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Contraindications to IUD and IUS use
Contraception 75 (2007) S76 – S81
Review article
Contraindications to IUD and IUS use Anita L. Nelson4 Harbor-UCLA Medical Center, Box 474, Torrance, CA 90509-2910, USA Received 26 December 2006; accepted 6 January 2007
Abstract Contraindications to IUD or IUS use can be found on product labeling, in the guidelines of various specialty groups and in recommendations from peer-reviewed articles. Overly restrictive contraindications block access to this top-tier method for many women who would be candidates based on current scientific evidence. Assuming that a condition should be listed as a contraindication only if the risk of IUD/IUS use by a woman with that condition exceeds her risk with pregnancy, the list of contraindications is reduced to pregnancy, active uterine infection, malignancy in the uterus or cervix, an inability to place or retain the device, unexplained abnormal bleeding and adverse reaction to product ingredients. D 2007 Elsevier Inc. All rights reserved. Keywords: IUD contraindications; IUD practice guidelines
1. Introduction Intrauterine contraceptives are in the top-tier of contraceptive efficacy with typical use. Intrauterine contraception provides convenient, cost-effective and intermediate- to long-term pregnancy protection with few systemic side effects. Patient satisfaction with intrauterine contraceptives is high, as reflected in high continuation rates. Worldwide, intrauterine contraceptives are the most frequently used method of reversible female contraception, but utilization varies considerably in different countries. In the United States, for example, fewer than 3% of reproductive-age women not seeking pregnancy rely upon this method. In resource-poor countries, lack of trained clinicians, cost and inadequate supplies may explain low utilization. In resource-rich countries, residual concerns about safety and medical liability arising from past experience with the Dalkon Shield may still be influencing prescribing patterns. In this context, in particular, unwarranted, over-restrictive product labeling may perpetrate concerns among clinicians. These restrictions can detract from the general appeal of contraceptives for patients [1,2], and it may place clinicians who practice evidence-based medicine at medicolegal risk. Labeling that inappropriately contraindicates product use by certain groups of women (especially women with serious
4 Tel.: +1 310 222 3871; fax: +1 310 782 2924. E-mail address: [email protected]. 0010-7824/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2007.01.004
illnesses) places those women at increased risk of pregnancy, which may have catastrophic consequences for both maternal and fetal health. Therefore, it is important to revisit the logic used in developing product contraindications. This paper reviews many of the existing official contraindications from product labeling, from authorities establishing international guidelines, from recent peer-reviewed literature and from patient education materials to suggest that profound changes may still be needed to remove many of the inappropriate barriers to intrauterine contraceptive use. 2. Definition of contraindication Simply stated, a contraceptive method should pose fewer risks to a woman’s health than pregnancy. The risks of each method should also include the risk of its failure. Since the impact pregnancy has on the health of an individual woman is dependent on her baseline health, this definition requires that risk evaluations be individualized. For women who have serious illnesses, greater contraceptive risks would be acceptable than for healthy women. Additionally, each of these calculations must be made without regard to other contraceptive options, since it is possible that an individual woman may have unrelated conditions that would also preclude her use of that other option or that she may not have access to other options. By the same analysis, in developing lists of contraindications, it is not possible to
A.L. Nelson / Contraception 75 (2007) S76 – S81
envision all the possible combinations of problems with which women may present. Therefore, it must be left to the clinician to calculate the total risks associated with method use and with pregnancy when evaluating an individual candidate’s eligibility. Contraindications should only include those conditions in which use of the method would always be more hazardous than pregnancy. 3. Contraindications from US product labeling The labeling in the United States of contraindications and warnings for the Copper T-380A intrauterine device (IUD) recently underwent substantial revision (see Table 1) [3], despite the fact that product labeling changes are biased in favor of adding warnings [4]. One fundamental change was the elimination of the brecommended patient profile,Q which restricted IUD use even more than the contraindications list. For example, nulliparity has never been a contraindication, but the brecommended patient profileQ specified that an IUD candidate should be parous. Other labeling improvements included replacement of the phrase babnormal Pap smearsQ with bknown or suspected uterine or cervical malignancy.Q Even with these revisions, however, the remaining contraindications are still too broad. For example, the contraindication babnormalities of the uterus resulting in distortion of the uterine cavityQ is excessively vague. Would a 1-cm submucous leiomyoma protruding from the posterior wall disallow IUD use? The contraindication in this category should really be a functional definition; endometrial distortion that precludes IUD placement and correct position would be a more relevant contraindication. bPostpartum endometritis in the past 3 monthsQ requires an excessively long delay in an era of effective antibiotic therapy. bMucopurulent cervicitisQ can be treated at the time that the IUD is inserted (or probably even after insertion) with no increased risk of pelvic inflammatory disease [5]. Direct evidence of harm for women with Wilson’s disease using the copper device is lacking. However, there is reasonable concern from indirect evidence. In Wilson’s disease, women are unable to metabolize or eliminate copper. Copper is stored in large amounts in the liver, kidney and brain where it is difficult to assess its levels. Copper levels are lowest in the blood. The Table 1 Copper T-380A IUD US labeling contraindications [3] ParaGardR should not be placed when one or more of the following conditions exist: 1. Pregnancy or suspicion of pregnancy. 2. Abnormalities of the uterus resulting in distortion of the uterine cavity. 3. Acute pelvic inflammatory disease, or current behavior suggesting a high risk for pelvic inflammatory disease. 4. Postpartum endometritis or postabortal endometritis in the past 3 months. 5. Known or suspected uterine or cervical malignancy. 6. Genital bleeding of unknown etiology. 7. Mucopurulent cervicitis. 8. Wilson’s disease. 9. Allergy to any component of ParaGardR. 10. A previously placed IUD that has not been removed.
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Table 2 LNG-IUS US labeling contraindications [7] MirenaR insertion is contraindicated when one or more of the following conditions exist: 1. Pregnancy or suspicion of pregnancy. 2. Congenital or acquired uterine anomaly including fibroids if they distort the uterine cavity. 3. Acute pelvic inflammatory disease or a history of pelvic inflammatory disease unless there has been a subsequent intrauterine pregnancy. 4. Postpartum endometritis or infected abortion in the past 3 months. 5. Known or suspected uterine or cervical neoplasia or unresolved, abnormal Pap smear. 6. Genital bleeding of unknown etiology. 7. Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital tract infections, until infection is controlled. 8. Acute liver disease or liver tumor (benign or malignant). 9. Woman or her partner has multiple sexual partners. 10. Conditions associated with increased susceptibility to infections with microorganisms. Such conditions include, but are not limited to, leukemia, acquired immune deficiency syndrome (AIDS), and I.V. drug abuse. 11. Genital actinomycosis. 12. A previously inserted IUD that has not been removed. 13. Hypersensitivity to any component of this product. 14. Known or suspected carcinoma of the breast. 15. History of ectopic pregnancy or condition that would predispose to ectopic pregnancy.
upper limit of normal copper in the serum is 286 Ag/dL, but toxic effects have been seen at 200 Ag/dL. Mean serum level in the general population is 110 Ag/dL, but is double that in Copper IUD users, who average 220 Ag/dL [6]. The levonorgestrel intrauterine system (LNG-IUS) carries much more restrictive labeling for product use in the United States [7]. Table 2 lists the numerous conditions that absolutely preclude LNG-IUS in the current labeling. Many of the listed contraindications are out-of-date and have been disproved by scientific evidence. The questions raised by the Copper T-380A labeling about uterine cavity distortion and endometritis within the last 3 months are also relevant to the LNG-IUS. In addition, a bhistory of PIDQ has no influence on the safety of the method for the woman presenting after treatment of that condition. bUnresolved abnormal Pap smearsQ is too restrictive; under this wording, an atypical squamous cells of undetermined significance smear would technically prevent use of the LNG-IUS. bUntreated vaginitisQ is also far too broad an exclusion. While insertion in the presence of Candida vaginitis may be more uncomfortable, it will not pose any health risks to the woman. bAcute liver diseaseQ is again too vague; the method should not be disallowed if the patient is still able to metabolize the low serum levels of levonorgestrel. Without any scientific basis, bconditions associated with increased susceptibility to infection . . .Q prevent use by women who need the most effective pregnancy protection, including those on chemotherapy or corticosteroids, HIVinfected women and women with advanced diabetes are contraindicated. In fact, evidence about IUD use in HIVinfected women was sufficient to remove this restriction from the labeling for the Cu T-380A device. bHistory of
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ectopic pregnancy or risk factors for ectopic pregnancyQ is inappropriate, because LNG-IUS use significantly reduces a woman’s risk for ectopic pregnancy. The total LNG-IUS failure rate in the first year (0.14%) is lower than the risk a woman not using contraception has for experiencing an ectopic pregnancy (1.0625%). In the postmarketing survey, only 64 ectopic pregnancies were reported in 17,300 women over 5 years [8]. 4. Contraindications from practice guidelines Given that product labeling often reflects the requirements of regulatory agencies or the concerns of the legal departments within the pharmaceutical companies rather than scientific evidence, practitioners turn to practice guidelines to provide them with more current information not available on product labeling [4]. It is interesting to note that most applications of drug use are not included as indications in the product labeling. This off-label use of drugs is particularly common in the field of obstetrics and gynecology. Virtually all drug use in pregnancy is off-label; treatments for preterm labor, Group B streptococci and chorioamnionitis are all off-label. In gynecology, the use of hormonal contraceptives for the treatment of dysmenorrhea is off-label. In the United States, even the use of the LNGIUS for the treatment of menorrhagia is off-label. The World Health Organization Medical Eligibility Criteria (MEC), while not intended for individual patient use, were developed to guide countries in developing local family planning practice guidelines [9]. Based on review of current evidence, these guidelines are periodically updated by a consensus process. Table 3 lists the MEC Category 4 conditions (contraindications) for each of the two intrauterine contraceptives. These criteria more accurately reflect current evidence. The only contraindication listed in the WHO guidelines that is overly restrictive applies to the
Table 3 WHO MEC — Category 4 conditions [9] Pregnancy Puerperal sepsis Immediate postseptic abortion Unexplained vaginal bleeding Malignant gestational trophoblastic disease Cervical cancer (awaiting treatment) Breast cancer ( V 5 years) Endometrial cancer Uterine fibroids with distortion of the uterine cavity Distorted uterine cavity PID V 3 months Current purulent cervicitis, chlamydial infection or gonorrhea Known pelvic tuberculosis indicates initiation or continuation.
Cu IUD
LNG IUS
Initiation
Initiation
Initiation Initiation
Initiation Initiation
Initiation Initiation
Initiation Initiation
Initiation
Initiation
LNG-IUS, bwomen with breast cancer in the prior 5 years.Q The LNG-IUS is clearly safer than pregnancy in women with current or recent breast cancer. Backman et al. [10] found that in no age group did the risk of breast cancer in LNG-IUS users achieve a statistically significant difference from the general population. Despite the fact that hormone levels are high in pregnancy, there is little evidence that pregnancy after mastectomy for breast cancer adversely affects survival [11,12]. Velentgas et al. [13] have shown that there is no difference in recurrences or distant metastases seen between women with or without subsequent pregnancy. Women have generally been advised to delay pregnancy for 2–3 years following treatment for breast cancer because pregnancy increases the density of the breast (decreasing the ability to detect a recurrence or second primary cancer) and delays treatment for any recurrence (for fear of harming the fetus), but recent research [14] recommends only a 6-month delay. Serum levels of LNG with the IUS are very low [15] and the LNG-IUS does not affect either the diagnosis or treatment of subsequent breast cancer. The American College of Obstetrics and Gynecology has published a list of contraindications (Table 4) which is overly restrictive because they contraindicate IUD use with bpelvic inflammatory disease (current or within the past 3 months),Q bsexually transmitted diseases (current),Q bpuerperal or postabortion sepsis (current or within the past 3 months)Q and bpurulent cervicitisQ [16]. Planned Parenthood Federation of America lists bliver diseaseQ and bbreast cancerQ as contraindications for the LNG-IUS. Its patient education website stated, bAn IUD is most likely to be expelled during the first few months of use, but this may occur laterQ [17]. 5. Contraindication/additional requirements from recent peer review publication Many interesting restrictive beliefs and practice recommendations can be found in peer-reviewed articles published in a variety of countries within the last 3 years. Viberga et al. [18] reported that over half of OB-GYNs surveyed in Latvia believed there is a causal relationship between intrauterine contraceptive use and pelvic inflammatory disease and nearly half routinely use prophylactic antibiotic therapy for insertion. On a similar note, Lassey et al. [19] in Ghana recommended prophylactic antibiotic for women who screen positive for potential pathogens, including bacterial vaginosis (BV). In Turkey, Tosun et al. [20] recommended routine Gram stain for BV prior to insertion . Dikensoy et al. [21] in the United States recommended that all women who had history of breech delivery, preterm labor or a spontaneous abortion should undergo ultrasound evaluation to rule out intrauterine distortion, such as vaginal septa prior to being offered IUDs. In India, Agarwal et al. [22] reported women had lower hemoglobin or bcervical erosionQ with use of an intrauterine contraceptive and need close follow-up.
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6. Developing consensus for relevant contraindications Relevant contraindications fall into distinct categories: infection, pregnancy, uterine factors, cancer and allergic or adverse reaction to contraceptive product. Infections may not be as obvious a contraindication as previously considered. Mohllajee et al. [23] found in a MEDLINE search of articles published from January 1966 to March 2006 that there were no comparative studies of contraceptive insertion with the presence of a cervical infection vs. no infection. However, six prospective studies included women who inadvertently had an IUD placed in the presence of laboratory-documented STIs; the authors calculated that the risk of PID with IUD placement was 0–2% without infection, and 0–3% when insertion was done in the face of documented cervical infection [23]. Earlier studies had estimated that the risk of PID in populations with a 10% prevalence of gonorrhea or chlamydia would be 0.15% [24]. The optimal approach to the questions of STIs will differ in different populations. Standards of care for IUD use are needed in areas with high prevalence of STDs and limited (or no) ability to assess potential infection [25]. One algorithm to triage patients based on patient risk factors in areas of moderate or high STI prevalence has proven useful in Thailand and Uganda [26]. It must be remembered that areas of high STI prevalence are often areas where the risk of unintended pregnancy is also high. Reynolds et al. [27] have calculated that currently used contraceptives prevent the birth of 173,000 HIV-infected infants in sub-Saharan Africa each year. More widespread use of intrauterine contraceptives could greatly increase these numbers. The remaining recommendations for contraindication and their rationale are listed in Table 5. Pregnancy, uterine condition that preclude placement of the device, an infection in the uterus, unexplained abnormal uterine bleeding, cancer and allergic reaction to the ingredients (including Wilson’s disease for copper-bearing IUDs) are the only valid contraindication at this time. These contraindications are valid for the use of IUDs for long-term contraception and for the Copper T-380A inserted as the most effective form of emergency contraception [28,29]. Although the contraindication lists do not list uterine size as a cause for rejection of IUS/IUD candidacy, each of the
Table 4 ACOG contraindications to IUD use [15] 1. 2. 3. 4. 5. 6. 7. 8.
Pregnancy. Pelvic inflammatory disease (current or within the past 3 months). Sexually transmitted diseases (current). Puerperal or postabortion sepsis (current or within the past 3 months). Purulent cervicitis. Undiagnosed abnormal vaginal bleeding. Malignancy of the genital tract. Known uterine anomalies or fibroids distorting the cavity in a way incompatible with intrauterine device (IUD) insertion. 9. Allergy to any component of the IUD or Wilson’s disease (for copper-containing IUDs).
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Table 5 Reasonable contraindications Condition
Rationale
Pregnancy Uterine stenosis, distortion Uterine cavity too small Uterine cavity too large Uterus infected Uterine cancer Unexplained abnormal bleeding
No benefit, distinct harm Unable to insert Expulsion rates high? Decreases efficacy? Complicate infection, perforation Damage with insertion? Damage with insertion or delay of diagnosis Cu IUD may worsen disease Standard of care
Wilson’s disease Allergy to ingredients
products specifies that it is only to be used in a uterus that sounds to 6–9 cm in depth. The basis for these instructions is not clear. Uterine cavities have different shapes and cervical lengths vary [30]. Zhang et al. [31] reported that expulsion rates are not related to the length of the uterine cavity from the external os to the fundus, as measured with uterine sounding. Even earlier work by Hasson et al. [32] found that the lowest risk of pain, bleeding and expulsion occurred when the endometrial cavity (measured from above the internal os to the fundus) was 1.25–1.75 cm longer than the length of the device. In general, the event rates were greatest when the cavity exceeded the device length by b0.5 cm or by N 2 cm [33]. Since normal cervixes vary in length from 2.5 to 4.0 cm, it may be more relevant to express candidacy for IUD use in terms of endometrial cavity depths. Uterine anomalies reportedly occur in 3.2–4.0% of reproductive-age women [34,35]. Theoretically, uterine anomalies might obstruct the endometrial cavity which would prevent insertion; the anomalous cavity may not accommodate the intrauterine contraceptive; the risk of perforation and/or expulsion may be higher in anomalous uteri; and, if the device cannot be correctly placed, effectiveness may be compromised. However, all uterine anomalies should not be considered contraindications. Faundes et al. [36] reported that there is no evidence of reduced efficacy of an intrauterine contraceptive that migrates to a lower position in the uterine cavity, and there was a case report of successful use of two copper devices in a uterine didelphys [37]. Leiomyomas that mildly distort the uterine cavity and cause increased menstrual blood loss do not necessarily prevent use of intrauterine contraceptive. In fact, the LNG IUS may successfully treat menorrhagia due to Type II myoma when the uterine volume is b380 mL [38]. 7. Women’s concerns Beyond medical contraindications, it is important to consider what women may be worried about and what makes them hesitate to use intrauterine contraception. Asker et al. [39] found that women reported that they felt that they lacked objective information about intrauterine
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contraception. Beyond that informational issue, women said they feared side effects, were anxious about the insertion process and were concerned about infection risks they might face with use of intrauterine contraceptives. Intriguingly, women were also worried that they would lose personal control of their method after insertion because it would require clinician action to remove the device to restore their fertility [39]. 8. Changing prescribing patterns Even when new changes are made in product labeling and in practice guidelines, studies show that clinicians and counselors are often more influenced by their personal experience with intrauterine contraception than they are by scientific knowledge [40] and that they follow their own opinions [41]. In a concerted effect to modify clinician utilization of IUDs in areas of low rates of IUD insertion, Hubacher et al. [42] tested four different strategies. In one arm, medical education was provided; in a second arm, an IUD checklist was provided to help clinicians identify possible candidates; a third arm had both education and the IUD checklist intervention; and the fourth arm was placebo, which involved no intervention. Discouragingly, follow-up found that the area that did the worst (actually had decreased IUD utilization) was the comprehensive intervention while the placebo group (no intervention) experienced the highest increase in utilization of intrauterine contraceptive.
9. Conclusions Absolute contraindications to IUD/IUS use based on current scientific evidence are few in number and should include only those conditions in which the risk of IUD/IUS use would exceed the risk of pregnancy. Listing of inappropriate conditions on product labeling reduces women’s access to this very effective method. WHO MEC most accurately reflect current understanding of the risks, although small changes in that list may be appropriate. Other professional organizations should review their lists of contraindications to ensure that they are evidence based, and peer reviewers should caution would-be authors not to make practice recommendations that are not consistent with the fundamental definition of absolute contraindication. References [1] Grubb GS. Women’s perceptions of the safety of the pill: a survey in eight developing countries. Report of the perceptions of the pill survey group. J Biosoc Sci 1987;19:313 – 21. [2] Berry DC, Raynor DK, Knapp P, Bersellini E. Patients’ understanding of risk associated with medication use: impact of European Commission guidelines and other risk scales. Drug Saf 2003;26:1 – 11. [3] ParaGard T 380A intrauterine copper contraceptive prescribing information. N. Tonawanda (NY)7 FEI Products LLC; 2005 [Accessed 12/21/06 at http://www.paragard.com/paragard/custom_ images/Prescribing-Info.pdf].
[4] Grossman D, Ellertson C, Abuabara K, Blanchard K, Rivas FT. Barriers to contraceptive use in product labeling and practice guidelines. Am J Public Health 2006;96:791 – 9. [5] Skjeldestad FE, Halvorsen LE, Kahn H, Nordbo SA, Saake K. IUD users in Norway are at low risk for genital C. trachomatis infection. Contraception 1996;54:209 – 12. [6] De la Cruz D, Cruz A, Arteaga M, Castillo L, Tovalin H. Blood copper levels in Mexican users of the T380A IUD. Contraception 2005;72:122 – 5. [7] MirenaR prescribing information. Montville (NJ)7 Berlex; 2006 [Accessed 12/21/06 at http://www.berlex.com/html/products/pi/ Mirena_PI.pdf]. [8] Backman T, Rauramo I, Jaakkola K, et al. Use of the levonorgestrelreleasing intrauterine system and breast cancer. Obstet Gynecol 2005;106:813 – 7. [9] WHO Reproductive Health and Research. Medical eligibility criteria for contraceptive use. 3rd ed. Geneva7 World Health Organization; 2004 [Accessed 12/18/06 at http://www.who.int/reproductive-health/ publications/mec/index.htm]. [10] Backman T, Rauramo I, Huhtala S, Koskenvuo M. Pregnancy during the use of levonorgestrel intrauterine system. Am J Obstet Gynecol 2004;190:50 – 4. [11] Averette HE, Mirhashemi R, Moffat FL. Pregnancy after breast carcinoma: the ultimate medical challenge. Cancer 1999;85:2301 – 4. [12] Dow KH, Harris JR, Roy C. Pregnancy after breast-conserving surgery and radiation therapy for breast cancer. J Natl Cancer Inst Monogr 1994;16:131 – 7. [13] Velentgas P, Daling JR, Malone KE, et al. Pregnancy after breast carcinoma: outcomes and influence on mortality. Cancer 1999; 85:2424 – 32. [14] Ives A, Saunders C, Bulsara M, Semmens J. Pregnancy after breast cancer: population based study. BMJ 2007;334:194. [15] Lockhat FB, Emembolu JE, Konje JC. Serum and peritoneal fluid levels of levonorgestrel in women with endometriosis who were treated with an intrauterine contraceptive device containing levonorgestrel. Fertil Steril 2005;83:398 – 404. [16] ACOG Committee on Practice Bulletins — Gynecology. ACOG practice bulletin. Clinical management guidelines for obstetrician– gynecologists, no. 59, January 2005. Intrauterine device. Obstet Gynecol 2005;105:223 – 32. [17] Planned Parenthood. Intrauterine devices [Accessed 12/18/06 at http:// www.plannedparenthood.org/birth-control-pregnancy/birth-control/ intrauterine-devices.htm]. [18] Viberga I, Odlind V, Zodzika J. Practices and perceptions on intrauterine contraception among Latvian obstetrician–gynecologists. Acta Obstet Gynecol Scand 2006;85:583 – 8. [19] Lassey AT, Newman MJ, Opintan JA. Vaginal flora of first time urban family planning attendants in Accra, Ghana. West Afr J Med 2005; 24:219 – 22. [20] Tosun I, Aydin F, Kaklikkaya N, Yazici Y. Frequency of bacterial vaginosis among women attending for intrauterine device insertion at an inner-city family planning clinic. Eur J Contracept Reprod Health Care 2003;8:135 – 8. [21] Dikensoy E, Kutlar I, Gocmen A, Graves CR. Two cases of uterine septum with intrauterine device. Br J Radiol 2005;78:952 – 3. [22] Agarwal K, Sharma U, Acharya V. Microbial and cytopathological study of intrauterine contraceptive device users. Indian J Med Sci 2004;58:394 – 9. [23] Mohllajee AP, Curtis KM, Peterson HB. Does insertion and use of an intrauterine device increase the risk of pelvic inflammatory disease among women with sexually transmitted infection? A systematic review. Contraception 2006;73:145 – 53. [24] Shelton JD. Risk of clinical pelvic inflammatory disease attributable to an intrauterine device. Lancet 2001;357:443. [25] Steen R, Shapiro K. Intrauterine contraceptive devices and risk of pelvic inflammatory disease: standard of care in high STI prevalence settings. Reprod Health Matt 2004;12:136 – 43.
A.L. Nelson / Contraception 75 (2007) S76 – S81 [26] Morrison CS, Murphy L, Kwok C, Weiner DH. Identifying appropriate IUD candidates in areas with high prevalence of sexually transmitted infections. Contraception 2007;75:185 – 92. [27] Reynolds HW, Steiner MJ, Cates Jr W. Contraception’s proved potential to fight HIV. Sex Transm Infect 2005;81:184 – 5. [28] Trussell J, Ellertson C. Efficacy of emergency contraception. Fertil Control Rev 1995;4:8 – 11. [29] Zhou L, Xiao B. Emergency contraception with Multiload Cu-375 SL IUD: a multicenter clinical trial. Contraception 2001;64:107 – 12. [30] Kamal I, Hefnawi F, Ghoneim M, Talaat M, Abdalla M. Dimensional and architectural disproportion between the intrauterine device and the uterine cavity. A cause of bleeding. Fertil Steril 1971;22:514 – 21. [31] Zhang J, Feldblum PJ, Chi IC, Farr MG. Risk factors for copper T IUD expulsion: an epidemiologic analysis. Contraception 1992; 46:427 – 33. [32] Hasson HM, Berger GS, Edelman DA. Factors affecting intrauterine contraceptive device performance: I. Endometrial cavity length. Am J Obstet Gynecol 1976;126:973 – 81. [33] Hasson HM. Clinical experience with intrauterine devices in a private practice. Adv Contracept 1985;1:51 – 61. [34] Simon C, Martinez L, Pardo F, Tortajada M, Pellicer A. Mullerian defects in women with normal reproductive outcome. Fertil Steril 1991;56:1192 – 3.
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[35] Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simon C, Pellicer A. Reproductive impact of congenital Mullerian anomalies. Hum Reprod 1997;12:2277 – 81. [36] Faundes D, Perdigao A, Faundes A, Bahamondes L, Petta CA. T-shaped IUDs accommodate in their position during the first 3 months after insertion. Contraception 2000;62:165 – 8. [37] Espey E, Ogburn T, Hall R, Byrn F. Use of intrauterine device in the setting of uterus didelphys. Obstet Gynecol 2006;108:774 – 6. [38] Soysal S, Soysal ME. The efficacy of levonorgestrel-releasing intrauterine device in selected cases of myoma-related menorrhagia: a prospective controlled trial. Gynecol Obstet Invest 2005;59:29 – 35. [39] Asker C, Stokes-Lampard H, Beavan J, Wilson S. What is it about intrauterine devices that women find unacceptable? Factors that make women non-users: a qualitative study. J Fam Plann Reprod Health Care 2006;32:89 – 94. [40] Bianchi-Demicheli F, Perrin E, Dupanloup A, et al. Contraceptive counselling and social representations: a qualitative study. Swiss Med Wkly 2006;136:127 – 34. [41] Vos AA, Veldhuis HM, Lagro-Janssen TL. Intrauterine contraception: the role of general practitioners in four Dutch general practices. Contraception 2004;69:283 – 7. [42] Hubacher D, Vilchez R, Gmach R, et al. The impact of clinician education on IUD uptake, knowledge and attitudes: results of a randomized trial. Contraception 2006;73:628 – 33.
Review article
Contraindications to IUD and IUS use Anita L. Nelson4 Harbor-UCLA Medical Center, Box 474, Torrance, CA 90509-2910, USA Received 26 December 2006; accepted 6 January 2007
Abstract Contraindications to IUD or IUS use can be found on product labeling, in the guidelines of various specialty groups and in recommendations from peer-reviewed articles. Overly restrictive contraindications block access to this top-tier method for many women who would be candidates based on current scientific evidence. Assuming that a condition should be listed as a contraindication only if the risk of IUD/IUS use by a woman with that condition exceeds her risk with pregnancy, the list of contraindications is reduced to pregnancy, active uterine infection, malignancy in the uterus or cervix, an inability to place or retain the device, unexplained abnormal bleeding and adverse reaction to product ingredients. D 2007 Elsevier Inc. All rights reserved. Keywords: IUD contraindications; IUD practice guidelines
1. Introduction Intrauterine contraceptives are in the top-tier of contraceptive efficacy with typical use. Intrauterine contraception provides convenient, cost-effective and intermediate- to long-term pregnancy protection with few systemic side effects. Patient satisfaction with intrauterine contraceptives is high, as reflected in high continuation rates. Worldwide, intrauterine contraceptives are the most frequently used method of reversible female contraception, but utilization varies considerably in different countries. In the United States, for example, fewer than 3% of reproductive-age women not seeking pregnancy rely upon this method. In resource-poor countries, lack of trained clinicians, cost and inadequate supplies may explain low utilization. In resource-rich countries, residual concerns about safety and medical liability arising from past experience with the Dalkon Shield may still be influencing prescribing patterns. In this context, in particular, unwarranted, over-restrictive product labeling may perpetrate concerns among clinicians. These restrictions can detract from the general appeal of contraceptives for patients [1,2], and it may place clinicians who practice evidence-based medicine at medicolegal risk. Labeling that inappropriately contraindicates product use by certain groups of women (especially women with serious
4 Tel.: +1 310 222 3871; fax: +1 310 782 2924. E-mail address: [email protected]. 0010-7824/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2007.01.004
illnesses) places those women at increased risk of pregnancy, which may have catastrophic consequences for both maternal and fetal health. Therefore, it is important to revisit the logic used in developing product contraindications. This paper reviews many of the existing official contraindications from product labeling, from authorities establishing international guidelines, from recent peer-reviewed literature and from patient education materials to suggest that profound changes may still be needed to remove many of the inappropriate barriers to intrauterine contraceptive use. 2. Definition of contraindication Simply stated, a contraceptive method should pose fewer risks to a woman’s health than pregnancy. The risks of each method should also include the risk of its failure. Since the impact pregnancy has on the health of an individual woman is dependent on her baseline health, this definition requires that risk evaluations be individualized. For women who have serious illnesses, greater contraceptive risks would be acceptable than for healthy women. Additionally, each of these calculations must be made without regard to other contraceptive options, since it is possible that an individual woman may have unrelated conditions that would also preclude her use of that other option or that she may not have access to other options. By the same analysis, in developing lists of contraindications, it is not possible to
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envision all the possible combinations of problems with which women may present. Therefore, it must be left to the clinician to calculate the total risks associated with method use and with pregnancy when evaluating an individual candidate’s eligibility. Contraindications should only include those conditions in which use of the method would always be more hazardous than pregnancy. 3. Contraindications from US product labeling The labeling in the United States of contraindications and warnings for the Copper T-380A intrauterine device (IUD) recently underwent substantial revision (see Table 1) [3], despite the fact that product labeling changes are biased in favor of adding warnings [4]. One fundamental change was the elimination of the brecommended patient profile,Q which restricted IUD use even more than the contraindications list. For example, nulliparity has never been a contraindication, but the brecommended patient profileQ specified that an IUD candidate should be parous. Other labeling improvements included replacement of the phrase babnormal Pap smearsQ with bknown or suspected uterine or cervical malignancy.Q Even with these revisions, however, the remaining contraindications are still too broad. For example, the contraindication babnormalities of the uterus resulting in distortion of the uterine cavityQ is excessively vague. Would a 1-cm submucous leiomyoma protruding from the posterior wall disallow IUD use? The contraindication in this category should really be a functional definition; endometrial distortion that precludes IUD placement and correct position would be a more relevant contraindication. bPostpartum endometritis in the past 3 monthsQ requires an excessively long delay in an era of effective antibiotic therapy. bMucopurulent cervicitisQ can be treated at the time that the IUD is inserted (or probably even after insertion) with no increased risk of pelvic inflammatory disease [5]. Direct evidence of harm for women with Wilson’s disease using the copper device is lacking. However, there is reasonable concern from indirect evidence. In Wilson’s disease, women are unable to metabolize or eliminate copper. Copper is stored in large amounts in the liver, kidney and brain where it is difficult to assess its levels. Copper levels are lowest in the blood. The Table 1 Copper T-380A IUD US labeling contraindications [3] ParaGardR should not be placed when one or more of the following conditions exist: 1. Pregnancy or suspicion of pregnancy. 2. Abnormalities of the uterus resulting in distortion of the uterine cavity. 3. Acute pelvic inflammatory disease, or current behavior suggesting a high risk for pelvic inflammatory disease. 4. Postpartum endometritis or postabortal endometritis in the past 3 months. 5. Known or suspected uterine or cervical malignancy. 6. Genital bleeding of unknown etiology. 7. Mucopurulent cervicitis. 8. Wilson’s disease. 9. Allergy to any component of ParaGardR. 10. A previously placed IUD that has not been removed.
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Table 2 LNG-IUS US labeling contraindications [7] MirenaR insertion is contraindicated when one or more of the following conditions exist: 1. Pregnancy or suspicion of pregnancy. 2. Congenital or acquired uterine anomaly including fibroids if they distort the uterine cavity. 3. Acute pelvic inflammatory disease or a history of pelvic inflammatory disease unless there has been a subsequent intrauterine pregnancy. 4. Postpartum endometritis or infected abortion in the past 3 months. 5. Known or suspected uterine or cervical neoplasia or unresolved, abnormal Pap smear. 6. Genital bleeding of unknown etiology. 7. Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital tract infections, until infection is controlled. 8. Acute liver disease or liver tumor (benign or malignant). 9. Woman or her partner has multiple sexual partners. 10. Conditions associated with increased susceptibility to infections with microorganisms. Such conditions include, but are not limited to, leukemia, acquired immune deficiency syndrome (AIDS), and I.V. drug abuse. 11. Genital actinomycosis. 12. A previously inserted IUD that has not been removed. 13. Hypersensitivity to any component of this product. 14. Known or suspected carcinoma of the breast. 15. History of ectopic pregnancy or condition that would predispose to ectopic pregnancy.
upper limit of normal copper in the serum is 286 Ag/dL, but toxic effects have been seen at 200 Ag/dL. Mean serum level in the general population is 110 Ag/dL, but is double that in Copper IUD users, who average 220 Ag/dL [6]. The levonorgestrel intrauterine system (LNG-IUS) carries much more restrictive labeling for product use in the United States [7]. Table 2 lists the numerous conditions that absolutely preclude LNG-IUS in the current labeling. Many of the listed contraindications are out-of-date and have been disproved by scientific evidence. The questions raised by the Copper T-380A labeling about uterine cavity distortion and endometritis within the last 3 months are also relevant to the LNG-IUS. In addition, a bhistory of PIDQ has no influence on the safety of the method for the woman presenting after treatment of that condition. bUnresolved abnormal Pap smearsQ is too restrictive; under this wording, an atypical squamous cells of undetermined significance smear would technically prevent use of the LNG-IUS. bUntreated vaginitisQ is also far too broad an exclusion. While insertion in the presence of Candida vaginitis may be more uncomfortable, it will not pose any health risks to the woman. bAcute liver diseaseQ is again too vague; the method should not be disallowed if the patient is still able to metabolize the low serum levels of levonorgestrel. Without any scientific basis, bconditions associated with increased susceptibility to infection . . .Q prevent use by women who need the most effective pregnancy protection, including those on chemotherapy or corticosteroids, HIVinfected women and women with advanced diabetes are contraindicated. In fact, evidence about IUD use in HIVinfected women was sufficient to remove this restriction from the labeling for the Cu T-380A device. bHistory of
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ectopic pregnancy or risk factors for ectopic pregnancyQ is inappropriate, because LNG-IUS use significantly reduces a woman’s risk for ectopic pregnancy. The total LNG-IUS failure rate in the first year (0.14%) is lower than the risk a woman not using contraception has for experiencing an ectopic pregnancy (1.0625%). In the postmarketing survey, only 64 ectopic pregnancies were reported in 17,300 women over 5 years [8]. 4. Contraindications from practice guidelines Given that product labeling often reflects the requirements of regulatory agencies or the concerns of the legal departments within the pharmaceutical companies rather than scientific evidence, practitioners turn to practice guidelines to provide them with more current information not available on product labeling [4]. It is interesting to note that most applications of drug use are not included as indications in the product labeling. This off-label use of drugs is particularly common in the field of obstetrics and gynecology. Virtually all drug use in pregnancy is off-label; treatments for preterm labor, Group B streptococci and chorioamnionitis are all off-label. In gynecology, the use of hormonal contraceptives for the treatment of dysmenorrhea is off-label. In the United States, even the use of the LNGIUS for the treatment of menorrhagia is off-label. The World Health Organization Medical Eligibility Criteria (MEC), while not intended for individual patient use, were developed to guide countries in developing local family planning practice guidelines [9]. Based on review of current evidence, these guidelines are periodically updated by a consensus process. Table 3 lists the MEC Category 4 conditions (contraindications) for each of the two intrauterine contraceptives. These criteria more accurately reflect current evidence. The only contraindication listed in the WHO guidelines that is overly restrictive applies to the
Table 3 WHO MEC — Category 4 conditions [9] Pregnancy Puerperal sepsis Immediate postseptic abortion Unexplained vaginal bleeding Malignant gestational trophoblastic disease Cervical cancer (awaiting treatment) Breast cancer ( V 5 years) Endometrial cancer Uterine fibroids with distortion of the uterine cavity Distorted uterine cavity PID V 3 months Current purulent cervicitis, chlamydial infection or gonorrhea Known pelvic tuberculosis indicates initiation or continuation.
Cu IUD
LNG IUS
Initiation
Initiation
Initiation Initiation
Initiation Initiation
Initiation Initiation
Initiation Initiation
Initiation
Initiation
LNG-IUS, bwomen with breast cancer in the prior 5 years.Q The LNG-IUS is clearly safer than pregnancy in women with current or recent breast cancer. Backman et al. [10] found that in no age group did the risk of breast cancer in LNG-IUS users achieve a statistically significant difference from the general population. Despite the fact that hormone levels are high in pregnancy, there is little evidence that pregnancy after mastectomy for breast cancer adversely affects survival [11,12]. Velentgas et al. [13] have shown that there is no difference in recurrences or distant metastases seen between women with or without subsequent pregnancy. Women have generally been advised to delay pregnancy for 2–3 years following treatment for breast cancer because pregnancy increases the density of the breast (decreasing the ability to detect a recurrence or second primary cancer) and delays treatment for any recurrence (for fear of harming the fetus), but recent research [14] recommends only a 6-month delay. Serum levels of LNG with the IUS are very low [15] and the LNG-IUS does not affect either the diagnosis or treatment of subsequent breast cancer. The American College of Obstetrics and Gynecology has published a list of contraindications (Table 4) which is overly restrictive because they contraindicate IUD use with bpelvic inflammatory disease (current or within the past 3 months),Q bsexually transmitted diseases (current),Q bpuerperal or postabortion sepsis (current or within the past 3 months)Q and bpurulent cervicitisQ [16]. Planned Parenthood Federation of America lists bliver diseaseQ and bbreast cancerQ as contraindications for the LNG-IUS. Its patient education website stated, bAn IUD is most likely to be expelled during the first few months of use, but this may occur laterQ [17]. 5. Contraindication/additional requirements from recent peer review publication Many interesting restrictive beliefs and practice recommendations can be found in peer-reviewed articles published in a variety of countries within the last 3 years. Viberga et al. [18] reported that over half of OB-GYNs surveyed in Latvia believed there is a causal relationship between intrauterine contraceptive use and pelvic inflammatory disease and nearly half routinely use prophylactic antibiotic therapy for insertion. On a similar note, Lassey et al. [19] in Ghana recommended prophylactic antibiotic for women who screen positive for potential pathogens, including bacterial vaginosis (BV). In Turkey, Tosun et al. [20] recommended routine Gram stain for BV prior to insertion . Dikensoy et al. [21] in the United States recommended that all women who had history of breech delivery, preterm labor or a spontaneous abortion should undergo ultrasound evaluation to rule out intrauterine distortion, such as vaginal septa prior to being offered IUDs. In India, Agarwal et al. [22] reported women had lower hemoglobin or bcervical erosionQ with use of an intrauterine contraceptive and need close follow-up.
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6. Developing consensus for relevant contraindications Relevant contraindications fall into distinct categories: infection, pregnancy, uterine factors, cancer and allergic or adverse reaction to contraceptive product. Infections may not be as obvious a contraindication as previously considered. Mohllajee et al. [23] found in a MEDLINE search of articles published from January 1966 to March 2006 that there were no comparative studies of contraceptive insertion with the presence of a cervical infection vs. no infection. However, six prospective studies included women who inadvertently had an IUD placed in the presence of laboratory-documented STIs; the authors calculated that the risk of PID with IUD placement was 0–2% without infection, and 0–3% when insertion was done in the face of documented cervical infection [23]. Earlier studies had estimated that the risk of PID in populations with a 10% prevalence of gonorrhea or chlamydia would be 0.15% [24]. The optimal approach to the questions of STIs will differ in different populations. Standards of care for IUD use are needed in areas with high prevalence of STDs and limited (or no) ability to assess potential infection [25]. One algorithm to triage patients based on patient risk factors in areas of moderate or high STI prevalence has proven useful in Thailand and Uganda [26]. It must be remembered that areas of high STI prevalence are often areas where the risk of unintended pregnancy is also high. Reynolds et al. [27] have calculated that currently used contraceptives prevent the birth of 173,000 HIV-infected infants in sub-Saharan Africa each year. More widespread use of intrauterine contraceptives could greatly increase these numbers. The remaining recommendations for contraindication and their rationale are listed in Table 5. Pregnancy, uterine condition that preclude placement of the device, an infection in the uterus, unexplained abnormal uterine bleeding, cancer and allergic reaction to the ingredients (including Wilson’s disease for copper-bearing IUDs) are the only valid contraindication at this time. These contraindications are valid for the use of IUDs for long-term contraception and for the Copper T-380A inserted as the most effective form of emergency contraception [28,29]. Although the contraindication lists do not list uterine size as a cause for rejection of IUS/IUD candidacy, each of the
Table 4 ACOG contraindications to IUD use [15] 1. 2. 3. 4. 5. 6. 7. 8.
Pregnancy. Pelvic inflammatory disease (current or within the past 3 months). Sexually transmitted diseases (current). Puerperal or postabortion sepsis (current or within the past 3 months). Purulent cervicitis. Undiagnosed abnormal vaginal bleeding. Malignancy of the genital tract. Known uterine anomalies or fibroids distorting the cavity in a way incompatible with intrauterine device (IUD) insertion. 9. Allergy to any component of the IUD or Wilson’s disease (for copper-containing IUDs).
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Table 5 Reasonable contraindications Condition
Rationale
Pregnancy Uterine stenosis, distortion Uterine cavity too small Uterine cavity too large Uterus infected Uterine cancer Unexplained abnormal bleeding
No benefit, distinct harm Unable to insert Expulsion rates high? Decreases efficacy? Complicate infection, perforation Damage with insertion? Damage with insertion or delay of diagnosis Cu IUD may worsen disease Standard of care
Wilson’s disease Allergy to ingredients
products specifies that it is only to be used in a uterus that sounds to 6–9 cm in depth. The basis for these instructions is not clear. Uterine cavities have different shapes and cervical lengths vary [30]. Zhang et al. [31] reported that expulsion rates are not related to the length of the uterine cavity from the external os to the fundus, as measured with uterine sounding. Even earlier work by Hasson et al. [32] found that the lowest risk of pain, bleeding and expulsion occurred when the endometrial cavity (measured from above the internal os to the fundus) was 1.25–1.75 cm longer than the length of the device. In general, the event rates were greatest when the cavity exceeded the device length by b0.5 cm or by N 2 cm [33]. Since normal cervixes vary in length from 2.5 to 4.0 cm, it may be more relevant to express candidacy for IUD use in terms of endometrial cavity depths. Uterine anomalies reportedly occur in 3.2–4.0% of reproductive-age women [34,35]. Theoretically, uterine anomalies might obstruct the endometrial cavity which would prevent insertion; the anomalous cavity may not accommodate the intrauterine contraceptive; the risk of perforation and/or expulsion may be higher in anomalous uteri; and, if the device cannot be correctly placed, effectiveness may be compromised. However, all uterine anomalies should not be considered contraindications. Faundes et al. [36] reported that there is no evidence of reduced efficacy of an intrauterine contraceptive that migrates to a lower position in the uterine cavity, and there was a case report of successful use of two copper devices in a uterine didelphys [37]. Leiomyomas that mildly distort the uterine cavity and cause increased menstrual blood loss do not necessarily prevent use of intrauterine contraceptive. In fact, the LNG IUS may successfully treat menorrhagia due to Type II myoma when the uterine volume is b380 mL [38]. 7. Women’s concerns Beyond medical contraindications, it is important to consider what women may be worried about and what makes them hesitate to use intrauterine contraception. Asker et al. [39] found that women reported that they felt that they lacked objective information about intrauterine
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contraception. Beyond that informational issue, women said they feared side effects, were anxious about the insertion process and were concerned about infection risks they might face with use of intrauterine contraceptives. Intriguingly, women were also worried that they would lose personal control of their method after insertion because it would require clinician action to remove the device to restore their fertility [39]. 8. Changing prescribing patterns Even when new changes are made in product labeling and in practice guidelines, studies show that clinicians and counselors are often more influenced by their personal experience with intrauterine contraception than they are by scientific knowledge [40] and that they follow their own opinions [41]. In a concerted effect to modify clinician utilization of IUDs in areas of low rates of IUD insertion, Hubacher et al. [42] tested four different strategies. In one arm, medical education was provided; in a second arm, an IUD checklist was provided to help clinicians identify possible candidates; a third arm had both education and the IUD checklist intervention; and the fourth arm was placebo, which involved no intervention. Discouragingly, follow-up found that the area that did the worst (actually had decreased IUD utilization) was the comprehensive intervention while the placebo group (no intervention) experienced the highest increase in utilization of intrauterine contraceptive.
9. Conclusions Absolute contraindications to IUD/IUS use based on current scientific evidence are few in number and should include only those conditions in which the risk of IUD/IUS use would exceed the risk of pregnancy. Listing of inappropriate conditions on product labeling reduces women’s access to this very effective method. WHO MEC most accurately reflect current understanding of the risks, although small changes in that list may be appropriate. Other professional organizations should review their lists of contraindications to ensure that they are evidence based, and peer reviewers should caution would-be authors not to make practice recommendations that are not consistent with the fundamental definition of absolute contraindication. References [1] Grubb GS. Women’s perceptions of the safety of the pill: a survey in eight developing countries. Report of the perceptions of the pill survey group. J Biosoc Sci 1987;19:313 – 21. [2] Berry DC, Raynor DK, Knapp P, Bersellini E. Patients’ understanding of risk associated with medication use: impact of European Commission guidelines and other risk scales. Drug Saf 2003;26:1 – 11. [3] ParaGard T 380A intrauterine copper contraceptive prescribing information. N. Tonawanda (NY)7 FEI Products LLC; 2005 [Accessed 12/21/06 at http://www.paragard.com/paragard/custom_ images/Prescribing-Info.pdf].
[4] Grossman D, Ellertson C, Abuabara K, Blanchard K, Rivas FT. Barriers to contraceptive use in product labeling and practice guidelines. Am J Public Health 2006;96:791 – 9. [5] Skjeldestad FE, Halvorsen LE, Kahn H, Nordbo SA, Saake K. IUD users in Norway are at low risk for genital C. trachomatis infection. Contraception 1996;54:209 – 12. [6] De la Cruz D, Cruz A, Arteaga M, Castillo L, Tovalin H. Blood copper levels in Mexican users of the T380A IUD. Contraception 2005;72:122 – 5. [7] MirenaR prescribing information. Montville (NJ)7 Berlex; 2006 [Accessed 12/21/06 at http://www.berlex.com/html/products/pi/ Mirena_PI.pdf]. [8] Backman T, Rauramo I, Jaakkola K, et al. Use of the levonorgestrelreleasing intrauterine system and breast cancer. Obstet Gynecol 2005;106:813 – 7. [9] WHO Reproductive Health and Research. Medical eligibility criteria for contraceptive use. 3rd ed. Geneva7 World Health Organization; 2004 [Accessed 12/18/06 at http://www.who.int/reproductive-health/ publications/mec/index.htm]. [10] Backman T, Rauramo I, Huhtala S, Koskenvuo M. Pregnancy during the use of levonorgestrel intrauterine system. Am J Obstet Gynecol 2004;190:50 – 4. [11] Averette HE, Mirhashemi R, Moffat FL. Pregnancy after breast carcinoma: the ultimate medical challenge. Cancer 1999;85:2301 – 4. [12] Dow KH, Harris JR, Roy C. Pregnancy after breast-conserving surgery and radiation therapy for breast cancer. J Natl Cancer Inst Monogr 1994;16:131 – 7. [13] Velentgas P, Daling JR, Malone KE, et al. Pregnancy after breast carcinoma: outcomes and influence on mortality. Cancer 1999; 85:2424 – 32. [14] Ives A, Saunders C, Bulsara M, Semmens J. Pregnancy after breast cancer: population based study. BMJ 2007;334:194. [15] Lockhat FB, Emembolu JE, Konje JC. Serum and peritoneal fluid levels of levonorgestrel in women with endometriosis who were treated with an intrauterine contraceptive device containing levonorgestrel. Fertil Steril 2005;83:398 – 404. [16] ACOG Committee on Practice Bulletins — Gynecology. ACOG practice bulletin. Clinical management guidelines for obstetrician– gynecologists, no. 59, January 2005. Intrauterine device. Obstet Gynecol 2005;105:223 – 32. [17] Planned Parenthood. Intrauterine devices [Accessed 12/18/06 at http:// www.plannedparenthood.org/birth-control-pregnancy/birth-control/ intrauterine-devices.htm]. [18] Viberga I, Odlind V, Zodzika J. Practices and perceptions on intrauterine contraception among Latvian obstetrician–gynecologists. Acta Obstet Gynecol Scand 2006;85:583 – 8. [19] Lassey AT, Newman MJ, Opintan JA. Vaginal flora of first time urban family planning attendants in Accra, Ghana. West Afr J Med 2005; 24:219 – 22. [20] Tosun I, Aydin F, Kaklikkaya N, Yazici Y. Frequency of bacterial vaginosis among women attending for intrauterine device insertion at an inner-city family planning clinic. Eur J Contracept Reprod Health Care 2003;8:135 – 8. [21] Dikensoy E, Kutlar I, Gocmen A, Graves CR. Two cases of uterine septum with intrauterine device. Br J Radiol 2005;78:952 – 3. [22] Agarwal K, Sharma U, Acharya V. Microbial and cytopathological study of intrauterine contraceptive device users. Indian J Med Sci 2004;58:394 – 9. [23] Mohllajee AP, Curtis KM, Peterson HB. Does insertion and use of an intrauterine device increase the risk of pelvic inflammatory disease among women with sexually transmitted infection? A systematic review. Contraception 2006;73:145 – 53. [24] Shelton JD. Risk of clinical pelvic inflammatory disease attributable to an intrauterine device. Lancet 2001;357:443. [25] Steen R, Shapiro K. Intrauterine contraceptive devices and risk of pelvic inflammatory disease: standard of care in high STI prevalence settings. Reprod Health Matt 2004;12:136 – 43.
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[35] Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simon C, Pellicer A. Reproductive impact of congenital Mullerian anomalies. Hum Reprod 1997;12:2277 – 81. [36] Faundes D, Perdigao A, Faundes A, Bahamondes L, Petta CA. T-shaped IUDs accommodate in their position during the first 3 months after insertion. Contraception 2000;62:165 – 8. [37] Espey E, Ogburn T, Hall R, Byrn F. Use of intrauterine device in the setting of uterus didelphys. Obstet Gynecol 2006;108:774 – 6. [38] Soysal S, Soysal ME. The efficacy of levonorgestrel-releasing intrauterine device in selected cases of myoma-related menorrhagia: a prospective controlled trial. Gynecol Obstet Invest 2005;59:29 – 35. [39] Asker C, Stokes-Lampard H, Beavan J, Wilson S. What is it about intrauterine devices that women find unacceptable? Factors that make women non-users: a qualitative study. J Fam Plann Reprod Health Care 2006;32:89 – 94. [40] Bianchi-Demicheli F, Perrin E, Dupanloup A, et al. Contraceptive counselling and social representations: a qualitative study. Swiss Med Wkly 2006;136:127 – 34. [41] Vos AA, Veldhuis HM, Lagro-Janssen TL. Intrauterine contraception: the role of general practitioners in four Dutch general practices. Contraception 2004;69:283 – 7. [42] Hubacher D, Vilchez R, Gmach R, et al. The impact of clinician education on IUD uptake, knowledge and attitudes: results of a randomized trial. Contraception 2006;73:628 – 33.