Advertisement
Research Article| Volume 206, P32-35, November 2016

Hysteroscopic metroplasty for the septate uterus with diode laser: a pilot study

      Abstract

      Objective

      To evaluate the feasibility and safety of office hysteroscopic metroplasty using a 980 nm diode laser.

      Study design

      18 patients were treated for septate uterus between 2013 and 2016. The indications for hysteroscopic metroplasty were recurrent abortion in 11 of the women and primary infertility in the other seven. We used a 5 mm-office hysteroscope with a diode laser fibre. After exploration of the cavity, the septum was divided with use of the laser fibre.

      Results

      Operating time was 13,16 ± 1,33 min. Intraoperative pain was 3,05 ± 0,72. No intraoperative or postoperative complications were observed. Follow-up performed 2 months after the hysteroscopic metroplasty confirmed the complete removal of the septum and no evidence of intrauterine synechiae.

      Conclusion

      Office hysteroscopic metroplasty with use of a diode laser is safe and feasible; we believe that vaporization of the septum with a diode laser could reduce the formation of adhesions and consequently reduce the occurrence of septum persistence.

      Keywords

      Introduction

      Septate uterus is the most common congenital uterine anomaly, and it is a known factor in infertility and a cause of first and second trimester spontaneous miscarriage and preterm delivery. Fetal malpresentation and placental anomalies have also been reported [
      • Colacurci N.
      • De Franciscis P.
      • Fornaro F.
      • Fortunato N.
      • Perino A.
      The significance of hysteroscopic treatment of congenital uterine malformations.
      ]. A failure in the absorption of the partition between the two fused mullerian ducts results in a septum that divides the uterine cavity, although externally, there is a normal single uterus. The American Society for Reproductive Medicine (ASRM) classifies the uterine septa as class Va (complete septate uterus, with a frequency of 30–35%) or class Vb (partial septate uterus, 65–70%) [
      • Buttram Jr., V.C.
      • Gomel V.
      • Siegler A.
      • DeCherney A.
      • Gibbons W.
      • March C.
      The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, Müllerian anomalies and intrauterine adhesions.
      ]. The CONUTA ESHRE-ESGE Working group has developed a new classification system for congenital anomalies of the female genital tract, with a septate uterus (Class U2) further classified according to the degree of uterus corpus deformity: In sub-class U2a there is a partial septate (a septum partially divides the uterine cavity above the level of the internal cervical os), and in sub-classs U2b there is a completely septate uterus (where the uterine cavity is divided up to the level of the internal cervical os) [
      • Grimbizis G.F.
      • Gordts S.
      • Di Spiezio Sardo A.
      • et al.
      The ESHRE-ESGE consensus on the classification of female genital tract congenital anomalies.
      ]. Several studies have showed unfavourable obstetric outcomes when a complete or incomplete septum is not treated. Metroplaty improves pregnancy outcomes between 5% and 90% [
      • Paradisi R.
      • Barzanti R.
      • Natali F.
      • et al.
      Hysteroscopic metroplasty: reproductive outcome in relation to septum size.
      ,
      • Shokeir T.
      • Abdelshaheed M.
      • El-Shafie L.
      • Badawy A.
      Determinants of fertility and reproductive success after hysteroscopic septoplasty for women with unexplained infertility: a prospective analysis of 88 cases.
      ]. Due to the adverse effects of a septate uterus on reproductive outcomes, treatment is indicated for women with this anomaly, and this should preferably be done before any potential obstetric complications occur. This is particularly true for women with reduced fertility (>35 years old), with reproductive disorders (unexplained infertility), and before assisted reproductive techniques are engaged. There is no need to treat women with no wish for pregnancy [
      • Paradisi R.
      • Barzanti R.
      • Natali F.
      • Battaglia C.
      • Venturoli S.
      Metroplasty in a large population of women with septate uterus.
      ,
      • Lourdel E.
      • Cabry-Goubet R.
      • Merviel P.
      • Grenier N.
      • Olieric M.F.
      • Gondry J.
      Septate uterus: role of hysteroscopic metroplasty.
      ,
      • Litta P.
      • Conte L.
      • De Marchi F.
      • Saccardi C.
      • Angioni S.
      Pregnancy outcome after hysteroscopic myomectomy.
      ].
      Surgical correction is applied as a prophylactic procedure to avoid the high incidence of spontaneous abortions and the complications that a woman with a septate uterus could experience during labour. Hysteroscopy is the gold standard for uterine metroplasty; it can be performed with scissors or a resectoscope. Choe and Baggish [
      • Choe J.K.
      • Baggish M.S.
      Hysteroscopic treatment of septate uterus with Neodymium-YAG laser.
      ] and Donnez and Nisolle [
      • Donnez J.
      • Nisolle M.
      Endoscopic laser treatment of uterine malformations.
      ] have used the Nd-Yag laser while Daniell [
      • Daniell J.F.
      The role of lasers in infertile surgery.
      ] have used the KTP or Argon laser. We present a pilot study of treatment of incomplete uterine septum using a diode laser with office hysteroscopy. A diode is an electronic laser consisting of two semiconductor materials the size of a grain of sand. A microprocessor-controlled system regulates the flow of electrical current through the diode and generates the laser beam. This beam is transmitted through an optical system to an optical fibre, which is the medium through which light reaches the location requiring surgery. The diode laser produces two wavelengths from 980 to 1470 nm. These wavelengths cut and vaporize the tissue while simultaneously promoting absorption of haemoglobin and H2O resulting in excellent haemostasis, cutting and vaporization. The diode laser creates a significantly higher haemostasis than the CO2 laser. The thermal penetration of the diode laser is smaller than that of the Nd-YAG laser enabling the surgery to be precise and safe even when close to delicate anatomical structures. The device has already been used in hysteroscopic and laparoscopic procedures [
      • Lara-Domínguez M.D.
      • Arjona-Berral J.E.
      • Dios-Palomares R.
      • Castelo-Branco C.
      Outpatient hysteroscopic polypectomy: bipolar energy system (Versapoint®) versus diode laser – randomized clinical trial.
      ,
      • Angioni S.
      • Mais V.
      • Pontis A.
      • Peiretti M.
      • Nappi L.
      First case of prophylactic salpingectomy with single port access laparoscopy and a new diode laser in a woman with BRCA mutation.
      ,
      • Angioni S.
      • Pontis A.
      • Sorrentino F.
      • Nappi L.
      Bilateral salpingo-oophorectomy and adhesiolysis with single port access laparoscopy and use of diode laser in a BRCA carrier.
      ,
      • Nappi L.
      • Angioni S.
      • Sorrentino F.
      • Cinnella G.
      • Lombardi M.
      • Greco P.
      Anti-Mullerian hormone trend evaluation after laparoscopic surgery of monolateral endometrioma using a new dual wavelengths laser system (DWLS) for hemostasis.
      ].
      To the best of our knowledge, this is the first study on hysteroscopic metroplasty using the diode laser.

      Purpose

      The aim of this study was to assess the feasibility, safety and efficacy of the continuous diode laser in the treatment of septate uterus and to evaluate the reproductive outcomes.

      Materials and methods

      This pilot study included 18 women with a partial septate uterus as diagnosed in the Endoscopic Centres of the Universities of Cagliari and Foggia between November 2013 and March 2016.
      All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients to be included in the study. All women underwent a transvaginal ultrasound 3-dimensional (3-D) test to evaluate their uterine morphology and to omit those with bicornuate uterus [
      • Apirakviriya C.
      • Rungruxsirivorn T.
      • Phupong V.
      • Wisawasukmongchoi W.
      Diagnostic accuracy of 3D-transvaginal ultrasound in detecting uterine cavity abnormalities in infertile patients as compared with hysteroscopy.
      ]. Women recruited for the study presented with V-b or Class U2a septate uterus, in according with ASRM guidelines [
      • Buttram Jr., V.C.
      • Gomel V.
      • Siegler A.
      • DeCherney A.
      • Gibbons W.
      • March C.
      The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, Müllerian anomalies and intrauterine adhesions.
      ] and the ESHRE-ESGE classification [
      • Grimbizis G.F.
      • Gordts S.
      • Di Spiezio Sardo A.
      • et al.
      The ESHRE-ESGE consensus on the classification of female genital tract congenital anomalies.
      ]. Starting on day one of the menstrual cycle, every patients received 5 mg per day of nomegestrol acetate (Nomegestrolo Acetato, Farmitalia, Italy) for 14 days before operative hysteroscopy for a better visualization during the procedure as previously described [
      • Florio P.
      • Imperatore A.
      • Litta P.
      • et al.
      The use of nomegestrol acetate in rapid preparation of endometrium before operative hysteroscopy in pre-menopausal women.
      ]. All procedures were performed by the two operators (L.N. and S.A.) using a 5 mm Bettocchi® hysteroscope (Karl Storz GmbH & Co., Tuttlingen, Germany) with a vaginoscopic approach, without the use of a speculum or tenaculum forceps [
      • Pluchino N.
      • Ninni F.
      • Angioni S.
      • et al.
      Office vaginoscopic hysteroscopy in infertile women: effects of gynecologist experience, instrument size, and distention medium on patient discomfort.
      ,
      • Di Spiezio Sardo A.
      • Bettocchi S.
      • Spinelli M.
      • et al.
      Review of new office based hysteroscopic procedures 2003–2009.
      ]. Metroplasty was performed through the 5 Fr working channel with a polyfibre (PolyFiber™, IC, Biolitec, Milano, Italy) connected to a 980 nm Biolitec Ceralas HPD laser device (Biolitec AG, Vienna, Austria). The power was set at 20 W using a continuous mode. Uterine distension was achieved by using an automatic pump with saline solution at a pressure of 60–70 mmHg (Hamou Endomat, Karl Storz GmbH & Co.). Intraoperative pain was assessed using a VAS intensity rating from 0 to 10 (0 being no pain and 10 being unbearable pain).
      For hysteroscopic metroplasty, based on our experience in this specific field, we adopted the following three “diagnostic” anatomy- and physiology-related criteria [
      • Bettocchi S.
      • Ceci O.
      • Nappi L.
      • Pontrelli G.
      • Pinto L.
      • Vicino M.
      Office hsyteroscopy metroplasty: three “diagnostic criteria” to differentiate between septate and bicornute uteri.
      ]:
      • (1)
        Colour of the cut tissue: A septum, due to its fibrotic nature, will appear as a whitish tissue while the myometrium will be pinkish, due to its muscle fibres.
      • (2)
        Vascularization: A septum, due to its fibrotic nature, has no vessels until the border with the myometrium is reached at which point some convoluted vessels appear.
      • (3)
        Sensitive innervation: The procedure is performed without any analgesia or anaesthesia. Due to its fibrotic nature, a septum has no sensitive innervation. Sensitive terminations, physiologically located in the myometrium, start to be present when the first myometrial fibres blend with the collagen tissue of the septum. Therefore, the onset of pain during cutting is indicative of the presence of muscle fibres.
      Considering the above criteria, we assumed that their presence, while cutting the supposed septum, would clearly indicate if the structure we were incising was a true septum (whitish, nonvascularised, and not painful on incision) or the wall of a bicornuate uterus (pinkish, vascularized, and painful if cut). The septum was cut and coagulated by contact with the fibre laser progressively, starting from the proximal part, equidistant from the anterior and the posterior walls, while carefully evaluating the three criteria. The septum incision, in the presence of whitish, non-vascularised tissue and without evident discomfort for the patient, was performed until at least 2 of the criteria became apparent. This obliged us, in all cases, to leave a fundal notch, no longer than 0.5–1 cm, at the end of the procedure. The procedure was considered complete when the operator visualized the first pole-pink myometrial bundle (Fig. 1). The operating time was determined from the introduction into vagina until complete septum resection. At the end of the examination, an assistant recorded whether the procedure was correctly performed and monitored each patient for at least 1 h, evaluating blood pressure, heart frequency, the pain score provided by each patient and side effects observed during the procedure. Post-operatively, patients received sequential oral contraception for 2 months. A second look hysteroscopy (Bettocchi® hysteroscope 5 mm) was performed on all patients two months after the hysteroscopic metroplasty to check for the presence of intra uterine adherences or partial persistence of the septum [
      • Danilidis A.
      • Pantelis A.
      • Dinas K.
      • et al.
      Indications of diagnostic hysteroscopy, a brief review of literature.
      ]. No antibiotic prophylaxis was administered in either procedures [
      • Gregoriu O.
      • Bakas P.
      • Grigoriadis C.
      • Creatsa M.
      • Sofoudis C.
      • Creatsas G.
      Antibiotic prophylaxis in diagnostic hysteroscopy: it is necessary or not?.
      ]. Pregnancy outcomes within the first year after the procedure were investigated by contacting all patients by telephone and the responses were recorded.
      Figure thumbnail gr1
      Fig. 1Hysteroscopic metroplasty with diode laser.

      Results

      Characteristics of patients are reported in Table 1. Operating time was 13,16 ± 1,33 min. Blood loss during the procedure was minimal. There were no intraoperative complication. Intraoperative pain was 3,05 ± 0,72. No side effects were observed in any patients. Office hysteroscopy follow-up performed two months after the hysteroscopic metroplasty confirmed complete removal of the septum and no evidence of intrauterine synechiae (Table 2). We analyzed the pregnancy outcomes (follow-up post-surgery for 6–30 months). Twelve pregnancies were reported, of which 6 (50%) reached term, one (8,33%) ended in pregnancy loss in the first trimester; and five (41,66%) were on-going at the time of analysis. Table 3 shows pregnancy outcomes related to previous fertility history (Table 3). One patient had post-partum haemorrhage due to a retained placenta. No uterine rupture during pregnancy or delivery occurred and one case of placenta accrete was noted.
      Table 1Characteristic of patients.
      Age (years)32,66 ± 2,74
      BMI (kg/m2)21,58 ± 1,63
      Infertility7 (38,88%)
      Miscarriage11 (61,12%)
      Septum18 Class U2aC0 (Eshre-Esge) or Vb (ASRM)
      Values are given as mean ± SD or number (percentage).
      Table 2Results of hysteroscopic metroplasty with diode laser.
      MetroplastyControl hysteroscopy (2 months after surgery)
      Mean operating time (min)13,16 ± 1,33
      Intraoperative pain (Vas)3,05 ± 0,72
      Side effects
      Hypothermia0 (0%)
      Tremor0 (0%)
      Vagal symptoms0 (0%)
      Intrauterine adhesions0(0%)
      Residual septum (>1 cm)0(0%)
      Values are given as mean ± SD or number (percentage).
      Table 3Post-operative reproductive outcome (follow-up 6–30 months).
      Primary infertility (n = 7)Repeated early spontaneous Abortions (≥2) (n = 11)
      Clinical pregnancy rate5 (71,42%)7 (63,63%)
      Spontaneous abortion rate1 (14,28%)0
      Term delivery rate3/4
      5 ongoing pregnancy at 19, 20, 23, 24, 26 weeks.
      3/7
      5 ongoing pregnancy at 19, 20, 23, 24, 26 weeks.
      Live birth rate33
      a 5 ongoing pregnancy at 19, 20, 23, 24, 26 weeks.

      Comment

      Several factors have been proposed to explain the adverse effects of a septate uterus on the course of pregnancy. According to the most widely accepted theory, the septum is thought to consist of fibroblastic tissue with inadequate vascularization and altered relations between myometrial and endometrial vessels, thus exerting a negative effect on fetal placentation. Hysteroscopic metroplasty has out-dated and replaced transabdominal metroplasty by enabling a vaginal approach to the correction of septate uterus and by providing several advantages such as simple and short surgery with a shorter hospitalization time, a decreased need for analgesia, a shorter interval before conception (3–6 months), a lower risk of uterine rupture during pregnancy [
      • Pontis A.
      • Prasciolu C.
      • Litta P.
      • Angioni S.
      Uterine rupture in pregnancy: two cases reports and review of literature.
      ], and the possibility of planning a vaginal delivery. Such factors combine to make hysteroscopic metroplasty the gold standard.
      Several authors propose metroplasty using 4 mm endoscopic scissors introduced into the uterine cavity; this approach has resulted in a pregnancy rate of 91,7% with a delivery rate of 72,7%.
      Other authors prefer using a resectoscope (with a pregnancy rate of 80–85% and a delivery rate of 81–89%) while others prefer use of a laser with a pregnancy and delivery rate similar to that of a resectoscope [
      • Litta P.
      • Spiller E.
      • Saccardi C.
      • Ambrosini G.
      • Caserta D.
      • Cosmi E.
      Resectoscope or versapoint for hysteroscopic metroplasty.
      ]. Laser types used include argon, krypton, neodymyum-ytrium-aluminium garnet (Nd-Yag), and all have been successfully used, although only the Nd-Yag laser has been widely used in hysteroscopic procedures [
      • Choe J.K.
      • Baggish M.S.
      Hysteroscopic treatment of septate uterus with Neodymium-YAG laser.
      ,
      • Daniell J.F.
      The role of lasers in infertile surgery.
      ]. Recently, the diode laser has been introduced into hysteroscopy. Due to its 980 nm wavelength, it achieves high absorption simultaneously for haemoglobin and water, thereby providing its haemostatic properties, and thus offers a high capacity for ablation and vaporization [
      • Lara-Domínguez M.D.
      • Arjona-Berral J.E.
      • Dios-Palomares R.
      • Castelo-Branco C.
      Outpatient hysteroscopic polypectomy: bipolar energy system (Versapoint®) versus diode laser – randomized clinical trial.
      ]. A diode laser can be used in direct contact with the tissue (contact mode) or at a distance from the tissue (non-contact mode).
      In our study, we demonstrated the efficacy and safety of use of diode laser in the hysteroscopic metroplasty without general or local anaesthesia or cervical dilatation. Moreover, we were able to evidence very good patient compliance associated with low scores at VAS during operation period. In our opinion the very high precision of the laser vaporization, with strict observance of the technique used, enabled us to achieve the removal of the septum while avoiding the stimulation of sensitive nerves inside the myometrium; these are the key factors in the very low pain scores evidenced during the treatment [
      • Mazzon I.
      • Favilli A.
      • Horvath S.
      • et al.
      Pain during diagnostic hysteroscopy: what is the role of the cervical canal? A pilot study.
      ,
      • Cobellis L.
      • Castaldi M.A.
      • Giordano V.
      • De Franciscis P.
      • Signoriello G.
      • Colacurci N.
      Is it possible to predict office hysteroscopy failure?.
      ]. In the hysteroscopic second look, performed two months after surgery, we did not observe any adhesions or any residual septum. The rational for performing the second look hysteroscopy two months is due to the fact that any adhesions formed within two months are initially loosely attached and easy to lyse, while if left for too long (more than two months) they can become fibrotic and difficult to separate. We believe that the ability of diode laser to vaporize tissue could reduce the formation of adhesions inside the uterus. Moreover, the vaporization of septum tissue instead of simply cutting it away, as was previously done by cold scissors or electrosurgery, might decrease the occurrence of residual septum at follow up, which is a common finding using these techniques. The main disadvantage for the clinical application of the diode laser might be its cost. Laser equipment currently tends to be expensive, which significantly reduces its widespread use [
      • Lara-Domínguez M.D.
      • Arjona-Berral J.E.
      • Dios-Palomares R.
      • Castelo-Branco C.
      Outpatient hysteroscopic polypectomy: bipolar energy system (Versapoint®) versus diode laser – randomized clinical trial.
      ,
      • Haimovich S.
      • Mancebo G.
      • Alameda F.
      • et al.
      Feasibility of a new two-step procedure for office hysteroscopy resection of submucous myomas: results of a pilot study.
      ]. Although the hysteroscopy findings at follow up and the obstetrical outcomes seem very promising, the current study was limited to a small number of patients. However, this study is the first to report hysteroscopic metroplasty in an office setting without the need for cervical dilatation and using a diode laser.
      In conclusion, hysteroscopic metroplasty with a diode laser is a feasible and safe alternative to the scissor, bipolar twizzle and bipolar or monopolar resectoscope techniques. The diode laser allows the vaporization of the uterine septum without diffusion of laser energy to the surrounding muscle tissue. The laser energy makes possible immediately visible results obtained through precise and constant control of tissue vaporization, in the complete absence of bleeding.
      The results in term of efficacy and pregnancy outcomes need further larger randomized studies.

      Conflict of interest

      The authors report no conflict of interests.

      Funding

      No funding was sought for the purpose of this study

      References

        • Colacurci N.
        • De Franciscis P.
        • Fornaro F.
        • Fortunato N.
        • Perino A.
        The significance of hysteroscopic treatment of congenital uterine malformations.
        Reprod Biomed [Online]. 2002; 4: 52-54
        • Buttram Jr., V.C.
        • Gomel V.
        • Siegler A.
        • DeCherney A.
        • Gibbons W.
        • March C.
        The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, Müllerian anomalies and intrauterine adhesions.
        Fertil Steril. 1988; 49: 944-955
        • Grimbizis G.F.
        • Gordts S.
        • Di Spiezio Sardo A.
        • et al.
        The ESHRE-ESGE consensus on the classification of female genital tract congenital anomalies.
        Hum Reprod. 2013; 28: 2032-2044
        • Paradisi R.
        • Barzanti R.
        • Natali F.
        • et al.
        Hysteroscopic metroplasty: reproductive outcome in relation to septum size.
        Arch Gynecol Obstet. 2014; 289: 671-676
        • Shokeir T.
        • Abdelshaheed M.
        • El-Shafie L.
        • Badawy A.
        Determinants of fertility and reproductive success after hysteroscopic septoplasty for women with unexplained infertility: a prospective analysis of 88 cases.
        Eur J Obstet Gynecol Reoprod Biol. 2011; 155: 54-57
        • Paradisi R.
        • Barzanti R.
        • Natali F.
        • Battaglia C.
        • Venturoli S.
        Metroplasty in a large population of women with septate uterus.
        J Minim Invasive Gynecol. 2011; 18: 449-454
        • Lourdel E.
        • Cabry-Goubet R.
        • Merviel P.
        • Grenier N.
        • Olieric M.F.
        • Gondry J.
        Septate uterus: role of hysteroscopic metroplasty.
        Gynecol Obstet Fertil. 2007; 35: 811-818
        • Litta P.
        • Conte L.
        • De Marchi F.
        • Saccardi C.
        • Angioni S.
        Pregnancy outcome after hysteroscopic myomectomy.
        Gynecol Endocrinol. 2014; 30: 149-152
        • Choe J.K.
        • Baggish M.S.
        Hysteroscopic treatment of septate uterus with Neodymium-YAG laser.
        Fertil Steril. 1992; 57: 81-84
        • Donnez J.
        • Nisolle M.
        Endoscopic laser treatment of uterine malformations.
        Human Reprod. 1997; 12: 1381-1387
        • Daniell J.F.
        The role of lasers in infertile surgery.
        Fertil Steril. 1984; 42: 815-823
        • Lara-Domínguez M.D.
        • Arjona-Berral J.E.
        • Dios-Palomares R.
        • Castelo-Branco C.
        Outpatient hysteroscopic polypectomy: bipolar energy system (Versapoint®) versus diode laser – randomized clinical trial.
        Gynecol Endocrinol. 2016; 32: 196-200
        • Angioni S.
        • Mais V.
        • Pontis A.
        • Peiretti M.
        • Nappi L.
        First case of prophylactic salpingectomy with single port access laparoscopy and a new diode laser in a woman with BRCA mutation.
        Gynecol Oncol Case Rep. 2014; 9: 21-23
        • Angioni S.
        • Pontis A.
        • Sorrentino F.
        • Nappi L.
        Bilateral salpingo-oophorectomy and adhesiolysis with single port access laparoscopy and use of diode laser in a BRCA carrier.
        Eur J Gynaecol Oncol. 2015; 36: 479-481
        • Nappi L.
        • Angioni S.
        • Sorrentino F.
        • Cinnella G.
        • Lombardi M.
        • Greco P.
        Anti-Mullerian hormone trend evaluation after laparoscopic surgery of monolateral endometrioma using a new dual wavelengths laser system (DWLS) for hemostasis.
        Gynecol Endocrinol. 2016; 32: 34-37
        • Apirakviriya C.
        • Rungruxsirivorn T.
        • Phupong V.
        • Wisawasukmongchoi W.
        Diagnostic accuracy of 3D-transvaginal ultrasound in detecting uterine cavity abnormalities in infertile patients as compared with hysteroscopy.
        Eur J Obstet Gynecol Reoprod Biol. 2016; 200: 24-28
        • Florio P.
        • Imperatore A.
        • Litta P.
        • et al.
        The use of nomegestrol acetate in rapid preparation of endometrium before operative hysteroscopy in pre-menopausal women.
        Steroids. 2010; 75: 912-917
        • Pluchino N.
        • Ninni F.
        • Angioni S.
        • et al.
        Office vaginoscopic hysteroscopy in infertile women: effects of gynecologist experience, instrument size, and distention medium on patient discomfort.
        J Minim Inv Gynecol. 2010; 17: 344-350
        • Di Spiezio Sardo A.
        • Bettocchi S.
        • Spinelli M.
        • et al.
        Review of new office based hysteroscopic procedures 2003–2009.
        J Minim Invasive Gynecol. 2010; 17: 436-448
        • Bettocchi S.
        • Ceci O.
        • Nappi L.
        • Pontrelli G.
        • Pinto L.
        • Vicino M.
        Office hsyteroscopy metroplasty: three “diagnostic criteria” to differentiate between septate and bicornute uteri.
        J Minim Invasive Gynecol. 2007; 14: 324-328
        • Danilidis A.
        • Pantelis A.
        • Dinas K.
        • et al.
        Indications of diagnostic hysteroscopy, a brief review of literature.
        Gynecol Surg. 2012; 9: 23-28
        • Gregoriu O.
        • Bakas P.
        • Grigoriadis C.
        • Creatsa M.
        • Sofoudis C.
        • Creatsas G.
        Antibiotic prophylaxis in diagnostic hysteroscopy: it is necessary or not?.
        Eur J Obstet Gynecol Reoprod Biol. 2012; 163: 190-192
        • Pontis A.
        • Prasciolu C.
        • Litta P.
        • Angioni S.
        Uterine rupture in pregnancy: two cases reports and review of literature.
        Clin Exp Obstet Gynecol. 2016; 43: 304-309
        • Litta P.
        • Spiller E.
        • Saccardi C.
        • Ambrosini G.
        • Caserta D.
        • Cosmi E.
        Resectoscope or versapoint for hysteroscopic metroplasty.
        Int J Gynaecol Obstet. 2008; 101: 39-42
        • Mazzon I.
        • Favilli A.
        • Horvath S.
        • et al.
        Pain during diagnostic hysteroscopy: what is the role of the cervical canal? A pilot study.
        Eur J Obstet Gynecol Reprod Biol. 2014; 183: 169-173
        • Cobellis L.
        • Castaldi M.A.
        • Giordano V.
        • De Franciscis P.
        • Signoriello G.
        • Colacurci N.
        Is it possible to predict office hysteroscopy failure?.
        Eur J Obstet Gynecol Reprod Biol. 2014; 181: 328-333
        • Haimovich S.
        • Mancebo G.
        • Alameda F.
        • et al.
        Feasibility of a new two-step procedure for office hysteroscopy resection of submucous myomas: results of a pilot study.
        Eur J Obstet Gynecol Reprod Biol. 2013; 168: 191-194