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.

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.

Effects of combined desogestrel-ethinylestradiol treatment on lipid profiles in women with polycystic ovarian disease.

A longitudinal study was conducted to determine the effect of combined desogestrel-ethinylestradiol treatment on lipid profiles in 28 women with polycystic ovarian disease. Mean patient age was 26.3 years (range, 16 to 36 years). Mean patient weight and height were 59.2 kg and 153.8 cm, respectively. After initial assessment, all patients were treated with a cyclical pill containing 150 micrograms desogestrel and 30 micrograms ethinylestradiol. Clinical, hormonal, and lipid determinations were evaluated after 3 and 6 cycles of treatment. The results revealed that, during the treatment course, serum luteinizing hormone, testosterone (T), free testosterone, and dehydroepiandrosterone sulfate decreased significantly, while serum follicle-stimulating hormone and prolactin levels did not change. Increased levels of total triglyceride, alpha, and prebeta lipoproteins, and decreased levels of beta lipoproteins, were observed. The ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol, although showing no significant change, had a tendency to decrease. This lipoprotein change seems to have a favorable rather than an adverse effect on the patients.

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.

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.

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.

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.

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.

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.

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.

Effects of combined ethinylestradiol and desogestrel on hormone profiles and sex hormone binding globulin in women with polycystic ovarian disease.

A longitudinal study to determine the effects of combined ethinylestradiol (EE) and desogestrel (DG) on hormone profiles and levels of sex hormone binding globulin (SHBG) were carried out in 19 Thai women with polycystic ovarian disease (PCOD). Evaluations were performed before and after 3 and 6 cycles of treatment. Regularity of cycles was observed in all patients. Most of them had improvement of androgenic symptoms. Body weight decreased slightly after 6 cycles of treatment. During the treatment course, serum luteinizing hormone (LH), testosterone (T), free T and dehydroepiandrosterone sulfate decreased significantly. Serum follicle stimulating hormone (FSH) and prolactin levels did not change. LH-to-FSH ratio markedly decreased. SHBG level increased to the control level. After discontinuation of the pill, menstrual disturbances recurred in all patients. It appears that low-dose combined OCs containing DG is suitable for use in women with PCOD. However, long-term treatment may be needed since the abnormal menstrual pattern returned after stopping the pill.

The use of the laparoscope in rural Thailand.

A survey of the use of laparoscopy in rural Thailand was undertaken between June 1974 and December 1977. All the physicians were trained at either Ramathibodi Hospital, Bangkok, or The Johns Hopkins Program for International Education in Gynecology and Obstetrics and the USA; about 30% and 46% of the physicians, respectively, were endoscopically inactive. The complication rate of rural laparoscopy was high and was inversely proportional to the degree of utilization. It is concluded that for a developing country with limited resources, laparoscopic sterilization in rural areas is not cost-effective; a technique using simpler and hardier equipment should be chosen.

PIP: During the June 1974 through December 1977 period, a survey of the use of laparoscopy in rural Thailand was undertaken. Examined were the results of training physicians, equipping national programs and maintaining and using the laparoscopy. Data were obtained from the following sources: quarterly reports prepared at each peripheral center; a questionnaire completed by physicians at each of the centers that had equipment registered at the Repair and Maintenance (RAM) Center in Thailand; and training files for each of the Ramathibodi Hospital trained physicians. The physicians were trained either at Ramathibodi Hospital in Bangkok or at the Johns Hopkins Program for International Education in Gynecology and Obstetrics in the United States. About 30% and 46% of the physicians, respectively, were endoscopically inactive. During the survey period, there were 5632 laparoscopic operations performed during 628 laparoscope-months. The most frequent maintenance problems were broken grasping forceps and burned-out light bulbs. The complication rate of rural laparoscopy was high: 8 cases of bowel burns; 6 cases of uncontrolled bleeding that required laparotomy; 1 case of vascular trauma; and 4 deaths. 2 patients died from secondary peritonitis due to bowel burns that were not recognized at the time of the operation. 1 patient died because of direct trauma to a major vessel, and the other patient died suddenly on the operating table from cardiac arrest. It appears that for a developing country with limited resources laparoscopic sterilization in rural areas is not cost effective. A technique that uses simpler and hardier equipment should be chosen.

Failed instrumental delivery: Ramathibodi Hospital, 1980-1988.

All cases (70) of failed instrumental deliveries which occurred between 1980 and 1988 at Ramathibodi Hospital, Bangkok, Thailand were critically reviewed. The incidence of failure was 0.5%, and failure occurred more often in primigravidae. Failure to appreciate the true level of the fetal head and too early intervention accounted for failure in 50% of the cases. Failed instrumental delivery can be minimized if the prerequisites for the procedure are strictly adhered to.

Obstetric hysterectomy: Ramathibodi's experience 1969-1987.

Obstetric hysterectomy was performed on 121 women at Ramathibodi Hospital, Bangkok, between 1969 and 1987, an incidence of 1:875 deliveries. Of 88 women whose records were available, 91% had emergency hysterectomy, with uterine atony as the most common indication (32.5%), followed by placenta accreta (26.2%), uterine rupture (10.0%), extension of cervical tear to the lower uterine segment (8.7%), broad ligament hematoma (6.2%) and placenta previa (5.0%). The intraoperative and postoperative problems included febrile morbidity (52%), intraoperative hypotension (41%), and disseminated intravascular coagulation (5.7%). Late complications included Sheehan's syndrome (3.4%), post-transfusion hepatitis (2.3%), hematoma (2.3%) and wound infection (2.3%).

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 lipids and lipoproteins in women with polycystic ovarian disease with different body mass index.

A study to determine serum lipids and lipoproteins in 54 women with polycystic ovarian disease (PCOD) who had varying body mass index (BMI) compared to the normal regular menstruating women was carried out. All patients had similar hormonal profiles of PCOD and differed from the control group. The significant observations were high level of triglyceride and low percentage of alpha lipoprotein in obese PCOD. The BMI was positively correlated with serum triglyceride level, beta and prebeta lipoproteins but inversely correlated with high density lipoprotein (HDL) cholesterol, the low density lipoprotein (LDL) cholesterol/HDL cholesterol ratio and alpha lipoprotein. No significant correlation between lipids, lipoproteins and testosterone levels was observed. It appeared that the alteration of serum lipids and lipoproteins in PCOD is due to the effect of obesity.

Training physicians of developing nations in female surgical contraception.

The majority of developing nations in the Third World (including Thailand) face similar medicosocioeconomic situations arising from uncontrolled population growth which outstrips developmental planning. One of the most effective medical means of combating these problems is surgical contraception. This study describes how the Ramathibodi National Training Program was developed and implemented in Thailand to increase the availability of sterilization services by training local physicians to perform the necessary operations. The success of this program is measured by the increase in the number of service delivery stations (182) and in the number of sterilization procedures performed (24 436 in a 32-month period).

Assessment of fetal well-being: fetal movement count versus non stress test.

In this prospective study, comparisons were made between the results of fetal movement count as performed by either the attending staff or by the patients using the non stress test (NST). A total of 283 NSTs were performed in 200 patients who had singleton pregnancy of at least 32 weeks gestation with indications for assessment of fetal well-being. Fetal movement counts performed by the attending staff and by the patients were recorded on 241 and 170 occasions, respectively. The results showed that the best correlation between fetal movement count by the attending staff with NST was when the criteria of three or more fetal movements within 10 min was used. Likewise, the best correlation between fetal movement count by patients with NST was found when ten fetal movements within 2 h was used as a cut off point. The result of this study suggests the usefulness of fetal movement count performed either by attending staff or patients as a cheap and effective method of screening for good fetal well-being in places where NST is not readily available and may also be used as a screening for patients prior to further evaluation.