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Does hyaluronic acid gel reduce intrauterine adhesions after dilation and curettage in women with miscarriage? A Multicentric randomized controlled trial (HYFACO Study)

      Background

      Miscarriage is a frequent problem that requires dilation and curettage in 30% of cases. This routine surgery may lead to intrauterine adhesions and severe infertility. Hyaluronic acid gel is known to reduce intrauterine adhesions after hysteroscopic surgery.

      Objective

      This study aimed to evaluate the rate of intrauterine adhesions after dilation and curettage for miscarriage with and without hyaluronic acid gel.

      Study Design

      This was a multicentric (9 hospitals in France), prospective, open-label randomized trial. Patients who had a miscarriage between weeks 7 and 14 of gestation, required dilation and curettage, and wanted another pregnancy were eligible for the study. Women were randomly assigned in a 1:1 ratio to surgery alone (control group) or surgery with intrauterine instillation of hyaluronic acid gel (gel group). An office hysteroscopy was planned at 6 to 8 weeks after surgery. The primary endpoint was the rate of intrauterine adhesions during this office follow-up hysteroscopy. Two different follow-up fertility surveys were sent at 6 months and 1 year after the end of the intervention, respectively.

      Results

      Among the 343 patients who had curettage, 278 had hysteroscopy. After multiple imputation, the rate of intrauterine adhesions was lower in the gel group than in the control group (9.1% vs 18.4%, respectively; P=.0171). Among the 110 responders to the surveys, the overall pregnancy rate at 12 months after surgery was 64.5% (71/110), and similar in both groups (57.4% [27/47] in the control group vs 69.8% [44/63] in the gel group; P=.1789).

      Conclusion

      Intrauterine instillation of hyaluronic acid gel reduces the rate of intrauterine adhesions in women treated with dilation and curettage for miscarriage.

      Key words

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      References

        • Wang X.
        • Chen C.
        • Wang L.
        • Chen D.
        • Guang W.
        • French J.
        Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study.
        Fertil Steril. 2003; 79: 577-584
        • Linnakaari R.
        • Helle N.
        • Mentula M.
        • et al.
        Trends in the incidence, rate and treatment of miscarriage-nationwide register-study in Finland, 1998-2016.
        Hum Reprod. 2019; 34: 2120-2128
        • Hooker A.B.
        • Lemmers M.
        • Thurkow A.L.
        • et al.
        Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome.
        Hum Reprod Update. 2014; 20: 262-278
        • Yu D.
        • Wong Y.M.
        • Cheong Y.
        • Xia E.
        • Li T.C.
        Asherman syndrome - one century later.
        Fertil Steril. 2008; 89: 759-779
        • Asherman J.G.
        Traumatic intra-uterine adhesions.
        J Obstet Gynaecol Br Emp. 1950; 57: 892-896
        • Schenker J.G.
        • Margalioth E.J.
        Intrauterine adhesions: an updated appraisal.
        Fertil Steril. 1982; 37: 593-610
        • Golan A.
        • Schneider D.
        • Avrech O.
        • Raziel A.
        • Bukovsky I.
        • Caspi E.
        Hysteroscopic findings after missed abortion.
        Fertil Steril. 1992; 58: 508-510
        • Friedler S.
        • Margalioth E.J.
        • Kafka I.
        • Yaffe H.
        Incidence of post-abortion intra-uterine adhesions evaluated by hysteroscopy - a prospective study.
        Hum Reprod. 1993; 8: 442-444
        • Römer T.
        • Bojahr B.
        • Müller J.
        • Lober R.
        [Early diagnosis of congenital and acquired intrauterine causes of abortion by post-abortion hysteroscopy].
        Geburtshilfe Frauenheilkd. 1996; 56: 542-545
        • Salzani A.
        • Yela D.A.
        • Gabiatti J.R.
        • Bedone A.J.
        • Monteiro I.M.
        Prevalence of uterine synechia after abortion evacuation curettage.
        Sao Paulo Med J. 2007; 125: 261-264
        • Kuzel D.
        • Horak P.
        • Hrazdirova L.
        • Kubinova K.
        • Sosna O.
        • Mara M.
        “See and treat” hysteroscopy after missed abortion.
        Minim Invasive Ther Allied Technol. 2011; 20: 14-17
        • Cogendez E.
        • Dolgun Z.N.
        • Sanverdi I.
        • Turgut A.
        • Eren S.
        Post-abortion hysteroscopy: a method for early diagnosis of congenital and acquired intrauterine causes of abortions.
        Eur J Obstet Gynecol Reprod Biol. 2011; 156: 101-104
        • Hooker A.B.
        • de Leeuw R.
        • van de Ven P.M.
        • 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: 1223-1231.e3
        • Li X.
        • Wu L.
        • Zhou Y.
        • et al.
        New crosslinked hyaluronan gel for the prevention of intrauterine adhesions after dilation and curettage in patients with delayed miscarriage: a prospective, multicenter, randomized, controlled trial.
        J Minim Invasive Gynecol. 2019; 26: 94-99
        • Acunzo G.
        • Guida M.
        • Pellicano M.
        • et al.
        Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective, randomized, controlled study.
        Hum Reprod. 2003; 18: 1918-1921
        • Guida M.
        • Acunzo G.
        • Di Spiezio Sardo A.
        • et al.
        Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study.
        Hum Reprod. 2004; 19: 1461-1464
        • Zheng F.
        • Xin X.
        • He F.
        • Liu J.
        • Cui Y.
        Meta-analysis on the use of hyaluronic acid gel to prevent intrauterine adhesion after intrauterine operations.
        Exp Ther Med. 2020; 19: 2672-2678
      1. The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, Mullerian anomalies and intrauterine adhesions.
        Fertil Steril. 1988; 49: 944-955
        • Hooker A.B.
        • de Leeuw R.A.
        • van de Ven P.M.
        • Brölmann H.A.M.
        • Huirne J.A.F.
        Reproductive performance after the application of hyaluronic acid gel after dilation and curettage in women who have experienced at least one previous curettage: long-term results of a multicenter prospective randomized trial.
        Fertil Steril. 2018; 110: 1231-1238
        • Hooker A.B.
        • de Leeuw R.A.
        • Twisk J.W.R.
        • Brölmann H.A.M.
        • Huirne J.A.F.
        Pregnancy and neonatal outcomes 42 months after application of hyaluronic acid gel following dilation and curettage for miscarriage in women who have experienced at least one previous curettage: follow-up of a randomized controlled trial.
        Fertil Steril. 2020; 114: 601-609