Early chorionic activity in women bearing inert IUD, copper IUD and levonorgestrel-releasing IUD

Early chorionic activity was assessed in the premenstrual days by means of serum HCG beta-fraction. As control, a group of women with no contraceptive use was studied; early chorionic activity was detected in 31.8% of the cycles. In the group bearing an inert IUD the incidence was 20%, which did not differ from the control; while in the medicated IUD groups (Cu-IUD and LNG-IUD) the incidences were 4.8% and nil, respectively. Both medicated IUD groups showed a significant difference when compared with the control, as well as the inert IUD groups. The meaning of these findings, pointing out differences in the main mechanism of action between inert and medicated IUDs, is discussed.     

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.     

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.     

Determination of plasma concentrations of d-norgestrel during a one year follow-up in women with a d-norgestrel-releasing IUD

Eight healthy women had a d-norgestrel-releasing intrauterine device inserted postmenstrually and maintained in the uterine cavity for a one year period. Plasma concentrations of d-norgestrel were measured by radioimmunoassay during the one year treatment period. d-Norgestrel could be detected in the plasma of all the subjects within a fairly narrow range during the whole period. The release rate of d-norgestrel was calculated from two IUDs removed after the treatment.     

Breast milk retinol concentrations are not associated with systemic inflammation among breast-feeding women in Malawi

The acute phase response and inflammation are associated with lower plasma retinol concentrations, but their effect on breast milk retinol concentrations is unclear. We measured plasma retinol concentrations, acute phase proteins, and breast milk retinol concentrations in 237 breast-feeding women at 2 wk postpartum in Blantyre, Malawi; 16.5% of the women had plasma retinol < 0.70 micromol/L and 14.8% had breast milk retinol < 1.05 micromol/L. Among women with and without inflammation [alpha(1)-acid glycoprotein (AGP) > 1 g/L and/or C-reactive protein (CRP) > 5 mg/L], geometric mean (95% CI) plasma retinol was 0.89 (0.84, 0.94) and 1.05 (1.01, 1.17) mumol/L, respectively (P < 0.0001). Among women with and without inflammation, geometric mean (95% CI) breast milk retinol was 2.12 (1.89, 2.36) and 2.05 (1.75, 2.39) micromol/L, respectively (P = 0.74). In multiple linear regression models adjusting for age, parity, education, BMI, and days postpartum, plasma retinol concentrations were associated with plasma AGP and CRP concentrations (P < 0.0001 and P = 0.01, respectively), whereas breast milk retinol concentrations were unaffected by plasma AGP and CRP concentrations (P = 0.22 and P = 0.86, respectively). These findings suggest that breast milk retinol concentrations are not affected by systemic inflammation.     

Duration of breast-feeding and development of children after insertion of a levonorgestrel-releasing intrauterine contraceptive device

IUDs releasing levonorgestrel, 10 μg per day (30 patients) and 30 μg per day (40 patients), and copper-releasing IUDs (Nova-T) (40 patients) were inserted six weeks after delivery in 110 breast-feeding amenorrheic women. The infants were carefully followed-up by recording monthly weight gain and growth, age of eruption of the first tooth, age of being able to walk without support and morbidity to infective diseases. No differences were noticed between the study groups. Plasma samples were collected from 13 children at the age of eight months, while the mothers were breast-feeding. Six mothers had a levonorgestrel-releasing IUD and seven others the Nova-T or no hormonal or intrauterine contraceptive. No differences were noticed between the groups in Na, K, Cl, Ca, P, protein, albumin, creatinine, urate, Fe, cholesterol, triglyceride, bilirubin, alkaline phosphatase, aspargine aminotransferase, alanine aminotransferase, lactate-dehydrogenase or high density lipoprotein cholesterol serum concentrations in the children. The duration of breast-feeding and initiation of supplementary feeding was recorded. The continuation of breast-feeding 75 days after the insertion of a 30-μg per day levonorgestrel-releasing IUD was 56 percent while in the Nova-T group only 21 percent had discontinued which is a statistically significant difference (p < 0.05); later the difference disappeared. Compared with the lactation time of their previous breast-feeding reported by women in both groups, the present lactation time increased by ten weeks. The infants received substitute foods including substitute milk, juices, etc., in the Nova-T group at 3.9 months and in the levonorgestrel-releasing IUD group at 3.4 months after delivery.     

Uterine perforation in women using a levonorgestrel-releasing intrauterine system

OBJECTIVE: To determine an estimated incidence of uterine perforations related to the insertion of a levonorgestrel-releasing intrauterine system (LNG IUS) and to identify possible risk factors. DESIGN: Retrospective, case report study. SETTING: Hospitals in Limburg, the Netherlands. METHODS: Gynecologists in hospitals in Limburg were asked about uterine perforations related to the insertion of a LNG IUS between 1999 and 2002. The charts of the reported perforations were studied. Data on the patient, doctor, insertion, diagnosis and removal were collected for every reported uterine perforation. RESULTS: In Limburg, the estimated incidence of uterine perforations related to the insertion of a LNG IUS is 2.6 per 1000 insertions. Insertion in lactating women, even beyond 6 weeks after delivery, was shown to be an important risk factor. CONCLUSIONS: Complete registration of complications provides a greater insight into the actual incidence of LNG IUS-related uterine perforations and their possible consequences. This may eventually lead to a decrease in complications.     

Serum SHBG levels during normal menstrual cycle and after insertion of levonorgestrel-releasing IUD

Daily serum sex hormone binding globulin (SHBG) levels were measured during normal ovulatory menstrual cycles in ten women between the ages of 23 and 34 by the method of precipitation with ammonium sulfate. The results showed that the mean SHBG levels in a cycle were quite different among individuals, but that the SHBG levels were constant during a certain menstrual cycle. Neither SHBG peaks on day LH-0 (52.64±19.89 nmol/L) (x±SD) nor the mean SHBG levels between the follicular phase (57.10±17.64 nmol/L) and luteal phase (64.75±23.42 nmol/L) show any significant differences.The correlations between the mean SHBG levels and the mean concentrations of progesterone (P), estradiol (E2) and androstenedione during the menstrual cycles were insignificant, whereas the mean SHBG levels during the follicular and luteal phase and on LH-0 day were significantly correlated with the mean concentrations of testosterone (t=0.474;p<0.05).In ten women between the ages of 5 and 34, serum SHBG, E2, P, and levonorgestrel (LNG) levels were measured once on day 20–21 of the pretreatment cycle and 3 times/week during the 1st, and 2 times/week during the 6th treatment cycle after insertion of a levonorgestrel-releasing IUD (LNG-IUD). The mean value of SHBG in the pretreatment blood samples (62.09±23.09 nmol/L) was higher than that after insertion of the LNG-IUD (41.82±20.50 nmol/L), though the difference was not significant (p>0.05). The correlation between LNG and SHBG was highly significant (r=0.89,p<0.01). The significance of this correlation and the degree of suppression of ovarian function are discussed.

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Resumen Se midieron durante los ciclos ovulatorios menstruales normales en diez mujeres, de 23 a 34 años, por el método de precipitación con sulfato ámonico, los niveles séricos diarios de la globulina que enlaza las hormonas sexuales (SHBG). Los resultados demostraron que los niveles medios de SHBG en un ciclo variaban considerablemente según la persona, pero eran constantes durante un ciclo dado. Ni los picos de SHBG en el día 0 de HL (52,64±19,89 nmol/L) (x±SD) ni los niveles medios de SHBG entre la fase folicular (57,10±17,64 nmol/L) y la fase lútea (64,75±23,42 nmol/L) presentan diferencias significativas.Las correlaciones entre los niveles medios de SHBG y las concentraciones medias de progesterona (P), estradiol (E2) y androstenediona durante los ciclos menstruales eran insignificantes, mientra sque los niveles medios de SHBG durante las fases folicular y lútea y en el día 0 de LH presentaban correlaciones significativas con las concentraciones de testosterona (t=0,474,p<0,05).Se midieron en 10 mujeres de 25 a 34 años los niveles de SHBG, E2, P y levonorgestrel (LNG) una vez por día en el día 20–21 del ciclo anterior al tratamiento y 3 veces por semana durante la primera semana, 2 veces por semana durante la sexta semana del ciclo de tratamiento después de la inserción de un DIU que liberaba levonorgestrel (DIU-LNG). El valor medio de SHBG en las muestras de sangre anteriores al tratamiento (62,09±23,09 nmol/L) era más alto que después de la inserción del DIU-LNG, si bien la diferencia no era significativa (p>0,05). En cambio, la correlación entre LNG y SHBG era muy significativa (r=0,89p<0,01). Este artículo examina lo que representa esta correlación y el grado de supresión de la función ovárica.

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Resumé On a mesuré durant des cycles ovulatoires menstruels normaux chez dix femmes, âgées de 23 à 34 ans, par la méthode de précipitation avec du sulfate d'ammonium, les niveaux sériques journaliers de la globuline liant les hormones sexuelles (SHBG). Les résultats ont montré que les niveaux moyens de SHBG durant un cycle variaient considérablement selon les individus, mais qu'ils étaient constants pendant un cycle donné. Ni les pics de SHBG au jour 0 de HL (52,64±19,89 nmol/L) (x±SD) ni les niveaux moyens de SHBG entre la phase folliculaire (57,10±17,64 nmol/L) et la phase lutéale (64,75±23,42 nmol/L) ne présentent de différences significatives.Les corrélations entre les niveaux moyens de SHBG et les concentrations moyennes de progestérone (P), oestradiol (E2) et androstènedione pendant les cycles menstruels étaient insignifiants, alors que le niveaux moyens de SHBG pendant les phases folliculaire et lutéale et au jour 0 de LH présentaient des corrélations significatives avec les concentrations de testostérone (t=0,474,p<0,05).On a mesuré chez 10 femmes âgées de 25 à 34 ans, les niveaux de SHBG, E2, P et lévonorgestrel (LNG) une fois au jour 20–21 du cycle précédant le traitement et trois fois par semaine pendant la première semaine, 2 fois par semaine pendant la sixième semaine du cycle sous traitement après l'insertion d'un DIU libérant du lévonorgestrel (DIU-LNG). La valeur moyenne de SHBG dans les échantillons sanguins antérieurs au traitement (62,09±23,09 nmol/L) étaient plus élevés qu'après l'insertion du (DIU-LNG), encore que la différence n'ait pas été significative (p>0,05). La corrélation entre LNG et SHBG par contre était très significative (r=0,89p<0,01). L'article examine ce que représente cette corrélation et le degré de suppression de la fonction ovarienne.

     

Experience with the levonorgestrel-releasing intrauterine system among HIV-infected women

BACKGROUND: Safe and effective contraception is needed for women infected with human immunodeficiency virus (HIV). The levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective long-term contraceptive that reduces menstrual bleeding and may reduce the risk of pelvic inflammatory disease. Yet, little is known about LNG-IUS use in HIV-infected women. SUBJECTS AND METHODS: Six HIV-infected women had the LNG-IUS inserted between March 1998 and October 2002, and were systemically followed for a mean of 45 months. Indications for LNG-IUS use were contraception in four women and menorrhagia in two women. RESULTS: The LNG-IUS was well tolerated, and menstrual bleeding was reduced in all women. Blood hemoglobin levels increased in each subject, with mean levels being 123 g/L (SD=11.7) before LNG-IUS insertion and 135 g/L (SD=8.7) at 1 year (p=.01). Levels of circulating CD4 lymphocytes and Pap smear findings remained unchanged. CONCLUSIONS: Our limited experience with LNG-IUS use in HIV-infected women is encouraging. The LNG-IUS may be used as an alternative to uterine surgery in HIV-infected women with menorrhagia.     

5896例带器妊娠妇女资料分析

目的:探讨使用宫内节育器(IUD)带器妊娠的可能影响因素和特点,为临床安全使用IUD提供参考建议。方法:回顾性分析2016-2018年全国116个国家级避孕药具不良反应监测点提交的使用IUD带器妊娠不良事件报告5896例资料。结果:对象中首次置器4206例(71.3%),IUD位置改变2814例(47.7%)。IUD在使用初期发生带器妊娠占比较多,之后呈下降趋势。结论:IUD使用早期对年轻对象加强IUD位置的影像学检查可有效减少部分带器妊娠发生,对发生异位妊娠占比高的IUD有必要开展进一步研究。     

Levels of contraceptive steroids in breast milk and plasma of lactating women

Hormonal contraceptives have been used in breast feeding women by many clinicians. However, secretion of these drugs in the breast milk has not been adequately investigated. In the present study, radioimmunoassay methods were used for estimating the contraceptive drug levels in breast milk and plasma samples. In 7 lactating women, after the injection of 150 mg medroxyprogesterone acetate = MPA (Depo-Provera), MPA levels in breast milk were similar to plasma; the ratio being almost 1: 1 throughout the study period (up to 87 days). In a group of women using oral pills (2 women took a combination pill containing 150 μg d-norgestrel (d-Ng) and 30 μg ethinylestradiol, another 5 women took progestogen-only pills containi 350 μg norethisterone (NET)), the levels of d-Ng and NET in breast milk were about 1/10th or less than those found in plasma.     

剖宫产妇女放置固定式宫内节育器的临床调查

目的观察剖宫产妇女宫腔大小分布及放置固定式宫内节育器的效果和心得体会。方法对511例在本站自愿放置固定式节育器（IUD）的有剖宫产史的育龄妇女跟踪随访1年,对宫腔大小、副反应情况、续用情况逐一调查。结果子宫腔平均深度（8．24±0．5）cm,〈6cm者占1．4％,宫腔大于9cm者占8．3％,调查发现其1年脱落率为1．77％,1年的妊娠率和因症取出率分别为0．78％、0．6％。结论剖宫产妇女子宫形态多不规则,宫腔偏大。固定式IUD设计合理,脱落率低,副反应小、续用率高,不受宫腔大小的限制,有剖宫产史者更适宜,值得推广。     

Levonorgestrel plasma concentrations and hormone profiles after insertion and after one year of treatment with a levonorgestrel-IUD

Plasma concentrations of levonorgestrel, progesterone, estradiol, FSH and LH were measured in seven volunteers who had a levonorgestrel-releasing IUD inserted postmenstrually. Blood samples were collected twice weekly during a mean of 93 days immediately postmenstrually and during a mean of 41 days over the twelfth to fifteenth month of treatment. Patterns of bleeding were studied during the first year of treatment. The IUDs used were designed to release 25 micrograms/day of levonorgestrel. The mean +/- SD plasma concentration of levonorgestrel for all subjects during the first three months was 260 +/- 68 pg/ml, and 129 +/- 28 pg/ml after one year of treatment. During the initial period of blood sampling only two of the subjects ovulated, while only two did not ovulate after one year of treatment. Intermenstrual spotting occurred during the first sixty days of treatment. Three subjects developed amenorrhea at the end of the first year. All the subjects continued the use of the IUD and no pregnancies occurred.     

Clinical chemistry in women treated with six levonorgestrel covered rods or with a copper IUD

A group of women treated with six levonorgestrel covered rods participated in a study on general chemistry and blood levels of selected hormones at treatment months 20 and 65. A comparable group of Copper T users served as control. Parameters analyzed were the SMA 12 chemistry profile, estradiol, testosterone, cortisol, T3, T4 and TSH. Samples from treated and control subjects were drawn within the same calendar period and were run simultaneously for the assay of each parameter. The values observed were within the normal limits. Significantly higher values of total protein and albumin and lower levels of estradiol and testosterone were found among implant users when compared to the control group. The results suggests little or no metabolic changes in users of six levonorgestrel covered rods which release a daily dose of approximately 105 micrograms.     

Cholesterol and its precursors in human milk during prolonged exclusive breast-feeding

Concentrations of cholesterol and its precursors were investigated in human milk from 88 mothers at 2 mo, 28 mothers at 6 mo, and 6 mothers at 9 mo of lactation. These mothers, who were exclusively breast-feeding their infants, collected fore- and hindmilk samples at every feeding over a 24-h period. Samples were analyzed by gas-liquid chromatography and mass spectrometry. Mean (+/- SD) cholesterol concentrations were 0.41 +/- 0.094, 0.46 +/- 0.094, and 0.49 +/- 0.10 mmol/L, respectively. The following cholesterol precursors were identified: squalene, lanosterol, dimethylsterol, delta 8.24-methostenol, lathosterol, and desmosterol. Mean concentrations were 0.04 +/- 0.11, 0.35 +/- 0.13, and 0.29 +/- 0.012 mmol/L for desmosterol, 0.0094 +/- 0.0027, 0.012 +/- 0.0039, and 0.011 +/- 0.0039 mmol/L for squalene, and from 0.0011 to 0.0027 mmol/L for all the other precursors. The precursors' equally low concentrations, except for desmosterol and squalene, and the significant correlations with each other suggest that the mammary gland synthesizes cholesterol from lanosterol by preserving the side-chain double bond and that the rate-limiting step may be the conversion of desmosterol to cholesterol.     

Levonorgestrel plasma levels during continuous administration with different models of subdermal implants

Plasma concentrations of levonorgestrel were determined in women using subdermal levonorgestrel implants. One group had 6 Silastic capsules (NORPLANT), one group had 4 and one group had 6 covered Silastic rods for variable lengths of time. Levonorgestrel concentrations remained constant around 0.4 ng/ml up until 6 years of use in the Norplant group. The observation period was shorter for the covered rods; plasma concentrations were, however, constant around 0.55 ng/ml and 0.70 ng/ml for 3.5 years with the 4 rods and 6 covered rods, respectively. The difference in mean levonorgestrel concentrations between the three groups were statistically significant (p less than 0.0005). Plasma levels of levonorgestrel were twice to three times higher in blood obtained from the arm with the implants compared to the levels found in the other arm. The application of a tourniquet for variable periods before blood sampling did not influence the plasma concentrations of levonorgestrel.     

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.