Reproductive Performance of Females With and Without Intrauterine Adhesions Diagnosis - European Medical Journal


Reproductive Performance of Females With and Without Intrauterine Adhesions Diagnosis

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EMJ Reproductive Health 7.1 2021 Feature Image
*Angelo Hooker,1,2 Robert de Leeuw,2 Jos Twisk,2 Hans Brölmann,2 Judith Huirne2

The authors have declared no conflicts of interest.


The authors are grateful to the people who participated in this study. The authors thank the research nurses, local study coordinators and staff of all participating hospitals.

EMJ Repro Health. ;7[1]:34-36. Abstract Review No. AR1.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

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Intrauterine adhesions (IUAs) are considered one of the main reproductive system diseases affecting females worldwide, characterised by endometrial fibrosis with partial to complete obliteration of the uterine cavity and/or cervical canal.1-4 The Prevention of Adhesions Post Abortion (PAPA) study showed that application of auto-crosslinked hyaluronic acid (ACP) gel, an absorbable barrier in those undergoing recurrent dilatation and curettage (D&C) for miscarriage, resulted in a lower rate of IUAs, 13% versus 31% (relative risk: 0.43; 95% confidence interval [CI]: 0.22–0.83), lower mean adhesion score and significant less moderate to severe IUAs.5 After a follow-up, the question remains if the long-term reproductive outcomes following recurrent D&C for miscarriage in individuals with identified and treated IUAs are comparable to individuals without IUAs.6


This was a follow-up of the PAPA study, a multicentre randomised controlled trial evaluating the application of ACP gel in females undergoing recurrent D&C for miscarriage.5 In the trial, 152 females who had undergone a first-trimester miscarriage with at least one previous D&C were randomised for D&C alone or D&C with immediate intrauterine application of ACP gel. All included females who had received a diagnostic hysteroscopy 8–12 weeks after randomisation to evaluate the uterine cavity and for adhesiolysis if IUAs were present. Participants were approached at least 30 months after randomisation to evaluate reproductive performance, obstetric, and neonatal outcomes. The main outcome was ongoing pregnancy. Outcomes of subsequent pregnancies, time to conception, and time to live birth were also recorded.


Reproductive outcomes of individuals with and without an IUA diagnosis after a mean follow-up of 46 months are presented in Table 1. In those pursuing a pregnancy, 14/24 (58%) ongoing pregnancies were recorded in individuals with identified and treated IUAs versus 80/89 (90%) ongoing pregnancies in people without IUAs diagnosis (odds ratio [OR]: 0.18; 95% CI: 0.06–0.50, p<0.001).6 Documented live birth was also lower in those diagnosed with IUAs; 13/24 (54%) with versus 75/89 (84%) without IUAs diagnosis (OR: 0.22; 95% CI: 0.08–0.59; p=0.004). The median time to conception was 7 months in females with identified and treated IUAs versus 5 months in females without IUAs diagnosis (hazard ratio: 0.84; 95% CI: 0.54–1.33) and time to conception leading to a live birth 15 months versus 5 months (hazard ratio: 0.54; 95% CI: 0.30–0.97). In females with identified and treated IUAs, premature deliveries were recorded in 3/16 (19%) versus 4/88 (5%) in females without IUAs; p=0.01. Complications were recorded in respectively 12/16 (75%) versus 26/88 (30%); p=0.001.6 No differences were recorded in mean birth weight between the groups.

Table 1 Reproductive outcomes of females with and without intrauterine adhesions diagnosis.

Table 1: Reproductive outcomes of females with and without intrauterine adhesions diagnosis.
IUAs: intrauterine adhesion


Reproductive outcomes in females with identified and treated IUAs following recurrent D&C for miscarriage are decreased compared to females without IUAs diagnosis. As IUAs have an impact on reproductive performance, even after hysteroscopic adhesiolysis, primary prevention is essential.

Expectative and medical management should therefore be considered as serious alternatives for D&C in females with a miscarriage. In case D&C is necessary, application of ACP gel should be considered.


In the original PAPA study, randomisation was applied for ACP gel application. Comparing females with and without IUAs diagnosis is not in line with the randomisation and therefore confounding of the results cannot be excluded. IUAs, if visible during routine hysteroscopy after randomisation were removed as part of the study protocol.

Bosteels J et al. Anti-adhesion barrier gels following operative hysteroscopy for treating female infertility: a systematic review and meta-analysis. Gynecol Surg 2014;11(2):113-27. Johary J et al. Efficacy of estrogen therapy in patients with intrauterine adhesions: systematic review. J Minim Invasive Gynecol. 2014;21(1):44-54. McCulloch TA et al. The pathology hysterectomy specimens following trans-cervical resection of the endometrium. Histopathology. 1995;27(6):541-7. Katz Z et al. Reproductive outcome following hysteroscopic adhesiolysis in Asherman’s syndrome. Int J Fertil Menopausal Stud. 1996;41(5):462-5. Hooker AB et al. Prevalence of intrauterine adhesions after the application of hyaluronic acid gel after dilatation and curettage in women with at least one previous curettage: short-term outcomes of a multicenter, prospective randomized controlled trial. Fertil Steril. 2017;107(5):1223-31. Hooker AB et al. Reproductive performance of women with and without intrauterine adhesions following recurrent dilatation and curettage for miscarriage: long-term follow-up of a randomized controlled trial. Hum Reprod. 2021;36(1):70-81.