Misoprostol dose and route after mifepristone for early medical abortion: a randomised controlled noninferiority trial.

OBJECTIVE: To compare 400 and 800 microg sublingual or vaginal misoprostol 24 hours after 200 mg mifepristone for noninferiority regarding efficacy in achieving complete abortion for pregnancy termination up to 63 days of gestation. DESIGN: Placebo-controlled, randomised, noninferiority factorial trial, stratified by centre and length of gestation. Misoprostol 400 or 800 microg, administered either sublingually or vaginally, with follow up after 2 and 6 weeks. SETTING: Fifteen obstetrics/gynaecology departments in ten countries. POPULATION: Pregnant women (n = 3005) up to 63 days of gestation requesting medical abortion. METHODS: Two-sided 95% CI for differences in failure of complete abortion and continuing pregnancy, with a 3% noninferiority margin, were calculated. Proportions of women with adverse effects were recorded. OUTCOME MEASURES: Complete abortion without surgical intervention (main); continuing live pregnancies, induction-to-abortion interval, adverse effects, women's perceptions (secondary). RESULTS: Efficacy outcomes analysed for 2962 women (98.6%): 90.5% had complete abortion after 400 microg misoprostol, 94.2% after 800 microg. Noninferiority of 400 microg misoprostol was not demonstrated for failure of complete abortion (difference: 3.7%; 95% CI 1.8-5.6%). The 400-microg dose showed higher risk of incomplete abortion (P < 0.01) and continuing pregnancy (P < 0.01) than 800 microg. Vaginal and sublingual routes had similar risks of failure to achieve complete abortion (P = 0.47, difference in sublingual minus vaginal -0.7%, 95% CI -2.6-1.2%). A similar pattern was observed for continuing pregnancies (P = 0.21). Fewer women reported adverse effects with vaginal than sublingual administration and with the 400-microg dose than the 800-microg dose. Of the women, 94% were satisfied or highly satisfied with the regimens, 53% preferred the sublingual route and 47% preferred the vaginal route. CONCLUSIONS: A 400-microg dose of misoprostol should not replace the 800-microg dose when administered 24 hours after 200 mg mifepristone for inducing abortion in pregnancies up to 63 days. Sublingual and vaginal misoprostol have similar efficacy, but vaginal administration is associated with a lower frequency of adverse effects.

The use and maintenance of instruments for large loop excision of transformation zone at Ramathibodi Hospital.

The average use of LLETZ in Ramathibodi Hospital from 1993 to 1998 was 73.3 cases per year (range 26-116 cases). The endocervical box (F2) loop electrode was the most frequently damaged at the rate of 4 pieces per 100 procedures. The damage rate of the 25 mm loop electrode was 3 pieces per 100 procedures and 20 mm loop electrode was 2 pieces per 100 procedures. The life of the instrument can be prolonged through proper care and continuous maintenance as well as by experienced operators and the assisting team.

Bone mineral density during long-term treatment with Norplant implants and depot medroxyprogesterone acetate. A cross-sectional study of Thai women.

This cross-sectional study compares bone mineral density (BMD) in long-term Norplant implants and depot medroxyprogesterone acetate (DMPA) users. The objectives of this study were to evaluate and compare the bone mineral density between women using these contraceptives. Forty-one current users of Norplant implants and 50 DMPA users participated in the study. The BMD was measured by dual energy x-ray absorptiometry in the nondominant distal and ultradistal forearm. Serum estradiol was measured by microparticle enzyme immunoassay technique. The demographic characteristics were similar in both groups. The mean durations +/- SD of DMPA and Norplant implants were 59.14 +/- 30.73 and 31.1 +/- 11.2 months, respectively. The BMD of long-term Norplant implant and DMPA users was similar. The serum estradiol in the Norplant implant group was significantly higher than in DMPA users. However, the serum estradiol level in DMPA users ranged into normal for the follicular phase, which is higher than for postmenopausal women. This study suggests that two long-acting progestogen contraceptives do not differ with respect to their impact on BMD in long-term users.

Effect of zidovudine treatment in late pregnancy on HIV-1 in utero transmission.

In Thailand, the prevalence of paediatric HIV-1 infection has increased rapidly through vertical transmission. According to the ACTG 076 trial regimen, zidovudine treatment in HIV-infected pregnancy can reduce vertical transmission. However, this treatment is complex and costly. It is not applicable for developing countries. We conducted a study to evaluate the effect of zidovudine treatment in late pregnancy on HIV-1 in utero transmission. Fifty cases of asymptomatic HIV-1 infected-women were voluntarily enrolled to the study. Zidovudine 250 mg orally twice a day was given to these patients from gestational age 36 weeks until labour. The newborns were evaluated at birth by a neonatologist and peripheral blood was tested for HIV genome by PCR technique within 48 hours of birth. The study revealed that no HIV genome was detected from the peripheral blood of newborns. It is suggested that zidovudine treatment in late pregnancy could reduce HIV-1 in utero transmission.

PIP: In 1995, Ramathibodi Hospital in Bangkok, Thailand, introduced zidovudine (ZDV) treatment in late pregnancy to prevent vertical transmission of HIV infection. The effectiveness of this strategy was assessed in 50 HIV-1-infected pregnant women who were receiving prenatal services at the hospital. The protocol consisted of 250 mg of ZDV orally twice a day from 36 weeks of gestation until the onset of labor. No ZDV was administered in the intrapartum and newborn period. Mothers were urged not to breast feed. The mean duration of ZDV treatment was 24.8 +or- 9.3 days. The most common side effect was nausea and vomiting (16%). Mean birth weight was 3010.25 +or- 301.0 g. No HIV-1 genome was detected in the peripheral blood of any of the 50 infants within 48 hours of birth. This preliminary finding suggests that a short course of ZDV late in pregnancy reduces in utero transmission of HIV infection as effectively as the more complex ZDV regimen. The 50 infants will be followed for up to 18 months to assess the rate of intrapartum and postpartum HIV and the long-term effects of treatment.

Bone mineral density in long-term depot medroxyprogesterone acetate acceptors.

The study of bone density in long-term DMPA users is reported. The aims were to study and compare bone density in long-term DMPA users with intrauterine device (IUD) users. Fifty current users of DMPA with a minimum 36 months previous use were compared to 50 current IUD users as control. The bone mineral density was measured by dual energy x-ray absorptiometry (DEXA) at the non-dominant distal and ultradistal forearm. Serum estradiol was measured by microparticle enzyme immunoassay technique in both groups. Age, income, weight, height, BMI, and parity of both groups were matched. The mean bone mineral density of distal forearm in DMPA and IUD users was 0.48 +/- 0.05 g/cm2 in both groups. The mean bone mineral density of ultradistal forearm was 0.38 +/- 0.06 g/cm2 in DMPA users and 0.4 +/- 0.05 g/cm2 in IUD users. No differences in mean bone mineral density of distal and ultradistal forearm between DMPA and IUD users was demonstrated (95% CI -0.02, 0.02 and -0.04, 0.001, respectively). However, the serum estradiol levels were significantly different between DMPA and IUD users (95% CI -122, -68.1). From this study, it is suggested that long-term DMPA use should not have any adverse effect on bone density even if it reduces serum estradiol.

PIP: To assess the long-term effect of depot medroxyprogesterone acetate (DMPA) on bone mineral density, 50 current DMPA users with a minimum of 36 months (mean, 59.14 months) of continuous use recruited from a family planning clinic in Bangkok, Thailand, were compared with 50 current IUD users. Bone mineral density was measured by dual energy x-ray absorptiometry at the non-dominant distal and ultradistal forearm. Cases and controls were matched for age, income, weight, height, body mass index, and parity. Women with conditions known to affect bone density (e.g., smoking, alcohol consumption, metabolic bone disease) were excluded from both groups. The mean bone mineral density of distal forearm was 0.48 +or- 0.05 g/sq. cm in both groups, while the mean bone mineral density of ultradistal forearm was 0.38 +or- 0.06 g/sq. cm in DMPA users and 0.4 +or- 0.05 g/sq. cm in IUD users, a non-significant difference. However, serum estradiol levels measured within 5 days after cessation of menstruation were significantly reduced in DMPA users (52.67 +or- 25.1 pg/mL) compared to controls (147.51 +or- 91.9 pg/mL). These findings indicate that, even though DMPA induces estrogen deficiency, there seems to be no adverse effect on bone density.

Modified minilaparotomy technique of interval female sterilization.

The study of a modified minilaparotomy technique of interval female sterilization is reported. The modified minilaparotomy technique of interval female sterilization is performed under local anesthesia using the Ramathibodi uterine manipulator, bivalve speculum, and a low midline incision. Sixty cases were treated with this technique. From the study, it was revealed that the mean age of patients +/- SD was 31.2 +/- 5.6 years, the mean body weight +/- SD was 43.3 +/- 5.1 kg, and the mean height +/- SD was 152.1 +/- 8.2 cm. The mean operating time was 24.3 +/- 5.5 min with a range from 15 to 35 min. All patients recovered and were allowed home within 2 h after operation. No immediate or late complications were observed. It was concluded that this technique is quick, safe, inexpensive, and easy to perform as an outpatient procedure.

PIP: The modified minilaparotomy technique of interval female sterilization is performed under local anesthesia using the Ramathibodi uterine manipulator, bivalve speculum, and low midline incision. This outpatient technique is considered particularly appropriate to the situation in Thailand, where families prefer to defer sterilization until the last child is old enough to ensure survival. During 1995-96, 60 Thai women seeking permanent contraception underwent this procedure at Ramathibodi Hospital in Bangkok. The mean age of sterilization acceptors was 31.2 years; mean body weight was 43.3 kg and mean height was 152.1 cm. The mean operating time was 24.3 minutes (range, 15-35 minutes). No immediate or late complications occurred, and all patients returned home within 2 hours of the procedure. These findings confirm that modified minilaparotomy is quick, safe, inexpensive, and easily performed on an outpatient basis.

Outpatient laparoscopic interval female sterilization.

A 23-year retrospective review of laparoscopic sterilization in Ramathibodi Hospital, Bangkok, Thailand, is reported. A total of 9041 cases of outpatient laparoscopic interval female sterilizations were done from January 1973 to December 1995. Intraoperative complications occurred in 35 cases (0.39%) and hospital admissions totalled 65 cases (0.72%). Adnexal injuries were the most frequent complication. There was one case of death from anesthetic complication. Management and prevention of complications are discussed.

PIP: To evaluate outpatient laparoscopic sterilization, a retrospective review was conducted of all 9041 such procedures performed at Ramathibodi Hospital in Bangkok, Thailand, during 1973-95. Intraoperative complications occurred in 35 cases (0.39%) and there were 65 hospital admissions (0.72%). The 1 death in this series (mortality rate, 11/100,000 procedures) was due to an adverse reaction to neuroleptanalgesic drugs. Adnexal injuries, present in 20 cases, were the most frequent complication. There were 5 cases of bowel and mesenteric injuries, 3 retroperitoneal injuries, 3 uterine injuries, and 2 bladder injuries. By type of instrument, 26 cases involved electrocautery (generally mesosalpingeal and meso-ovarian bleeding); in another 7 cases, trocar insertion was implicated. Use, at this facility, of the Ramathibodi uterine elevator as a uterine manipulator is believed to have significantly reduced the incidence of uterine perforation, a major complication in studies from other settings. However, the overall safety of laparoscopic female sterilization depends on the skill and experience of the surgeon.

Use of Norplant implants in asymptomatic HIV-1 infected women.

The study of Norplant implants use in HIV-1 infected women was conducted at the Family Planning Clinic, Department of Obstetrics and Gynaecology. Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, from January 1993 to June 1996. The purpose of the study was to evaluate efficacy, clinical effects, side effects, and menstrual patterns of the Norplant system in HIV-1 infected acceptors. Forty one cases of asymptomatic HIV-1 positive women voluntarily participated in using Norplant implants after delivery or abortion. The mean age was 25.4 years. The most common menstrual pattern was irregular bleeding (63.4%). Mean blood pressure, body weight, and hemoglobin level were not different at insertion and at 12 months (p > 0.05). No pregnancy occurred during a 12-month period. It was concluded that the Norplant system was safe, efficacious, and well tolerated in HIV-1 positive women and is an appropriate contraception in these women.

PIP: Although Thailand's National Family Planning Program introduced Norplant contraceptive implants in 1986, few women infected with human immunodeficiency virus (HIV) select this method, and its efficacy, clinical effects, and side effects in this population have not been investigated. To address these issues, a prospective cohort study was conducted during 1993-96 of 41 asymptomatic HIV-infected women who presented to the Family Planning Clinic at Ramathibodi Hospital in Bangkok, Thailand, and voluntarily accepted Norplant implants. All implants were inserted within 4 weeks after delivery or abortion. 63.4% of acceptors had not used any contraceptive method prior to pregnancy. At 6 and 12 months after insertion, 26% and 23%, respectively, reported irregular menstrual periods and 24.4% and 36.6%, respectively, reported amenorrhea. Side effects, reported by 3-10% of women, included headache, acne/chloasma, anorexia, and nausea. There were no significant changes in body weight, blood pressure, and hemoglobin between insertion and the 12-month follow-up. No pregnancies occurred during the study period. These findings suggest that Norplant implants are an effective, appropriate contraceptive method for HIV-infected women who want to avoid pregnancy but are not interested in sterilization.

Association of contraceptives and HIV-1 infection in Thai female commercial sex workers.

We conducted a case-control study to evaluate the association between contraceptive methods and HIV infection among Thai female commercial sex workers in Khon Kaen and Lumpang provinces, Thailand; 118 cases of HIV-1 infected sex workers were eligible for inclusion and 258 HIV-1 negative women were recruited as controls during the period of October 1, 1993 to December 31, 1994. Cases and controls were matched by age, education, parity, age at first exposure to commercial sex, number of clients per night, duration of work and sexual practice during menstruation. The ratio of case per control was 1:2. Both cases and controls were interviewed and underwent blood testing by a team of investigators. The study revealed no significant association between oral pill, injection, other contraceptives and HIV-1 infection. However, condom usage showed a significant protective effect. It is suggested that these contraceptives in this high-risk group of women do not increase the risk of HIV infection. In contrast, the use of condoms could reduce the risk of HIV infection.

PIP: The authors conducted a case-control study to evaluate the association between contraceptive methods and HIV infection among Thai female commercial sex workers in Khon Kaen and Lumpang provinces, Thailand; 118 cases of HIV-1-infected sex workers were eligible for inclusion and 258 HIV-1-negative women were recruited as controls during the period of October 1, 1993, to December 31, 1994. Cases and controls were matched by age, education, parity, age at first exposure to commercial sex, number of clients per night, duration of work, and sexual practice during menstruation. The case/control ratio was 1:2. Both cases and controls were interviewed and underwent blood testing by a team of investigators. The study revealed no significant association between oral pills, injections, other contraceptives and HIV-1 infection. However, condom usage showed a significant protective effect. It is suggested that these contraceptives in this high-risk group of women do not increase the risk of HIV infection. In contrast, the use of condoms could reduce the risk of HIV infection.

Bone density in women receiving Norplant implants for contraception.

The aim of this study was to determine whether long-term Norplant uses is associated with changes in bone density. The study group consisted of forty one healthy women aged 19-42 years who had used Norplant for 31.1 +/- 11.2 months with a minimum period of 12 months. Fifty current IUD users constituted the control group. The bone density was measured by dual energy X-ray absorptiometry (DEXA) at the non dominant distal and ultradistal forearm. Serum estradiol was measured by microparticle enzyme immunoassay technique. Age, parity, income, weight, height and body mass index (BMI) of both groups were no differences. Our analysis did not find any differences in bone mineral density of distal forearm and ultradistal forearm between Norplant and IUD users (95% CI -0.01, -0.03 and -0.02, 0.02 respectively). Serum estradiol was not different in the two groups (95% CI -24.9, 110). This study revealed that the Norplant implants do not have any adverse effect on bone mineral density.

Laparoscopic sterilization in HIV-1-positive women.

Laparoscopic sterilizations in HIV-1-positive women were performed. Patients, who were HIV-1-positive, underwent voluntary laparoscopic sterilization. The mean age of patients was 27.5 +/- 3.8 years. Most were of low socioeconomic status. The mean duration of the operation was 14.4 +/- 5.4 min. No accidental injury to the surgical team was recorded, and no complications occurred among the patients. It was concluded that laparoscopic sterilization in HIV-positive patients was safe with low risk of HIV transmission to the surgical team.

Female sterilization in Ramathibodi Hospital: 1987-1993.

A 7 year (1987-1993) restropective review of female sterilization in the Department of Obstetrics and Gynecology, Ramathibodi Hospital was reported. This paper is part of a continuing study of female sterilization in Ramathibodi Hospital. A total of 9,968 cases of female sterilization was done from January 1987 to December 1993. Post partum acceptors accounted for 63 per cent of total female sterilization, the overall postpartum female sterilization rate was 117.4 per 1,000 deliveries. 37 per cent was interval sterilization. The peak of interval sterilization was in March. 69.8 per cent of interval sterilization was performed by minilaparotomy technique, the remainder were by laparoscopy.

PIP: A retrospective study of the 9968 female sterilizations performed in Ramathibodi Hospital, Bangkok, Thailand, during 1987-93 identified trends in utilization and methods selected. The annual number of procedures performed was highest in 1988 (1596 cases) and lowest in 1991 (1294 cases), with an overall trend of decline. The annual proportion of postpartum sterilizations ranged from 51% to 72% (average, 63%), while that of interval procedures ranged from 28% to 49% (average, 37%). The interval sterilization rate was highest in March and lowest in December. Minilaparotomy was used in 69.8% of interval sterilizations; the remaining 30.2% were performed by the laparoscopic technique. The mean age of women undergoing interval sterilization increased from 32.09 years in 1987 to 32.99 years in 1993, reflecting the rising age at marriage. The overall decline in female sterilizations at Ramathibodi Hospital is presumed to reflect the expanded availability of interval sterilization at other facilities and more widespread use of other long-term contraceptive methods (e.g., Norplant and long-acting IUDs).

Modified needle elevation technique for misplaced Norplant implants removal.

This study reports on a simple, feasible and easily learned technique for Norplant implants removal. This technique is modified from the needle elevation technique. The objective of this study was to introduce an alternative Norplant implants removal technique, especially for misplaced capsules. Fifteen Norplant implants clients whose capsules were difficult to palpate had removal by this technique. The mean duration of Norplant implants use was 18.4 +/- 12.5 months. The mean length of removal time was 10.4 +/- 4.5 minutes. None of the capsules was damaged during the removal. No immediate or late complications were observed. The conclusion is that the modified needle elevation technique is a simple and easy method of removing misplaced Norplant capsules with less complications.

PIP: A clinical study conducted in Thailand among 15 Norplant implant acceptors whose capsules were difficult to palpate indicated that the modified needle elevation technique is a safe, simple method of removal in such cases. This technique involves placement of a 21-gauge hypodermic needle between the middle of the long axis of the Norplant rods and elevation of the capsules to identify the proximal ends. A single, small (3-4 mm) removal incision is made at the same site as the insertion incision. No special instruments are required. The technique was tested in 15 women who presented to Ramathibodi Hospital in 1995-96 for removal complicated by deep placement, misplacement, or inability to identify all six capsules. The mean duration of Norplant use was 18.4 months (range, 8-60 months). The mean removal time was 10.4 minutes (range, 5-20 minutes) for the modified needle-elevation technique compared with previously reported averages of 19.87 minutes for the standard technique and 12 minutes for the needle elevation technique. On the other hand, the Emory method and "U"-technique have resulted in even shorter removal times (8 and 6.79 minutes, respectively). No capsules were damaged during removal, and there were no early or late complications. More widespread use of this technique is urged to increase the ease of removal of implants, whether misplaced or not.

Cesarean and postpartum hysterectomy.

OBJECTIVE: To review the cases of cesarean and postpartum hysterectomy. METHOD: A retrospective study of all cases of cesarean and postpartum hysterectomy during 1985-1994. Maternal characteristics, method of delivery, indications for hysterectomy and complications were reviewed. RESULTS: The rate of cesarean and postpartum hysterectomy was 1:1667 deliveries. Half of these cases were delivered by cesarean section. The main indications for hysterectomy were massive bleeding due to uterine atony, abnormal placental adhesions or uterine rupture. Maternal morbidity was high and there was one maternal death. CONCLUSION: Cesarean and postpartum hysterectomy is a necessary life-saving operation. Although maternal mortality is rare, morbidity remains high. Prevention of complications that give rise to hysterectomy and optimally timed surgery should decrease maternal morbidity and mortality.

Serum vitamin A and beta-carotene levels in pregnant women infected with human immunodeficiency virus-1.

OBJECTIVE: To determine if low levels of serum vitamin A and beta-carotene are present in pregnant women with human immunodeficiency virus-1 (HIV-1) infection. METHODS: Serum concentrations of vitamin A and beta-carotene were measured in 74 pregnant women seropositive for HIV-1 infection (17 with CD4 count below 200 cells/microliter) and in 148 pregnant seronegative controls in the first trimester. Comparisons were made between groups stratified by CD4 count. RESULTS: Compared with controls, women with HIV-1 infection and CD4 count below 200 cells/microliter exhibited 37% lower mean serum vitamin A levels (0.820 versus 1.308 micromol/L, P < .001) and 37% lower mean serum beta-carotene levels (1.486 versus 2.362 micromol/L, P < .001). Mean maternal age, parity, gestational age, hemoglobin levels, and body mass index at entry into the study did not differ significantly between the control and HIV-1 infection groups. In addition, serum vitamin A levels correlated significantly with the percentage of CD4 lymphocytes (r = 0.589, P < .001), CD4 count (r = 0.772, P < .001), and CD4 to CD8 ratio (r = 0.593, P < .001). Serum beta-carotene levels correlated with the percentage of CD4 lymphocytes (r = 0.407, P < .001), CD4 count (r = 0.614, P < .001), and CD4 to CD8 ratio (r = 0.434, P < .001). CONCLUSION: Compared with levels in uninfected women, serum vitamin A and beta-carotene are decreased in HIV-1-infected pregnant women in the first trimester with CD4 counts lower than 200 cells/microliter. These micronutrient concentrations also correlate with CD4 count.