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 Table of Contents  
Year : 2021  |  Volume : 28  |  Issue : 3  |  Page : 193-197

The efficacy of oral naproxen and cervical lidocaine spray on perceived pain during hysterosalpingography

1 Department of Radiology, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Nigeria
2 Department of Radiology, Obafemi Awolowo Teaching Hospital Complex, Ile-Ife, Osun State, Nigeria

Date of Submission07-Jun-2021
Date of Decision07-Sep-2021
Date of Acceptance10-Sep-2021
Date of Web Publication22-Oct-2021

Correspondence Address:
Dr. Temitope Olugbenga Bello
Department of Radiology, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Osun State
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/npmj.npmj_577_21

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Objective: This study was carried out to evaluate the efficacy of the combined use of oral naproxen and cervical lidocaine spray during hysterosalpingography (HSG) compared to the use of oral naproxen or cervical lidocaine spray alone. Materials and Methods: This prospective randomised controlled study was carried out using a total of 240 patients who were randomly assigned to four groups. Group 1 received cervical lidocaine spray only, Group 2 received oral naproxen only, Group 3 received cervical lidocaine spray and naproxen tablet, whereas Group 4 was the control group. A visual analogue scale was used for subjective pain assessment at three pre-defined steps. Results: The mean pain scores of the patients in each of the four groups are Group 1 (3.6 ± 2.0, 5.1 ± 1.8, 5.8 ± 2.2); Group 2 (2.7 ± 1.4, 3.6 ± 2.0 and 3.9 ± 1.9); Group 3 (2.8 ± 1.5, 3.4 ± 2.0 and 4.2 ± 2.3); Group 4 (4.7 ± 1.7, 5.9 ± 1.7 and 5.3 ± 1.7) at T1, T2 and T3, respectively. Pain perception was statistically significantly reduced by naproxen and combined naproxen plus lidocaine spray at all the stages of HSG while cervical lidocaine spray had a statistically significant reduction in pain perception only during cervical instrumentation. Conclusion: Oral naproxen and combined naproxen plus cervical lidocaine spray were effective in reducing HSG-associated pain during all the stages of HSG. However, combined oral naproxen and lidocaine spray did not show superior efficacy over oral naproxen alone. Cervical lidocaine spray was not an effective method.

Keywords: Hysterosalpingography, infertility, lidocaine, naproxen, pain

How to cite this article:
Jayeola DK, Bello TO, Oyedepo VO, Famurewa OC. The efficacy of oral naproxen and cervical lidocaine spray on perceived pain during hysterosalpingography. Niger Postgrad Med J 2021;28:193-7

How to cite this URL:
Jayeola DK, Bello TO, Oyedepo VO, Famurewa OC. The efficacy of oral naproxen and cervical lidocaine spray on perceived pain during hysterosalpingography. Niger Postgrad Med J [serial online] 2021 [cited 2022 Nov 29];28:193-7. Available from: https://www.npmj.org/text.asp?2021/28/3/193/328775

  Introduction Top

Infertility is a worldwide reproductive health issue. It is essential to investigate tubal factors as a possible cause of female infertility because tubal obstruction and peritubular adhesions are responsible for 30%–35% of infertility.[1] Hysterosalpingography (HSG) is an essential investigation in evaluating female infertility. It is utilised to assess tubal patency and uterine cavity contour. It is an efficient method for detecting tubal patency and is less invasive and cheaper than laparoscopy and transvaginal hydrolaparoscopy.[2] The pain experienced during and after HSG can impair the patient's ability to fully co-operate with the procedure, therefore limiting the usefulness of hysterosalpingogram.[3] Furthermore, pain has been found to cause tubal spasm, thereby leading to non-spillage of contrast medium into the peritoneum, and this could be misinterpreted as tubal blockage.[4] Different methods have been considered for reducing pain during the HSG procedure, such as using a balloon catheter in place of a metal cannula and using iodinated hydro-soluble contrast media instead of oil-based media.[5],[6] Analgesic agents such as paracetamol, naproxen and local anaesthetics have been assessed for pain relief in HSG.[1],[7]

Some studies on pain relief in HSG were centred on using a single analgesic, anaesthetic agent or instruments other than metal cannula with no significant pain improvement during HSG.[6],[7] Very few studies have combined an analgesic and a local anaesthetic agent to reduce pain during and after HSG. This study aims to assess the efficacy of combining a local analgesic (cervical lidocaine spray) and a non-steroidal anti-inflammatory agent (oral naproxen) in reducing pain during HSG.

  Materials and Methods Top

This prospective, randomised, controlled, patient-blind study was conducted between February 2016 and May 2017. Approval for the study was obtained on 4th November 2015 from the Ethical Committee of the Ladoke Akintola University of Technology, Osogbo, Osun State with protocol number LTH/EC/2015/11/235 and also registered with Research Registry, ID 6370. Two hundred and forty participants were recruited from women referred to the Radiology Department for HSG undergoing evaluation for infertility from the Obstetrics and Gynaecology Outpatient Department of Lautech Teaching Hospital, Osogbo, Osun State, Nigeria.

Written informed consent was obtained from each patient after the procedure had been explained to them. Before the procedure, each woman completed a demographic form. Participants were assigned randomly to one of four groups. Sequentially numbered, non-transparent sealed envelopes were randomly assigned to each of the four groups before HSG. Each group consisted of 60 participants. Therefore, Group 1 participants received two puffs (20 mg) of cervical lidocaine spray alone (Xylocaine 10% Pump Spray, AstraZeneca, Cambridge, UK) 2 min before the procedure. Group 2 participants received 500 mg naproxen tablet alone 2 h before the procedure. Group 3 participants received both 500 mg naproxen and two puffs (20 mg) of cervical lidocaine spray 2 h and 2 min before the procedure, respectively. Finally, group 4 subjects received no drug. Participants' compliance was confirmed before beginning the study. Adequate blinding of the patient was done as the knowledge of the content of the spray and tablets given to different patients were not made known to the patients before and during the procedure.

The sample size calculation was based on the study by Dogan et al. with a power of 80% and a sample size of 60 in each group. The sample size for the study was determined using the formula:

(sample size for comparison of means).[8]

where N = sampling size

Zα = standard normal deviation

=1.96 corresponding to 95% confidence level

Zβ =0.842 at 80% power

Sd1 = standard deviation of pain scores of oral naproxen is 2.2.[9]

Sd2 = standard deviation of pain scores of cervical lidocaine spray is 2.3 (inferred from the previous study).

d = least expected difference between the mean values of pain scores between the combined oral naproxen plus cervical lidocaine spray group and no treatment group.



N = 55.

Hence, allowing for attrition, 60 participants were used in each group, making a total of 240 subjects in this study.

All HSGs were performed in the follicular phase of the menstrual cycle (8th–10th day). All the patients in the four groups were pre-medicated with intramuscular 10 mg Hyoscine-N-butyl bromide (Buscopan) just before the procedure's commencement (to prevent tubal spasm). The patients were instructed on how to score their pain before the procedure by grading their pains on a scale of 0–10, with 0 being no pain and ten the highest pain possible.

Each participant was then put in a modified lithotomy position at the end of a fluoroscopic table. The perineum was prepared with antiseptic solution (Chlorhexidine Irrigation Solution 0.1%). The water-soluble contrast medium (Ultravist-300, Schering Pvt. Ltd., Sydney, Australia) was diluted in a 1:1 ratio with normal saline or sterile water for injection. A sterile bivalve CUSCO speculum was introduced into the vagina for visualisation of the cervix. The cervix was localised and cleansed with the antiseptic solution. A single-toothed tenaculum was then used to grab the anterior lip of the cervix to stabilise it.

The HSG was then performed under fluoroscopic guidance, and appropriate spot films were obtained. A volume of 15–20 ml of diluted contrast medium was used.

Each participant was asked to rate her pain at three different time points (T1, T2 and T3) during HSG using 0–10 cm linear visual analogue scale. Time of pain measurement during the procedure was taken as follows: T1: Cervical instrumentation with placement and traction of tenaculum on the cervix and application of Leech Wilkinson's cannula; T2 was the instillation of contrast (uterine filling). T3 was immediately after HSG is completed and instruments removed. Participants were also asked to report any side effects of the drug (s) given. The Statistical Package for the Social Sciences (SPSS) version 20 software for Windows (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Statistical analysis was performed using a Chi-square test or Fisher's exact test, as appropriate. P ≤ 0.05 was considered statistically significant. A one-way ANOVA test was also used for the analysis.

  Results Top

In this prospective randomised controlled study, a total of 240 participants within the age range of 20–40 years with infertility were investigated. There were no statistically significant differences among age, parity, type of infertility, number of abortions and previous HSG as shown in [Table 1]. [Table 2] shows that naproxen tablets and combined naproxen and lignocaine spray had the lowest mean pain scores during the various stages of the procedure. During cervical instrumentation (T1), Group 2 (naproxen only) had the least mean pain score (2.7 ± 1.4), followed by Group 3 (naproxen plus lidocaine) with a mean pain score of 2.8 ± 1.5 as shown in [Table 2].
Table 1: Background characteristics of subjects across the four groups

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Table 2: Mean pain scores, visual analogue scale and analysis of variance of pain scores across the groups at three different points

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During uterine distension with contrast (T2), Group 3 had the least mean pain score of 3.4 ± 2.0. Immediately after the procedure (T3), Group 2 had the least mean pain score of 3.9 ± 1.9, whereas Group 1 had the highest mean pain score of 5.8 ± 2.2 [Table 2]. There was a significant reduction in pain for the intervention group (Group 1–3) compared with the control at all the stages of the procedure. At time T1 F (3, 236) = 18.5, P < 0.01, T2 F (3, 236) = 24.5, P < 0.01 and at time T3 F (3, 236) = 10.9, P < 0.01.

We performed a post-hoc test to compare the mean pain scores between intervention groups and control and comparison within the intervention groups. During cervical instrumentation (T1), pain perception was highly statistically significantly lower in Groups 1, 2 and 3 compared with Group 4 (P < 0.001). There was a statistically significant reduction in pain perception during uterine distension with contrast and completion of the procedure in Groups 2 and 3 than group controls [P < 0.001; [Tables 3].
Table 3: Comparison of pain perception between intervention groups and control, and comparison within intervention groups

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[Table 4] shows the effect size of our interventions compared with controls using the Cohen formula. During cervical instrumentation, the effect sizes of cervical lidocaine spray, naproxen alone and combined naproxen plus cervical lidocaine spray were − 0.61, −1.26, −1.19, respectively. During uterine distension with contrast, the effect sizes were − 0.49, −1.24 and −1.37 for lidocaine spray, naproxen and combined naproxen plus lidocaine, respectively. After the procedure, the effect sizes were 0.23, −0.75, and −0.55 for cervical lidocaine, naproxen and combined naproxen plus lidocaine, respectively.
Table 4: Effect size (Cohen's d) of the interventions (drugs) across the groups compared with control

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  Discussion Top

During cervical instrumentation in this study, all the drug/combination of drugs (lidocaine spray, oral naproxen, oral naproxen plus lidocaine spray) produced a statistically significant reduction in pain perception compared with control (P < 0.05). Oral naproxen produced the most significant pain perception reduction, followed by combined oral naproxen plus cervical lidocaine spray. The pain reduction is significant compared to lidocaine spray alone. However, the difference in pain perception produced by oral naproxen compared with combined naproxen plus lidocaine spray was not statistically significant (P > 0.05). This shows that oral naproxen plus lidocaine spray combination failed to show superiority in reducing pain perception than naproxen alone during cervical instrumentation. This is contrary to results obtained in a similar study by Unlu et al., who reported that a lower pain score was achieved by combined oral Naproxen and paracervical lidocaine cream (a topical anaesthetic) with oral naproxen alone during cervical instrumentation.[10] The disparity in the results could be due to the difference in interval between topical lidocaine and cervical instrumentation. In this study, the interval between the application of lidocaine spray and cervical instrumentation was 2 min, while in their study, the interval was 30 min.

However, combined oral naproxen and lidocaine spray produced a statistically insignificant pain perception reduction than cervical lidocaine spray alone (P > 0.05), as shown in [Table 4]. This showed that combined oral naproxen and lidocaine spray produced no synergistic effect during cervical instrumentation.

Cervical lidocaine spray alone had significant pain perception reduction only during cervical instrumentation when compared with controls. However, during uterine distension and after completion of the procedure, the mean pain score is similar to that of controls. This is supported by Bachman et al., who found no statistically significant difference in pain perception between topical benzocaine and placebo immediately after the procedure.[11]

During uterine filling and distension with contrast, the combination of oral naproxen and cervical lidocaine spray produced the greatest statistically significant reduction in pain perception compared with control (P < 0.05), followed by oral naproxen alone. This is in concordance with the study done by Unlu et al. in which the combined oral naproxen plus paracervical lidocaine cream also produced more significant pain relief than oral naproxen alone.[10]

At the end of the procedure (T3), naproxen produced the most significant pain perception reduction, followed by naproxen plus lidocaine spray combination. However, combined naproxen plus cervical lidocaine spray failed to produce superior pain relief than naproxen only. This is similar to previous works documenting that the difference in the two methods' perception in pain reduction was not statistically significant.[10],[11]

Interestingly, the cervical lidocaine spray group showed a slightly higher pain perception than control immediately after the procedure. This may explain the failure of combined naproxen and lidocaine spray to produce significantly better pain relief than naproxen alone immediately after the procedure.[12],[13],[14]

Furthermore, naproxen alone produced the most significant effect magnitude during the various stages of pain perception assessment. These findings are similar to those of Owen et al. The fenoprofen (a non-steroidal anti-inflammatory drug) was more effective than a placebo.[14] Nevertheless, some studies have shown no statistical difference between oral non-opioid analgesics and placebo with standard mean difference of −0.30, 95% confidence interval −1.03–0.43).[1],[15],[16]

Cervical lidocaine spray alone produced the least effect size. A similar meta-analysis from a recent Cochrane review also revealed no evidence of the beneficial effect of topical analgesics than placebo in pain reduction within 30 min after HSG.[15] These findings further showed that the use of topical analgesics alone like cervical lidocaine spray is generally not an effective method of pain relief during and immediately after HSG and should not be used alone.

Cervical lidocaine spray alone is not effective in reducing pain perception. The use of oral naproxen alone and combined oral naproxen plus lidocaine spray effectively reduced pain during HSG. However, combined oral naproxen plus lidocaine spray had no superior benefit over oral naproxen alone.

  Conclusion Top

The use of oral naproxen alone and combined oral naproxen plus lidocaine spray were effective methods of reducing pain during HSG. However, combined oral naproxen plus lidocaine spray had no superior benefit over oral naproxen alone. Cervical lidocaine spray alone is not effective in reducing pain perception during HSG and may increase pain after the procedure.


To significantly reduce pain perception during HSG for patient's comfort and wider acceptability of the procedure, there is a need for adequate analgesia. Naproxen alone could be effectively used to achieve this purpose. There is a need for more research to further characterise the role of cervical lidocaine spray in HSG-associated pain.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Bello TO, Osinaike BB, Adeniyi TO. Tramadol as a prophylactic analgesic for hysterosalpingography in African women. Afr J Med Sci 2008;37:157-60.  Back to cited text no. 1
Chauhan MB, Lakra P, Jyotsna D, Nanda S, Malhotra V. Pain relief during hysterosalpingography: Role of hysterosalpingography. Arch Gynecol Obstet 2013;287:155-9.  Back to cited text no. 2
Ahmad G, Duffy J, Watson AJ. Pain relief in hysterosalpingography. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD006106. doi: 10.1002/14651858.CD006106.pub2.  Back to cited text no. 3
Atalabi OM, Osinaike BB. Do abnormal findings on hystero-salphingographic examination correlate with intensity of procedure associated pain? Afr J Reprod Health 2014;18:147-51.  Back to cited text no. 4
Mansour R, Nada A, El-Khayat W, Abdel-Hak A, Inany H. A simple and relatively painless technique for hysterosalpingography, using a thin catheter and closing the cervix with the vaginal speculum: A pilot study. Postgrad Med J 2011;87:468-71.  Back to cited text no. 5
Stoop D, De Brucker M, Haentjens P, Talebian A, de Mey J, Devroey P. Fast-release orodispersible tramadol as analgesia in hysterosalpingography with a metal cannula or a balloon catheter. Hum Reprod 2010;25:1451-7.  Back to cited text no. 6
Guzel AI, Kuyumcuoglu U, Erdemoğlu M. The effect of flurbiprofen as prophylactic analgesic before hysterosalpingography. J Int Med Res 2010;38:1780-4.  Back to cited text no. 7
Kirkwood BR, Sterne JA. Calculation of required sample size. In: Essential Medical Statistics. 2nd ed., Vol. 35. London: Blackwell Publishing Limited; 2003. p. 420.  Back to cited text no. 8
Dogan E, Celiloglu M, Sarihan E, Demir A. Anaesthetic effect of intrauterine lidocaine plus naproxen sodium in endometrial biopsy. Am Coll Obstet Gynaecol 2004;103:347-51.  Back to cited text no. 9
Unlu BS, Yilmazer M, Koken G, Arioz DT, Unlu E, Baki ED, et al. Comparison of four different pain relief methods during hysterosalpingography: A randomized controlled study. Pain Res Manag 2015;20:107-11.  Back to cited text no. 10
Bachman EA, Senapati S, Sammel MD, Kalra SK. Randomized controlled trial of benzocaine versus placebo spray for pain relief at hysterosalpingogram. Reprod Biomed Online 2014;28:748-52.  Back to cited text no. 11
Costello MF, Horrowitz S, Steigrad S, Saif N, Bennett M, Ekangaki A. Transcervical intrauterine topical local anesthetic at hysterosalpingography: A prospective, randomized, double-blind, placebo-controlled trial. Fertil Steril 2002;78:1116-22.  Back to cited text no. 12
Kafali H, Cengiz M, Demir N. Intrauterine lidocaine gel application for pain relief during and after hysterosalpingography. Int J Gynaecol Obstet 2003;83:65-7.  Back to cited text no. 13
Owens OM, Schiff I, Kaul AF, Cramer DC, Burt RA. Reduction of pain following hysterosalpingogram by prior analgesic administration. Fertil Steril 1985;43:146-8.  Back to cited text no. 14
Hindocha A, Beere L, O'Flynn H, Watson A, Ahmad G. Pain relief in hysterosalpingography. Cochrane Database Syst Rev. 2015 Sep 20;(9):CD006106. doi: 10.1002/14651858.CD006106.pub3.  Back to cited text no. 15
Cengiz M, Kafali H, Artuc H, Baysal Z. Opioid analgesia for hysterosalpingography: Controlled double-blind prospective trial with remifentanil and placebo. Gynecol Obstet Invest 2006;62:168-72.  Back to cited text no. 16


  [Table 1], [Table 2], [Table 3], [Table 4]


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