Considering the risks and benefits of intrauterine devices: should clinician advice now be changed?

Transcription

1 Cliical Perspective Cosiderig the risks ad beefits of itrauterie devices: should cliicia advice ow be chaged? Luis Bahamodes*1 & Maria Valeria Bahamodes1 Practice poits There are o restrictios cocerig age or parity with respect to the isertio of ay kid of itrauterie cotraceptive (IUC). There is o differece i the pregacy rate betwee adolescets ad adult wome either with the copper-releasig itrauterie device or the levoorgestrel-releasig itrauterie system. Isertio is simple with both types of IUC i ulligravidas ad parous wome, with isertio failure due to cervical steosis costitutig a rare evet. Fear of pai represets a barrier to the use of IUCs ad has bee reported to occur prior to placemet, durig the procedure ad after the procedure. The risk of expulsio of the IUC is similar i ulligravidas ad parous wome. Uterie perforatio is a rare evet; however, the risk is higher whe the device is iserted by healthcare providers with less experiece i the isertio techique. Pelvic iflammatory disease is caused by sexually trasmitted ifectios ad ot by the use of the IUC. The use of a IUC does ot cause ifertility ad, after usig the device, retur of fertility is similar to that of ever users. Itrauterie cotraceptives (IUCs) are the most widely used cotraceptive method i the world, the two most commo models curretly i use beig the TCu380A itrauterie device ad the levoorgestrel-releasig itrauterie system. IUCs ad subdermal implats are referred to as log-actig reversible cotraceptives because they provide Summary Huma Reproductio Uit, Departmet of Obstetrics & Gyecology, Medical Scieces, Uiversity of Campias (UNICAMP), Caixa Postal 6181, Campias, São Paulo, Brazil *Author for correspodece: Tel.: ; Fax: ; bahamod@caism.uicamp.br /CPR Future Medicie Ltd Cli. Pract. (2013) 10(1), part of ISSN

2 Cliical Perspective Bahamodes & Bahamodes cotraceptio for at least 3 years with a sigle itervetio. Both IUCs ad the cotraceptive implat have very low rates of cotraceptive failure, these rates beig similar i wome over ad uder 21 years of age. They are safe, with few side effects, have a high cotiuatio rate ad ca be used irrespective of age or parity. However, eve ow, may healthcare professioals discourage the use of these devices by adolescets, youg wome ad ulli gravidas, although the WHO makes o restrictios i this respect. IUCs represet a excellet tool for prevetig uplaed pregacy ad should be cosidered as a first-lie cotraceptive choice for ay woma with o medical cotraidicatios. Itrauterie cotraceptives (IUCs) are the most prevalet cotraceptive method i use worldwide. Models curretly i use iclude copperreleasig itrauterie devices (IUDs), of which the most commo model worldwide is the T-shaped TCu380A, ad the levoorgestrelreleasig itrauterie system (LNG IUS). IUCs, together with cotraceptive implats, are cosidered log-actig reversible cotraceptives (LARCs) or forgettable cotraceptives because they provide cotraceptio for at least 3 years of use with oly oe itervetio ad do ot deped o user compliace [1]. I fact, the TCu380A IUD is approved for 10 years of use; however, reports have show its efficacy ca last for 15 ad 20 years [2,3]. The approved duratio of use of the LNG IUS is up to 5 years [4] ; ever theless, it has a wide timeframe durig which replacemet ca be made [5]. It has bee well established that the pregacy rate with LARCs is lower tha that foud with o-larc methods. I additio, whe youg adult wome uder 21 years of age were compared with wome over 21 years of age, this low pregacy rate was similar i both groups [6], which could be explaied by the fact that these cotraceptive methods do ot deped o wome s daily or mothly compliace. I fact, pregacy rates with both models of IUCs are similar or lower tha those foud with female sterilizatio [6 8]. Cotiuatio rates for both IUCs at 3 years were better tha the cotiuatio rates foud i wome usig o-larc methods. I additio, the repeat occurrece of a uplaed pregacy was foud to be less likely i users of the copperiud ad the LNG IUS compared with users of combied oral cotraceptives (COCs), patch or vagial rig [6]. Despite the low pregacy rate, the high cotiuatio rate ad the low frequecy of side effects reported with IUCs [4,9], the umber of wome usig the most commo IUCs remais 20 Cli. Pract. (2013) 10(1) small i may coutries, albeit the prevalece of use varies greatly from coutry to coutry [101]. For example, the 2008 Natioal Survey of Family Growth i the USA [102] reported that oly 5.5% of wome usig cotraceptio stated that they used a IUD [103]. I a recet USA-based study with 503 wome aged years [104], 77% wated a cotra ceptive method that does ot require them to have to remember it every day or that has to be used durig sex. However, oly 7% used LARC methods or depot medroxyprogesteroe acetate ijectios, ad oly 1% of the remaiig wome were aware of these methods. Furthermore, 77% of the wome iterviewed who were usig COCs had forgotte at least oe pill. Oe of the mai reasos for the uderutilizatio of IUCs is the may restrictios imposed by healthcare professioals (HCPs) as a cosequece of the myths ad miscoceptios that surroud the use of these cotraceptive methods, pric ipally cocerig their use i wome ad adole scets who have ever bee pregat ad i youg wome i geeral. Nevertheless, i view of curret evidece o the efficacy ad safety of IUCs, it is importat that cliicias are advised that it is time for chage [10]. Restrictios imposed by HCPs The pricipal reasos give for the limited use of IUCs i the USA ad UK refer to the misperceptios ad misgivigs of HCPs regardig the eligibility criteria for IUCs, particularly with respect to the age ad parity of the potetial users [10 12]. Oe USA-based survey, i which members of the America College of Obstetrics ad Gyecology (ACOG) were iterviewed, showed that 68% of physicias would ot recommed copper-iuds to ulliparous wome, although 95% reported havig a positive attitude towards the IUD ad 95% were well iformed o the efficacy ad safety of these devices [13].

3 Itrauterie devices: should cliicia advice be chaged? I aother study ivolvig approximately 800 family plaig professioals based i Califoria (USA), just uder 50% of the professioals who participated i the iterview stated that ulliparous wome, adolescets, ad wome who had pelvic iflam m atory disease (PID) withi the previous 5 years, were ot cadidates for a IUC. Wome i the postpartum or postabortio periods were also ot cosidered eligible to use these devices [14]. Likewise, a similar Australia-based survey ivolvig 701 fellows of the Royal Australia ad New Zealad College of Obstetricias ad Gyecologists reported that oly approximately oe-third (39.1%) ad two-thirds (69.4%) of the HCP iterviewed believed that the copper-iud ad the LNG IUS, respectively, were appropriate for ulliparous wome [15]. I additio, a survey coducted i the UK showed that oly approximately 2% of HCPs reported that they might recommed a IUD to a adolescet ulliparous woma [12]. I the aforemetioed study, coducted with ACOG members i the USA [13], whe doctors were asked what makes wome eligible for a IUC, oly 62.0% agreed that these devices are appropriate for ulliparous wome, while 30.7% agreed that they were appropriate for adolescets, 45.3% for a woma with a history of a sexually trasmitted ifectio (STI) i the past 2 years ad 36.5% for a woma who had PID i the past 5 years. Oly 49.6% of these HCPs reported that they would offer a IUC to a sigle, moogamous adolescet with oe child, ad 19% said they would offer this form of cotraceptio to a adolescet ulligravida. The misgivigs of HCPs regardig the use of IUCs i ulligravidas may origiate from whe the TCu380A IUD was first itroduced oto the USA market i At that time, it was recommeded that eligible wome should have had at least oe child; however, this requiremet was removed i 2005 ad ulliparous wome are ow cosidered eligible to use the TCu380A IUD [105]. However, the package isert that accompaies the LNG IUS still recommeds (although it is ot madatory) that cadidates for the use of this device should be parous [106], despite the fact that the eligibility criteria established by the WHO classifies ay IUC as category 2 both for ulligravidas ad parous wome [107]. These restrictios have resulted i a scarcity of studies i the scietific literature o Cliical Perspective the use of IUCs i ulligravidas, adolescets ad youg wome, leavig HCPs with isufficiet evidece to chage the patter of use of these devices i these specific groups of wome. However, adolescets ad youg wome are those at a high risk of uplaed pregacy ad IUCs represet a excellet strategy for icreasig effective cotraceptive use. Lack of traiig i IUC isertio & maagemet It is importat to poit out that the restrictios i providig IUCs may reflect a lack of traiig i may medical schools, particularly durig medical residecy. To provide IUCs, physicias ad other HCPs must be willig to offer these cotraceptives to all wome ad isert them, the oly exceptios beig the restrictios defied i the medical eligibility criteria [107]. A study coducted i St Louis (MO, USA) questioed HCPs o the subject of traiig ad their attitudes with respect to IUCs [16]. Results showed that 36% of HCPs had received o traiig i IUC isertio durig their residecy or, i the case of urses, at advaced cliical practice courses. I additio, the HCPs who were traied at Catholic istitutios were less likely to have received traiig i IUC isertio durig residecy compared with HCPs who traied at secular istitutios. Difficulty at isertio & pai durig the procedure Oe of the pricipal cocers of HCPs with respect to IUC isertio refers to the myth that isertio is difficult, particularly i ulligravidas ad adolescet wome. This myth origiated from the idea that the cervical caal or iteral os is arrow i these populatios of wome, makig isertio more difficult or paiful. Nulliparous wome have bee reported to have a arrower iteral cervical os ad/or a arrower cervical caal, ad a higher failure rate or difficulty at isertio has bee described i ulliparous wome compared with parous wome [17]. However, several studies have show that isertio of a copper-iud or LNG IUS i ulliparous wome is just as safe ad simple a procedure as i parous wome [18 20], with the advatage of a high cotiuatio rate. A study coducted i 24 sites i Swede evaluated the isertio procedure of the LNG IUS i 224 ulliparous wome icludig 21

4 Cliical Perspective Bahamodes & Bahamodes 181 ulligravidas [21]. The isertios were performed mostly by midwives ad were classified as easy by 72% of HCPs. The isertio failure rate was oly 2.7%, ad 72% of the wome who iserted a LNG IUS cosidered the procedure moderately paiful, with oly 17% reportig it was severely paiful. I aother study [19], 315 questioaires were set to HCPs who had iserted a LNG IUS i ulligravidas. These professioals reported a relative risk (RR) of 2.0 (95% CI: ) for a difficult isertio i ulliparous wome whe compared with isertios of the same device i parous wome, with the level of difficulty beig directly correlated with the umber of isertios carried out by the HCP. Those HCPs who had performed fewer isertios were more likely to experiece difficulty at isertio (RR: 2.2; 95% CI: ). Aother study compared the ease of isertio ad failure rates of the LNG IUS i two cohorts: oe group of ulligravidas ad aother of parous wome [22]. The pricipal results showed ease of isertio i almost 80% of the wome i both groups ad isertio failure i oly 0.4%, with o differeces betwee the ulligravidas ad the parous wome. The cotiuatio rate at the ed of the first year was almost 90% i both groups of ulligravidas ad parous wome. Fear of pai durig isertio may play a role i whether or ot wome choose to use a IUC [23,24]. I additio, HCP s misgivigs regardig paiful ad difficult isertios may make them reluctat to offer IUCs as a cotraceptive method or to cousel wome o IUCs, particularly whe the woma is a ulligravida ad/or adolescet. Pai at IUC isertio has bee reported to be greater i ulliparous wome [25] ; however, this remais a cotroversial issue. I a prospective study coducted with 117 ulliparous wome [26], 62% reported that the pai at IUC isertio was similar to that experieced durig mestruatio ad 75% of the wome were still usig the device for up to 1 year, which may be a idicator of the high levels of satisfactio that have bee reported with this method. Furthermore, i a study i which most of the wome were parous, almost 89% reported either o pai or mild or moderate pai durig IUC isertio, with severe pai beig reported by oly approximately 11% [27]. Risk of expulsio Oe of the pricipal cocers of HCP ad wome regardig IUCs is the risk of iadvertet 22 Cli. Pract. (2013) 10(1) expulsio, sice this may lead to a uplaed pregacy. Despite the body of evidece o the expulsio rates of differet IUCs, cotroversies remai regardig which wome are more likely to experiece expulsios. Higher expulsio rates have bee reported i ulliparous compared with parous wome usig the TCu380A IUD [28] ; however, other authors have reported coflictig fidigs [29 31]. Oe hypothesis that has bee proposed to explai expulsios of ay model of IUC refers to the legth of the uterie cavity. If we take ito accout that the TCu380A IUD is 3.6 cm i legth ad the LNG IUS is 3.2 cm, the associatio betwee expulsio ad uterie size may be differet for the two IUC models. This is oe of the reasos why may HCPs are reluctat to isert a IUC i wome with a total uterie legth (from the exteral os to the distal ed of the fudus) of less tha 6.0 cm or greater tha 9.5 cm, although some authors have failed to fid ay associatio betwee expulsio rate ad the legth of the uterie cavity [32,33]. I additio, oe of the reasos why HCPs are reluctat to isert a IUC i a woma whose uterie legth is less tha 6.0 cm is the maufacturer s recommedatios o the package isert, which iforms that the risk of expulsio is greater i these wome [105,106]. There have also bee speculatios regardig the substatial differece i uterie legth betwee ulligravidas ad parous wome, hece ulligravidas eedig shorter IUCs owig to a shorter uterie legth costitutes yet aother myth. Due to the cotroversies regardig the eed for smaller or shorter IUCs that could reduce the expulsio rate, oe study used uterie soudig ad ultrasoography to assess the legth of the edometrial cavity i 260 ulligravidas ad 310 parous wome [34]. The pricipal fidigs demostrated that the mea differece i legth was oly 0.28 cm, whe comparig uterie soudig ad ultrasoography. I additio, the mea legth of the edometrial cavity (± stadard error of the mea) was 3.84 ± 0.03 cm i ulligravidas ad 4.25 ± 0.03 cm i parous wome accordig to uterie soudig, ad 3.70 ± 0.03 ad 3.84 ± 0.03 cm, respectively, accordig to ultrasoography [34]. Cosequetly, the mea legth of the edometrial cavity was greater tha the legth of the TCu380A ad the LNG IUS, although it is importat to take

5 Itrauterie devices: should cliicia advice be chaged? ito accout that i almost 33% of the wome edometrial legth was less tha 3.2 cm, which is the legth of the LNG IUS. Dueñas et al. coducted a retrospective study to evaluate 461 users of IUDs, icludig 129 ulliparous wome. These authors reported o differece i the expulsio rates betwee ulliparous ad parous wome [35]. Although the review coducted by Hubacher regardig the performace of copper-iuds i ulliparous wome foud that i 13 out of the 20 studies evaluated, expulsio rates were higher i ulli parous wome [28], the curret TCu380A IUD was evaluated i oly oe of these studies. I additio, aother study coducted with the LNG IUS reported a expulsio rate of 3.7% i ulligravidas ad 4.6% i parous wome, with o statistically sigificat differece betwee the two groups [22]. I a recet study that evaluated whether the expulsio rates with the TCu380A IUD ad the LNG IUS correlated with the legth of the edometrial cavity, 235 ulligravidas ad parous wome received oe of the two models of IUC ad were followed-up for up to 1 year [36]. Uterie soudig ad ultrasoography were used to measure the legth of the uterie cavity. The two expulsios observed i users of the LNG IUS did ot occur i wome with a edometrial legth of less tha 3.2 cm. I users of the TCu380A, IUD expulsios occurred i three wome (4.8%) whose edometrial legth was less tha 3.6 cm ad i five wome (6.0%) with a edometrial legth of 3.6 cm or more. Furthermore, whe the edometrial cavity of the te wome i whom expulsio of the IUC occurred was assessed by ultrasoography, the legth was foud to be 3.9 ± 0.3 cm compared with 3.9 ± 0.0 cm i those wome i whom expulsio did ot occur. I a study coducted by the WHO [37], the cumulative expulsio rates i users of the TCu380A IUD raged from 2.5 to 6.1% up to the first ad eighth years of use, respectively, with higher rates beig associated with a lack of experiece i the HCPs who iserted the device. However, it must be take ito accout that wome who expel a IUC ad have a replacemet device iserted are more likely to experiece expulsio agai, irrespective of the IUC model [38,39]. Oe study showed et cumulative re-expulsio rates at 6 ad 12 moths of 21.7 ad 31.4%, respectively [40]. Cliical Perspective Risk of uterie perforatio Aother major cocer of HCPs whe isertig ay model of IUC is the risk of uterie perforatio. However, the risk at the time of IUC isertio has bee reported to rage from 0.0 to oly 1.3% [40]. Apparetly, the risk of uterie perforatio may be higher i ulliparous wome compared with parous wome; however, to the best of our kowledge, there are o comparative studies i which uterie perforatio rates were compared betwee ulliparous ad parous wome. If the IUC strigs are missig at the exteral cervical os at ay follow-up visit, this may be a idicatio of uterie perforatio; however, it may also be a idicator of uoticed IUC expulsio. If the woma reports pai i the lower abdome or pelvis, if a previous ameorrheic user of the LNG IUS reports ormal bleedig occurrig durig use of the device or if a accidetal pregacy occurs, the HCP should suspect uterie perforatio. However, cases have bee reported of wome with uterie perforatio ad o complaits [41]. I additio, perforatio should be suspected if the HCP who performed the isertio was i traiig, if the isertio was difficult, if dilatatio of the cervix was required, if cervical steosis was preset, if the woma has a history of cesarea sectio, if she experieced severe pai at isertio ad/or presets with a extremely retroverted or retroflexed uterus [42]. Nevertheless, it is extremely importat to follow the maufacturer s istructios to avoid or reduce the risk of perforatio [43 45]. Risk of pelvic ifectio & future ifertility Oe of the mai cocers from the poit of view of the HCP is the possibility that the use of a IUC could provoke PID, leadig to ifertility i the future whe iserted i adolescets ad/or ulligravidas. I the aforemetioed study i which HCPs were iterviewed [16], almost all of the respodets (98.5%) agreed o the safety of IUCs; however, a cotradictory fidig was that 29% of the HCPs reported that IUCs icrease a woma s risk of developig PID, eve outside the period immediately followig isertio. These cocers arose maily from the use of the IUD rather tha the LNG IUS ad particularly followig use of the Dalko Shield IUD may years ago. This IUD is o loger available; however, a relatioship was reported betwee its use ad a icreased risk of PID. This may be due to the fact that the device had a 23

6 Cliical Perspective Bahamodes & Bahamodes multifilamet strig that facilitates the ascesio of microbes ito the female geital tract [46]. This IUD was the subject of may lawsuits [47]. However, there is sufficiet scietific evidece that the use of moder IUCs, icludig the copper-iud ad the LNG IUS, offers o risk durig use; however, the risk of ifectio is elevated i the first 21 days after isertio before returig to baselie risk [48]. Neither copper-iud users or LNG IUS users are at ay icreased risk of PID ad this statemet is also valid for ulligravidas [49]. It has bee show that moder devices with moofilamet strigs do ot icrease a woma s risk of PID. The risk of PID is higher aroud the time of isertio, particularly i the first 20 days after isertio [50 53] ad this risk is related to previous cervical ifectios, pricipally Chlamydia trachomatis. After that period, the risk of PID is associated with uprotected sexual itercourse ad the cosequet risk of STI, which is the mai reaso to develop a PID. Nevertheless, rates of PID appear to be lower i users of the LNG IUS compared with copper-iud users [54]. Aother retrospective study assessed the complicatio rates of 194 users of either the TCu380A IUD or the LNG IUS [55]. Although 33% of the users had a history of STI, o icreased risk of PID was foud. I additio, i a retrospective study coducted with the TCu380A IUD ad the LNG IUS i adolescets ad youg adults, the risk of PID was lower i users of the LNG IUS [56]. PID poses a additioal risk to future ifertility, ad this is a cocer maily i the case of wome who have ot yet completed their family ad pricipally ulli gravidas. This cocer costitutes aother limitatio to the use of ay IUC. However, there is o evidece that the use of the copper-iud or the LNG IUS icreases the woma s risk of ifertility i the future. Regardig the retur of fertility, albeit there is evidece that there is o delay followig the use of moder models of copper-iuds or the LNG IUS [57], the evidece is still cotroversial [58]. I a UK-based report [59], 558 ulliparous wome participated i a study that evaluated the retur of fertility after the use of a IUD. The authors showed that amog wome who discotiued use of IUD or barrier methods, 39 ad 54%, respectively delivered after 1 year (p = 0.002). Furthermore, it was observed that 24 Cli. Pract. (2013) 10(1) log-term use of IUDs was associated with decreasig fertility (p = 0.005) ad 79% of wome who used a IUD for 78 moths or more delivered at 36 moths i compariso to 91% of wome who used the IUD for a short time. Oe case cotrol study with 1895 wome, icludig 358 wome with primary ifertility due to tubal obstructio, 953 ifertile wome without tubal obstructio ad 584 pregat wome, tested for C. trachomatis atibodies i the blood of all the participats [60]. Whe ifertile wome with tubal obstructio were compared with the ifertile cotrols, the odds ratio (OR) for tubal obstructio associated with a history of copper-iud use was 1.0 (95% CI: ) ad whe compared with primigravidas, the OR was 0.9 (95% CI: ). I additio, ifertility due to tubal obstructio was ot associated with the duratio of IUD use; however, positivity for C. trachomatis atibodies was associated with ifertility. I aother case cotrol study ivolvig 215 wome who were ifertile due to tubal obstructio, a history of pelvic surgery ad alcohol cosumptio were show to be factors sigificatly associated with the risk of ifertility caused by tubal obstructio [61] ; however, i wome with secodary ifertility, a history of pelvic surgery ad the umber of lifetime sexual parters were foud to be sigificat risk factors [61]. A history of IUD use was ot associated with future tubal ifertility. I fact, the probability of becomig pregat followig removal of ay IUD is similar to that observed i the geeral populatio of wome ot usig ay cotraceptive method. Oe study evaluated the retur to fertility i 372 wome who iterrupted the use of differet cotraceptive methods, icludig the LNG IUS ad the copper-iud, because they wished to become pregat [9]. Life-table aalysis showed 12 ad 24 moth pregacy rates of 80 ad 92/100 wome-years, respectively. It is importat to ote that 34% of LNG IUS users ad 43% of copper-iud users became pregat withi 3 moths of discotiuig the method, with youger age at removal beig the most importat factor for predictig a fast retur to fertility. I a multiceter study coducted i several Europea coutries, the LNG IUS was compared with the Nova-T copper-iud with respect to wome s retur to fertility after discotiuatio of the device [62]. A total of 209 wome (138 users

7 Itrauterie devices: should cliicia advice be chaged? of the LNG IUS ad 71 users of the copper-iud), who discotiued use of the device because they wished to become pregat, were followed-up for 2 years after removal. The gross cumulative pregacy rates were 71.2 ad 79.7/100 wome at 12 ad 24 moths, respectively, for the copperiud ad 79.1 ad 86.6/100 wome at 12 ad 24 moths, respectively, for the LNG IUS. There was o statistically sigificat differece betwee the two IUCs. I additio, 96% of the pregacies i both groups occurred durig the first year followig removal. Use restrictios for adolescets & youg adults Although IUCs have bee show to be highly effective with few side effects, accordig to the 2010 USA Natioal Survey of Family Growth oly 2% of wome of years of age have ever used these cotraceptive methods [63]. Due to the wide discrepacy betwee the beefits offered by IUCs ad the low prevalece of use of these devices, particularly i adolescets, ACOG released a committee opiio statig that IUC is a first-lie aget for prevetig uplaed pregacy i both ulliparous wome ad adolescets [64]. I additio, NICE released a documet i 2005 statig that there are o restrictios to IUC use based o age or parity [108]. A similar statemet was released i 2009 by the WHO statig that the beefits of IUD use geerally outweigh the risks i wome from mearche owards, ad that the IUD was desigated a category 2 cotraceptive method for adolescets [107]. It is probable that the cocers regardig the use of ay IUC i adolescets arose partly because of the scarcity of iformatio o the subject i the medical literature. However, due to the umber of adolescets who become pregat [109], the questio is why should the IUC be deied to adolescets, eve parous adolescets? Oe study evaluated the cliical performace of the TCu 200B IUD (a IUD o loger o the market) i a cohort of 995 parous adolescets, with each teeager beig compared with a cotrol 10 years older with idetical parity [65]. The results showed that pregacy rates, expulsio rates ad discotiuatios due to bleedig ad/or pai were higher i the group of adolescets; however, removals due to ifectio were i the same proportio with o differeces betwee the adolescets ad adults. Cliical Perspective O the other had, aother study [66] cod ucted with 1603 ulliparous wome (40.6% were 20 years old), usig three differet models of copper-iuds icludig the TCu380A IUD, reported a cotiuatio rate at the ed of the first year of 81.9/100 wome-years. Furthermore, other authors, i a review with data from differet studies, have show a cumulative cotiuatio rate of 55.7/100 wome-years of use at 2 years with the TCu380A IUD i ulliparous wome ad a average (betwee the differet studies) aual rate of 74.6/100 wome-years of use [29]. Aother study with 179 adolescets of up to 19 years of age who received a LNG IUS reported a expulsio rate of 8% ad a 1-year cotiuatio rate of 85% [67]. Suhoe et al. evaluated the cliical performace of IUDs compared with COCs i youg wome of years of age [18]. Approximately 20%, however, were ot ulligravidas. The IUD was foud to be well tolerated, with a cotiuatio rate of 79.8/100 wome-years of use at the ed of the first year i these youg wome. I a review study coducted at three US-based cliics, the authors reviewed the charts of 223 wome uder 21 years of age who received a TCu380A IUD ( = 11; 4.7%) or a LNG IUS ( = 222; 95.2%) [56]. Oly 71 wome (30%) were ulliparous ad 90% of the isertios were performed for cotraceptive purposes. Dilatio was required i oly 4.3% of the wome, while difficulty at isertio was recorded i 1.3% ad isertio failure i a similar proportio (1.3%). I additio, the risk of expulsio was foud to be higher i ulligravidas (RR: 10.6; p = 0.006), while wome with a history of previous reproductive tract ifectio were foud to be at a greater risk of ifectio. The 5-year cotiuatio rate was 50% for wome uder 18 years of age at isertio ad 71.5% for those of years of age. I aother retrospective study [67], the authors evaluated 307 wome uder 19 years of age, 77.5% of whom were ulliparous. IUDs were successfully iserted i the majority of the wome ( = 296; 96.4%), while expulsios withi the first year of follow-up accouted for 2.9% (five out of 172). There were o statistically sigificat differeces betwee ulliparous ad parous adolescets with respect to ay of the other reasos for removal. Although o pregacies occurred, it is importat to ote that PID was diagosed i eight wome (4.6%). The authors 25

8 Cliical Perspective Bahamodes & Bahamodes cocluded that although the discotiuatio rate was higher tha rates reported for adults, it was lower tha those foud with other cotraceptive methods i adolescets [68]. Lack of awareess regardig the ocotraceptive beefits of IUCs Cotraceptive methods were developed to provide protectio agaist uplaed or udesired pregacy. However, sice the itroductio of the first COC 50 years ago, may ocotraceptive beefits have bee reported. Nevertheless, may users, potetial users ad eve HCPs remai uaware of these beefits or, if aware of them, HCPs fail to commuicate these beefits to their patiets. Oe of the well-established beefits of the copper-iud ad potetially of the LNG IUS is a reductio i the risk of edometrial cacer [69 72]. I a recet review [69], the authors idetified ie case cotrol studies ad oe cohort study, all of which showed a protective effect agaist edometrial cacer i wome who had used a IUD at ay time (pooled adjusted OR: 0.6, 95% CI ). No associatio was foud betwee the type of IUD ad the histologic type of cacer. I additio, three studies failed to fid ay lik betwee IUD use ad hydatidiform moles or maligat sequela. Regardig the LNG IUS, there are several publicatios o the successful treatmet of edometrial cacer ad edometrial hyperplasia. However, the use of LNG IUS as a prevetive strategy of the disease is still speculative, albeit there are authors i favor of the use of the LNG IUS as therapy to prevet edometrial cacer [73]. Regardig the associatio betwee IUD use ad the risk of cervical cacer, this remaied a cotroversial issue util last year [74]. A study evaluated several large epidemiological studies o huma papillomavirus coducted i various coutries with differet populatios ad assessed the associatio betwee IUD use ad the risk of cervical huma papillomavirus ifectio ad cervical cacer. After adjustig for cofouders, these authors foud a iverse associatio betwee the use of IUDs ad cervical cacer (OR: 0.55; 95% CI: ), icludig a protective effect agaist squamous-cell carcioma (OR: 0.56; 95% CI: ), adeocarcioma ad adeosquamous carcioma (OR: 0.46; 95% CI: ). The authors suggested that 26 Cli. Pract. (2013) 10(1) the protective effect of the IUD works through cellular immuity triggered by the IUD, amog other factors. With respect to the LNG IUS, it has bee well established that this device represets a excellet optio for the medical treatmet of wome with heavy mestrual bleedig (HMB) [75,76], which is oe of the most commo complaits i gyecology, the pathology for which use of the LNG IUS has bee most itesely evaluated as a alterative to hysterectomy. Chroic HMB is a health problem that affects wome of reproductive age, may of whom also require cotraceptive protectio. May studies have show that the use of the LNG IUS leads to a reductio i the umber of bleedig days ad bleedig episodes ad i the amout of bleedig, eve i wome with hematological disorders ad those i use of aticoagulats [27,75,76]. I wome who were waitig for a hysterectomy [77], surgery was cacelled after 6 moths i 64.3% of wome i the LNG IUS group ad 14.3% of the cotrols. Whe wome with HMB were radomized to a LNG IUS or hysterectomy [78], 48% of the wome allocated to the LNG IUS remaied i use of the device 5 years after isertio, thus avoidig surgery. HMB is also a commo complait i wome with hematological diseases ad/or wome receivig warfari for a thrombotic disorder [79], ad the LNG IUS also represets a optio for these wome because, i additio to the cotraceptive protectio offered by the device, it reduces mestrual blood loss ad provokes ameorrhea i a high proportio of wome [80]. I additio, this device has bee used off-label to treat pai-associated edometriosis, with excellet results; however, there have bee few publicatios so far o this subject [81 84]. It is importat to take ito accout that ulligravidas may also request the LNG IUS ot oly for cotraceptio, but also for the treatmet of HMB. I the Brazilia study coducted with cohorts of ulligravidas ad parous wome, HMB costituted a additioal reaso for wome to use the LNG IUS, either idiopathic HMB or HMB followig weight loss after bariatric surgery or as a result of fibroids [22]. The improvemet i mestrual bleedig patters or the ameorrhea iduced by the device may prevet the developmet of iro deficiecy aemia [85].

9 Itrauterie devices: should cliicia advice be chaged? Coclusio Presetly, the umber of wome of reproductive age aroud the world who eed effective LARCs is substatial, ad the proportio of sexually active wome who are ulliparous or ulligravida is also high ad risig steadily [85,109,110]. This is occurrig because may wome choose to remai childless, or delay the birth of their first child, ad because cesarea sectio rates have icreased [85]. IUCs are a excellet tool for reducig the rate of uplaed pregacies or udesirable pregacies, ad age ad parity must ot be used as a reaso for refusig wome the opportuity to use a copper-iud or LNG IUS should they wish to do so. Over recet years, the umber of articles i the scietific literature o the eed to put IUC use ito its true perspective with respect to the high efficacy, safety, few side effects ad high cotiuatio rate of these devices has icreased. May uplaed pregacies could be avoided if IUCs were widely used aroud the world. Future perspective The legth of the most commo copper-iud, the TCu380A, is 3.6 cm, while that of the LNG IUS is 3.2 cm. May HCPs are cocered that these IUCs are ot appropriate for all wome, pricipally ulligravidas, sice these wome have small edometrial cavities ad cosequetly may be more proe to expulsios ad side effects compared with parous wome. There is oly oe model of the TCu380A IUD ad also oly oe model of the LNG IUS o the market, the former beig of 3.6 cm ad the latter of 3.2 cm i legth. The curret LNG IUS releases 20 µg of LNG per day. Some HCPs call for smaller IUCs [28] with the argumet that the curret IUCs are iappropriate for ulligravidas, despite the body of evidece showig that both devices are ideed appropriate for ulligravidas, as demostrated i this review. Recetly, Gemzell-Daielso et al. preseted data o the cliical performace of two ew low-dose LNG IUS ad compared them with the device curretly available o the market (LNG IUS20 ) [86]. The developmet of ew devices that release low doses of LNG is based o the cocept that a ew LNG IUS that releases a lower dose of LNG may reduce the icidece of side effects. Furthermore, if the device is smaller tha the curret oe, isertio may be easier ad less paiful. A difficult or paiful procedure may result i failure to isert the device [23]. The two Cliical Perspective low-dose LNG IUS use the same T-frame ad release 12 µg/day (LNG IUS12) ad 16 µg/day (LNG IUS16). The mai differeces are that the curret LNG IUS20 measures mm ad the diameter of the iserter is 4.75 mm, whereas the two ew devices measure mm with a iserter of 3.80 mm i diameter [23]. The cumulative 3-year Kapla Meier aa lysis for cotraceptive failure was 0.005, ad per 100 wome/years, while expulsios accouted for 0.4, 2.0 ad 1.6% for the LNG IUS12, LNG IUS16 ad LNG IUS20, respectively. At the ed of the 3-year period, ameorrhea was recorded i 12.7, 18.9 ad 23.6% of users of the LNG IUS12, LNG IUS16 ad LNG IUS 20, respectively. Successful isertios occurred at the first attempt i 98.5% of cases ad cervical dilators were used i 9.4% of the LNG IUS20 group ad i 3.9% of the LNG IUS12/LNG IUS16 acceptors (p = 0.004). The wome reported sigificatly less pai at isertio with the ew devices compared with the curret device. This study showed that cotraceptive effectiveess with the ew smaller LNG IUS was similar to that foud with the device curretly o the market [23]. Although isertios were less difficult with the two smaller LNG IUS, the authors failed to differetiate betwee ulligravidas ad parous wome; however, acceptors of the ew smaller LNG IUS reported less pai at isertio. I our opiio, this is probably the most importat fidig because fear of pai could reduce the umber of wome optig to use a IUC, pricipally if we cosider that the actios take to reduce pai are usuccessful [24]. We believe that the developmet of these ew LNG IUS is welcome, particularly because lower-dose LNG IUS may have some beefit ad the iserters are arrower, which may make the isertio procedure easier, pricipally i ulligravidas. The large Phase III trial curretly beig coducted by Bayer Healthcare (NJ, USA) is still ogoig. Fiacial & competig iterests disclosure The authors have o affiliatios or fiacial ivolvemet with ay orgaizatio or etity with a fiacial iterest i or fiacial coflict with the subject matter or materials discussed i the mauscript. This icludes employmet, cosultacies, hooraria, stock owership or optios, expert testimoy, grats or patets received or pedig, or royalties. No writig assistace was utilized i the productio of this mauscript. 27

10 Cliical Perspective Bahamodes & Bahamodes Mirea levoorgestrel-releasig itrauterie system (LNG IUS) ad Paragard CuT380A itrauterie devices i ulliparous wome. Cotraceptio 81(5), (2010). Refereces Papers of special ote have bee highlighted as: of iterest of cosiderable iterest Grimes DA. Forgettable cotraceptio. Cotraceptio 80(6), (2009). Itroduces the cocept of log-actig reversible cotraceptives. Bahamodes L, Faudes A, Sobreira-Lima B, Lui-Filho JF, Pecci P, Matera S. TCu 380A itrauterie devices (IUD): a reversible permaet cotraceptive method i wome over 35 years of age. Cotraceptio 72(5), (2005). Sivi I. Utility ad drawbacks of cotiuous use of a copper T IUD for 20 years. Cotraceptio 75(Suppl. 6), S70 S75 (2007). Luukkaie T, Toivoe J. Levoorgestrelreleasig itrauterie IUD as a method of cotraceptio with therapeutic properties. Cotraceptio 52(5), (1995). Hidalgo MM, Hidalgo-Regia C, Bahamodes MV, Moteiro I, Petta CA, Bahamodes L. Serum levoorgestrel levels ad edometrial thickess durig exteded use of the levoorgestrel-releasig itrauterie system. Cotraceptio 80(1), (2009). Wier B, Peipert JF, Zhao Q et al. Effectiveess of log-actig reversible cotraceptio. N. Egl. J. Med. 366(21), (2012). Results of the CHOICE project, the largest study o the effectiveess ad cotiuatio rates of log-actig reversible cotraceptives, which also demostrated o differeces i the performace of the devices betwee youg ad adult wome. Stubbs E, Schamp A. The evidece is i. Why are IUDs still out?: family physicias perceptios of risk ad idicatios. Ca. Fam. Physicia 54(4), (2008). 12 Welligs K, Zhihog Z, Kretel A, Barretta G, Glasier A. Attitudes towards logactig reversible methods of cotraceptio i geeral practice i the UK. Cotraceptio 76(3), (2007). Stawood NL, Garrett JM, Korad TR. Obstetricia gyecologists ad the itrauterie device: a survey of attitudes ad practice. Obstet. Gyecol. 99(2), (2002). Survey highlightig the limitatios faced by healthcare professioals regardig the use of IUCs. Marios L, Lövkvist L, Taube A, Johasso M, Dalvik H, Øverlie I. Use of the levoorgestrel releasig-itrauterie system i ulliparous wome a o-itervetioal study i Swede Eur. J. Cotracept. Reprod. Health Care 16(2), (2011). 22 Bahamodes MV, Hidalgo MM, Bahamodes L, Moteiro I. Ease of isertio ad cliical performace of the levoorgestrel-releasig itrauterie system i ulligravidas. Cotraceptio 84(5), e11 e16 (2011). 23 Alle RH, Bartz D, Grimes DA et al. Itervetios for pai with itrauterie device isertio. Cochrae Database Syst. Rev. 3, CD (2009). 24 Hubacher D, Reyes V, Lillo S et al. Pai from copper itrauterie device isertio: radomized trial of prophylactic ibuprofe. Am. J. Obstet. Gyecol. 195(5), (2006). 25 Lasser KJ, Che CH, Kropsch LA, Oberle MW, Lopes IM, Morris L. Comparative study of safety ad efficacy of IUD isertios by physicias ad ursig persoel i Brazil. Bull. Pa. Am. Health Orga. 29(3), (1995). Harper CC, Blum M, de Bocaegra HT et al. Challeges i traslatig evidece to practice: the provisio of itrauterie cotraceptio. Obstet. Gyecol. 111(6), (2008). 15 Black KI, Sakhaei T, Garlad SM. A study ivestigatig obstetricias ad gyaecologists maagemet of wome requestig a itrauterie device. Aust. N. Z. J. Obstet. Gyaecol. 50(2), (2010). 16 Madde T, Allsworth JE, Hladky KJ, Secura GM, Peipert JF. Itrauterie cotraceptio i Sait Louis: a survey of obstetricia ad gyecologists kowledge ad attitudes. Cotraceptio 81(2), (2010). 26 Brockmeyer A, Kishe M, Webb A. Experiece of IUD/IUS isertios ad cliical performace i ulliparous wome a pilot study. Eur. J. Cotracept. Reprod. Health Care 13(3), (2008). Restrictios reported by healthcare professioals regardig recommedatios for the use of IUCs. 27 Heikiheimo O, Iki P, Kuz M et al. Double-blid, radomized, placebocotrolled study o the effect of misoprostol o ease of cosecutive isertio of the levoorgestrel-releasig itrauterie system. Cotraceptio 81(6), (2010). 28 Hubacher D. Copper itrauterie device use by ulliparous wome: review of side effects. Cotraceptio 75(Suppl. 6), S8 S11 (2007). 17 Hatcher RA, Trussell J, Nelso A, Cates W, Stewart F, Kowal D. Cotraceptive Techology (19th Editio). PDR Network, NJ, USA (2008). Farmer M, Webb A. Itrauterie device isertio-related complicatios: ca they be predicted? J. Fam. Pla. Reprod. Health Care 29(4), (2003). 18 Suhoe S, Haukkamaa M, Jakobsso T, Rauramo I. Cliical performace of a levoorgestrel-releasig itrauterie system ad oral cotraceptives i youg ulliparous wome: a comparative study. Cotraceptio 69(5), (2004). Lyus R, Lohr P, Prager S. Board of the Society of Family Plaig. Use of the Bedarek PH, Jese JT. Safety, efficacy ad patiet acceptability of the cotraceptive ad o-cotraceptive uses of the LNG IUS. It. J. Womes Health 1, (2009). Sivi I, Ster J, Diaz S et al. Rates ad outcomes of plaed pregacy after use of Norplat capsules, Norplat II rods, or levoorgestrel-releasig or copper TCu 380Ag itrauterie cotraceptive devices. Am. J. Obstet. Gyecol. 166(4), (1992). Sivi I, el Mahgoub S, McCarthy T et al. Log-term cotraceptio with the levoorgestrel 20 mcg/day (LNg 20) ad the copper T 380Ag itrauterie devices: a fiveyear radomized study. Cotraceptio 42(4), (1990); erratum i: Cotraceptio 43(1), 100 (1991). Recommedatios of the US Society of Family Plaig o the use of itrauterie devices (IUCs) i ulliparous wome Zhou L, Harriso-Woolrych M, Coulter DM. Use of the New Zealad itesive medicies moitorig programme to study the levoorgestrel-releasig itrauterie device (Mirea). Pharmacoepidemiol. Drug Saf. 12(5), (2003). Cli. Pract. (2013) 10(1) Reviews the use of IUCs i ulliparous wome. 29 Sivi I, Ster J. Log-actig, more effective copper T IUDs: a summary of US experiece, Stud. Fam. Pla. 10(10), (1979). 30 Mishell DR Jr, Israel R, Freid N. A study of the copper T itrauterie cotraceptive device (TCu 200) i ulliparous wome. Am. J. Obstet. Gyecol. 116(8), (1973).

11 Itrauterie devices: should cliicia advice be chaged? 31 Veldhuis H, Vos A, Lagro-Jasse A. Complicatios of the itrauterie device i ulliparous ad parous wome. Eur. J. Ge. Pract. 10(3), (2004). 32 Johso BA. Isertio ad removal of itrauterie devices. Am. Fam. Physicia 71(1), (2005) Peterse KR, Brooks L, Jacobse N, Skoby SO. Cliical performace of itrauterie devices i ulligravidae: is the legth of the edometrial cavity of sigificace? Acta Eur. Fertil. 22(4), (1991). Cateiro R, Bahamodes MV, dos Satos Ferades A, Espejo-Arce X, Marchi NM, Bahamodes L. Legth of the edometrial cavity as measured by uterie soudig ad ultrasoography i wome of differet parities. Cotraceptio 81(6), (2010). Meirik O, Rowe PJ, Peregoudov A, Piaggio G, Petzold M; IUD Research Group at the UNDP/UNFPA/WHO/World Bak Special Programme of Research, Developmet ad Research Traiig i Huma Reproductio. The frameless copper-iud (GyeFix) ad the TCu380A IUD: results of a 8-year multiceter radomized comparative trial. Cotraceptio 80(2), (2009). Bahamodes L, Díaz J, Marchi NM, Petta CA, Cristofoletti ML, Gomez G. Performace of copper itrauterie devices whe iserted after a expulsio. Hum. Reprod. 10(11), (1995). Merki-Feld GS, Schwarz D, Imthur B, Keller PJ. Partial ad complete expulsio of the Multiload 375 IUD ad the levoorgestrelreleasig IUD after correct isertio. Eur. J. Obstet. Gyecol. Reprod. Biol. 137(1), (2008). 40 Sivi I, Ster J, Coutiho E et al. Prologed itrauterie cotraceptio: a seve year radomized study of the levoorgestrel 20 mcg/day (LNg 20) ad the copper T380 Ag IUDs. Cotraceptio 44(5), (1991). 41 Marchi NM, Castro S, Hidalgo MM et al. Maagemet of missig strigs i users of itrauterie cotraceptives. Cotraceptio 86(4), (2012). 42 Blaas K, Theodora M, Hassaaie M. Icidetal discovery of two levoorgestrelreleasig itrauterie systems misplaced i the peritoeal cavity. Eur. J. Cotracept. Reprod. Health Care 15(6), (2010) Harriso-Woolrych M, Ashto J, Coulter D. Uterie perforatio o itrauterie device isertio: is the icidece higher tha previously reported? Cotraceptio 67(1), (2003). Campbell SJ, Cropsey KL, Matthews CA. Itrauterie device use i a high-risk populatio: experiece from a urba uiversity cliic. Am. J. Obstet. Gyecol. 197(2), 193 e1 e6 (2007) Chi I. What we have leared from recet IUD studies: a researcher s perspective. Cotraceptio 48(2), (1993). 45 Va Houdehove K, va Kaam KJ, va Grootheest AC, Salemas TH, Duselma GA. Uterie perforatio i wome usig a levoorgestrel-releasig itrauterie system. Cotraceptio 73(3), (2006). Alto TM, Brock GN, Yag D, Wilkig DA, Hertweck SP, Loveless MB. Retrospective review of itrauterie device i adolescet ad youg wome. J. Pediatr. Adolesc. Gyecol. 25(3), (2012). 46 Dueñas JL, Albert A, Carrasco F. Itrauterie cotraceptio i ulligravid vs parous wome. Cotraceptio 53(1), (1996). Bahamodes MV, Moteiro I, Cateiro R, Ferades Ados S, Bahamodes L. Legth of the edometrial cavity ad itrauterie cotraceptive device expulsio. It. J. Gyaecol. Obstet. 113(1), (2011). Maagemet of IUCs with missig strigs ad uterie perforatios with IUC use. Cliical Perspective 58 Doll H, Vessey M, Paiter R. Retur of fertility i ulliparous wome after discotiuatio of the itrauterie device: compariso with wome discotiuig other methods of cotraceptio. BJOG 108(3), (2001). 59 Hubacher D, Lara-Ricalde R, Taylor DJ, Guerra-Ifate F, Guzma-Rodriguez R. Use of copper itrauterie devices ad the risk of tubal ifertility amog ulligravid wome. N. Egl. J. Med. 345(8), (2001). 60 Prager S, Darey PD. The levoorgestrel itrauterie system i ulliparous wome. Cotraceptio 75(Suppl. 6), S12 S15 (2007). Bahamodes L, Bueo JG, Hardy E, Vera S, Pimetel E, Ramos M. Idetificatio of mai risk factors for tubal ifertility. Fertil. Steril. 61(3), (1994). 61 Farley TM, Roseberg MJ, Rowe PJ, Che JH, Meirik O. Itrauterie devices ad pelvic iflammatory disease: a iteratioal perspective. Lacet 339(8796), (1992). Adersso K, Batar I, Rybo G. Retur to fertility after removal of a levoorgestrelreleasig itrauterie device ad Nova-T. Cotraceptio 46(6), (1992). 62 Rivera R, Yacobso Y, Grimes D. The mechaism of actio of hormoal cotraceptives ad itrauterie cotraceptive devices. Am. J. Obstet. Gyecol. 181(5 Pt 1), (1999). Abma JC, Martiez GM, Cope CE. Teeagers i the Uited States: sexual activity, cotraceptive use, ad childbearig, atioal survey of family growth Vital Health Stat. 23(30), 1 (2010). 63 America College of Obstetricias ad Gyecologists. Adolescets ad Log-Actig Reversible Cotraceptio: Implats ad Itrauterie Devices. ACOG Committee Opiio No. 539, October America College of Obstetricias ad Gyecologists, Washito, DC, USA (2012). Tatum HJ, Schmidt FH, Phillips D, McCarty M, O Leary WM. The Dalko Shield cotroversy. Structural ad bacteriological studies of IUD tails. JAMA 231(7), (1975). 48 Grimes DA. The itrauterie device, pelvic iflammatory disease, ad ifertility: the cofusio betwee hypothesis ad kowledge. Fertil. Steril. 58(4), (1992) Study cofirmig the lack of ay associatio betwee the use of ay type of IUC ad pelvic iflammatory disease. 52 Lee NC, Rubi GL, Ory HW, Burkma RT. Type of itrauterie device ad the risk of pelvic iflammatory disease. Obstet. Gyecol. 62(1), 1 6 (1983). 53 Lee NC, Rubi GL, Borucki R. The itrauterie device ad pelvic iflammatory disease revisited: ew results from the Wome s Health Study. Obstet. Gyecol. 72(1), 1 6 (1988). 54 Oe of the largest case series o the use of IUCs by adolescets. Radic L, Vlasic S, Matrlja I, Waszak CS. Retur to fertility after IUD removal for plaed pregacy. Cotraceptio 32(3), (1985). Burkma RT. Itrauterie devices ad pelvic iflammatory disease: evolvig perspectives o the data. Obstet. Gyecol. Surv. 51(Suppl. 12), S35 S41 (1996) levoorgestrel o pelvic ifectio: 3 years comparative experiece of levoorgestrel- ad copper-releasig itrauterie devices. Obstet. Gyecol. 77(2), (1991). Toivoe J, Luukkaie T, Alloe H. Protective effect of itrauterie release of 64 A US statemet o the use of IUCs by adolescets. Díaz J, Pito Neto AM, Bahamodes L, Díaz M, Arce XE, Castro S. Performace of the copper T 200 i parous adolescets: are copper-iuds suitable for these wome? Cotraceptio 48(1), (1993). 29