Ultrasound Obstet Gynecol 2015; 45: 346–350 Published online 11 February 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.14646
Pain during Fallopian-tube patency testing by hysterosalpingo-foam sonography D. VAN SCHOUBROECK, T. VAN DEN BOSCH, L. AMEYE, A. S. BOES, T. D’HOOGHE and D. TIMMERMAN Department of Development and Regeneration, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium
K E Y W O R D S: Fallopian-tube patency tests; female; infertility; microbubbles; ultrasonography
ABSTRACT Objectives To evaluate perception of pain during Fallopian-tube patency testing by hysterosalpingo-foam sonography (HyFoSy). Methods In this cross-sectional study, 216 consecutive women presenting at a university fertility clinic for HyFoSy examination were included. Patients were instructed to take ibuprofen 1 hour before the procedure. Immediately after the procedure, patients filled in a questionnaire concerning discomfort or pain experienced during the process, including a visual analog scale (VAS) score for perception of pain. Results The median VAS score for perception of pain during transvaginal ultrasound examination and during HyFoSy examination was 1.5 (95% CI, 1.2–1.7) and 3.6 (95% CI, 3.0–4.0), respectively. One-third of women reported that the level of discomfort or pain during HyFoSy examination was similar to that during the preceding transvaginal ultrasound examination and 48% of women considered HyFoSy examination to be neutral/unpleasant, but not painful. There was an inverse association between both patients’ age and parity and the pain experienced. Conclusions HyFoSy examination is tolerated well and allows for reliable tubal patency testing without exposing the patient to ionizing radiation in an outpatient setting with a low technical failure rate. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
INTRODUCTION Tubal patency testing is performed during female subfertility evaluation. Hysterosalpingo-foam sonography (HyFoSy) assesses the patency of the Fallopian tubes by allowing observation of the passage of a mixture of fluid
and air, a gel foam, from the uterine cavity through the Fallopian tubes into the peritoneal cavity1,2 . A major advantage of HyFoSy compared to hysterosalpingography (HSG) is the absence of radiation exposure. Especially in the case of suspected transient tubal spasm, in which examination duration may increase considerably while awaiting resolution of the spasm, necessitating repeated fluoroscopy and hence exposure of the ovaries of women of reproductive age to substantial doses of radiation3 – 5 . The contrast agent used in HyFoSy examination is not associated with allergic reactions as it is composed of air, purified water and a gel to keep air bubbles in suspension1 . Furthermore, HyFoSy examination is performed in an outpatient ultrasound clinic for patients with infertility, in the same setting that transvaginal sonography is performed routinely to evaluate the uterus and ovaries and to screen for endometriosis6 . This setting can be considered as less stressful for women when compared to the radiology department in which HSG is performed on a hard and flat X-ray table. Other water-based contrast agents have been used to assess tubal patency by ultrasound (hysterosalpingo-contrast sonography or HyCoSy). Products such as Echovist or Levovist (Schering AG, Berlin, Germany) and SonoVue (Bracco International BV, Amsterdam, The Netherlands) are also based on microbubbles and yield images similar to those obtained during HyFoSy examination7 – 11 , but their use is limited by restricted commercial availability and high cost. The alternated injection of water and air12 – 14 is inexpensive but highly dependent on the operator; it usually requires larger instillation volumes and actual passage through the Fallopian tubes is more difficult to visualize. Finally, the recently introduced coded contrast imaging (CCI)14,15 requires special software and a second-generation contrast medium. Pain during HyCoSy examination is reported to be acceptable, but may differ according
Correspondence to: Dr T. Van den Bosch, Department of Development and Regeneration, University Hospitals Leuven, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium (e-mail: [email protected]) Accepted: 22 July 2014
Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
ORIGINAL PAPER
HyFoSy and pain to the contrast agent and/or the instillation volume used13,16,17 . It is important that women have realistic expectations about the procedure they are about to undergo18 . If a woman anticipates an extremely painful test, she may experience unnecessary stress preceding the examination. However, if procedure-related discomfort is minimized, she may feel betrayed if the pain experienced exceeds her expectation, which may result in a loss of confidence in the medical team. The aim of this study was to evaluate the degree of pain or discomfort associated with HyFoSy examination.
METHODS In this prospective observational study, 216 consecutive women referred for tubal patency evaluation from the Leuven University Fertility Centre between August 2011 and March 2013 answered a questionnaire immediately after HyFoSy examination. The study was registered at the Clinical Trial Center (CTC) of the Leuven University Hospital (S-52595) and was approved by the local Ethics Committee; oral informed consent was obtained from all patients and Institutional Review Board approval was obtained. HyFoSy examination was scheduled during the proliferative phase of the menstrual cycle in women with a natural cycle, or at random (excluding menstruation) in women using contraception. All women were instructed to take a non-steroidal anti-inflammatory drug (NSAID), ibuprofen 400 mg, approximately 1 hour before the appointment. Exclusion criteria for this study were refusal to participate (n = 1) or inability to complete the questionnaire because of insufficient knowledge of the Dutch language (n = 1) (99.1% response rate). Initially, a transvaginal ultrasound (TVS) examination was performed to evaluate the uterine cavity and ovaries and to exclude a hydrosalpinx. This TVS examination was referred to as ‘TVS only’ throughout the study and was not considered part of the HyFoSy procedure. Subsequently, HyFoSy examination was performed as described elsewhere2 . With respect to the examiner’s skills and the instruments used, all HyFoSy procedures were performed by a team of two experienced gynecologists; one performed the TVS examination (D.V.S.) and the other inserted the balloon catheter and instilled the gel-foam (T.V.D.B. or A.B.). Briefly, the cervix was visualized with the patient in the lithotomy position, using an appropriately sized open-sided vaginal speculum and was cleaned with an aqueous chlorhexidine solution. Using swab forceps, a 2-mm pediatric Foley’s balloon catheter with stylet (Pediatric Folysil® Catheter, Coloplast A/S, Humlebaek, Denmark) was inserted through the cervical canal into the lower part of the uterine cavity where the balloon was inflated slowly with 0.5–1 mL water. The use of a tenaculum or a cervical dilatator to introduce the catheter was avoided whenever possible but was necessary in four (2%) cases. After catheter insertion, the speculum
Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
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was removed and a syringe filled with gel-foam was connected to the catheter. The gel-foam was prepared by mechanically mixing 10 mL sterile water and 10 mL ExEm® gel (ExEm®; GynaecologIQ, Delft, The Netherlands) according to instructions of the manufacturer1,2 . A second operator reinserted the endovaginal ultrasound probe and a transverse ultrasound section was obtained at the level of the interstitial segments of the Fallopian tubes. Small aliquots of gel-foam (0.5–1 mL) were injected slowly and repeatedly under direct ultrasound guidance, until its passage or non-passage through both Fallopian tubes had been assessed. High infusion rates using aliquot boluses exceeding 1 mL were avoided. Ample information was provided before, during and after the procedure in an attempt to minimize anxiety19 . HyFoSy was performed in the gynecological department of the study center. If so wished, women could be accompanied by a partner or someone else of choice and could be provided with a separate screen on which to view the ultrasound images20 . Following HyFoSy examination and discussion of the results, the women remained for 10–15 min in a quiet seating area and answered a questionnaire about the pain or discomfort perceived during the TVS-only examination and another about the pain or discomfort perceived during the HyFoSy procedure. Both questionnaires consisted of the same multiple choice questions: (1) general impression of discomfort or pain during the examination: ‘neutral/unpleasant but not painful/painful but bearable/really painful’; (2) discomfort or pain perceived in relation to blood sampling: ‘less/equally/more painful’; (3) discomfort or pain perceived in relation to a cervical cytology smear: ‘less/equally/more painful’. Finally, women were asked to score the discomfort or pain experienced using a 10.0-cm visual analog scale (VAS) score: starting from 0.0 cm, representing no discomfort or pain at all, up to 10.0 cm, representing the worst pain imaginable. Completed questionnaires were given to the unit secretary before the women left the department.
Statistical analysis Distribution-free confidence limits were calculated for the median VAS score. To assess the difference between the ultrasound VAS score and the HyFoSy VAS score, the Wilcoxon signed-rank test was used. The relative difference between the VAS scores for HyFoSy and ultrasound was calculated as: (VAS HyFoSy – VAS ultrasound only)/(VAS ultrasound only). Bowker’s test for symmetry was used to test agreement between HyFoSy and ultrasound for categorical variables. The Mann–Whitney U-test was used to assess differences in HyFoSy VAS score between patient subgroups; women with or without bilateral Fallopian-tube patency and nulliparous vs parous women. Spearman’s rank correlation was used to calculate the correlation between HyFoSy VAS score and the patient’s age. A P-value < 0.05 was considered statistically significant. Multivariate analysis was performed to determine which variables,
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in addition to the method (HyFoSy or ultrasound), were independently related to the pain VAS score. As dependency between the HyFoSy VAS score and the ultrasound VAS score were corrected for each patient, the multivariate analysis was performed using generalized estimating equation modeling, with a compound symmetry working correlation matrix. All statistical analyses were performed with SAS 9.3 (SAS System, SAS Institute Inc., Cary, NC, USA).
RESULTS In total, 216 patients underwent TVS and subsequent HyFoSy, with no technical failure during the latter. The median age of the cohort was 31 (range, 18–45) years with a median parity of 0 (range, 0–7) and a median number of previous miscarriages of 0 (range, 0–6). Of the 432 Fallopian tubes evaluated, 85% were found to be patent on HyFoSy examination. Two of the patients did not complete the questionnaires and were excluded from the subsequent analysis. Table 1 shows the comparison of discomfort or pain experienced during TVS and HyFoSy examinations. Approximately half (102/214) of the patients perceived HyFoSy examination as neutral/unpleasant but not really painful. One in three (64/214) women reported the same level of discomfort or pain for TVS examination as for HyFoSy examination and 8% (17/214) considered HyFoSy examination to be really painful (P < 0.001; Bowker’s test for symmetry). Table 2 shows the levels of discomfort or pain experienced during the TVS and HyFoSy examinations in comparison to peripheral blood sampling and to the cervical cytology smear procedure; 53% (113/213) of patients reported HyFoSy examination to be more painful than peripheral blood sampling (P < 0.001; Bowker’s test for symmetry) and 47% (97/207) reported HyFoSy examination to be more painful than the cervical smear procedure, whereas 5% (11/207) reported TVS examination to be more painful than the smear procedure (P < 0.001; Bowker’s test for symmetry). In Figure 1 VAS scores for pain experienced during TVS and HyFoSy examinations are plotted for each patient. Median VAS scores for TVS and HyFoSy examinations were 1.5 (95% CI, 1.2–1.7) and 3.6 (95% CI, 3.0–4.0), respectively (P < 0.001; Wilcoxon signed-rank test). In the four cases that required a tenaculum, the median TVS and HyFoSy VAS scores were 3.4 (range, 0.0–5.6) and 4.8 (range, 0.9–6.4), respectively. There was no significant difference (P = 0.71; Wilcoxon signed-rank test) in pain perception according to tubal patency; the median VAS score for HyFoSy examination in cases in which both Fallopian tubes were patent was 3.6 (95% CI, 2.9–4.0) and, if at least one Fallopian tube was not patent, a median VAS score of 3.9 (95% CI, 2.5–4.9) was reported. There was an inverse association between the patient’s age and her perception of pain; younger women reported higher VAS scores. The median VAS scores
Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
Table 1 Pain or discomfort experienced during transvaginal ultrasound (TVS) examination in comparison to pain during subsequent hysterosalpingo-foam sonography (HyFoSy), according to the questionnaire results of 214 women Pain during HyFoSy Painful but Really Neutral Unpleasant bearable painful Total
Pain during TVS Neutral Unpleasant Painful but bearable Really painful Total
19 5 0 0 24
36 41 1 0 78
41 50 4 0 95
8 7 2 0 17*
104 103 7 0 214
Data are given as n. *P < 0.001 (Bowker’s test for symmetry). Table 2 Pain or discomfort perceived during transvaginal ultrasound (TVS) examination and subsequent hysterosalpingofoam sonography (HyFoSy) in comparison to pain during blood sampling and during the cervical cytology smear procedure Pain during HyFoSy Less Pain during TVS Less Equal More Total Pain during TVS Less Equal More Total
Equal
More
Total
Vs pain during blood sampling 35 34 44 113 1 29 44 74 0 1 25 26 36 64 113* 213 Vs pain during cervical smear procedure 17 39 46 102 4 49 41 94 0 1 10 11* 21 89 97 207
Data are given as n. *P < 0.001 (Bowker’s test for symmetry).
reported in the age groups of < 30 years, 30–39 years and > 39 years were 4.4 (95% CI, 3.3–5.0), 3.2 (95% CI, 2.5–4.0) and 2.6 (95% CI, 1.7–4.5), respectively (Spearman’s rank correlation, −0.17 (95% CI, −0.29 to −0.03); P = 0.01). When scores were categorized into age groups, the same trend was observed for pain reported during HyFoSy examination (P = 0.03) as compared to that reported during blood sampling (P = 0.10) and the cervical cytology smear procedure (P = 0.02). There was an inverse association between parity and pain; nulliparous women experienced more pain than parous women as indicated by a median VAS score for HyFoSy examination of 3.9 (95% CI, 3.2–4.9) compared to 2.6 (95% CI, 2.0–3.5) (Spearman’s rank correlation, –0.23 (95% CI, –0.35 to –0.09); P = 0.001), respectively. The effect of parity was also significant for the pain reported during HyFoSy examination (P = 0.01) and when this procedure was compared to the pain reported during blood sampling (P = 0.006) and the cervical cytology smear procedure (P < 0.001). A previous miscarriage had no effect on the level of pain experienced (P = 0.36). Multivariate analysis showed that differences in pain perceived can be explained mainly by the method used
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10.0
HyFoSy VAS score
8.0 6.0 4.0 2.0 0.0 0.0
2.0
4.0
6.0
8.0
10.0
TVS VAS score
Figure 1 Visual analog scale (VAS) scores for pain experienced during transvaginal ultrasound (TVS) examination only and during hysterosalpingo-foam sonography (HyFoSy). Median VAS scores were 1.5 (95% CI, 1.2–1.7) and 3.6 (95% CI, 3.0–4.0), respectively (P < 0.001).
(HyFoSy or TVS; P < 0.001) and parity of the patient (parous vs nulliparous; P = 0.04) while the patient’s age did not improve the prediction of the VAS score (P = 0.33) when compared to the model that included the method and parity alone.
DISCUSSION This is the first report on pain or discomfort experienced by patients during HyFoSy examination. This procedure is well tolerated generally and HyFoSy-associated pain or discomfort is as expected and is in line with reported patient perceptions during HyCoSy examination11,13,16 . The information given to patients about any procedure should go beyond the rationale and technical aspects and should include information regarding the discomfort or pain to be expected. This part of an informed consent should also be supported by evidence. The pain reported may depend on multiple factors such as the patient’s capacity to cope with pain, the examiner’s skills, the nature of the procedure and the instruments used. This is a single-center study and all HyFoSy procedures were performed by the same team, using a strict protocol as described previously2 . A limitation of the study is the absence of validation studies in other centers and future studies are awaited to validate our data. We used the pain scores during TVS examination as the ‘baseline’ assessment, against which the pain scores during HyFoSy examination could be weighed. One third of women reported the same level of discomfort or pain for HyFoSy examination as for the preceding TVS examination. A median VAS score of 3.6, and a general impression of HyFoSy examination being unpleasant but not painful for almost half of the women in this study are reassuring findings. Nevertheless, we acknowledge that 67 % of women perceived HyFoSy examination to be more painful than TVS examination, which is not surprising in view of the semi-invasive nature of the HyFoSy procedure.
Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
Previously, the same research team in the same unit21,22 reported pain scores for diagnostic office hysteroscopy, endometrial sampling and levonorgestrel intrauterine system insertion. The median VAS score for hysteroscopy was significantly lower than that for HyFoSy: 1.7 (95% CI, 1.3–2.0) vs 3.6 (95% CI, 3.0–4.0), respectively, whereas the median (95% CI) VAS scores for endometrial sampling and levonorgestrel intrauterine system insertion were similar; 4.0 (95% CI, 3.0–4.0) and 4.0 (95% CI, 4.0–5.0), respectively. Although we acknowledge the weakness of a comparison using historical controls, the fact that HyFoSy examination is more painful compared to diagnostic office hysteroscopy is within expectation. Indeed, HyFoSy examination, unlike hysteroscopy, is associated with cervical canal sealing by balloon insufflation in order to allow an increase in the intracavitary pressure. There was no significant difference in pain perception according to the presence or absence of bilateral tubal patency. Uni- or bilateral tubal spasm may temporarily hinder passage of the contrast agent. In the context of HSG, NSAIDs have been reported to reduce the incidence of tubal spasms and of uterine cramps during and after the procedure, but this is controversial23 – 27 . We cannot comment on the effect of NSAIDs on tubal spasm in this study as all women had been instructed to take them beforehand. In the case of non-passage of the gel-foam, it was our experience that some women reported cramps while others did not. We adopted the policy of waiting and temporarily withholding further gel-foam injection. In several cases, the Fallopian tube(s) proved to be patent for gel-foam after a certain period, suggesting that the apparent proximal block had been caused by tubal spasm. The occurrence of tubal spasm and its association with both non-patent ‘blocked’ and eventually patent tubes may be one of the factors explaining why there was no difference in pain perception between the groups with or without blocked tubes. The effect of NSAIDs on perceived pain related to an intrauterine procedure is uncertain28,29 . According to a systematic review, NSAIDs were of no benefit when used prophylactically before intrauterine contraceptive device insertion28 . However, because of the possible beneficial effect in the prevention of tubal spasm, patients were instructed to take ibuprofen before the HyFoSy procedure. Surprisingly, half of the women in the study reported the cervical cytology smear procedure to be more painful than HyFoSy examination. Speculum insertion is part of the HyFoSy procedure also. We suspect that many women are apprehensive of speculum insertion because of past experience. Special attention should be given to make every step of the procedure as comfortable as possible, which includes choosing an appropriately sized speculum and the use of lubrication for a gentle and careful insertion30,31 . Our observation that younger women and nulliparous women experienced more pain compared to older or parous women32 can be explained by the likelihood that older and parous women are more familiar with pain of gynecological origin, uterine cramps, cervical smear procedures and TVS examination.
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We conclude that HyFoSy is an acceptable procedure for the patient. Moreover, HyFoSy has a low failure rate and allows for reliable tubal patency testing in an outpatient setting2 .
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Pain during Fallopian-tube patency testing by hysterosalpingo-foam sonography D. VAN SCHOUBROECK, T. VAN DEN BOSCH, L. AMEYE, A. S. BOES, T. D’HOOGHE and D. TIMMERMAN Department of Development and Regeneration, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium
K E Y W O R D S: Fallopian-tube patency tests; female; infertility; microbubbles; ultrasonography
ABSTRACT Objectives To evaluate perception of pain during Fallopian-tube patency testing by hysterosalpingo-foam sonography (HyFoSy). Methods In this cross-sectional study, 216 consecutive women presenting at a university fertility clinic for HyFoSy examination were included. Patients were instructed to take ibuprofen 1 hour before the procedure. Immediately after the procedure, patients filled in a questionnaire concerning discomfort or pain experienced during the process, including a visual analog scale (VAS) score for perception of pain. Results The median VAS score for perception of pain during transvaginal ultrasound examination and during HyFoSy examination was 1.5 (95% CI, 1.2–1.7) and 3.6 (95% CI, 3.0–4.0), respectively. One-third of women reported that the level of discomfort or pain during HyFoSy examination was similar to that during the preceding transvaginal ultrasound examination and 48% of women considered HyFoSy examination to be neutral/unpleasant, but not painful. There was an inverse association between both patients’ age and parity and the pain experienced. Conclusions HyFoSy examination is tolerated well and allows for reliable tubal patency testing without exposing the patient to ionizing radiation in an outpatient setting with a low technical failure rate. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
INTRODUCTION Tubal patency testing is performed during female subfertility evaluation. Hysterosalpingo-foam sonography (HyFoSy) assesses the patency of the Fallopian tubes by allowing observation of the passage of a mixture of fluid
and air, a gel foam, from the uterine cavity through the Fallopian tubes into the peritoneal cavity1,2 . A major advantage of HyFoSy compared to hysterosalpingography (HSG) is the absence of radiation exposure. Especially in the case of suspected transient tubal spasm, in which examination duration may increase considerably while awaiting resolution of the spasm, necessitating repeated fluoroscopy and hence exposure of the ovaries of women of reproductive age to substantial doses of radiation3 – 5 . The contrast agent used in HyFoSy examination is not associated with allergic reactions as it is composed of air, purified water and a gel to keep air bubbles in suspension1 . Furthermore, HyFoSy examination is performed in an outpatient ultrasound clinic for patients with infertility, in the same setting that transvaginal sonography is performed routinely to evaluate the uterus and ovaries and to screen for endometriosis6 . This setting can be considered as less stressful for women when compared to the radiology department in which HSG is performed on a hard and flat X-ray table. Other water-based contrast agents have been used to assess tubal patency by ultrasound (hysterosalpingo-contrast sonography or HyCoSy). Products such as Echovist or Levovist (Schering AG, Berlin, Germany) and SonoVue (Bracco International BV, Amsterdam, The Netherlands) are also based on microbubbles and yield images similar to those obtained during HyFoSy examination7 – 11 , but their use is limited by restricted commercial availability and high cost. The alternated injection of water and air12 – 14 is inexpensive but highly dependent on the operator; it usually requires larger instillation volumes and actual passage through the Fallopian tubes is more difficult to visualize. Finally, the recently introduced coded contrast imaging (CCI)14,15 requires special software and a second-generation contrast medium. Pain during HyCoSy examination is reported to be acceptable, but may differ according
Correspondence to: Dr T. Van den Bosch, Department of Development and Regeneration, University Hospitals Leuven, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium (e-mail: [email protected]) Accepted: 22 July 2014
Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
ORIGINAL PAPER
HyFoSy and pain to the contrast agent and/or the instillation volume used13,16,17 . It is important that women have realistic expectations about the procedure they are about to undergo18 . If a woman anticipates an extremely painful test, she may experience unnecessary stress preceding the examination. However, if procedure-related discomfort is minimized, she may feel betrayed if the pain experienced exceeds her expectation, which may result in a loss of confidence in the medical team. The aim of this study was to evaluate the degree of pain or discomfort associated with HyFoSy examination.
METHODS In this prospective observational study, 216 consecutive women referred for tubal patency evaluation from the Leuven University Fertility Centre between August 2011 and March 2013 answered a questionnaire immediately after HyFoSy examination. The study was registered at the Clinical Trial Center (CTC) of the Leuven University Hospital (S-52595) and was approved by the local Ethics Committee; oral informed consent was obtained from all patients and Institutional Review Board approval was obtained. HyFoSy examination was scheduled during the proliferative phase of the menstrual cycle in women with a natural cycle, or at random (excluding menstruation) in women using contraception. All women were instructed to take a non-steroidal anti-inflammatory drug (NSAID), ibuprofen 400 mg, approximately 1 hour before the appointment. Exclusion criteria for this study were refusal to participate (n = 1) or inability to complete the questionnaire because of insufficient knowledge of the Dutch language (n = 1) (99.1% response rate). Initially, a transvaginal ultrasound (TVS) examination was performed to evaluate the uterine cavity and ovaries and to exclude a hydrosalpinx. This TVS examination was referred to as ‘TVS only’ throughout the study and was not considered part of the HyFoSy procedure. Subsequently, HyFoSy examination was performed as described elsewhere2 . With respect to the examiner’s skills and the instruments used, all HyFoSy procedures were performed by a team of two experienced gynecologists; one performed the TVS examination (D.V.S.) and the other inserted the balloon catheter and instilled the gel-foam (T.V.D.B. or A.B.). Briefly, the cervix was visualized with the patient in the lithotomy position, using an appropriately sized open-sided vaginal speculum and was cleaned with an aqueous chlorhexidine solution. Using swab forceps, a 2-mm pediatric Foley’s balloon catheter with stylet (Pediatric Folysil® Catheter, Coloplast A/S, Humlebaek, Denmark) was inserted through the cervical canal into the lower part of the uterine cavity where the balloon was inflated slowly with 0.5–1 mL water. The use of a tenaculum or a cervical dilatator to introduce the catheter was avoided whenever possible but was necessary in four (2%) cases. After catheter insertion, the speculum
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was removed and a syringe filled with gel-foam was connected to the catheter. The gel-foam was prepared by mechanically mixing 10 mL sterile water and 10 mL ExEm® gel (ExEm®; GynaecologIQ, Delft, The Netherlands) according to instructions of the manufacturer1,2 . A second operator reinserted the endovaginal ultrasound probe and a transverse ultrasound section was obtained at the level of the interstitial segments of the Fallopian tubes. Small aliquots of gel-foam (0.5–1 mL) were injected slowly and repeatedly under direct ultrasound guidance, until its passage or non-passage through both Fallopian tubes had been assessed. High infusion rates using aliquot boluses exceeding 1 mL were avoided. Ample information was provided before, during and after the procedure in an attempt to minimize anxiety19 . HyFoSy was performed in the gynecological department of the study center. If so wished, women could be accompanied by a partner or someone else of choice and could be provided with a separate screen on which to view the ultrasound images20 . Following HyFoSy examination and discussion of the results, the women remained for 10–15 min in a quiet seating area and answered a questionnaire about the pain or discomfort perceived during the TVS-only examination and another about the pain or discomfort perceived during the HyFoSy procedure. Both questionnaires consisted of the same multiple choice questions: (1) general impression of discomfort or pain during the examination: ‘neutral/unpleasant but not painful/painful but bearable/really painful’; (2) discomfort or pain perceived in relation to blood sampling: ‘less/equally/more painful’; (3) discomfort or pain perceived in relation to a cervical cytology smear: ‘less/equally/more painful’. Finally, women were asked to score the discomfort or pain experienced using a 10.0-cm visual analog scale (VAS) score: starting from 0.0 cm, representing no discomfort or pain at all, up to 10.0 cm, representing the worst pain imaginable. Completed questionnaires were given to the unit secretary before the women left the department.
Statistical analysis Distribution-free confidence limits were calculated for the median VAS score. To assess the difference between the ultrasound VAS score and the HyFoSy VAS score, the Wilcoxon signed-rank test was used. The relative difference between the VAS scores for HyFoSy and ultrasound was calculated as: (VAS HyFoSy – VAS ultrasound only)/(VAS ultrasound only). Bowker’s test for symmetry was used to test agreement between HyFoSy and ultrasound for categorical variables. The Mann–Whitney U-test was used to assess differences in HyFoSy VAS score between patient subgroups; women with or without bilateral Fallopian-tube patency and nulliparous vs parous women. Spearman’s rank correlation was used to calculate the correlation between HyFoSy VAS score and the patient’s age. A P-value < 0.05 was considered statistically significant. Multivariate analysis was performed to determine which variables,
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in addition to the method (HyFoSy or ultrasound), were independently related to the pain VAS score. As dependency between the HyFoSy VAS score and the ultrasound VAS score were corrected for each patient, the multivariate analysis was performed using generalized estimating equation modeling, with a compound symmetry working correlation matrix. All statistical analyses were performed with SAS 9.3 (SAS System, SAS Institute Inc., Cary, NC, USA).
RESULTS In total, 216 patients underwent TVS and subsequent HyFoSy, with no technical failure during the latter. The median age of the cohort was 31 (range, 18–45) years with a median parity of 0 (range, 0–7) and a median number of previous miscarriages of 0 (range, 0–6). Of the 432 Fallopian tubes evaluated, 85% were found to be patent on HyFoSy examination. Two of the patients did not complete the questionnaires and were excluded from the subsequent analysis. Table 1 shows the comparison of discomfort or pain experienced during TVS and HyFoSy examinations. Approximately half (102/214) of the patients perceived HyFoSy examination as neutral/unpleasant but not really painful. One in three (64/214) women reported the same level of discomfort or pain for TVS examination as for HyFoSy examination and 8% (17/214) considered HyFoSy examination to be really painful (P < 0.001; Bowker’s test for symmetry). Table 2 shows the levels of discomfort or pain experienced during the TVS and HyFoSy examinations in comparison to peripheral blood sampling and to the cervical cytology smear procedure; 53% (113/213) of patients reported HyFoSy examination to be more painful than peripheral blood sampling (P < 0.001; Bowker’s test for symmetry) and 47% (97/207) reported HyFoSy examination to be more painful than the cervical smear procedure, whereas 5% (11/207) reported TVS examination to be more painful than the smear procedure (P < 0.001; Bowker’s test for symmetry). In Figure 1 VAS scores for pain experienced during TVS and HyFoSy examinations are plotted for each patient. Median VAS scores for TVS and HyFoSy examinations were 1.5 (95% CI, 1.2–1.7) and 3.6 (95% CI, 3.0–4.0), respectively (P < 0.001; Wilcoxon signed-rank test). In the four cases that required a tenaculum, the median TVS and HyFoSy VAS scores were 3.4 (range, 0.0–5.6) and 4.8 (range, 0.9–6.4), respectively. There was no significant difference (P = 0.71; Wilcoxon signed-rank test) in pain perception according to tubal patency; the median VAS score for HyFoSy examination in cases in which both Fallopian tubes were patent was 3.6 (95% CI, 2.9–4.0) and, if at least one Fallopian tube was not patent, a median VAS score of 3.9 (95% CI, 2.5–4.9) was reported. There was an inverse association between the patient’s age and her perception of pain; younger women reported higher VAS scores. The median VAS scores
Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
Table 1 Pain or discomfort experienced during transvaginal ultrasound (TVS) examination in comparison to pain during subsequent hysterosalpingo-foam sonography (HyFoSy), according to the questionnaire results of 214 women Pain during HyFoSy Painful but Really Neutral Unpleasant bearable painful Total
Pain during TVS Neutral Unpleasant Painful but bearable Really painful Total
19 5 0 0 24
36 41 1 0 78
41 50 4 0 95
8 7 2 0 17*
104 103 7 0 214
Data are given as n. *P < 0.001 (Bowker’s test for symmetry). Table 2 Pain or discomfort perceived during transvaginal ultrasound (TVS) examination and subsequent hysterosalpingofoam sonography (HyFoSy) in comparison to pain during blood sampling and during the cervical cytology smear procedure Pain during HyFoSy Less Pain during TVS Less Equal More Total Pain during TVS Less Equal More Total
Equal
More
Total
Vs pain during blood sampling 35 34 44 113 1 29 44 74 0 1 25 26 36 64 113* 213 Vs pain during cervical smear procedure 17 39 46 102 4 49 41 94 0 1 10 11* 21 89 97 207
Data are given as n. *P < 0.001 (Bowker’s test for symmetry).
reported in the age groups of < 30 years, 30–39 years and > 39 years were 4.4 (95% CI, 3.3–5.0), 3.2 (95% CI, 2.5–4.0) and 2.6 (95% CI, 1.7–4.5), respectively (Spearman’s rank correlation, −0.17 (95% CI, −0.29 to −0.03); P = 0.01). When scores were categorized into age groups, the same trend was observed for pain reported during HyFoSy examination (P = 0.03) as compared to that reported during blood sampling (P = 0.10) and the cervical cytology smear procedure (P = 0.02). There was an inverse association between parity and pain; nulliparous women experienced more pain than parous women as indicated by a median VAS score for HyFoSy examination of 3.9 (95% CI, 3.2–4.9) compared to 2.6 (95% CI, 2.0–3.5) (Spearman’s rank correlation, –0.23 (95% CI, –0.35 to –0.09); P = 0.001), respectively. The effect of parity was also significant for the pain reported during HyFoSy examination (P = 0.01) and when this procedure was compared to the pain reported during blood sampling (P = 0.006) and the cervical cytology smear procedure (P < 0.001). A previous miscarriage had no effect on the level of pain experienced (P = 0.36). Multivariate analysis showed that differences in pain perceived can be explained mainly by the method used
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10.0
HyFoSy VAS score
8.0 6.0 4.0 2.0 0.0 0.0
2.0
4.0
6.0
8.0
10.0
TVS VAS score
Figure 1 Visual analog scale (VAS) scores for pain experienced during transvaginal ultrasound (TVS) examination only and during hysterosalpingo-foam sonography (HyFoSy). Median VAS scores were 1.5 (95% CI, 1.2–1.7) and 3.6 (95% CI, 3.0–4.0), respectively (P < 0.001).
(HyFoSy or TVS; P < 0.001) and parity of the patient (parous vs nulliparous; P = 0.04) while the patient’s age did not improve the prediction of the VAS score (P = 0.33) when compared to the model that included the method and parity alone.
DISCUSSION This is the first report on pain or discomfort experienced by patients during HyFoSy examination. This procedure is well tolerated generally and HyFoSy-associated pain or discomfort is as expected and is in line with reported patient perceptions during HyCoSy examination11,13,16 . The information given to patients about any procedure should go beyond the rationale and technical aspects and should include information regarding the discomfort or pain to be expected. This part of an informed consent should also be supported by evidence. The pain reported may depend on multiple factors such as the patient’s capacity to cope with pain, the examiner’s skills, the nature of the procedure and the instruments used. This is a single-center study and all HyFoSy procedures were performed by the same team, using a strict protocol as described previously2 . A limitation of the study is the absence of validation studies in other centers and future studies are awaited to validate our data. We used the pain scores during TVS examination as the ‘baseline’ assessment, against which the pain scores during HyFoSy examination could be weighed. One third of women reported the same level of discomfort or pain for HyFoSy examination as for the preceding TVS examination. A median VAS score of 3.6, and a general impression of HyFoSy examination being unpleasant but not painful for almost half of the women in this study are reassuring findings. Nevertheless, we acknowledge that 67 % of women perceived HyFoSy examination to be more painful than TVS examination, which is not surprising in view of the semi-invasive nature of the HyFoSy procedure.
Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
Previously, the same research team in the same unit21,22 reported pain scores for diagnostic office hysteroscopy, endometrial sampling and levonorgestrel intrauterine system insertion. The median VAS score for hysteroscopy was significantly lower than that for HyFoSy: 1.7 (95% CI, 1.3–2.0) vs 3.6 (95% CI, 3.0–4.0), respectively, whereas the median (95% CI) VAS scores for endometrial sampling and levonorgestrel intrauterine system insertion were similar; 4.0 (95% CI, 3.0–4.0) and 4.0 (95% CI, 4.0–5.0), respectively. Although we acknowledge the weakness of a comparison using historical controls, the fact that HyFoSy examination is more painful compared to diagnostic office hysteroscopy is within expectation. Indeed, HyFoSy examination, unlike hysteroscopy, is associated with cervical canal sealing by balloon insufflation in order to allow an increase in the intracavitary pressure. There was no significant difference in pain perception according to the presence or absence of bilateral tubal patency. Uni- or bilateral tubal spasm may temporarily hinder passage of the contrast agent. In the context of HSG, NSAIDs have been reported to reduce the incidence of tubal spasms and of uterine cramps during and after the procedure, but this is controversial23 – 27 . We cannot comment on the effect of NSAIDs on tubal spasm in this study as all women had been instructed to take them beforehand. In the case of non-passage of the gel-foam, it was our experience that some women reported cramps while others did not. We adopted the policy of waiting and temporarily withholding further gel-foam injection. In several cases, the Fallopian tube(s) proved to be patent for gel-foam after a certain period, suggesting that the apparent proximal block had been caused by tubal spasm. The occurrence of tubal spasm and its association with both non-patent ‘blocked’ and eventually patent tubes may be one of the factors explaining why there was no difference in pain perception between the groups with or without blocked tubes. The effect of NSAIDs on perceived pain related to an intrauterine procedure is uncertain28,29 . According to a systematic review, NSAIDs were of no benefit when used prophylactically before intrauterine contraceptive device insertion28 . However, because of the possible beneficial effect in the prevention of tubal spasm, patients were instructed to take ibuprofen before the HyFoSy procedure. Surprisingly, half of the women in the study reported the cervical cytology smear procedure to be more painful than HyFoSy examination. Speculum insertion is part of the HyFoSy procedure also. We suspect that many women are apprehensive of speculum insertion because of past experience. Special attention should be given to make every step of the procedure as comfortable as possible, which includes choosing an appropriately sized speculum and the use of lubrication for a gentle and careful insertion30,31 . Our observation that younger women and nulliparous women experienced more pain compared to older or parous women32 can be explained by the likelihood that older and parous women are more familiar with pain of gynecological origin, uterine cramps, cervical smear procedures and TVS examination.
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We conclude that HyFoSy is an acceptable procedure for the patient. Moreover, HyFoSy has a low failure rate and allows for reliable tubal patency testing in an outpatient setting2 .
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