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Fırat Tıp Dergisi
2013, Cilt 18, Sayı 1, Sayfa(lar) 007-010
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Our Office-Based Diagnostic Hysteroscopy Results of Pre-IVF Patients
Zehra Sema OZKANa, Banu KUMBAK, Remzi ATILGAN, Mehmet SIMSEK, Ekrem SAPMAZ
Fırat Üniversitesi Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, Elazığ, Türkiye
Keywords: Office hysteroscopy, IVF failure, endometrial pathology, Ofis histeroskopi, IVF başarısızlığı, Endometrial patoloji
Summary
Objective: To evaluate the intrauterine pathologies using office-based hysteroscopy (OH) in patients scheduled for assisted reproductive technologies (ART).

Materials and Methods: This study was conducted at the In Vitro Fertilization (IVF) Unit of Firat University Hospital, between March 2010- January 2012. The 219 patients with no OH within the previous 6 months were enrolled the study with rigid hysteroscope (continous flow; 30-degree forward-oblique view) assembled in a 4-mm diameter diagnostic sheath with an atraumatic tip. After OH investigation, endometrial sampling was performed with biopsy catheter. The patients in whom the findings were normal proceeded to an IVF cycle within 1 month.

Results: The procedure was succesful in 219 patients, with mean (±SD) age of 31.9 (±5.2) years, duration of infertility of 6.2 (±4.5) years and number of previous ART trials 1.6 (±1.1). The type of infertility were as follows: 150 primary (68.5%) and 69 secondary infertility (31.5%). Endometrial polyp and uterine subseptum were the major intracavitary abnormalities. Chronic endometritis and endometrial polyp were the major histopathologic abnormalities. Chronic endometritis, uterine subseptum and endometrial hyperplasia were higher in patients ≥35 years (p<0.01). There was a decrease in the pregnancy rate (40% vs 46%), implantation rate (51% vs 56%) and fertilization rate (69% vs 74%) in the patients with hysteroscopic abnormality compared to patients without abnormality respectively.

Conclusion: To improve the outcome of ART cycles, OH could be performed as a routine procedure for the patients who will experience IVF treatment.

  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Introduction
    Uterine cavity pathologies such as fibroids, polyps, Mullerian anomalies and others have an important role in causing infertility. The evaluation of the uterine cavity could be performed either indirectly by hysterosalpingography (HSG), transvaginal ultrasonography (TVU) and sonohysterography (SH) or directly by hysteroscopy1-3. Hysteroscopy offers a three dimensional direct visual examination of the uterine cavity. It gives the opportunity to identify the nature of endometrial abnormalities in terms of polyps, submucous fibroids, differences in endometrial thickness4. Hysteroscopy is an easy, fast and well tolerated diagnostic procedure that can be performed on an outpatient basis. It is known that submucosal or intramural fibroids that distort the endometrial cavity and are therefore visible at hysteroscopy adversely affect in vitro fertilization (IVF) outcome5-7. Endometrial polyps might also affect embryo implantation, and thus hysteroscopic polypectomy performed prior to an assisted reproductive technique should be considered8. A condition that is easily diagnosed by hysteroscopy and is known to affect embryo implantation is septate uterus and it can be corrected by hysteroscopic metroplasty9,10. The hysteroscopic evaluation for repeated implantation failures in IVF- embryo transfer cycles has also been advised11.

    Hysteroscopy is feasible in an office setting, that employs thinner instruments and saline solution infusion distension, becoming minimally invasive and effective in the detection of intra-uterine pathologies12. In this study we reported our results about the uterine cavity pathologies that were detected during pre-IVF evaluation.

  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Methods
    This study was conducted at the IVF Unit of Firat University Hospital, between March 2010- January 2012. The women attending the infertility outpatient clinic were subjected to history taking, gynecological examination and routine infertility investigations (if not previously done), including transvaginal sonography, hormonal profile and hysterosalpingography. Among the women attended infertility unit during two years period, 219 patients with decision of IVF treatment but no OH within the previous 6 months were enrolled the study. Rigid hysteroscope (continous flow; 30-degree forward-oblique view) assembled in a 4-mm diameter diagnostic sheath with an atraumatic tip. The distension medium was normal saline. Vaginal douche and antibiotic prophylaxis with azitromicin (1 g, 3 h before the examination) were prescribed to all patients. Analgesic and anaesthetic premedication were not prescibed to all patients. Misoprostol medication were used to 4 patients in the situation of cervical stenosis. The patients in which the findings were normal proceeded to an IVF cycle within 1 month.

    Endometrial polyps were defined as smooth margined masses with a homogeneous texture of variable size and shape, bulging from the endometrium. Submucosal myomas were defined as solid, round structures protruding into the uterine cavity, covered by intact epithelium. Endocavitary polyps and submucosal myomas were distinguished, their location, number and size were noted. Septum or subseptum resection, polypectomy and adhesiolysis were performed with operative hysteroscopy. Only endometrial polyps which were extirped during OH were not exceeded to operative intervention. Endometrial injury was performed after office or operative hysteroscopy with biopsy catheter. The collected endometrial samplings were analysed by histopathologic evaluation.

    Data were analyzed using SPSS Version 12.0 (SPSS, Chicago, IL, USA). Results were reported as mean ± standard deviation. Ki- square statistics were used to compare discontinuous data and student's t-test were used to compare continuous data. A p value of <0.05 was considered as statistically significant.

  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Results
    The procedure was succesful in 219 patients, with mean (±SD) age of 31.9 (±5.2) years, duration of infertility of 6.2 (±4.5) years and number of previous ART trials 1.6 (±1.1). The type and the etiology of infertility were as presented in Table 1. Hysteroscopic abnormalities were classified as uterine septum, uterine subseptum, endometrial polyp, unicorn cavity, intrauterine adhesions. Histopathologic findings were as follows: chronic endometritis, endometrial hyperplasia with or without atypia, endometrial polyp and normal ( proliferative or secretory) endometrium. Doxycycline with ornidazole antibiotherapy were prescribed to patients with the result of chronic endometritis.


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    Table 1: Characteristics of all patients in the study

    The frequency of office and operative hysteroscopy findings were presented in Table 2. The major OH findings were endometrial polyp and uterine subseptum. After histopathologic evaluation, the major abnormality was chronic endometritis and than endometrial polyp was reported. Among 219 women, 31 intrauterine abnormality was observed and 15 operative intervention was performed. In the ROC analysis to determine the possibility of OH abnormality according to age, the area under curve was 0.73 and the highest LR+ value was 6,02 in the point of 35 years. The comparison of histopathologic abnormalities according to cut off value of 35 years revealed out increament in the percentage of chronic endometritis and endometrial hyperplasia over 35 years (p=0.002). And also endometrial polyp, uterine septum/ subseptum and intrauterine adhesion were significantly high in the women over 35 years (p=0.035).


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    Table 2: Office H/S findings and histopathologic evaluation of all women in the study

    During IVF procedure, 19 women did not experience embryo transfer. Among 200 women, 92 women came pegnant and the comparison of OH abnormalities between pregnant and nonpregnant women revealed no significant difference (Table 3). Although the differences were not significant, the pregnancy rate (46.9 % vs 40%), implantation rate (56% vs 51%) and fertilization rate (74% vs 69%) of women without OH abnormality were higher than that women with OH abnormality.


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    Table 3: Comparison of H/S results according to IVF outcome

  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Discussion
    Office hysteroscopy (OH) is a minimally invasive and well tolerated procedure that allows accurate visual assesment of uterine cavity with the ability to treat uterine pathology in infertile patients. OH was found to strongly reduce the amount of pain compared with the use of traditional hysteroscopes, significantly improving the patients' compliance13. When routinely performed in a diagnostic work-up of an IVF unit, a significant percentage of patients has been found to carry uterine pathology that may impair the success of fertility treatment14. We aimed to understand the incidence of uterine pathology among infertile women, and the role that hysteroscopy could play in ruling out infertility causes and improving the way they can be treated.

    In particular, a very high incidence of chronic endometritis and endometrial polyp were observed in our study, but the real influence of these pathologies on the outcome of infertility and IVF techniques is still a matter of debate8,15,16. An investigator reported endometrial polyps in 41% of 82 infertile patients with no dysfunctional uterine bleeding17. In an another study, endometrial polyps were detected in 46.7% infertile patients with endometriosis and in 15% infertile controls18. The higher incidence of uterine septum/subseptum among infertile patients, which has already been reported by other authors seems to be confirmed in our study population, too19,20. However, no clear evidence showing potential impairment of reproduction because of this pathology has been reported21-23.

    OH is applicable at any time of the menstrual cycle1. However, endometrial polyps are best visualized during the follicular phase, and submucosal myomas during the secretory phase with SH3. Suboptimal timing during the menstrual cycle may give false results by SH. This limitations makes the SH second choice in infertility practice. There is little risk for intracavitary infection during fluid instillation of procedure24. This could be excluded with antibiotherapy before (patients with signs of infection)/after the procedure. We concurrently performed endometrial sampling for histopathologic evaluation. This procedure was a kind of endometrial injury and it was suggested that endometrial injury before ART cycle improves the outcome by the way of increased endometrial receptivity25-29. In this study we did not have the ability of comparing the effect of endometrial injury on IVF outcome because of the absence of control group and heterogenous IVF population. For our study population, comparison of the incidence of intracavitary pathologies between women according to becaming pregnant, revealed out no significant difference. On the other hand when the pregnancy rate compared according to the presence of intracavitary pathology, the pregnancy rate was high in the absence of intrauterine pathology.

    Flushing of malignant cells from the uterine cavity to the peritoneal cavity during hysteroscopy and SH may also happen30. However, the slower and low-pressure infusion of saline should be expected to carry a lower risk of cell transportation. Moreover, this risk does not appear to be greater than that involved in HSG.

    In conclusion, we suggested that OH is an easy, fast, well tolerated evaluation procedure before the ART cycles to improve the IVF outcome.

  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Discussion
  • References
  • References

    1) Grønlund L, Hertz J, Helm P, Colov NP. Transvaginal sonohysterography and hysteroscopy in the evaluation of female infertility, habitual abortion or metrorrhagia. A comparative study. Acta Obstet Gynecol Scand 1999; 78: 415-8.

    2) Granberg S, Wikland M, Karlsson B, Norstrom A, Friberg LG. Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormalities. Am J Obstet Gynecol 1991; 164: 47–52.

    3) Parsons AK, Lense JJ. Sonohysterography for endometrial abnormalities: Preliminary results. J Clin Ultrasound 1993; 21: 87–95.

    4) Ayida G, Chamberlain P, Barlow D, Kennedy S. Uterine cavity assesment prior to in vitro fertilization: comparison of transvaginal scanning, saline contrast hysterosonography and hysteroscopy. Ultrasound Obstet Gynecol 1997; 10: 59–62.

    5) Eldar-Geva T, Meagher S, Healy DL, MacLachlan V, Breheny S, Wood C. Effect of intramural, subserosal, and submucosal uterine fibroids on the outcome of assisted reproductive technology treatment. Fertil Steril 1998; 70: 687–91.

    6) Healy DL. Impact of uterine fibroids on ARToutcome. Environ Health Perspect 2000; 108: 845–7.

    7) ES. Impact of intramural leiomyomata on in-vitro fertilization embryo transfer cycle outcome. Curr Opin Obstet Gynecol 2003; 15: 239-42.

    8) Perez-Medina T, Bajo-Arenas J, Salazar F et al. Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: a prospective, randomized study. Hum Reprod 2005; 20: 1632–5.

    9) Pabuccu R, Gomel V. Reproductive outcome after hysteroscopic metroplasty in women with septate uterus and otherwise unexplained infertility. Fertil Steril 2004; 81: 1675–8.

    10) Hollett-Caines J, Vilos GA, Abu-Rafea B, Ahmad R. Fertility and pregnancy outcomes following hysteroscopic septum division. J Obstet Gynaecol Can 2006; 28: 156–9.

    11) Dicker D, Ashkenazi J, Feldberg D, Farhi J, Shalev J, Ben-Rafael Z. The value of repeat hysteroscopic evaluation in patients with failed in vitro fertilization transfer cycles. Fertil Steril 1992; 58: 833–5.

    12) Dueholm M, Lundorf E, Hansen ES, Ledertoug S, Olesen F. Evaluation of the uterine cavity with magnetic resonance imaging, transvaginal sonography, hysterosonographic examination, and diagnostic hysteroscopy. Fertil Steril 2001; 76: 350–7.

    13) De Angelis C, Santoro G, Re ME, Nofroni I. Office hysteroscopy and compliance: mini-hysteroscopy versus traditional hysteroscopy in a randomized trial. Hum Reprod 2003; 18: 2441–5.

    14) Hinckley MD, Milki AA. 1000 office-based hysteroscopies prior to in vitro fertilization: feasibility and findings. JSLS 2004; 8: 103–7.

    15) Varasteh NN, Neuwirth RS, Levin B, Keltz MD. Pregnancy rates after hysteroscopic polypectomy and myomectomy in infertile women. Obstet Gynecol 1999; 94: 168–71.

    16) Spiewankiewicz B, Stelmachow J, Sawicki W, Cendrowski K, Wypych P, Swiderska K. The effectiveness of hysteroscopic polypectomy in cases of female infertility. Clin Exp Obstet Gynecol 2003; 30: 23–5.

    17) Guven MA, Bese T, Demirkiran F, Idil M, Mgoyi L. Hydrosonography in screening for intracavitary pathology in infertile women. Int J Gynaecol Obstet 2004; 86: 377-83.

    18) Kim MR, Kim YA, Jo MY, Hwang KJ, Ryu HS. High frequency of endometrial polyps in endometriosis. J Am Assoc Gynecol Laparosc 2003; 10: 46-8.

    19) Acien P. Incidence of Mullerian defects in fertile and infertile women. Hum Reprod 1997; 12: 1372–6.

    20) Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simon C, Pellicer A. Reproductive impact of congenital Mullerian anomalies. Hum Reprod 1997; 12: 2277–81.

    21) Daly DC, Maier D, Soto-Albors C. Hysteroscopic metroplasty: six years’ experience. Obstet Gynecol 1989; 73: 201–5.

    22) Goldenberg M, Sivan E, Sharabi Z, Mashiach S, Lipitz S, Seidman DS. Reproductive outcome following hysteroscopic management of intrauterine septum and adhesions. Hum Reprod 1995; 10: 2663–5.

    23) Grimbizis G, Camus M, Clasen K, Tournaye H, De Munck L, Devroey P. Hysteroscopic septum resection in patients with recurrent abortions or infertility. Hum Reprod 1998; 13: 1188–93.

    24) Hamilton JA, Larson AJ, Lower AM, Hasnain S, Grudzinskas JG. Routine use of saline hysterosonography in 500 consecutive, unselected, infertile women. Hum Reprod 1998; 13: 2463-73.

    25) Barash A, Dekel N, Fieldust S, Segal I, Schechtman E, Granot I. Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization. Fertil Steril 2003; 79: 1317-22.

    26) Zhou L, Li R, Wang R, Huang HX, Zhong K. Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates. Fertil Steril 2008; 89: 1166-76.

    27) Karimzadeh MA, Ayazi Rozbahani M, Tabibnejad N. Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: a randomised clinical trial. Aust N Z J Obstet Gynaecol 2009; 49: 677-80.

    28) Gnainsky Y, Granot I, Aldo PB et al. Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertil Steril 2010; 94: 2030-6.

    29) Almog B, Shalom-Paz E, Dufort D, Tulandi T. Promoting implantation by local injury to the endometrium. Fertil Steril 2010; 94: 2026-9.

    30) Romano S, Shimoni Y, Muralee D. Retrograde seeding of endometrial carcinoma during hysteroscopy. Gynecol Oncol 1992; 44: 116-8.

  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Discussion
  • References
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