LETTERS TO THE EDITOR

Difficult intrauterine deviceinsertionSir,We read the report by Dijkhuizen et al. (2011) entitled ‘Vaginal miso-prostol prior to insertion of an intrauterine device: an RCT’ with interest.We appreciate that the authors cited our previous publication—the useof overnight pretreatment with vaginal 400 mg misoprostol could over-come the difficulty of intrauterine device (IUD) insertion in patients whohad previously failed IUD insertion (Li et al., 2005). We also welcomethis larger study, conducted to test the efficacy of misoprostol amongpatients having difficulty with IUD insertion as we suggested previously,although we have questions about the study.

The time interval between administration of misoprostol and IUDinsertion is of concern. The rationale of the 3 h interval before IUD inser-tion in their original design was based on Singh’s report (Singh et al.,1999a), which was agreed with by Dr Fiala (Fiala et al., 2007).However, the original articles only compared the differences between2 and 3 or 4 h, and in addition, Singh et al. (1999b) further suggestedthat a minimal evacuation time interval should be 3 h (most effective).Therefore, the comment ‘longer intervals do not improve the effecton the cervix (Fiala et al., 2007)’ needs further confirmation.

In contrast, we have reason to believe that the time intervalbetween the use of vaginal 400 mg misoprostol and further cervicaldilatation procedures, such as IUD insertion, hysteroscopy orothers, is critical. If the time lag between misoprostol use and the pro-cedures is not long enough, the effectiveness of the drug might bedecreased. One study, Choksuchat et al., (2006), showed an intervalof 10–12 h after misoprostol administration results in increased cervi-cal dilatation, and ease of further cervical dilatation, if required. Arecent report showed the benefits of using overnight vaginal misopros-tol on day-care hysteroscopy (Oppegaard et al., 2010), suggesting thatthe cervical ripening requires overnight use of misoprostol. In ourreport, the time lag was longer, up to half of a day or more (8–24 h), with resultant success in all eight cases (Li et al., 2005). Wetherefore suggest that the negative results of this clinical trial mightbe due to the inadequate time interval between misoprostol adminis-tration and IUD insertion.

Conflict of interestNo benefit of any kind will be received either directly or indirectly bythe authors.

ReferencesChoksuchat C, Cheewadhanaraks S, Getpook C, Wootipoom V,

Dhanavoravibul K. Misoprostol for cervical ripening in non-pregnantwomen: a randomized double-blind controlled trial of oral versusvaginal regimens. Hum Reprod 2006;21:2167–2170.

Dijkhuizen K, Dekkers OM, Holleboom CA, de Groot CJ,Hellebrekers BW, van Roosmalen GJ, Janssen CA, Helmerhorst FM.Vaginal misoprostol prior to insertion of an intrauterine device: anRCT. Hum Reprod 2011;26:323–329.

Fiala C, Gemzell-Danielsson K, Tang OS, von Hertzen H. Cervical primingwith misoprostol prior to transcervical procedures. Int J Gynaecol Obstet2007;99:S168–S171.

Li YT, Kuo TC, Kuan LC, Chu YC. Cervical softening with vaginalmisoprostol before intrauterine device insertion. Int J Gynaecol Obstet2005;89:67–68.

Oppegaard KS, Lieng M, Berg A, Istre O, Qvigstad E, Nesheim BI. Acombination of misoprostol and estradiol for preoperative cervicalripening in postmenopausal women: a randomised controlled trial. Br JObstet Gynaecol 2010;117:53–61.

Singh K, Fong YF, Prasad RN, Dong F. Evacuation interval after vaginalmisoprostol for preabortion cervical priming: a randomized trial.Obstet Gynecol 1999a;94:431–434.

Singh K, Fong YF, Prasad RN, Dong F. Vaginal misoprostol for pre-abortioncervical priming: is there an optimal evacuation time interval? Br J ObstetGynaecol 1999b;106:266–269.

Li Yiu-Tai1, Lee Wen-Ling2,3,4 and Wang Peng-Hui4,5,*1Department of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan

2Department of Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan3Department of Life Science, National Central University, Tao-Yuan, Taiwan

4Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei,Taiwan

5Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei,Taiwan

*Correspondence address. E-mail: phwang@vghtpe.gov.tw; phwang@ym.edu.twdoi:10.1093/humrep/der272

Advanced Access publication on August 16, 2011

Reply: Difficult intrauterinedevice insertionSir,We thank Li et al. for their response to our article ‘Vaginal misoprostolprior to insertion of an intrauterine device: a randomized controlledtrial’, in which they argue that the negative results of our trial mightbe secondary to an inadequate time interval between misoprostoladministration and intrauterine device (IUD) insertion.

In a recently published meta-analysis comparing misoprostol andplacebo prior to hysteroscopy (both diagnostic and therapeutic), theincluded randomized controlled trials dealt in general with doses of200 or 400 mg misoprostol and time intervals between administrationand hysteroscopy of 10–12 h (range 4–24 h) (Gkrozou et al., 2011).Their conclusion is that no reduced need for cervical dilatation in pre-menopausal women after pretreatment with misoprostol wasobserved. Nor were hysteroscopy-related complications reduced.Side effects of misoprostol were significantly more common in themisoprostol group. These findings correspond with our data.

& The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.For Permissions, please email: journals.permissions@oup.com

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