Which medication and when should it be administered for reducing pain in intrauterine device insertion?

Article In Press

Like Comment
Related Content

Author:

Zeev Blumenfeld, M.D.

Abstract:

Reflections on "Effect of self-administered vaginal dinoprostone on pain perception during copper intrauterine device insertion in parous women: a randomized controlled trial" by Samy et al.

Read the full text here. 

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

1 Comments

Go to the profile of Ahmed Said Ali
Ahmed Said Ali about 2 months ago

 

Which medication and when should it be administered for reducing pain in IUD insertion? We still need further research

 

Ahmed Said Alia*, Ahmed M. Abdelhakimb, Ahmed SA Ashourc

a MBBCh., Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

b MBBCh., Kasr Al-Ainy, Faculty of Medicine, Cairo University, Cairo, Egypt.

c (MD), Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt.

* Correspondence:

Name: Ahmed Said Ali.

Institution: Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

Institutional address: Madinet Nasr, Abbassia, and Cairo, Egypt (Postal code: 11651)

Home address: mokattum city, Cairo, Egypt (Postal code: 11571)

Email: ahmedsaidali987@gmail.com

Mobile: +201125930140

ORCID: 0000-0001-9616-3709

 

Running title: IUD insertion

Keywords: IUD, Pain, Multipara, Nulligravida, IUD Insertion.

Grants/fellowships supporting the writing of the paper: None.

Disclosure summary: No conflict of interest.

 

 

 

 

 

 

Long-acting reversible contraceptives (LARC), including levonorgestrel-releasing intrauterine system (LNG-IUS) and copper intrauterine device (Cu-IUD), are highly effective, safe, and cost-effective in preventing pregnancy with a low failure rate similar to that of sterilization (1). However, fear of pain and difficulties at insertion are the main obstacles that may preclude IUD counseling and utilization, especially in nulliparous women and women with previous cesarean delivery (CD) (1).

The level of pain that women experience is highly variable, making it difficult to predict the level of discomfort that an individual is likely to experience or the need for pain relief (2). Although there is evidence that nulliparous women (nulligravidas and those who have been pregnant but never given birth) may experience more placement-related pain than their parous counterparts, the majority experience a level of pain that is similar in intensity to that of menstruation(2). Moreover, a proportion of both nulliparous and parous women might experience severe insertion-related pain and such individuals need effective pain relief (3,4).

Cervical ripening agents such as misoprostol and dinoprostone had beneficial effects in reducing pain and facilitating transcervical procedures such as office hysteroscopy (OH) (5–7) and IUD insertion (1,5,8,9). Dinoprostone is a synthetic preparation that is chemically and structurally identical to Prostaglandin E2 (PGE2). Dinoprostone facilitates remodeling of cervical extracellular collagen, increasing water content, and promoting changes in the glycosaminoglycan content of the cervical extracellular content (10). Together, these effects cause changes in cervical consistency with subsequent softening, effacement, and dilation of the cervix. Dinoprostone-induced cervical dilation is the result of cervical tissue remodeling and uterine contractions. By these local effects, dinoprostone could decrease pain and facilitate transcervical procedures (1,11,12) such as IUD insertion.

Based on our studies, dinoprostone had beneficial effects in reducing IUD insertion pain and facilitating the procedure for clinicians in different study populations such as nulliparous women (5,13), women delivered only by CD (1), and parous women (14). Our studies agreed with numerous studies in the literature addressing the value of cervical ripening agents in the context of IUD insertion. Similarly, misoprostol, which exerts a similar cervical ripening effect on the cervix as dinoprostone, was found effective in relieving IUD insertion pain in different study populations; in women with previous cesarean delivery (15,16), in nulligravid women (9), and parous women (17).

Upon literature searching, there is no optimal timing of dinoprostone administration before transcervical procedures. Dinoprostone was found effective at different timings prior to IUD insertion(1,5,13) and at different timings prior to OH(18–20). Similarly, misoprostol was effective when administered at different timings such as 3,4, and 6 hours prior to IUD insertion (9,15–17). Although the onset of action of vaginal dinoprostone suppository starts within 10 minutes and the duration of action lasts for up to 2-3 hours(14). Yet, the cervical ripening effect of dinoprostone is believed to extend beyond the duration of its action. This was evident in studies which found an  effectiveness of vaginal dinoprostone when administered 6 or 12 hours prior to IUD insertion (5,13).

We believe that 2 hours’ time interval is the shortest interval for dinoprostone administration prior to IUD insertion to produce a reasonable cervical ripening effect. It is better to wait for longer durations to obtain the maximal dinoprostone-induced cervical ripening and remodeling because histologic and immunohistochemical studies revealed the presence of dense collagen fibers in the cervical tissues of nonpregnant women(6). The concentration of collagen in the cervix at 10 weeks of gestation and at full term are, respectively, 70% and 30% of the concentration of collagen in the nonpregnant cervix(6). The more time interval between dinoprostone administration and IUD insertion, the more local effects of dinoprostone on cervical softening and dilatation, and consequently, more pain reduction and easier IUD insertion.

A systematic review and meta-analysis by Tassi et al. (8)  evaluated the effect of misoprostol administration on IUD insertion pain and reported that women taking misoprostol ≤ 2.5 h before IUD insertion had a higher VAS pain score compared with the placebo group. Misoprostol exerts a similar cervical ripening effect as dinoprostone. Moreover, Fouda et al. (6) found that vaginal misoprostol given 12 hours before OH was more effective in relieving pain and facilitating the procedure than when it was given 3 hours prior to OH in nullipara. The plasma concentration of vaginal misoprostol increases gradually, reaching its maximum level after 70-80 minutes before slowly declining with the detectable drug levels still present after 6 hours (21).

We agree with Dr. Zeev Blumenfeld that optimal timing of vaginal dinoprostone administration before IUD insertion has not yet been established and needs further investigation. Additionally, we also agree with Dr. Zeev Blumenfeld that the literature lacks comparative studies between misoprostol and dinoprostone in the context of IUD insertion, which we recommend in future studies; the present studies in the literature compare either dinoprostone or misoprostol with placebo. Vaginal dinoprostone was previously compared to vaginal misoprostol administration prior to OH with either superior (18) or comparable efficacy results (19).

Although we believe that every patient having IUD insertion deserves some form of analgesia, the practical clinical question of whether dinoprostone is necessary before any IUD insertion or only for those patients who have not experienced any previous vaginal delivery cannot be answered with a single randomized controlled trial (RCT) of dinoprostone administration prior to IUD insertion in every study population. Multi-center RCTs with larger sample sizes are needed to confirm its efficacy and safety in different study populations and with different IUD types. Additionally, comparative studies between misoprostol and dinoprostone regarding efficacy, safety, and cost-effectiveness are needed to clinically answer the question of generalizability before IUD insertion.

Finally, it is important to consider that our studies regarding dinoprostone administration prior to IUD insertion were performed by different research groups, not by the same group; however, they were led by a common principal investigator (PI), who had previous expertise in research work, family planning, multi-tasking, and research team management. In those research projects, the PI defined the goals, planned the studies designs, recruited different research teams, distributed team members over the different research projects, determined the time plans, assigned tasks, responsibilities, and expectations for the sharing investigators at the beginning of the studies. This was done to maintain the integrity of research works, proper study design, and minimize bias across the studies.

 

 

 

 

References

  1. Samy A, Abdelhakim AM, Latif D, Hamza M, Osman OM, Metwally AA. Benefits of vaginal dinoprostone administration prior to levonorgestrel-releasing intrauterine system insertion in women delivered only by elective cesarean section: a randomized double-blinded clinical trial. Arch Gynecol Obstet 2020;301:1463–71.
  2. Bahamondes L, Mansour D, Fiala C, Kaunitz AM, Gemzell-Danielsson K. Practical advice for avoidance of pain associated with insertion of intrauterine contraceptives. J Fam Plann Reprod Health Care 2014;40:54–60.
  3. Marions L, Lövkvist L, Taube A, Johansson M, Dalvik H, Øverlie I. Use of the levonorgestrel releasing-intrauterine system in nulliparous women--a non-interventional study in Sweden. Eur J Contracept Reprod Health Care Off J Eur Soc Contracept 2011;16:126–34.
  4. Heikinheimo O, Inki P, Kunz M, Parmhed S, Anttila A-M, Olsson S-E, et al. Double-blind, randomized, placebo-controlled study on the effect of misoprostol on ease of consecutive insertion of the levonorgestrel-releasing intrauterine system. Contraception 2010;81:481–6.
  5. Samy A, Kasem MFY, El Lithy A, Ibrahim AM, El Mahy M, Hussein AH, et al. Prophylactic vaginal dinoprostone administration six hours prior to copper-T380A intrauterine device insertion in nulliparous women: A randomized controlled trial. Contraception 2020;101:162–6.
  6. Fouda UM, Gad Allah SH, Elshaer HS. Optimal timing of misoprostol administration in nulliparous women undergoing office hysteroscopy: a randomized double-blind placebo-controlled study. Fertil Steril 2016;106:196–201.
  7. Abdelhakim AM, Gadallah A-H, Abbas AM. Efficacy and safety of oral vs vaginal misoprostol for cervical priming before hysteroscopy: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2019;243:111–9.
  8. Tassi A, Parisi N, Londero AP. Misoprostol administration prior to intrauterine contraceptive device insertion: a systematic review and meta-analysis of randomised controlled trials. Eur J Contracept Reprod Health Care 2020;25:76–86.
  9. Scavuzzi A, Souza ASR, Costa AAR, Amorim MMR. Misoprostol prior to inserting an intrauterine device in nulligravidas: a randomized clinical trial. Hum Reprod 2013;28:2118–25.
  10. Hawkins JS, Wing DA. Current pharmacotherapy options for labor induction. Expert Opin Pharmacother 2012;13:2005–14.
  11. Shirley M. Dinoprostone Vaginal Insert: A Review in Cervical Ripening. Drugs 2018;78:1615–24.
  12. Ghamry NK, Samy A, Abdelhakim AM, Elgebaly A, Ibrahim S, Ahmed AA, et al. Evaluation and ranking of different interventions for pain relief during outpatient hysteroscopy: A systematic review and network meta-analysis. J Obstet Gynaecol Res 2020;46:807-827
  13. Samy A, Ali AS, Latif D, Darweesh FF, Ghamry NK, Metwally AA. Benefits of Self-administered Vaginal Dinoprostone 12 Hours before Levonorgestrel-releasing Intrauterine Device Insertion in Nulliparous Adolescents and Young Women: A Randomized Controlled Trial. J Pediatr Adolesc Gynecol 2020; ;S1083-3188:30163-7.
  14. Ashour A, Nabil H, Yosif M, Hussein M, Allah A, Mahmoud M, et al. Effect of self-administered vaginal dinoprostone on pain perception during copper intrauterine device insertion in parous women: a randomized controlled trial. Fertil Steril 2020;In Press.
  15. Maged AM, Youssef G, Eldaly A, Omran E, El Naggar M, Abdel Hak A, et al. Benefits of vaginal misoprostol prior to IUD insertion in women with previous caesarean delivery: a randomised controlled trial. Eur J Contracept Reprod Health Care 2018;23:32–7.
  16. Abdellah MS, Abbas AM, Hegazy AM, El-Nashar IM. Vaginal misoprostol prior to intrauterine device insertion in women delivered only by elective cesarean section: a randomized double-blind clinical trial. Contraception 2017;95:538–43.
  17. Khalaf M, Amin AF, Sayed Z, El-Nashar IM, Abbas AM. A randomized double-blind controlled trial of two different doses of self-administered vaginal misoprostol for successful copper intrauterine device insertion. Middle East Fertil Soc J 2017;22:264–8.
  18. Inal HA, Ozturk Inal ZH, Tonguc E, Var T. Comparison of vaginal misoprostol and dinoprostone for cervical ripening before diagnostic hysteroscopy in nulliparous women. Fertil Steril 2015;103:1326–31.
  19. Abulnour AAE-R, Mohamed ME-M, Khalaf WM. Dinoprostone versus Misoprostol for Cervical Ripening before Diagnostic Hysteroscopy in Nulliparous Women : A Randomized Controlled Trial. Egypt J Hosp Med 2018;71:2287–93.
  20. Preutthipan S, Herabutya Y. A randomized comparison of vaginal misoprostol and dinoprostone for cervical priming in nulliparous women before operative hysteroscopy. Fertil Steril 2006;86:990–4.
  21. Zieman M, Fong SK, Benowitz NL, Banskter D, Darney PD. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol 1997;90:88–92.