Outpatient hysteroscopy: a routine investigation before assisted reproductive techniques?

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1 Outpatient hysteroscopy: a routine investigation before assisted reproductive techniques? Akmal El-Mazny, M.D., F.I.C.S., Nermeen Abou-Salem, M.D., Walid El-Sherbiny, M.D., and Walid Saber, M.D. Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt Objective: To evaluate the importance of subjecting the patient to an outpatient (office) hysteroscopy (OH) before assisted reproductive techniques (ART) and patient compliance, possible side effects, and complications of the procedure. Design: Comparative observational cross-sectional study. Setting: University hospital. Patient(s): One hundred fifty-two patients attending the outpatient infertility clinic for pre-art (IVF/ intracytoplasmic sperm injection [ICSI]-ET) investigations, with normal uterine findings on hysterosalpingography (HSG). Intervention(s): Transvaginal sonography (TVS) and OH (using a rigid, 30-degree, 4-mm hysteroscope) by the vaginoscopic no touch technique. Main Outcome Measure(s): Diagnostic value and compliance of OH. Result(s): The procedure was successful in 145 patients (95.4%); 51 of them (35.2%) had previous ART failures. Abnormal hysteroscopic findings were observed in 48 women (33.1%), in which endometrial polyp, submucous myoma, and intrauterine adhesions were the most common findings. The TVS was specific (100%) but not sensitive (41.7%) compared with OH. Abnormal hysteroscopic findings were significantly higher in patients with previous ART failure(s). The procedure was acceptable in almost all patients with no reported complications. Conclusion(s): The OH should be part of the infertility workup before ART even in patients with normal HSG and/ or TVS. This is especially relevant in cases with prior failed ART cycles. (Fertil Steril Ò 2011;95: Ó2011 by American Society for Reproductive Medicine.) Key Words: Assisted reproductive techniques, infertility, intrauterine pathology, IVF/ICSI-ET, office hysteroscopy, outpatient hysteroscopy Despite advances in the field of assisted reproductive techniques (ART), only one-third of cycles started end in a pregnancy and one-fourth result in a live birth (1). Intrauterine pathologies are found to be present in 25% of infertile patients (2). Structural abnormalities of the uterine endometrial cavity may affect the reproductive outcome adversely, by interfering with the implantation or causing spontaneous abortion. Therefore, exclusion of any intrauterine pathology becomes an important step before subjecting the patient to ART. Intrauterine abnormalities may be visualized using variety of techniques, including hysterosalpingography (HSG), transvaginal sonography (TVS)/sonohysterography (SHG), and hysteroscopy (3). The HSG, although very sensitive (98%), has low specificity (34.9%), a positive predictive value (PPV) of 69.9%, and a negative predictive value (NPV) of 92% (4). The TVS is more specific (96.3%) and sensitive (100%) than HSG, with a 91.3% PPV and a 100% NPV (5). Although hysteroscopy is considered the gold standard, controversies still exist between TVS and hysteroscopy in the diagnosis of intrauterine abnormalities. With the invention of the miniature hysteroscope, it is possible to perform hysteroscopy in an office setting for diagnostic indications and certain therapeutic interventions (6). Received April 3, 2010; revised May 25, 2010; accepted June 14, 2010; published online July 17, A.E-M. has nothing to disclose. N.A-S. has nothing to disclose. W.E-S. has nothing to disclose. W.S. has nothing to disclose. Reprint requests: Walid El-Sherbiny, M.D., Department of Gynecology and Obstetrics, Cairo University, Kasr El-Aini Street, Cairo, Egypt (FAX: þ ; wssherbiny@yahoo.com). In the present study we have evaluated intrauterine pathologies using TVS and outpatient (office) hysteroscopy (OH) in patients scheduled for ART IVF or intracytoplasmic sperm injection (ICSI) ET. Our objectives were to evaluate [1] the importance of subjecting the patient to OH before ART, and [2] patient compliance, possible side effects, and complications of the procedure. MATERIALS AND METHODS This comparative observational cross-sectional study was conducted at the Department of Obstetrics and Gynecology, Kasr El-Aini Teaching Hospital, Faculty of Medicine, Cairo University, between May 2009 and March The Research Ethics Committee approved the study protocol. The study population was recruited from women attending the infertility outpatient clinic for pre-art (IVF/ICSI-ET) investigations. The women were subjected to history taking, gynecological examination, and routine infertility investigations (if not previously done), including semen analysis, hormonal profile, HSG, and laparoscopy. The TVS (Toshiba ECCO CEE SSA-340 A, with a 7.5-MHz transvaginal probe; Toshiba, Otawara, Japan) was performed as a routine investigation before ART, and to compare its findings with those of OH. Inclusion criteria for the study were: [1] normal uterine findings on HSG, and [2] no diagnostic hysteroscopy within the previous 6 months. Eligible patients were counseled about the technique, diagnostic value, and potential risks of OH; 152 of them accepted to be examined by OH, and were enrolled in the study after obtaining their informed consent. The OH was performed using a rigid hysteroscope (continuous flow; 30-degree forward-oblique view) assembled in a 4-mm diameter 272 Fertility and Sterility â Vol. 95, No. 1, January /$36.00 Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc. doi: /j.fertnstert

2 diagnostic sheath with an atraumatic tip (Karl Storz Endoscopy, Tuttlingen Germany). A high-intensity cold light source and fiberoptic cable were used to illuminate the uterine cavity. Normal saline (0.9%) was used as the distention medium, keeping the pressure between 100 and 120 mm Hg using a pressure adjustable cuff system, with the aim to use the lowest pressure required to distend the uterine cavity adequately. Eligible and consenting patients underwent OH in the early follicular phase between the 7th and 11th day of the cycle. The gynecologists involved in the procedure were blinded to TVS results, thus minimizing performance bias. No analgesics or sedatives were required as the procedure is practically painless. The patient was positioned in the dorsolithotomy (semirecumbent) position using comfortable leg rests. The perineum should be at the edge of the couch with the coccyx and sacrum well supported by the table. Pelvic examination was performed to determine the size of the uterus and its orientation. Vaginoscopic no touch technique was adopted; no speculum or tenaculum were required. The hysteroscope with its light source and flowing fluid was gently introduced into the vagina allowing for gradual distention. Once this was accomplished, the hysteroscope was advanced under direct vision to the level of the ectocervix, and guided into the endocervical canal following the small microcavity produced by the fluid in front of the endoscope. Once the endocervical canal was completely explored, the endoscope was advanced across the internal cervical os to allow evaluation of the panoramic view of the uterine cavity. On entering the uterine cavity, a systematic inspection was conducted including the uterine cornua, tubal ostia, uterine fundus, lateral, anterior, and posterior uterine walls. The uterine cavity was re-examined, as is the endocervical canal, during withdrawal of the instrument. The use of a video system helped to explain findings to the patient observing the video screen, and to record the procedure for future reference. After the procedure, patients were observed for a minimum period of 30 minutes, for possible side effects and complications. The findings at OH were documented on a special data collection form that included the following information: [1] the appearance and shape of the endocervical canal (endocervicitis is characterized by congestion, contact bleeding, excessive discharge, hypertrophy of the mucosal lining, and mucous polyp); [2] the appearance of the endometrium (endometritis is characterized by congestion, hyperemia, hemorrhages, and adhesions; hyperplastic endometrium looks thickened and easily indented by pressure, with or without multipolyp appearance); [3] shape of the uterine cavity (normal vs. enlarged vs. restricted size; regular vs. irregular contour); and [4] presence and location of structural anomalies (congenital anomalies, adhesions, myomas, polyps). This form also included a part about patient feedback, duration, possible side effects, and complications of the procedure. TABLE 1 Patients characteristics. Characteristic Values (n [ 145) Age (y) Type of infertility Primary infertility 113 (77.9%) Secondary infertility 32 (22.1%) Duration of infertility (y) Etiology of infertility Male factor 49 (33.8%) Ovarian factor 28 (19.3%) Tubal/peritoneal factor 32 (22.1%) Combined factors 15 (10.3%) Unexplained 21 (14.5%) % with previous ART trial(s) 51 (35.2%) Mean no. of previous ART trials of 6.2 (1.5) years. The type and the etiology of infertility are represented in Table 1. Fifty-one patients (35.2%) had previous ART failure(s), with mean (SD) number of trials of 1.6 (0.3). Abnormal sonographic findings were observed in 20 women (13.8%), in which submucous myoma, endometrial polyp, and endometrial hyperplasia were the most common. Abnormal hysteroscopic findings were observed in 48 cases (33.1%) in which endometrial polyp, submucous myoma and intrauterine adhesions were the most common. It is worth mentioning that a woman with an intrauterine foreign body (retained unabsorbed suture for 7 years after cesarean section), missed by TVS, was diagnosed by OH (Fig. 1). According to these results, TVS was specific (100%) but not sensitive (41.7%) compared with OH (Table 2). FIGURE 1 Intrauterine unabsorbed suture after cesarean section. Statistical Analysis Data were reported as mean SD or number and percentage. Accuracy was represented using sensitivity (true positive/true positive þ false negative) and specificity (true negative/true negative þ false positive). The c 2 test was used to compare categorical variables; P%.05 was considered significant. Analyses were done using the Statistical Package for the Social Sciences, version 16 (SPSS, Chicago, IL). RESULTS The study population comprised 152 infertile women. In 7 patients (4.6%) the procedure was abandoned because of marked cervical stenosis. The procedure was successful in 145 patients (95.4%), with mean (SD) age of 33.2 (3.4) years and duration of infertility Fertility and Sterility â 273

3 TABLE 2 Ultrasonographic and hysteroscopic findings. Findings Ultrasonography (n [ 145) Hysteroscopy (n [ 145) Cervical stenosis 0 (0.0) 4 (2.8%) Endocervicitis 2 (1.4%) 4 (2.8%) Endocervical polyp 1 (0.7%) 3 (2.1%) Uterine cavity hypoplasia 0 (0.0) 2 (1.4%) Uterine septum 0 (0.0) 1 (0.7%) Intrauterine adhesions 0 (0.0) 6 (4.1%) Intrauterine foreign body 0 (0.0) 1 (0.7%) Endometritis 0 (0.0) 3 (2.1%) Submucous myoma 5 (3.4%) 6 (4.1%) Endometrial polyp 5 (3.4%) 8 (5.5%) Polypoid endometrium 3 (2.1%) 4 (2.8%) Endometrial hyperplasia 4 (2.8%) 4 (2.8%) Blocked ostia 0 (0.0) 2 (1.4%) Total findings 20 (13.8%) a 48 (33.1%) a Sensitivity 41.7%; specificity 100% versus hysteroscopy. Endometrial polyp, submucous myoma, and endometrial hyperplasia were the most common hysteroscopic abnormalities in patients R35 years, whereas intrauterine adhesions were the most common in younger patients. Abnormal findings were not significant in patients R35 years compared with younger patients (34.6% vs. 31.3%; c 2 ¼ 0.174; P¼.676). Endometrial polyp and intrauterine adhesions were the most common hysteroscopic abnormalities in patients with previous ART failure(s). Abnormal findings were significantly higher in patients with previous ART failure(s) compared with those with no previous ART (45.1% vs. 26.6%; c 2 ¼ 5.111; P¼.024) (Table 3). The duration of OH procedure ranged from minutes. The procedure was acceptable in almost all patients. The majority of the patients did not feel any significant pain during the procedure; only 18 patients (12.4%) had experienced mild lower abdominal cramping pain after the procedure and were reassured. All patients were discharged within 30 minutes after the procedure. No early or late, major or even minor complications were reported in our series from the use of OH. DISCUSSION Transvaginal sonography is considered a first-line noninvasive investigation to evaluate the uterine cavity, and to plan for hysteroscopy (5, 7, 8). Our results demonstrate that abnormal sonographic findings were observed in only 20 cases (13.8%), whereas 28 cases (19.3%) were missed; TVS was specific (100%) but not sensitive (41.7%) compared with OH. Loverro et al. (7) showed that TVS was in agreement with 86% of the pathological findings diagnosed at hysteroscopy; TVS had a 84.5% sensitivity and 98.7% specificity, 98% PPVand 89.2% NPV. Ragni et al. (8) evaluated the accuracy of TVS, SHG compared with hysteroscopy in the diagnosis of intrauterine pathology before IVF. They found that the TVS sensitivity, specificity, PPV, and NPV were 91%, 83%, 85.4%, and 90%, respectively. The SHG yielded better results: sensitivity, specificity, PPV, and NPV were 98%, 94%, 95%, and 98%, respectively. Hysteroscopy is considered the gold standard investigation for assessment of the uterine cavity, with the ability to treat uterine pathology in infertile patients, especially with repeated ART failures (2, 6, 9 29). According to our results, abnormal hysteroscopic findings were observed in 48 women (33.1%), in whom endometrial polyp, submucous myoma, and intrauterine adhesions were the most common. Makris et al. (17) performed 680 OHs for different indications including repeated failure of IVF (54.7%) and infertility. They observed abnormal findings in 276 cases (40.5%), among which intrauterine adhesions, endometrial hyperplasia, and polyps were the most common. Feghali et al. (19) performed OH before the first stimulation cycle in 145 patients who underwent ICSI. They observed pathological patterns in 45% of hysteroscopies, among which endometritis, polyps, myomas, and mucosal diseases were the most frequent. TABLE 3 Hysteroscopic findings according to age distribution and previous ART failure(s). Hysteroscopic findings Age <35 y (n [ 67) Age R35 y (n [ 78) No previous ART (n [ 94) Previous ART (n [ 51) Cervical stenosis 2 (3.0%) 2 (2.6%) 3 (3.2%) 1 (2.0%) Endocervicitis 3 (4.5%) 1 (1.3%) 2 (2.1%) 2 (3.9%) Endocervical polyp 2 (3.0%) 1 (1.3%) 3 (3.2%) 0 (0.0) Uterine cavity hypoplasia 1 (1.5%) 1 (1.3%) 2 (2.1%) 0 (0.0) Uterine septum 1 (1.5%) 0 (0.0) 1 (1.1%) 0 (0.0) Intrauterine adhesions 4 (6.0%) 2 (2.6%) 2 (2.1%) 4 (7.8%) Intrauterine foreign body 0 (0.0) 1 (1.3%) 0 (0.0) 1 (2.0%) Endometritis 2 (3.0%) 1 (1.3%) 1 (1.1%) 2 (3.9%) Submucous myoma 1 (1.5%) 5 (6.4%) 3 (3.2%) 3 (5.9%) Endometrial polyp 2 (3.0%) 6 (7.7%) 3 (3.2%) 5 (9.8%) Polypoid endometrium 1 (1.5%) 3 (3.8%) 3 (3.2%) 1 (2.0%) Endometrial hyperplasia 0 (0.0) 4 (5.1%) 1 (1.1%) 3 (5.9%) Blocked ostia 2 (3.0%) 0 (0.0) 1 (1.1%) 1 (2.0%) Total findings 21 (31.3%) 27 (34.6%) a 25 (26.6%) 23 (45.1%) b a Nonsignificant difference versus age <35 years group (c 2 ¼ 0.174; P¼.676). b Significant difference versus no previous ART group (c 2 ¼ 5.111; P¼.024). 274 El-Mazny et al. Techniques and Instrumentation Vol. 95, No. 1, January 2011

4 Our findings demonstrate that endometrial polyp, submucous myoma, and endometrial hyperplasia were the most common hysteroscopic abnormalities in patients R35 years, whereas intrauterine adhesions were the most common in younger patients. Abnormal findings were not significant in patients R35 years compared with younger patients (34.6% vs. 31.3%; c 2 ¼ 0.174; P¼.676). In agreement with our findings, Dicker et al. (9) showed that, in elderly women more than 40 years, age-related uterine pathology such as submucous myomata, endometrial hyperplasia, and polyps were more prominent, whereas in women less than 40 years other uterine lesions, such as adhesions and tubal ostia occlusion, were more common. Feghali et al. (19) also found that the patients aged more than 38 years did not show a higher rate of pathology (29% vs. 27% for younger patients). According to our experience, endometrial polyp and intrauterine adhesions were the most common hysteroscopic abnormalities in patients with previous ART failure(s). Abnormal findings were significantly higher in patients with previous ART failure(s) compared with those with no previous ART (45.1% vs. 26.6%; c 2 ¼ 5.111; P¼.024). Dicker et al. (10) revealed uterine abnormalities (mainly newly added endometrial lesions, i.e., hyperplasia, polyps, endometritis, and synechiae) in 18.2% of women with normal initial hysteroscopy who failed to conceive after three or more IVF-ET cycles and underwent repeat hysteroscopic evaluation. Schiano et al. (16) also showed abnormalities in half of the cases, mostly cervical abnormalities (synechia, polyp, and false passage) and hormonal-dependent abnormalities (polyp, hyperplasia, and submucous myoma) in uterine reassessment by hysteroscopy in women with two unsuccessful IVF-ET attempts. A recent systematic review and meta-analysis (25) of two randomized and three nonrandomized controlled trials, on 1,691 patients with two or more failed IVF attempts, concluded that OH significantly improve the pregnancy rate (PR) in the subsequent IVF cycle. However, the value of hysteroscopy as a routine investigation in the management of infertile women is a matter of debate. The European Society of Human Reproduction and Embryology (ESHRE) guidelines indicate hysteroscopy to be unnecessary, unless it is for the confirmation and treatment of doubtful intrauterine pathology (30). The two main problems that argue against the case of hysteroscopy are that it is an invasive procedure and that there is a debate about the real significance of the observed intrauterine pathology on fertility (30). Nevertheless, according to our experience, OH has clearly many advantages that need to be emphasized: 1. The procedure is minimally invasive, and unlike traditional hysteroscopy it can be performed in an office-based gynecological practice with no need for hospitalization, cervical dilatation, or anesthesia. 2. The procedure has a very low technical failure rate. In only 7 patients (4.6%) the procedure was abandoned because of marked cervical stenosis. 3. The procedure gives the ability to visualize the entire lower genital tract (vaginoscopy, cerviscopy); 11 cases (7.6%) had abnormalities in the cervical canal of which 8 cases (5.5%) were missed by TVS. Abnormalities, such as cervical stenosis, large nabothian cyst, or cervical polyp, may need treatment before ART to ensure easy ET. 4. The procedure gives reliable visual assessment of the uterine cavity; 37 cases (25.5%) had abnormalities in the uterine cavity of which 20 cases (13.8%) were missed by TVS. Abnormalities, such as endometrial polyp, submucous myoma, or intrauterine adhesions, may need surgical interference before ART to improve the PR and also to save the patient additional costs, especially in cases with recurrent failures. 5. The procedure takes only a few minutes and patient compliance was very high. No speculum or tenaculum was used minimizing discomfort to the patient. The ability of the patients to interact while performing the procedure increases their understanding and acceptability. 6. The patient being awake makes pain a safeguard against complications, such as faulty introduction or perforation. Likewise, as entry into the uterine cavity is made under vision, the risk of perforation is minimal. Normal saline was used as a distention medium to avoid the problem of fluid imbalance. No early or late, major or even minor complications were reported in our series from the use of OH. 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