T-shaped IUDs accommodate in their position during the first 3 months after insertion.

The objective of this study was to observe the position dynamics of the T-shaped intrauterine device (IUD) in the uterine cavity, from insertion to 90 days of use. IUD position was evaluated in 214 women by vaginal ultrasound, measuring the IUD-endometrium, IUD-myometrium, and IUD-fundus distances. The 90th percentile of the IUD-endometrium distance was 5, 6, and 8 mm at time of insertion, 30 and 90 days of use; 7, 9, and 10 mm for IUD-myometrium distance; and 23, 24, and 27 mm for IUD-fundus distance, respectively. Seventeen IUDs were classified as misplaced at insertion by using the 90th percentile of the IUD-myometrium distance as standard. Of these, only 6 remained misplaced after 90 days of use. On the other hand, 21 IUDs were beyond the 90th percentile at the 90-day observation, only 6 of which were considered misplaced at insertion. We conclude that the T-shaped IUD accommodates its position in the uterine cavity during the first 3 months following insertion, and that ultrasound evaluation of its position is not a good predictor of future evaluation.

The monomeric GTP binding protein, rab3a, is associated with the acrosome in mouse sperm.

Exocytosis of the sperm acrosome is an obligate precursor to successful egg penetration and subsequent fertilization. In most mammals, acrosomal exocytosis occurs at a precise time, after sperm binding to the zona pellucida of the egg, and is induced by a specific component of the zona pellucida. It may be considered an example of regulated secretion with the acrosome of the sperm analogous to a single secretory vesicle. Monomeric G proteins of the rab3 subfamily, specifically rab3a, have been shown to be important regulators of exocytosis in secretory cells, and we hypothesized that these proteins may regulate acrosomal exocytosis. Using alpha[32P] GTP binding to Immobilon blotted mouse sperm proteins, the presence of three or more monomeric GTP binding proteins was identified with Mr = 22, 24, and 26 x 10(3). Alpha[32P] GTP binding could be competed by GTP and GDP, but not GMP, ATP, or ADP. Anti-peptide antibodies specific for rab3a were used to identify the 24 kDa G protein as rab3a. Using immunocytochemistry, rab3a was localized to the head of acrosome-intact sperm and was lost during acrosomal exocytosis. It was identified in membrane and cytosolic fractions of sperm with the predominant form being membrane-bound, and its membrane association did not change upon capacitation. Immunogold labeling and electron microscopy demonstrated a subcellular localization in clusters to the periacrosomal membranes and cytoplasm. These data identify the presence of rab3a in acrosomal membranes of mouse sperm and suggest that rab3a plays a role in the regulation of zona pellucida -induced acrosomal exocytosis.

Forearm bone density in users of Depo-Provera as a contraceptive method.

OBJECTIVE: To determine the influence of depot medroxyprogesterone acetate (MPA) on bone mineral density when used as a contraceptive method. DESIGN: Cross-sectional study. SETTING: Academic tertiary-care hospital. PATIENT(S): Fifty premenopausal women who had used depot MPA as a contraceptive method for > or =1 year and 50 women who had never used hormonal contraceptive methods. INTERVENTION(S): Bone mineral density was evaluated at the midshaft and at the distal radius of the nondominant forearm using single x-ray absorptiometry. MAIN OUTCOME MEASURE(S): Bone mineral density. RESULT(S): Bone mineral density at the midshaft of the forearm was lower in depot MPA users than in women who had never used hormonal contraceptive methods, but the difference was not statistically significant. At the distal portion, bone mineral density was significantly lower in the study group. The duration of depot MPA use was not related to bone mineral density. CONCLUSION(S): Women > or =35 years of age presented with a lower bone mineral density only at the distal portion of the forearm after the use of depot MPA for > or =1 year. However, this decrease was not related to the duration of depot MPA use. It is not possible to conclude that women who use depot MPA are at risk of osteoporosis.

PIP: The impact of depot medroxyprogesterone acetate use on bone mineral density was assessed in a cross-sectional study of 100 women recruited from a teaching hospital in Campinas, Brazil, during 1996-98. Bone mineral density, as evaluated at the midshaft and distal radius of the nondominant forearm by single x-ray absorptiometry, was compared in 50 women 35-45 years of age who had been using Depo-Provera for contraception for 1 year or more (mean duration, 46.4 +or- 38.6 months) but had never used any other hormonal method and 50 age- and weight-matched women who had never used any form of hormonal contraception. Although mean bone mineral density at the midshaft of the forearm was lower in Depo-Provera users than nonusers of hormonal contraception (0.459 +or- 0.042 vs. 0.474 +or- 0.049 g/sq. cm), the difference was not statistically significant. At the distal portion, bone mineral density was significantly lower in Depo-Provera users than nonusers of hormonal methods (0.362 +or- 0.040 vs. 0.392 +or- 0.049 g/sq. cm, p 0.001). The duration of Depo-Provera use was not related to bone mineral density, even when women had used the method for more than 5 years. Multiple regression analysis indicated that 4 pregnancies, White race, and Depo-Provera use were significantly associated with lower bone mineral density at the midshaft section of the forearm; at the distal section of the forearm, these variables were Depo-Provera use, more than 4 pregnancies, White race, older age at menarche, and habitual coffee drinking. These findings do not provide sufficient evidence to conclude that Depo-Provera users are at increased risk of osteoporosis.

Timing of onset of contraceptive effectiveness in Depo-Provera users. II. Effects on ovarian function.

OBJECTIVE: To determine the timing of onset of contraceptive effectiveness after the first injection of 150 mg of depot medroxyprogesterone acetate (DMPA) administered between days 8 and 13 of the menstrual cycle. DESIGN: Descriptive, prospective study. SETTING: A tertiary university referral center. PATIENT(S): Thirty healthy women between 18 and 40 years of age. INTERVENTION: Volunteers were injected with DMPA between days 8 and 13 (5 women on each day) of the menstrual cycle. MAIN OUTCOME MEASURE(S): Ovarian function determined by serum levels of E2 and progesterone and follicular development evaluated by vaginal ultrasound. RESULT(S): In nine (30%) of 30 women studied, DMPA did not prevent ovulation. All ovulations occurred in women receiving DMPA between days 10 and 13 of the cycle. No woman who received injections on day 8 or 9 ovulated. Ovulation suppression was more effective in women with low ovarian activity. All ovulation occurred within 3 days after the injection. CONCLUSION: A back-up contraceptive method, used after the 7th day of the menstrual cycle, is recommended for up to 7 days after the first injection of DMPA.

PIP: To ensure ovulation does not occur, it is recommended that Depo-Provera injections be administered within the first 7 days of the menstrual cycle. In some settings, this requirement acts as a barrier to women's free access to injectable contraception. Thus, the present study investigated the timing of onset of contraceptive effectiveness when the first injection of depot medroxyprogesterone acetate is administered between days 8-13 of the menstrual cycle. 30 women 18-40 years of age attending a university referral center in Campinas, Brazil, in 1995-96, were enrolled. Ovulation, detected through serum progesterone and estradiol assays and confirmed by follicle rupture at vaginal ultrasound, occurred in 9 cases (30%). No ovulations occurred when injection was administered on day 8 (n = 5) or day 9 (n = 5) of the menstrual cycle; only 1 of the 5 women treated on day 10 ovulated. On the other hand, 4 of the 10 women treated on days 11 and 12 and 4 of the 5 injected on day 13 showed evidence of ovulation. All ovulation occurred within 3 days after injection. Ovulation occurred only among women who had serum estradiol levels of 100 pg/ml and above and a leading follicle diameter greater than 13 mm at the time of injection. Ovulation suppression was more effective in women with low ovarian activity. A back-up contraceptive method used for 4 days after Depo-Provera injection should provide sufficient protection when the method is administered after day 7 of the menstrual cycle. However, given the uncertainty of the assumption of short viability of the human oocyte, it is safer to recommend 1 week's use of a back-up method or abstinence.

The risk of inadvertent intrauterine device insertion in women carriers of endocervical Chlamydia trachomatis.

The most important complication attributed to the use of intrauterine device (IUD) is pelvic inflammatory disease (PID), often associated with Neisseria or Chlamydia infection. Consequently, the IUD should not be inserted in women at risk of infection or with symptoms of endocervicitis. To evaluate the effectiveness of such a policy, a systematic investigation of Chlamydia and Neisseria was carried out among 407 contraceptive acceptors. Twenty-seven cases were positive for Chlamydia and none were positive for Neisseria. There were no statistical differences in the proportion of women with and without Chlamydia who had vulvovaginal or cervical signs or symptoms, although twice as many women had pain at pelvic exam in the Chlamydia-infected group. In 29 women in whom infection was clinically suspected, two were found to be infected with Chlamydia. IUD were not inserted in women suspected of having infection, but 19 of 327 IUD acceptors were subsequently found to have a positive Chlamydia test result. Two women returned with symptoms of PID and 17 were asymptomatic, but all were treated. PID was not suspected in any other subject. These results reinforce the need for careful selection of IUD acceptors and for thorough counseling for symptoms of PID and the need for immediate consultation.

T-shaped IUD move vertically with endometrial growth and involution during the menstrual cycle.

Ultrasound has been used to detect and evaluate intrauterine device (IUD) position for some years. Different definitions of the IUD in the uterine cavity have been discussed trying to relate them to bleeding and pain complaints. Most of these definitions do not take into account the uterine wall or endometrial thickness. This is a secondary analysis of a previous cross-sectional study, in which 481 IUD users had their T-shaped IUD evaluated by transvaginal sonography. The correlation between the endometrium thickness and the IUD-myometral distance was studied, defined by the linear measurement between the upper end of the IUD and the myometrium/endometrium interface. These two measurements were highly correlated over the entire sample range (r = 0.29) and an even stronger correlation existed (r = 0.66) when only cases below the 90 percentile of the IUD-endometrial distance distribution were considered. These results suggest that the IUD position in the uterine cavity is influenced by the growth and thinning of the endometrium, and that this information should be considered when evaluating the IUD position by sonography.

Timing of onset of contraceptive effectiveness in Depo-Provera users: Part I. Changes in cervical mucus.

OBJECTIVE: To evaluate the changes in cervical mucus within the first hours or days after depot medroxyprogesterone acetate (MPA) injection so as to estimate the time at which cervical mucus becomes hostile enough to prevent pregnancy. DESIGN: Multicenter, clinical descriptive study. SETTING: Family planning clinic. PATIENT(S): Thirty women who were between days 8 and 13 of their menstrual cycle and who had requested Depo-Provera were enrolled in the study. INTERVENTION(S): Cervical mucus and blood samples were obtained; transvaginal ultrasonography was performed. MAIN OUTCOME MEASURE(S): Cervical mucus scores, sperm penetration distances, ovarian follicular size, and serum levels of progesterone and estradiol. RESULT(S): From 6 to 24 hours after injection, there was a sharp decline in the cervical mucus score for most of the subjects. All subjects exhibited poor mucus on day 3 after injection, and by day 7, all subjects had zero scores, with the exception of two outliers on each day. Sperm penetration, as measured by the vanguard sperm distance, was already poor (< 1 cm) in 7 of the 30 subjects at the time of injection and was reduced progressively up to 24 hours after injection, when only four subjects had a sperm penetration of > 1 cm. A rapid decline in the estimated number of sperm was observed at 12 hours and more so at 24 hours in the majority of subjects. CONCLUSION(S): The data presented in this report confirmed that depot MPA causes profound changes in cervical mucus after injection. Although very little change was seen at 6 hours, alterations were observed subsequently, with 90% of the subjects showing a poor cervical mucus score 24 hours after administration of the progestin. No reliable clinical marker is available to identify in which women depot MPA might exert its effect on cervical mucus within 3 days. Thus, we believe that at present, women should be informed of this uncertainty and should use a backup method of contraception for 7 days when the first injection of depot MPA is provided after the seventh day of the menstrual cycle.

PIP: More accurate knowledge of the time of onset of cervical mucus changes after Depo-Provera injection would enable family planning providers to counsel new acceptors to use a backup method only for the amount of time it is really needed. To obtain such data, 30 women from a family planning clinic in Campinas, Brazil, who requested Depo-Provera in 1995-96 were recruited. At baseline, 11 women had a poor cervical mucus score (0-4), 12 had a fair score (3-8), and 7 scored in the good range (9-12). Between 6 and 24 hours after injection, a sharp decline occurred in the cervical mucus score in all but 3 patients (each of whom had a "good" score at baseline). On day 3, 29 women had "poor" mucus and the remaining woman had a cervical mucus score in the fair range. By day 7, 29 women had zero mucus scores; the score in the last woman was 1. 24 hours after injection, sperm penetration (measured by vanguard sperm distance) had decreased to under 1 cm in all but 4 women. At day 3, 1 of the 2 women with good penetration at 24 hours maintained a vanguard sperm distance of 2.5 cm and an estimated sperm count of 15,363. By day 7, sperm penetration was zero in all but 1 woman (0.5 cm). These findings confirm that depot medroxyprogesterone acetate causes profound changes in cervical mucus after injection. The lack of a more complete hostility to sperm penetration at day 3 was unexpected, however. Given the nonavailability of a reliable clinical marker to verify a contraceptive effect at 3 days, it seems prudent to advise new Depo-Provera acceptors to use a backup method for the first 7 days.

No relationship between the IUD position evaluated by ultrasound and complaints of bleeding and pain.

The objectives of this study were to define the "normal" position of the T-shaped intrauterine device (IUD) in the endometrial cavity, using transvaginal ultrasound, and to compare the IUD's position in women with and without complaints of bleeding and/or pain. Vaginal ultrasound was carried out in women who had used a T-Cu 200 or T-Cu 380 for at least 6 months. Of these women, 236 registered bleeding complaints and/or pain and 245 had no complaints. The distances, IUD-endometrium, IUD-myometrium, and IUD-fundus, were measured in each woman. Our results showed that women with and without complaints presented no significant differences in age, parity, type of IUD, duration of use, previous contraceptive method used, hysterometry, uterine position, or period of the cycle in which the ultrasound was performed. The values of the three distances in users without complaints were widely dispersed. The 90th percentile of the IUD-endometrium, IUD-myometrium, and IUD-fundus distances were 7, 11, and 27 mm, respectively. The curve of the values for the three distances among women with complaints was similar to that of the subjects without complaints. Using the generally accepted measurement of 20 or 25 mm as the limits of normality of the distance IUD-fundus, and the 90th percentile of the distance IUD-endometrium as the gold standard, 77% and 43% of the women were false positives for "incorrect IUD position." Similar results were obtained when the 90th percentile of the distance IUD-myometrium was used as a gold standard. We concluded that the 90th percentiles of the distance IUD-endometrium, IUD-myometrium, and IUD-fundus were 7, 11 and 27 mm, respectively, among users without complaints. The ultrasonographic diagnosis of the IUD position was unable to discriminate between women who did or did not have complaints of bleeding and/or pain. If ultrasound were to be performed in T-shaped IUD users, the IUD-myometrium distance is likely to be the most reliable measurement.

The use of vaginal ultrasound to identify copper T IUDs at high risk of expulsion.

A total of 235 women who had a TCu 380A IUD inserted had a vaginal ultrasound scan performed to identify if the IUDs were correctly placed in the uterine fundus. Women identified as having a misplaced IUD had it removed. The remaining women were compared to 201 women who had an IUD inserted and had no ultrasound evaluation, matched by age and parity. Women were followed-up for one year. Gross cumulative discontinuation rates and continuation rates were calculated by life table analysis. Comparison between groups was done by the Gehan test. The study group had 34 IUDs removed because they were misplaced according to the established criteria. The expulsion rate was significantly higher in the control group, also influencing the continuation rate which was lower in the same group. Of the 34 women who had their IUD removed because it was not correctly placed, only 22 requested and had another IUD inserted. The removal of IUD determined by an ultrasound to be incorrectly placed significantly decreased expulsion rates. However, many IUDs may have been removed unnecessarily, probably resulting in many women not returning to the clinic or deciding to use another contraceptive method.

Composition of the human zona pellucida and modifications following fertilization.

The composition of individual human zonae pellucidae and modifications to this extracellular coat both before and after fertilization were analysed using a rapid, sensitive, non-radioactive biotinylation- or lectin-based detection system; these assays use commercially available reagents and can be performed on fragments of individual zonae pellucidae. The zona pellucida from unfertilized eggs is composed of three glycoprotein species designated as huZP1, huZP2 and huZP3. Under non-reducing conditions, the molecular weights of these proteins are approximately 150 kDa, approximately 100 kDa, and approximately 55-65 kDa respectively. Following fertilization, huZP1 was not detected under either non-reducing or reducing conditions. In contrast, after fertilization huZP2 was detected under non-reducing conditions, but not under reducing conditions. The ability to detect pre- and post-fertilization changes in a single human zona pellucida is discussed in relation to its value in assessing deficiencies in clinical and laboratory protocols used for in-vitro fertilization.

Follow-up of women seeking sterilization reversal: a Brazilian experience.

OBJECTIVE: To analyze the follow-up of a cohort of women who requested reversal of surgical sterilization. METHODS: This retrospective study was carried out at the State University of Campinas, Brazil. A cohort of 394 women who requested sterilization reversal was followed up for one year after reversal surgery. The analysis includes the percentage of women who completed the steps between the initial consultation up to one year after reversal surgery. RESULTS: After an initial consultation, 55.1% of the patients decided not to continue with the procedures. Of the patients who did undergo laparoscopy (n = 177), 48.6% had no possibility of a successful surgical reversal because the Fallopian tubes were in very poor condition. Only 17.5% of the initial patients requesting reversal ultimately underwent surgery and 3.3% became pregnant. CONCLUSIONS: The analysis of regret about surgical sterilization should include not only women who undergo surgery but also women requesting surgery. Better patient selection and counseling prior to sterilization are necessary in order to prevent increasing rates of sterilization regret in Brazil.

The influence of human chorionic gonadotrophin administration upon the next ovarian cycle.

We examined the influence of human chorionic gonadotrophin (HCG), used as an ovulation inducer and/or for supporting the luteal phase, on the next ovarian cycle. Four women received 10,000 IU of HCG at mid-cycle and another four received the same dose plus 1500 IU on the 17th, 19th and 21st days of the cycle. In the menstrual cycle prior to our experiments, venous blood samples were collected and vaginal ultrasound of the ovaries was performed every other day from day 21-28; the same data were also collected on days 1-10 of the experiment cycle. In such a way, control values were obtained. After the administration of HCG, venous blood samples were collected and ultrasound was performed in the same way and on the same days as in the controls. Follicle stimulating hormone (FSH) and luteinizing hormone were determined by radioimmunoassay in all blood samples, and HCG only in samples collected after the experiment. The results showed that only FSH was lower in the late luteal phase after the administration of 10,000 IU of HCG. Follicular diameters were higher during the follicular phase than during the previous cycle only in women who received the low dose of HCG. In addition, one woman presented with detectable HCG in the following ovarian cycle. The use of HCG in the preceding cycle may reduce FSH and develop persistent follicles in the subsequent cycle. We suggest that an ultrasound of the ovaries should be performed before starting a new ovulation induction cycle in a woman who has received HCG in the previous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical performance of the Copper T200B IUD after reinsertion following life-span expiration.

The purpose of this study was to evaluate the first year clinical performance of the TCu200B IUD in a cohort of women who had the IUD re-inserted immediately after a removal for life-span expiration, compared with a group of initial acceptors, and a cohort of women who continued using the device for more than 60 months. The sample consisted of 1066 users, 339 in each of the two first groups and 388 in the third. Life-table analysis was used to calculate continuation and gross discontinuation rates by reason. Statistical significance of the differences between groups was tested by log-rank method. Pregnancy rates were low, both in the group of re-insertions and first insertions, and no pregnancies occurred in the group using the device beyond the fifth year. The expulsion rate and lost-to-follow-up (LFU) rate were significantly lower in the group of women who used the device beyond the fifth year. In addition, this group showed a significantly higher rate of removal for investigator's choice. These results show that there is no reason to recommend the removal and replacement of the TCu200B before the end of the sixth year of use. When a new IUD is to be inserted after removal for life-span expiration, providers should be instructed to insert it immediately after the removal, because this procedure does not pose additional risks, reduces the number of clinic visits, and relieves the women of the use of a temporary method while waiting for the re-insertion.