
March and Israel, 1981 [ |
Lippes loop | 2 months | Yes | Yes | No | No |
Ismajovich et al., 1985 [ |
NR | 3 months | No | No | No | No |
Fedele et al., 1986 [ |
NR | 3 months | Yes | No | No | No |
Valle and Sciarra, 1988 [ |
NR | 3 months | Yes | No | No | No |
Bellingham, 1996 [ |
Copper | 3 months | Yes | No | No | No |
Roge et al., 1997 [ |
NR | 3 months | Yes | Yes | No | No |
Chen et al., 1997 [ |
Multiload Cu 375 | 2 weeks | Yes | No | No | No |
Feng et al., 1999 [ |
Multiload Cu 375 | 3 months | Yes | No | No | No |
Ozumba and Ezegwui, 2002 [ |
Lippes loop | 3 cycles | Yes | No | No | No |
Orhue et al., 2003 [ |
Lippes loop | 3 cycles | Yes | Yes | No | No |
Alborzi et al., 2003 [ |
NR | 1 month | Yes | No | No | No |
Zikopoulos et al., 2004 [ |
Multiload Cu 375 | 1 month | Yes | No | No | No |
Efetie, 2006 [ |
Lippes loop | 3 months | Yes | No | No | No |
Shokeir et al., 2008 [ |
NR | 3 months | Yes | No | No | No |
Yasmin et al., 2007 [ |
Lippes loop | 3 cycles | Yes | Yes | No | No |
Yu et al., 2008 [ |
Cu T | 3 months | Yes | No | No | No |
Pabuccu et al., 2008 [ |
Lippes loop | 2 months | Yes | No | No | No |
Roy et al., 2010 [ |
Cu T | 30 days | Yes | No | No | No |
Salma et al., 2011 [ |
Uterine-shaped | 1 month | Yes | Yes | Yes | No |
Myers and Hurst, 2012 [ |
Copper | 4–10 weeks | Yes | Yes | No | No |
Mohamed et al., 2012 [ |
Copper T 380A | 1–3 months | Yes | Yes | No | Yes |
Yamamoto and Takeuchi, 2013 [ |
NR | 2 cycles | Yes | No | No | No |
Lin et al., 2013 [ |
Copper coil | 2 months | Yes | Yes | Yes | No |
Şendağ et al., 2013 [ |
Cu T | 1–3 months | Yes | Yes | No | No |
NR = not reported. IUD = intrauterine device. “Yes” = studies that used IUD. “No” = studies that did not use IUD.
Types of IUD. (a) Lippes loop (patent number US3802425 A). Many investigators support the use of a Lippes loop of IUD. (b) T-shaped (patent number US4026281 A). IUDs are thought to have too small surface area to be truly effective in providing a physical barrier. (c) Uterine-shaped (patent number CN201220343083) IUD. The uterine-shaped IUD was originally manufactured in Chongqing, Sichuan. It is designed in the shape of the uterine cavity, consisting of a stainless steel coiled wire framework with copper added inside the coil wire, and releases anti-inflammatory agent. The uterine-shaped IUD is the most commonly used IUD in China. (d) Multiload Cu 375 (patent number EP2198815 A1). This IUD consists of a copper-bearing plastic shaft and two small flexible curved side arms. Some authors suggested that the copper-containing IUDs provoke an inflammatory reaction. (e) Recently, a new type of uterine-shaped IUDs was researched and manufactured in China with China patent number Zl 2008 2 0052366.3 and (f) another new product with a China patent number Zl 2012 20070407.8; this type of devices is only used for IUA.
Improvement of menstrual blood flow is the end result in most cases of adhesiolysis varying from 88.2% to 100%. The rate of restoration of menstrual flow was 4.3%, after 2 surgical procedures, in studies that did not use IUD, 90% in a study that used IUD alone, and 60% to 100% in studies that used IUD in combination with other ancillary treatments. Normal menstruations were restored in over 90% of the patients following lysis of the IUA (Table
Insofar as fertility outcomes, a wide range of pregnancy and live birth rates were reported. With respect to fertility, March and Israel’s [
Intrauterine adhesions occur after trauma of the basalis layer of the endometrium generally after endometrial curettage. It was first described by Heinrich Fritsch in 1894 and subsequently studied by Israeli gynecologist Asherman [
Intrauterine adhesion shows endometrial fibrosis in which the stroma is largely replaced with fibrous tissue and the glands are replaced by inactive cubocolumnar endometrial epithelium. The functional and basal layers are indistinguishable, with the functional layer replaced by an epithelial monolayer unresponsive to hormonal stimulation and fibrotic synechiae forming across the cavity [
The novel IUD causes local release of cytokines (such as growth factors), cytokines best known for their chemoattractive properties, attract leucocytes into tissues and are present in many leucocytes and endometrial epithelial, stromal, and vascular cells. Evidence now supports a broad range of functions for chemokines would play a positive role in the growth of exterior endometrial stem cells and final regeneration of functional endometrium [
Postoperative adhesion formation occurs in almost 50% of the most severe cases and in 21.6% of the moderate ones [
After hysteroscopic adhesiolysis the healed process occurs, with 96% of the women completing their wound healing within 2 months and subsequently endometrium reepithelization, or after hormone treatment to stimulate the endometrium and promote reepithelization [
Hormonal coil which releases a progestin into the endometrium prevents the desired proliferation produced by the postoperative oestrogen therapy. Therefore, its use is not advised. Uterine-shaped IUD [
The present systematic review and meta-analysis provides details and literature evidence of IUDs for the management of IUAs patients. However, some limitations of the present paper need to be acknowledged. Firstly, there is lack of appropriate clinical data regarding IUDs for the therapeutic approach of IUA patients. Secondly, most of the findings were based on a single-center study using small samples with different types of IUDs, which lead to many divergences between different reports. Therefore, it is necessary to conduct independent and large cohort studies to identify those IUDs with real value for the prevention of IUA after hysteroscopic adhesiolysis. Future research should focus on cellular and molecular aspects of endometrial tissue about the safety and efficacy of the new invented specific IUDs. These studies should provide an evidence based answer to the ideal IUD, the duration of course therapy, and the stage of adhesions in which IUD therapy will be most beneficial.
Hysteroscopic management of IUAs is a safe and effective method that ensures lysis of all adhesions. The IUD could be applied after hysteroscopic adhesiolysis to avoid regeneration of IUAs. It seems that IUD needs to be combined with other ancillary treatments such as hormone therapy, Foley catheter, hyaluronic acid gel, or amnion graft to obtain maximal outcomes, particularly in patients with moderate to severe IUA. Placement of an IUD to maintain the uterine cavity is safe and effective in ensuring the return of normal menstruation and later pregnancies with minimal complications. Several studies reported different postoperative outcome after using the IUD; however, no comparative studies have confirmed the ideal IUD, duration course of IUD therapy, and the combination of IUD. Therefore, well-designed prospective, randomized, multicentered clinical trial will be needed to evaluate the potential therapeutic outcome of IUD for the management of intrauterine adhesions.
The authors declare that there is no conflict of interests regarding the publication of this paper.