Intrauterine contraception with Nova-T and Copper-T-200 during three years

A randomized comparative trial on the clinical performance of two copper-releasing IUDs (Nova-T and Copper-T-200) was performed simultaneously in Denmark, Finland and Sweden. After three years the cumulative pregnancy rate was 1.9 for Nova-T and 5.0 for Copper-T. This difference in efficacy was statistically significant (p < 0.001). Copper-T had a lower expulsion rate (p < 0.05) in the total series but not in postmenstrual insertions. Differences between the two devices in other termination rates were not statistically significant. Analysis according to age and parity demonstrated that the pregnancy rate of Nova-T was lower than that of Copper-T in every age and parity group. The pregnancy rate of Nova-T was not affected by age or parity whereas the pregnancy rate and the expulsion rate of Copper-T decreased with increasing age and parity. The removal rate because of infection decreased markedly after the first year of use for both devices. The cumulative rate of removals for infection during the three years of use was not significantly correlated to age and there was no correlation to parity. The continuation rates increased with age and parity. The continuation rates of nulli- and primiparous women were almost identical with both devices and lower than continuation rates of women with 2 or three or more children. Only 11% of the women were lost to follow-up during 36 months. Nova-T had superior effectiveness in preventing undesired pregnancies when compared with Copper-T. The performance of Nova-T is less affected by age and parity than the performance of Copper-T. The silver core in copper wire gives a prolongation of the life-span for Nova-T. For these reasons, Nova-T appears to meet the requirements for an ideal IUD.     

Acceptability of an experimental intracervical device: results of a study controlling for selection bias

We analyzed baseline and 12-month follow-up interview data from 98 women who had volunteered to use an experimental intracervical device (ICD) and from 155 women who had been randomly assigned to two control groups, the levonorgestrel-releasing intrauterine device (LNG-IUD; N = 86) and the copper Nova-T IUD (N = 69). All participants were clinic patients in Helsinki, Finland. Initial analysis of 12-month discontinuation data indicated that a significantly higher percent of ICD users (22.4) discontinued their device than did either LNG-IUD (7.0) or Nova-T (8.7) users. However, we were no longer able to detect significant differences in discontinuation after controlling for baseline variables that assessed predisposition to be dissatisfied with contraception in general. Adjusted probabilities of discontinuing the ICD, LNG-IUD, and Nova-T were 11.8%, 6.2% and 7.9%, respectively. These data indicate that the ICD is likely to be acceptable to Helsinki clinic patients; moreover, they suggest a definite place for hormonal intrauterine devices in the contraceptive armamentarium. Most importantly, the methodology used here can be generalized to acceptability studies of other contraceptive devices and drugs undergoing Phase I and early Phase II clinical trials (in situations where randomization may not be feasible) in order to identify and control for the bias introduced by nonrandom assignment procedures.     

Two-year clinical experience with Nova-T 380, a novel copper–silver IUD

In 1992, an open single-group phase III clinical trial was started at three centers to investigate the clinical performance of the high copper surface area Nova-T 380, a modification of Nova-T. This report presents the interim results of the first two years of use. A total of 400 women volunteers were enrolled in the study. The mean age was 31.4 years (SD 5.5) with a minimum of 18 and a maximum of 44 years. At the cut-off date, 259 women had passed the 24-month visit. Gross cumulative life-table rates at the end of the first and second years, respectively, calculated by the Kaplan–Meier method, were as follows: pregnancy 0.5 and 1.6, expulsion 1.6 and 2.8, bleeding 4.7 and 8.7, pain 1.3 and 2.3, removal for other medical reasons 1.7 and 3.9, planning pregnancy 1.1 and 6.0, removal for other personal reasons 0.5 and 1.5, per 100 users. No ectopic pregnancies or PIDs occurred. The continuation rates were 89.0 and 75.5 at 12 and 24 months, respectively. The first two-year performance of the Nova-T 380 was good. Bleeding problems were in the same range as with devices with smaller copper surface areas. No unexpected serious adverse events were encountered.     

Ovarian function during use of a levonorgestrel-releasing IUD

Ovarian function was studied for two complete menstrual cycles in 9 regularly menstruating women and for 8 weeks in three amenorrhoeic women who had used levonorgestrel-releasing IUDs (LNG-IUD) for more than four years. Nine patients using copper IUDs (Nova-T) were studied for two complete menstrual cycles as controls. According to progesterone levels, 15/17 cycles in women using LNG-IUDs were ovulatory, whereas only 8/17 cycles showed normal follicular growth and rupture as judged by ultrasound. In ovulatory cycles, the peak progesterone levels were lower than in the controls. The preovulatory estradiol and LH peak levels were also lower than in control subjects. SHBG levels were lower in LNG-IUD users than in copper IUD users. It is concluded that, although the dose of levonorgestrel released from the IUD is very low, it probably exerts an effect on the gonadotrophin secretion, which disturbs follicular development in many of the women studied, which in addition to the local effect on the endometrium, contributes to its high contraceptive efficacy.     

Comparison of the clinical performance, contraceptive efficacy and acceptability of levonorgestrel-releasing IUD and Norplant-2 implants in China

The levonorgestrel-releasing IUD (LNG-IUD, 20 μg/d) and the Norplant^R-2 implants were studied in a randomized comparative clinical trial with 200 women for one year. No pregnancy or expulsion occurred with the Norplant^R-2. In the LNG-IUD group, there was one pregnancy at the 12th month of use after an unnoticed expulsion. The net cumulative pregnancy and expulsion rates of LNG-IUD were 1.0 and 3.0. The removal rate due to menstrual disturbances in both LNG-IUD and Norplant^R-2 groups was 3.0. The use-related discontinuation rates were 9.0 and 3.0, and the continuation rates were 90.0 and 96.0, respectively. The differences were not statistically significant.

Menstrual disturbance was the main side effect. It was improved after long time use, especially in the LNG-IUD group. After one year, the percentages of women with amenorrhea were 18.9 for the LNG-IUD and 8.3 for the Norplant^R-2. The menstrual blood loss was statistically significantly reduced in the LNG-IUD group, and blood haemoglobin concentration increased in both groups. The LNG-IUD and Norplant^R-2 are highly effective, safe, long-acting, and well accepted by the Chinese women.     

Contraception with levonorgestrel-releasing subdermal capsules,NorplantTM, after pregnancy termination

Six Silastic levonorgestrel-releasing capsules, Norplant^TM, were introduced subcutaneously into the ventral aspect of the left forearm or upper arm of thirty-eight patients immediately after first trimester pregnancy termination. In the control group, a Nova-T device was inserted immediately after pregnancy termination in thirty patients. Clinical examination was performed after three, six and twelve months of use. The continuation of the Norplant^TM at one year was 91.7 per cent and that of the Nova-T 73.9 per cent. No pregnancies occurred during the study period of one year. Hemoglobin concentrations and the diastolic blood pressures of the Norplant^TM users increased significantly. Dysmenorrhea and menstrual flow increased in the IUD group. Menstrual disturbances were the main side effects in the Norplant^TM group during the first five months of use.     

Return to fertility after IUD removal for planned pregnancy

The ability to conceive after discontinuing contraceptive practice is an important concern for women who have not completed their families. This paper focuses on 576 women who had their IUDs removed for planned pregnancy. The data from this study add further evidence that fertility subsequent to IUD removal is not impaired. Among these women followed-up, 94.3% conceived. The majority of these conceptions (55.9%) occurred during the first three months after IUD removal. In addition to analyzing conception rates, there were four factors that were considered in relationship to return to fertility. These were age at removal, duration of use, type of IUD (medicated vs non-medicated) and timing of insertion (interval vs postabortion). Age at removal was the only variable which seemed to influence conception rates.     

Postplacental insertion of the levonorgestrel intrauterine device after cesarean delivery vs. delayed insertion: a randomized controlled trial

Objective

This trial was designed to compare levonorgestrel intrauterine device (LNG-IUD) use at 1 year after delivery between women randomized to postplacental insertion at the time of cesarean delivery and delayed insertion 4–8 weeks after delivery.

Study design

This randomized controlled trial was conducted at two urban medical centers. Eligible pregnant women with planned cesarean deliveries were randomized to immediate postplacental insertion during cesarean or delayed insertion after 4–8 weeks. We used intention-to-treat analysis for the primary outcome of LNG-IUD use 12 months after delivery.

Results

Forty-two women were randomized, 20 into the postplacental group and 22 in the delayed group. Although confirmed use of the LNG-IUD 12 months after delivery was higher in the postplacental group (60.0% vs. 40.9%, p=.35), this difference was not statistically significance. Expulsion was significantly more common in the postplacental group (20.0% vs. 0%, p=.04). There were significant differences between the two sites in baseline population characteristics, follow-up and expulsion. The trial did not answer the intended question as it was halted early due to slow enrollment.

Conclusions

Our results show higher expulsion after postplacental insertion compared to delayed insertion but suggest similar IUD use at 12 months. Moreover, it provides valuable lessons regarding a randomized controlled trial of postplacental LNG-IUD placement due to the challenges of estimating effect size and the nature of the population who might benefit from immediate insertion.

Implications

Postplacental insertion of an IUD may improve use of highly effective contraception during the postpartum period. While our results suggest higher expulsion after postplacental insertion compared to delayed insertion and similar IUD use at 12 months, our trial was insufficient to definitively test our hypothesis.     

Premenopause contraception with monthly injectable Mesigyna with special emphasis on serum lipid and bone density patterns

This 2-year study compared Mesigyna(R) administered to 49 pre-menopausal women between 38 and 50 years, to 99 women fitted with an IUD (Nova-T). A complete lipoprotein assessment was carried out before treatment and at 6, 12, and 24 months of treatment. A bone densitometry was performed on half of the women, and an endometrial biopsy was taken from half of the Meisgyna group before and at the end of the first and second year. No pregnancy occurred with Mesigyna use while three pregnancies were observed with the IUD. The incidence of bleeding anomalies was higher in the Mesigyna group, with a discontinuation rate for these reasons of 20% versus 4% for IUD (p <0.05). The duration of bleeding days as well as dysmenorrhea were less with Mesigyna. No differences were seen in the pattern of intermenstrual bleeding and spinal bone density between both groups. No patient developed endometrial hyperplasia after treatment, thus endometrial risk seemed not to be increased. Total and LDL cholesterol, and apolipoproteins did not show modifications. A slight decrease in total triglycerides, HDL and HDL(2) cholesterol, and IDL lipoproteins was observed with Mesigyna. The present study appears to be the first using a monthly injectable hormonal contraceptive and monitoring its influence on lipid patterns in premenopausal women. Mesigyna proved to be a highly effective and low risk agent for premenopausal users.     

Levonorgestrel Intrauterine Device Use in Overweight and Obese Women

The levonorgestrel intrauterine device (LNG-IUD) is a safe, effective, long-acting, reversible contraceptive that reduces unintended pregnancy and decreases heavy menstrual bleeding. Many procedures such as IUD insertion are more challenging in overweight and obese women. The objective of this study was to describe LNG-IUD insertion, continuation, and complications in overweight and obese women in an ethnically diverse population in Hawai‘i. A retrospective cohort study of women who had a LNG-IUD inserted at the University of Hawai‘i, Department of Obstetrics and Gynecology Resident and Faculty practice sites between January 2009 and December 2010 was performed. A total of 149 women were followed. The most commonly reported races were Asian (32%), Native Hawaiian (26%), and non-Hawaiian Pacific Islander (20%). The mean BMI of the study population was 28.4 (standard deviation 7.2) with 37% classified as normal weight, 30% as overweight, and 33% as obese. Overall, 76% of women continued the LNG-IUD 12 months after insertion. No statistically significant difference emerged in 12-month IUD continuation between the BMI groups. Difficult (5%) and failed (3%) IUD insertions were rare for all BMI groups. IUD complications occurred in 9% of women and included expulsion and self-removal. In this diverse population, the majority of women continued to use the LNG-IUD one year after insertion with low rates of difficult insertions and complications.     

Norplant皮下埋植避孕剂对子宫内膜形态学影响的初步研究

采用组织及组织化学方法,对38例使用Norplant5～63月妇女的子宫内膜进行形态学研究,结果发现:分泌期取材标本中,埋植妇女无论有无出血问题,子宫内膜腺体均受到抑制,间质呈典型或不典型蜕膜样变,颗粒细胞多见,上皮下薄壁血管扩张。出血期取材标本中,埋植后月经正常组与正常对照组相似:子宫内膜腺体和间质破碎,网状纤维均匀一致地溶解,颗粒细胞大多已释放出颗粒。而埋埴后有出血问题组于出血3～5天后,仍可见子宫内膜碎片,网状纤维完整而致密,其中颗粒细胞大多充满颗粒。点滴出血时取材标本中,内膜呈顿挫分泌,间质有局灶性出血。上述结果提示:子宫内膜对激素的反应存在个体差异。Norplant引起的出血可能与内膜剥脱因素有关,其中子宫内膜颗粒细胞起着不可忽视的作用。     

Post insertion fertility behaviour of I.U.C.D. acceptors

Of 807 women 45 years or less who had Lippes loop IUDs inserted in 1969- 1970 at a south Calcutta clinic, 552 were interviewed at home to study post-IUD fertility in 1980-1981. 48 were excluded due to early menopause, separation or death of spouse. Pregnancy rates in the remaining 504 women were 1.2% for the 1st 24 months, 0% at 48 and 0.2% for 49-96 months for those using contraception, compared to 6.9, 7.3, and 1.6% at 12, 48 and 132 months for those not using contraception. 7.5%, 8.1% and 9.9% of the women not using contraception were not pregnant at 12, 28 and 132 months. 18.2% of these women had been sterilized, while 12.8% were using an IUD, 11.7% were using natural birth control, and 5.7% used condoms. 4.6% retained the original IUD for 11 years. There was a 1.2% failure rate among IUD acceptors during use of a re-inserted IUD. Women had fewer subsequent pregnancies if they had more children when accepting the IUD, intended to limit family size, or were older. Those with all daughters wanted more children and were less likely to use contraception. Since the overall fertility rate after marriage was 335, use of the IUD in this population was estimated to reduce fertility by 86%.     

Immediate postabortal insertion of a levonorgestrel-releasing IUD

Experimental IUDs releasing only 10 μg levonorgestrel per day and established copper-releasing IUDs (Nova-T) were inserted in 60 women in connection with legal first-trimester abortion. Bleeding and spotting and other events were recorded during the first year. Restoration of the menstrual cycle was studied. Blood samples were collected twice a week over a three-month period from five women receiving a levonorgestrel-releasing IUD to determine plasma levels of estradiol, progesterone, levonorgestrel, LH and FSH. FSH showed an increase approximately ten days (range 4–19) after abortion. LH/hCG concentrations reached a plateau approximately 24 days (range 9–42) after abortion. Initially, levonorgestrel concentrations were two-fold compared with concentrations of 90 pg/ml after four weeks. After four weeks the plasma levonorgestrel concentrations were stable. All five women had an ovulatory menstrual cycle. The first periods occurred 35 days after operation in the levonorgestrel-IUD group and 30 days after operation in the Nova-T group. The median duration of bleeding and spotting after the insertion was 12 days (range 3–26) in the Nova-T group and 12.5 days (range 3–93) in the levonorgestrel-IUD group. The difference was not statistically significant. From the second month on, menses-like bleeding was more common in the copper-releasing IUD group than in the levonorgestrel-IUD group. The difference was statistically significant (p < 0.001). After one year 75 percent of the patients continued with their IUDs in both groups. One pregnancy occurred in the experimental levonorgestrel-IUD group. One total expulsion was noticed in both groups, and one partial expulsion in the levonorgestrel-IUD group. Two levonorgestrel-IUDs and four Nova-Ts were removed because of bleeding and/or pain. One infection was noticed in the whole group six days after the operation. In the levonorgestrel-IUD group 74 percent of the women had a regular cycle after one year, while all Nova-T patients had a regular cycle. Twelve percent (7 women) were lost to follow-up at one year. The results of this study suggest that a levonorgestrel-releasing IUD can be inserted after legal first-trimester abortion and the results are comparable with those of previous studies that have been made using copper-releasing IUDs.     

Pregnancy outcomes associated with extended use of the 52-mg 20 μg/day levonorgestrel-releasing intrauterine system beyond 60 months: A chart review of 776 women in Brazil

Objective

To assess the contraceptive performance of the 52-mg 20 μg/day levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena; Bayer Oy, Turku, Finland) among women who maintain the same device without changes after 60 months.

Conception rates in women desiring pregnancy after levonorgestrel 52 mg intrauterine system (Liletta®) discontinuation

ObjectiveEvaluate reproductive function in nulligravid and gravid women after levonorgestrel 52 mg intrauterine system (IUS) discontinuation based on time to pregnancy.Study designWe evaluated women participating in the ACCESS IUS multicenter, Phase 3, open-label clinical trial of the Liletta(®) levonorgestrel 52 mg IUS who discontinued the IUS within 60 months of use and desired pregnancy. Study staff contacted participants every three months after IUS discontinuation for up to 12 months to determine whether pregnancy occurred. We excluded women who opted to stop attempting to conceive before 12 months. We evaluated 12-month conception rates in participants 16–35 years at IUS placement, comparing dichotomous outcomes using Fisher’s exact test. We performed a multivariable analysis to assess the association of baseline characteristics, age at discontinuation, duration of IUS use, and positive sexually transmitted infection testing during IUS use with conception.ResultsAmong 165 women who attempted to conceive, 142 (86.1%) did so within 12 months with a median time to conception of 92 days. The 12-month conception rates did not differ between nulligravid (66/76 [86.8%]) and gravid (76/89 [85.4%]) women (p = 0.83) and nulliparous (78/90 [86.7%]) and parous (64/75 [85.3%]) women (p = 0.83). In multivariable analysis, only obesity (aOR 0.3 [95% CI 0.1–0.8]) was associated with ability to conceive.ConclusionsAfter levonorgestrel 52 mg IUS discontinuation, women have rapid return of fertility in the year post-removal. Fertility rates after IUS removal do not vary based on gravidity, parity, age at discontinuation, or duration of IUS use.ImplicationsThis contemporary IUS study included a large population of nulligravid and nulliparous women. IUS use over many years does not effect spontaneous fertility after IUS discontinuation, regardless of gravidity or parity. Providers and patients should have no concern about the impact of IUS use on future fertility.     

A comparative study of the clinical performance of two copper-releasikg IUDs,NOVA-T & copper-T-200 in Lagos,Nigeria

A non-randomised study was performed to compare the use-effectiveness of the Copper-T-200 and Nova-T intrauterine devices. It was found that generally, results compared favourably with other world-wide studies. No accidental pregnancies were experienced and no significant difference was found between the expulsion rate of the Nova-T (5.0) and that of the Copper-T-200 (6.5) and the removal rates for bleeding and pain, which were 1.5 and 3.8, respectively. The continuation rate for the Nova-T was 91.3 compared with 88.2 for the Copper-T. The total experience was based on 815 woman-months of use.     

Return of fertility after the removal of Nova T or Copper T 200

The return of fertility after removal of Nova T or Copper T 200 IUDs was studied in 150 women who had a removal for planning pregnancy in a study performed for the comparison of the clinical performance of these IUDs in Denmark, Finland and Sweden. There was no significant difference in the return of fertility of women having used either device. The cumulative probability of pregnancy per 100 women after the removal of the IUD, as a net rate, was 77.3 at one year, 88.9 at two years and 92.4 at three years.The return of fertility was analyzed separately for those women who had used their IUD for less than two years and for two or more years. The duration of the use had no significant effect on the return of fertility. The outcome of pregnancy, the birth weight, the condition at delivery and the sex ratio of the newborns were normal in the participating countries.     

Long-term follow-up of women treated with NORPLANT implants

This report describes the long-term follow-up of 376 women who received NORPLANT^R implants in the period October 1974 through May 1979. One-hundred-and-ten subjects received replacement implants after variable lengths of use of the first set.

The average levonorgestrel plasma levels declined steadily through eight years of use of NORPLANT^R capsules (r = −.937). Values were 0.35 ng/ml, 0.29 ng/ml and 0.22 ng/ml at treatment years 1, 5 and 8, respectively. Levonorgestrel plasma levels after replacement with a second set of implants were similar to those observed after the first insertion, either when placed in the same site as the first set or in a different area.

Nineteen pregnancies occurred during 18,530 woman-months of use of the first set of implants, eleven of them during years 6 through 8 of treatment. The Pearl Index for the first 5 years of NORPLANT^R implants use was 0.63. No pregnancy has occurred in 4194 woman-months observed during treatment with a second set of capsules.

Fifty-six women (14.9%) out of 376 acceptors of the first implant and 10 (9.1%) out of 110 acceptors of the replacement implants were terminated for other medical reasons, mainly bleeding problems and side effects commonly associated with hormonal contraception. Two women died while using NORPLANT^R implants, one of a cardiac arrest after surgery for a gallbladder disease and one because of endocranial hypertension originating from the rupture of an aneurism of the median cerebral artery.

The bleeding pattern observed in the three months after NORPLANT^R capsules replacement was similar to that observed in the 90 days before replacement and different from that experienced by the same women in the first 90 days of implant use. This finding can be interpreted as an indicator of adaptive changes experienced by the target organs during long-term continuous administration of levonorgestrel. The prompt recovery of fertility after removal of NORPLANT^R implants suggests that these changes are reversible.     

Recovery of fertility and outcome of planned pregnancies after the removal of NORPLANT subdermal implants or Copper-T IUDs

The recovery of fertility after discontinuation of NORPLANT^R implant use was assessed in ninety women who stated a desire for a new child at the time of removal. Three subjects were lost to follow-up after removal. The cumulative probability of conception in the remaining 87 women was 25, 49, 73 and 86 percent at one, three, six and twelve months after removal, respectively. Nine observations were censored either because of the use of a contraceptive method soon after removal of the implants (n = 7) or separation (n = 2). All other cases were pregnant at the end of two years with exception of three subjects where a male factor for infertility was present. There was no significant correlation between the length of NORPLANT^R use and the length of the interval from removal to conception. A significantly higher frequency of intervals longer than 6 months was observed among women older than 30 years as compared to younger women. Pathology during pregnancy was cholestasia (n = 5), hypertension (n = 1) and gestational diabetes (n = 1). The outcome was term delivery in 59 cases, premature delivery in 4 cases, and spontaneous abortion in 7 cases. One woman is still pregnant and the outcome is unknown in 4 cases. One premature infant died. A contemporary control group of Copper Tusers enrolled under the same criteria as NORPLANT^R implant users provided 44 women who had the device removed to become pregnant. The cumulative probability of pregnancy was 27, 69, 84 and 89 at one, three, six and twelve months and all were pregnant by the end of the second year. Six censored observations occurred because of the use of another contraceptive method after removal (n = 3) or loss to follow-up (n = 3). The outcome of pregnancy was term delivery in 23 cases and abortion in 7 cases. Recovery of fertility occurred at a normal rate after NORPLANT^R implant removal and the incidence of problems detected in the ensuing pregnancy were within the expected range for Chilean women.     

Acceptability of randomization to levonorgestrel versus copper intrauterine device among women requesting IUD insertion for contraception

ObjectiveAssess feasibility of randomizing women to intrauterine device (IUD) type.Study DesignWomen enrolling in a 2-month study who desired an IUD for contraception were randomized 1:1 to receive a levonorgestrel-releasing 52-mg IUD (LNG-IUD) or copper T380A IUD (Cu-IUD), understanding they could switch IUD type at the end of the study.ResultsRandomization to IUD type was acceptable to 54/55 (98%) women who screened. All 32 enrolled participants completed follow-up. Two women exchanged their IUD (Cu-IUD to LNG-IUD), and two requested removal (one LNG-IUD, one Cu-IUD). Overall, 88% continued their assigned IUD.ConclusionsRandomization to IUD type is feasible, and few women change their IUD.