Comparison of expulsions following intracesarean placement of an innovative frameless copper-releasing IUD (Gyn-CS®) versus the TCu380A: A randomized trial.

OBJECTIVE: The intent of this study (primary outcome measure) is to assess the expulsion rate of a newly developed copper releasing frameless intrauterine IUD GyneFix® Cesarean Section (Gyn-CS®) at 3 months' follow-up, compared to the TCu-380A IUD, inserted immediately postplacental expulsion following cesarean section delivery. STUDY DESIGN: This is a randomized trial from one hospital research center in Istanbul, Turkey. Eligible pregnant women, the majority undergoing elective cesarean delivery (n=106), and the remaining emergency cesarean section cases (n=34), received intracesarean insertion of Gyn-CS or TCu380A insertion. Follow-up ended with a 3 month-visit. The Zeynep Kamil University Hospital Ethics Committee approved this study. RESULTS: The study explores the retention of 140 insertions, 70 Gyn-CS and 70 TCu380A. There were two follow-up visits after discharge from hospital at 6 weeks and 3 months. A single Gyn-CS expulsion occurred after approximately 6 weeks likely a consequence of improper anchoring. Expulsion was more common in the TCu380 A IUD group (11.4% vs 1.4%, p=.039). There were 4 removals for medical reasons in the Gyn-CS patients and 4 in the TCu380A patients, respectively, with 4 non-medical removals occurred, 2 in each group. No serious adverse events (e.g., PID, perforation) were reported. At the study conclusion of 3 months, 61 Gyn-CS (88%) and 54 TCu380A (79%) IUDs remain in place. CONCLUSION: This immediate postplacental study in cesarean section patients suggests that the anchoring technique employed resulted in the excellent retention of Gyn-CS. Insertion was easy, safe and quick requiring minimal physician training. The possibility of direct visualization of the anchor by ultrasound at insertion and follow-up allows the surgeon to verify the position of the IUD serving to enhance provider and patient confidence and assurance. IMPLICATIONS: The frameless anchored intrauterine IUD is effective in minimizing displacement and expulsion. The results of this study suggest that the Gyn-CS IUD is appropriate for wider intracesarean use.

Pain assessment by pupil dilation reflex in response to noxious stimulation in anaesthetized adults.

BACKGROUND: In response to noxious stimulation, pupillary dilation reflex (PDR) occurs even in anaesthetized patients. The aim of the study was to evaluate the ability of pupillometry with an automated increasing stimulus intensity to monitor intraoperative opioid administration. METHODS: Thirty-four patients undergoing elective surgery were enrolled. Induction by propofol anaesthesia was increased progressively until the sedation depth criteria (SeD) were attained. Subsequently, a first dynamic pupil measurement was performed by applying standardized nociceptive stimulation (SNS). A second PDR evaluation was performed when remifentanil reached a target effect-site concentration. Automated infrared pupillometry was used to determine PDR during nociceptive stimulations generating a unique pupillary pain index (PPI). Vital signs were measured. RESULTS: After opioid administration, anaesthetized patients required a higher stimulation intensity (57.43 mA vs 32.29 mA, P < .0005). Pupil variation in response to the nociceptive stimulations was significantly reduced after opioid administration (8 mm vs 28 mm, P < .0005). The PPI score decreased after analgesic treatment (8 vs 2, P < .0005), corresponding to a 30% decrease. The elicitation of PDR by nociceptive stimulation was performed without changes in vital signs before (HR 76 vs 74/min, P = .09; SBP 123 vs 113 mm Hg, P = .001) and after opioid administration (HR 63 vs 62/min, P = .4; SBP 98.66 vs 93.77 mm Hg, P = .032). CONCLUSIONS: During propofol anaesthesia, pupillometry with the possibility of low-intensity standardized noxious stimulation via PPI protocol can be used for PDR assessment in response to remifentanil administration.

Safety and comfort of long-term continuous combined transdermal estrogen and intrauterine levonorgestrel administration for postmenopausal hormone substitution - a review.

OBJECTIVE: To review the endometrial safety and patient acceptability of long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (LNG) in postmenopausal women. DESIGN: One-hundred and fifty-three women who utilized the regimen for 2 IUD cycles were followed-up for a period of 10 years. Histology of the endometrium was evaluated at the end of this period to assess endometrial safety and the acceptability of the method was assessed based on the replacement rate of the LNG-IUS and continuation of ET. RESULTS: The regimen, administered over a 10-year period, was very well tolerated and the IUD was retained well and no expulsions occurred. The dominant endometrial histologic picture was that of inactive endometrium characterized by glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found. CONCLUSION: The low systemic absorption of LNG could be desirable, thus allowing for maximization of the beneficial effects of ET on organ tissues (e.g. cardiovascular tissues and breast). Repeat LNG-IUS is associated with high patient satisfaction. If started before the age of 60, this regimen could be advised for lifelong prevention of cardiovascular disease and other prevention measures. The LNG-IUS was shown to effectively oppose the secondary effects of systemic estrogen on the endometrium tissue resulting in strong suppression during the entire period of EPT.

Use of a frameless LNG-IUS as conservative treatment for a pre-malignant uterine polyp in a premenopausal woman - a case report.

Prevention of progression to invasive carcinoma in patients with a premalignant endometrial lesion using longterm treatment with levonorgestrel (LNG) releasing intrauterine systems (IUS) remains controversial, especially when manifest cellular atypia has been found in the endometrial biopsy specimen. We present a case of a 44-year old premenopausal woman with a premalignant uterine polyp who declined hysterectomy and was followed-up for more than 12 years after the first LNG-IUS was inserted. Endometrial atrophy installed, no pathology was detected and hysterectomy was thereby successfully avoided. The positive experience in this case should encourage further studies as literature data indicate that conservative treatment of premalignant endometrial pathology is a real option with a high success rate for women who have a contra-indication for surgery, refuse the classical approach for personal reasons or want to preserve their fertility.

Successful treatment of early endometrial carcinoma by local delivery of levonorgestrel: a case report.

We describe a case of a 67-year-old Caucasian woman with an early, moderately-differentiated adenocarcinoma of the endometrium. A levonorgestrel-releasing intrauterine system was inserted, which she tolerated well. A full D&C, following removal of the device, was performed after 9 months, confirming absence of tumoral tissue. Examination after 24 months showed a very thin endometrium, indicating complete remission.

New intrauterine technologies for contraception and treatment in -nulliparous/adolescent and parous women.

The IUD (intra uterine device) is a highly effective method of contraception that is underused. New developments in intrauterine technology, smaller frameless copper and levonorgestrel-releasing devices, could help increase the prevalence-- of use in adolescents and nulliparous women. Because adolescents and young nulliparous women contribute disproportionately to the epidemic of unintended pregnancies, long-acting methods of contraception, particularly IUDs, should be considered as first-line choices for interval, emergency and immediate post-abortal contraception in this population of women. As the uterine cavity is generally much smaller in this group than in older women, adapted IUDs may be very useful. Compatibility of the IUD with the small uterine cavity leads to high acceptability and continuation of use, a prerequisite to reduce unintended pregnancies. A strategic advantage of IUDs is that, unlike the Pill, they are genuinely 'fit-and-forget'. In use, they are much more effective than Pills in this age group. However, copper intrauterine devices do not offer protection against sexually transmitted infections (STIs) and, therefore, they are not always the methods of first choice for teenagers and nulliparous women. New evidence, however, from the World Health -Organization and the American College of Obstetricians and Gynecologists, shows that IUDs can be used and that they are safe for most women, including adolescents.

Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up.

OBJECTIVES: Levonorgestrel (LNG), delivered locally into the uterine cavity has a profound effect on the endometrium. The aim of the study was to use a LNG intrauterine system to treat non-atypical and atypical endometrial hyperplasia in women and to evaluate the long-term cure (remission) rate. METHODS: Each of the 20 women in the study, of whom eight were diagnosed with atypical hyperplasia, received a LNG-IUS, releasing 20 microg LNG/day. The study is a non-comparative study with long-term follow-up (range 14-90 months). RESULTS: All women developed a normal endometrium, except one asymptomatic woman with atypical hyperplasia who still had focal residual non-atypical hyperplasia at 3 years follow-up in the presence of a thin (< 4 mm) endometrium. CONCLUSION: Continuous intrauterine delivery of LNG appears to be a promising alternative to hysterectomy for the treatment of endometrial hyperplasia and could enhance the success rate when compared with other routes of progestagen administration as well as intrauterine progesterone delivery. The significant reduction of the PR expression observed during treatment with the LNG-IUS appears to be a marker for the strong antiproliferative effect of the hormone at a cellular level resulting in an inhibition of estrogen bioactivity and endometrial suppression.

Endometrial safety after 5 years of continuous combined transdermal estrogen and intrauterine levonorgestrel delivery for postmenopausal hormone substitution.

OBJECTIVE: To investigate endometrial histology and thickness of the endometrium after long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (LNG) in postmenopausal women. DESIGN: A 5-year non-comparative prospective clinical trial. SUBJECTS: Out of 182 symptomatic postmenopausal women using estrogen substitution therapy (EST) combined with a novel T-shaped LNG-releasing intrauterine system (Femilis Slim LNG-IUS), to prevent endometrial proliferation and bleeding, only those women (n=102) who used two consecutive LNG-IUSs, were isolated with the aim to study the long-term effects on the endometrium. The mean age of the women was 57 years (range 47-71). The majority of women received percutaneous 17beta estradiol, 1.5mg daily, or an equivalent dose by patch or orally, on a continuous basis. MAIN OUTCOME MEASURES: Endometrial histology and ultrasonographic evidence of endometrial suppression, after a period of approximately 5 years of use. The mean duration of use of the regimen was 70 months (range 25-98). RESULTS: The dominant endometrial histologic picture was that of inactive endometrium characterized by glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found. On transvaginal ultrasound, this corresponds with a thin endometrium (< or = 5 mm). CONCLUSION: The results of this 5-year study in 102 postmenopausal women using EST demonstrates that the LNG-IUS effectively opposes the estrogenic effect on the endometrium resulting in strong suppression during the entire period of EST. Due to its high efficacy and absence of systemic effects on organ tissues (e.g., breasts), target delivery in the uterine cavity could be a preferred route to administer a progestagen in women using EST.

Assessment of menstrual blood loss in Belgian users of the frameless copper-releasing IUD with copper surface area of 200 mm2 and users of a copper-levonorgestrel-releasing intrauterine system.

OBJECTIVE: This study was conducted to evaluate the effect of a miniaturized frameless copper IUD (GyneFix 200 small) and a copper-levonorgestrel (GynePlant) intrauterine system (IUS) on the amount of menstrual blood loss (MBL). METHODS: In 60 Belgian women using GyneFix 200 and 21 using GynePlant, MBL was assessed with the visual assessment technique. RESULTS: MBL scores in GyneFix 200 users did not change from baseline during the mean observation period of 31 months. In GynePlant users, mean MBL scores decreased by at least 50% in all but one user. CONCLUSION: The impact of copper IUDs on MBL can be minimized by reducing the surface area of the foreign body. Reduction of MBL, without causing amenorrhea, can be obtained by adding levonorgestrel.

Assessment of menstrual blood loss in women with ideopathic menorrhagia using the frameless levonorgestrel-releasing intrauterine system.

OBJECTIVE: This study was conducted to evaluate the effect of a "low-dose" levonorgestrel (LNG)-releasing intrauterine system (IUS) on the amount of menstrual blood loss (MBL) in women with ideopathic menorrhagia. METHODS: Menstrual blood loss was assessed with the visual assessment technique in 12 Belgian FibroPlant-LNG users with menorrhagia. In addition, ferritin levels were measured. RESULTS: The median MBL, evaluated by the visual scoring technique, decreased by more than 90%. The ferritin levels increased significantly during treatment with the levonorgestrel system. CONCLUSION: This study confirms previous MBL studies conducted with the FibroPlant-LNG IUS demonstrating the efficacy of the LNG-IUS to significantly reduce the amount of MBL in women with menorrhagia. The strong endometrial suppression is the principal mechanism explaining the effect on MBL. The therapeutic effect of this contraceptive method is highly desirable, particularly in women with heavy bleeding or anemia, as other treatment modalities are less effective, more costly, more invasive or inaccessible. The simple design characteristics and anchoring system account for minimizing the occurrence of complaints of pain and expulsion.

Assessment of menstrual blood loss in Brazilian users of the frameless copper-releasing IUD with copper surface area of 330 mm2 and the frameless levonorgestrel-releasing intrauterine system.

OBJECTIVE: This study was conducted to evaluate the effect of two types of IUDs on the amount of menstrual blood loss (MBL): the frameless copper-releasing intrauterine device (IUD) with copper surface area of 330 mm2 (GyneFix; Contrel Research, Ghent, Belgium) and the frameless levonorgestrel (LNG)-releasing intrauterine system (IUS) releasing 14 microg per day (FibroPlant-LNG; Contrel Research). Heavy and abnormal MBL is the main reason for discontinuation of intrauterine devices. METHODS: In 20 Brazilian women using GyneFix 330 and 32 using FibroPlant-LNG, respectively, MBL was measured by the quantitative alkaline hematin technique. In addition, ferritin levels were measured in GyneFix 330 and FibroPlant-LNG users. RESULTS: MBL with GyneFix 330, measured over a 24-month period, increased but was less when compared with TCu380A. Ferritin levels with GyneFix 330 were not affected in contrast with TCu380A. In FibroPlant-LNG users, mean MBL decreased by about 90% and ferritin levels increased significantly. CONCLUSIONS: The authors confirm earlier reports that, especially for women with low body iron stores and heavy menstrual bleeding, there is an order of preference for IUD use to minimize MBL. The choice should first be a progestin-releasing IUS, then a copper IUD, which has the least effect on menstrual bleeding, such as the frameless GyneFix IUD.

Endometrial safety with a low-dose intrauterine levonorgestrel-releasing system after 3 years of estrogen substitution therapy.

OBJECTIVE: To evaluate the pharmacodynamic effects of a novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), on the endometrium in 24 postmenopausal women using estrogen substitution therapy (EST) to suppress climacteric symptoms. DESIGN: A 3-year non-comparative prospective clinical trial. SUBJECTS: The treatment with the FibroPlant-LNG intrauterine system (IUS), releasing 14 microg of LNG per day, was part of a regimen for estrogen substitution therapy in symptomatic postmenopausal women to prevent endometrial proliferation and bleeding. The majority of women received percutaneous 17 beta estradiol, 1.5 mg daily, or an equivalent dose by patch or orally, on a continuous basis. OUTCOME MEASURES: Menstrual pattern, endometrial histology and ultrasonographic evidence of endometrial suppression, after 3 years of use. RESULTS: The endometrial histology specimen showed profound endometrial suppression with glandular atrophy and stroma decidualization in all women. On transvaginal ultrasound, this corresponds with a thin endometrium (<5 mm) and clinically with a "bleed-free" menstrual pattern or amenorrhoea. CONCLUSION: The results of this 3-year study in 24 postmenopausal women using EST suggest that the FibroPlant-LNG IUS is effective in causing strong suppression of the endometrium during the entire period of EST. Target delivery in the uterine cavity could be the preferred route of administering a progestin to oppose estrogen stimulation of the endometrium.

Miniature, low-dose, intrauterine drug-delivery systems.

The safety of systemically administered sex steroids continues to be a major focus of researchers. The negative results of the Women's Health Initiative study (WHI), and follow-up reports published in JAMA, evaluating the safety of estro-progestogen in postmenopausal women, elicited an unprecedented reaction in the press by women and doctors alike. From these publications, it is clear that research should focus on new progestogens and on alternative administration routes to minimize adverse drug effects. One approach to the improvement of safety, efficacy, and acceptability of steroid hormones, including patient compliance, is to develop long-acting implantable methods that deliver the lowest possible dose to the key target tissues. This therapeutic concept of "minimal intervention" has been known for several decades, but the practical applications of the method were lacking. Intrauterine drug-delivery systems can be developed to achieve minimal intervention fertility control without influencing normal ovarian function and/or causing adverse hormonal effects. With hormone replacement therapy in postmenopausal women, research suggests that progestogens delivered directly to the uterine mucosa could reduce side effects and minimize reversal of the beneficial effect of estrogens. Various "frameless" and "framed" intrauterine systems are currently being clinically evaluated. They are less troublesome than the available intrauterine systems and could therefore be suitable for use in the majority of women for contraception and treatment purposes (e.g., menorrhagia, hormone replacement). These systems require a single short office procedure, and have a low morbidity, which is undeniably linked with more invasive methods and systemic hormonal contraceptives. Due to the technological progress miniature, low-dose, long-term intrauterine drug-delivery systems offer enhanced effectiveness, reduced side effects, and optimal user compliance. Although there is minimal absorption in the systemic circulation, they deserve the status of a locally acting method that should be regarded as fundamentally advantageous, if effective, to systemically applied medications that may have potentially inherent ill side effects.

Treatment of nonatypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system.

OBJECTIVE: A "frameless" intrauterine drug delivery system that releases 14 microg/d of levonorgestrel was used to treat nonatypical and atypical endometrial hyperplasia in 12 women. STUDY DESIGN: This noncomparative study had up to 3 to 4 years of follow-up. RESULTS: The cure rate was 100%, as confirmed by repeat endometrial biopsy. CONCLUSION: This method could be considered an alternative to hysterectomy.

Performance and acceptability of intrauterine release of levonorgestrel with a miniature delivery system for hormonal substitution therapy, contraception and treatment in peri and postmenopausal women.

OBJECTIVE: To evaluate the performance and acceptability of a novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), delivering approximately 14 microg per day. SUBJECT AND DESIGNS: A 1-year prospective clinical trial in 141 peri and postmenopausal women, including women with heavy or postmenopausal bleeding and women needing contraception. The majority received percutaneous 17beta-estradiol (Oestrogel), 1.5 mg daily. Clinical results and ultrasonographic effects were evaluated. RESULTS: Eighty-three insertions were done in perimenopausal women and 58 in postmenopausal women followed-up for 8-38 months. Fifty-two perimenopausal (64%) and virtually 100% of the postmenopausal women developed amenorrhoea, with occasional slight spotting. Eleven women with heavy bleeding, five of them with single or multiple intramural and subserosal fibroids of 3-6 cm or more, were all successfully treated, except one. There were no pregnancies. CONCLUSION: This study of 1432 women-months of use suggests that the frameless FibroPlant-LNG IUS is safe, well tolerated and effective in suppressing the endometrium during EST. The fact that the IUS also acts as a contraceptive, and significantly reduces menstrual bleeding, as demonstrated in earlier studies, is of added importance.

Contraception and treatment in the perimenopause with a novel "frameless" intrauterine levonorgestrel-releasing drug delivery system: an extended pilot study.

The objective of the study was to evaluate the contraceptive performance, acceptability, side effects, and adverse events of a novel "frameless" intrauterine drug delivery system (IUS), FibroPlant-levonorgestrel (LNG) releasing 14 microg of LNG/day, in perimenopausal women. An ancillary objective was to evaluate the effect of the new IUS on menstrual blood loss in women with or without fibroids. The study, consisting of 109 women, suggests that FibroPlant-LNG IUS is an effective contraceptive. No pregnancies occurred with the FibroPlant-LNG IUS. The total use-related discontinuation rate at 1 year is low (1.9) and results in a high rate of continuation of use (98.1). In addition, the FibroPlant-LNG IUS demonstrated a high level of effectiveness in reducing bleeding in women with excessive menstrual flow even when medium or large fibroids were present. However, an effect on the size of the fibroids could not be demonstrated. Patient satisfaction with the method is high, which is a prerequisite for continuance of the method, and may be linked with the advantageous design characteristics of the FibroPlant-LNG IUS, the virtual absence of hormonal side effects, and the low incidence of irregular bleeding and spotting even during the first 3 months after insertion of the FibroPlant IUS. Counseling remains important though to explain to women about the possible occurrence of changes in their menstrual pattern that may sometimes be annoying but harmless. It is concluded that many women over age 40 years could substantially benefit from the advantages of this intrauterine drug delivery technology which provides contraception and treatment of a possible associated condition such as menorrhagia. The treatment also creates the opportunity to pass through the transitional perimenopausal period smoothly and to benefit fully from the advantages hormone replacement therapy offers in terms of treatment of short-term symptoms and long-term prevention by gradually replacing the waning estrogens.

Return to fertility in nulliparous and parous women after removal of the GyneFix intrauterine contraceptive system.

OBJECTIVE: To evaluate the return to fertility following removal of the GyneFix intrauterine implant system in women wishing to conceive. STUDY DESIGN: A retrospective study was performed on a sample of healthy, sexually active nulligravid/nulliparous and parous women. The participants were 18-41 years of age, with no apparent infertility problem, living in a stable relationship and planning to become pregnant. Women who changed their mind and did not wish to become pregnant immediately after intrauterine device (IUD) removal were excluded from the study. Women were evaluated in terms of rates of conception and fertility outcome. A total of 128 women were evaluated. RESULTS: The study shows that 119 out of 128 (93%) past users of GyneFix have conceived, accounting for a net cumulative pregnancy rate of 88% at 12 months and 99% after 2 years' observation. No statistical differences in pregnancy rates were found for age and duration of use of the IUD. A strong significant difference in pregnancy rate was shown (p = 0.007) between parous and nulligravid/nulliparous women. Seventy-seven women (66.9%) gave birth to a term infant. There were no stillbirths. Twenty-five women (21.8%) are pregnant at the time of writing. Five (4.4%) spontaneous abortions occurred and in eight women (6.9%) the pregnancy was terminated. There were no ectopic pregnancies. CONCLUSION: The results obtained compare favorably with those obtained in previous studies conducted following the removal of copper IUDs. The use of the frameless IUD does not affect future fertility in nulligravid/nulliparous and parous women wishing to become pregnant following removal of the device. Nulliparous women conceive significantly earlier than parous women.

Treatment of menorrhagia with a novel 'frameless' intrauterine levonorgestrel-releasing drug delivery system: a pilot study.

OBJECTIVE: To evaluate the effect on menstrual blood loss of a novel 'frameless' intrauterine drug delivery system, the FibroPlant levonorgestrel intrauterine system (IUS), releasing 14 microg of levonorgestrel/day. An ancillary objective was to evaluate the contraceptive performance. STUDY DESIGN: This was an open-label, non-comparative ongoing pilot study. Thirty-two insertions were performed in fertile women aged between 31 and 51 years for the treatment of menorrhagia, as well as for contraceptive purposes. Fifteen women who developed excessive bleeding were fitted with the FibroPlant levonorgestrel IUS immediately following the removal of a copper-bearing intrauterine device (IUD), the GyneFix IUD. To discriminate between menorrhagia and normal menstrual blood loss, women were evaluated using a simple visual assessment technique. The trial covered a period from a minimum of 1 month up to 23 months. RESULTS: At the time of study analysis, the total number of woman-months was 361. Fourteen of the women had had the FibroPlant levonorgestrel IUS in place for more than 1 year, and 29 women for 6 months or more. All women reported greatly reduced bleeding. However, no cases of amenorrhea resulting from endometrial suppression were encountered. The reduction of bleeding was substantial after 1 month of treatment and decreased further over the next months to remain stable thereafter. The mean bleeding score before treatment was 338 (range 185-740) in the group who had had no prior use of an IUD and 368 (range 185-890) in the group with prior IUD use. The mean bleeding score dropped to a mean score of 70 (range 5-210) in the 'no prior IUD use' group and to a mean score of 52 (range 3-150) in the 'prior IUD use' group, after 1-23 months of follow-up. This result is highly statistically significant (p < 0.001). There were no statistical differences in bleeding scores before and during treatment between the two groups of women, with or without prior use of the copper IUD. Significant spotting was rare after the first 3 months following insertion. No complications (e.g. infection, expulsion or perforation) or pregnancies occurred. The FibroPlant levonorgestrel IUS was well tolerated by all women involved in the study and no systemic hormonal side-effects were reported. CONCLUSION: The FibroPlant levonorgestrel IUS is effective in significantly reducing the amount of menstrual blood loss in women with menorrhagia. Strong endometrial suppression is the principal mechanism explaining both the effect on menstrual blood loss and the contraceptive performance of the IUS. There were no differences in bleeding scores before and during treatment between the two groups of women with or without prior use of the copper IUD, suggesting that the development of heavy bleeding was not related to the use ofthe IUD. The therapeutic effect of this contraceptive method is highly desirable, particularly in women with heavy bleeding or anemia in developing countries, as other treatment modalities are less effective, more costly, more invasive or inaccessible. The low daily release rate of levonorgestrel from the FibroPlant levonorgestrel IUS results in a low incidence of hormonal side-effects and reduces the likelihood of amenorrhea. The simple design characteristics and revolutionary anchoring system minimize the occurrence of complaints of pain and the incidence of expulsion.