The Filshie clip for laparoscopic adnexal surgery.

BACKGROUND: Gynecologic endoscopic procedures are increasingly common and require the ability to control large vascular structures. METHOD: The Filshie clip is a silicone-lined, titanium occlusive device, originally designed and Food and Drug Administration (FDA) approved for surgical contraception. This device also has the potential for occluding vascular structures during laparoscopic surgery. EXPERIENCE AND RESULTS: We describe a salpingectomy, an excision of bilateral hydrosalpinges, and a salpingo-oopherectomy. We performed all procedures laparoscopically using this device as the primary modality for assuring hemostasis. CONCLUSION: The Filshie clip is a useful and economical device for assuring hemostasis during gynecologic endoscopic surgery.

Buprenorphine treatment of pregnant opioid--dependent women: maternal and neonatal outcomes.

This open-label prospective study examined maternal and neonatal safety and efficacy outcome measures during and following prenatal buprenorphine exposure. Three opioid-dependent pregnant women received 8 or 12 mg sublingual buprenorphine tablets daily for 15-16 weeks prior to delivery. Results showed that buprenorphine in combination with comprehensive prenatal care was safe and effective in these women. Prenatal exposure to buprenorphine resulted in normal birth outcomes, a mean of 4.33 days (minimum possible=4) hospitalization, and a 'relatively mild' neonatal abstinence syndrome comprised primarily of tremors (disturbed), hyperactive moro and shortened sleep after feeding. The infants required no pharmacological treatment. Onset of neonatal abstinence signs occurred within the first 12 h after birth, peaked by 72 h and returned to below pre-12 h levels by 120 h. It is concluded that buprenorphine has potential utility for the treatment of pregnant opioid-dependent women.

Effect of academic affiliation and obstetric volume on clinical outcome and cost of childbirth.

OBJECTIVE: To determine whether the academic affiliation and obstetric volume of the delivering hospital has an impact on clinical and economic outcomes. METHODS: We performed a cross-sectional analysis of data for all births in the State of Maryland during 1996. Acute hospital discharge data were obtained from the publicly available Maryland Health Services Cost Review Commission database. Institutions were classified as community hospitals, community teaching hospitals, and academic medical centers. Principal outcome variables included cesarean birth and complication rates, total hospital charges, and length of stay. RESULTS: A total of 63,143 cases were identified for analysis. The cesarean delivery rate was lower among academic medical centers, compared with community teaching hospitals and community hospitals (18.4% compared with 24.3% and 21.2%, respectively). After adjustment for patient case-mix, the adjusted odds ratio (OR) for cesarean birth was 0.66 at academic medical centers and 1.23 at community teaching hospitals compared with community hospitals (P <.01). Rates of episiotomy and serious complications were lower at academic medical centers compared with community hospitals. Adjusted total hospital charges were lower and length of stay was shorter for community hospitals compared with academic medical centers ($2937 compared with $3564 and 2.2 days compared with 2.5 days, respectively). CONCLUSION: Hospital academic affiliation was an important predictor of clinical outcomes. Better clinical outcomes were found primarily among patients at academic medical centers, although these institutions demonstrated moderately higher resource utilization, compared with community hospitals.

Human embryonic germ cell derivatives express a broad range of developmentally distinct markers and proliferate extensively in vitro.

Human pluripotent stem cells (hPSCs) have been derived from the inner cell mass cells of blastocysts (embryonic stem cells) and primordial germ cells of the developing gonadal ridge (embryonic germ cells). Like their mouse counterparts, hPSCs can be maintained in culture in an undifferentiated state and, upon differentiation, generate a wide variety of cell types. Embryoid body (EB) formation is a requisite step in the process of in vitro differentiation of these stem cells and has been used to derive neurons and glia, vascular endothelium, hematopoietic cells, cardiomyocytes, and glucose-responsive insulin-producing cells from mouse PSCs. EBs generated from human embryonic germ cell cultures have also been found to contain a wide variety of cell types, including neural cells, vascular endothelium, muscle cells, and endodermal derivatives. Here, we report the isolation and culture of cells from human EBs as well as a characterization of their gene expression during growth in several different culture environments. These heterogeneous cell cultures are capable of robust and long-term [>70 population doublings (PD)] proliferation in culture, have normal karyotypes, and can be cryopreserved, clonally isolated, and stably transfected. Cell cultures and clonal lines retain a broad pattern of gene expression including simultaneous expression of markers normally associated with cells of neural, vascular/hematopoietic, muscle, and endoderm lineages. The growth and expression characteristics of these EB-derived cells suggest that they are relatively uncommitted precursor or progenitor cells. EB-derived cells may be suited to studies of human cell differentiation and may play a role in future transplantation therapies.

Economic and clinical outcomes of microlaparoscopic and standard laparoscopic sterilization. A comparison.

OBJECTIVE: To compare micro-laparoscopic surgical sterilization and standard laparoscopic sterilization with respect to cost effectiveness and patient preferences. STUDY DESIGN: A retrospective study of all laparoscopic surgical sterilizations performed under general anesthesia at Johns Hopkins Bayview Medical Center--16 micro-laparoscopies and 34 standard laparoscopies. Cases selected for review were limited to patients undergoing surgical contraception and not requiring additional, concurrent procedures. Laparoscopic surgical sterilization was performed using a double-puncture technique with silicone band application. In each case either a standard, 10-mm laparoscope or a 2-mm micro-laparoscope was used, and the procedure was performed under general anesthesia. Postoperative pain management was achieved by nonsteroidal antiinflammatory drugs and/or narcotic analgesia. All cases were performed by residents under faculty supervision. Medical records and hospital billing records were reviewed, and a standardized telephone interview was conducted to assess postoperative quality of life and patient satisfaction. RESULTS: Both techniques were comparable in cost effectiveness. There was no significant difference in operating room time, average operating room costs, average ancillary department costs, instrument and supply costs, or length of stay. Postoperative discomfort was significantly less with microlaparoscopy (P = .05), and patient satisfaction was higher in the microlaparoscopy group. CONCLUSION: Microlaparoscopy and the standard laparoscopic approach for surgical sterilization are associated with similar hospital charges. Postoperative pain and overall patient satisfaction were significantly better with microlaparoscopy than standard laparoscopy.

Partner effects on a woman's intention to conceive: 'not with this partner'.

CONTEXT: Current definitions of pregnancy intention that are useful at aggregate levels are weak at the individual level. This is especially true in social contexts where childbearing and pregnancy often occur within casual or transient relationships. METHODS: Extensive data on lifetime partnerships and sexual behaviors, including pregnancies and births, from 250 low-income women who had experienced a total of 839 pregnancies are used to explore correlates of intention to conceive, as well as the extent to which women attribute their intentions to a current partnership. RESULTS: Some 57% of reported pregnancies were unintended. Overall, 21% of the women had not wished to conceive at least one of their pregnancies with the partner who impregnated them; that proportion rose to 33% among women who had had only unintended pregnancies. Even among women who had had no unintended pregnancies, 18% had had at least one conception that they had not wanted with their partner at the time of conception. Women were less likely to say they had not wanted to conceive with a particular partner if they were living with that partner than if they were not. The likelihood of not having wanted a pregnancy with a given partner rose with the lifetime number of serious partners. Pregnancies that were not wanted with a particular partner were more than twice as likely to end in abortion as were those that were (33% vs. 14%). CONCLUSIONS: Among these women, the desire to avoid childbearing relates more to the couple involved in the conception than to abstract notions of completed family size. It would therefore be useful to include items pertaining to partner relationships in future studies of pregnancy intention.

Derivation of pluripotent stem cells from cultured human primordial germ cells.

Human pluripotent stem cells would be invaluable for in vitro studies of aspects of human embryogenesis. With the goal of establishing pluripotent stem cell lines, gonadal ridges and mesenteries containing primordial germ cells (PGCs, 5-9 weeks postfertilization) were cultured on mouse STO fibroblast feeder layers in the presence of human recombinant leukemia inhibitory factor, human recombinant basic fibroblast growth factor, and forskolin. Initially, single PGCs in culture were visualized by alkaline phosphatase activity staining. Over a period of 7-21 days, PGCs gave rise to large multicellular colonies resembling those of mouse pluripotent stem cells termed embryonic stem and embryonic germ (EG) cells. Throughout the culture period most cells within the colonies continued to be alkaline phosphatase-positive and tested positive against a panel of five immunological markers (SSEA-1, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) that have been used routinely to characterize embryonic stem and EG cells. The cultured cells have been continuously passaged and found to be karyotypically normal and stable. Both XX and XY cell cultures have been obtained. Immunohistochemical analysis of embryoid bodies collected from these cultures revealed a wide variety of differentiated cell types, including derivatives of all three embryonic germ layers. Based on their origin and demonstrated properties, these human PGC-derived cultures meet the criteria for pluripotent stem cells and most closely resemble EG cells.

Cost-effectiveness of treatment for drug-abusing pregnant women.

Neonatal intensive care unit (NICU) and drug treatment costs were compared in two groups of pregnant drug abusing women: 100 admissions to a multidisciplinary treatment program and active in care at the time of delivery and 46 controls not entering drug treatment. Clinical measures included urine toxicology at delivery, infant birthweight. Apgar scores and need for and duration of NICU services. Cost measures included drug treatment and NICU costs. Treatment patients showed better clinical outcome at delivery, with less drug use and higher infant estimated gestational age, birthweight and Apgar scores. Infants of treatment patients were also less likely to require NICU services and, for those that did, had a shorter stay. When total cost was examined (including drug treatment), mean net savings for treatment subjects was $4644 per mother/infant pair. The study demonstrates the cost-effectiveness of treatment for pregnant drug abusing women, with savings in NICU costs exceeding costs of drug treatment.

Contraceptive outcomes among post-partum and post-abortal adolescents.

Between January 1992 and January 1993, there were 280 teens (ages 13-18) who either delivered a baby or terminated a pregnancy at Johns Hopkins Bayview Medical Center. Of these, 92 chose to contracept with Norplant implants, and 188 chose another method including "no" method. In July 1993, telephone interviews were conducted with 37 of those who chose Norplant implants and 41 of the non-Norplant implants users. After 1 year, 47% of oral contraceptive (COC) users had discontinued the method compared to only 16% of Norplant implants users (P < 0.03). Reasons for discontinuation centered on side effects for both groups but with some COC and condom users, discontinuing use due to "forgetfulness" or failure (pregnancy). Among the COC group (which was the most common choice after Norplant implant), 25% of the adolescents had experienced a subsequent unplanned pregnancy compared to 0% of the Norplant implant group (P < 0.01). Norplant implants were clearly an acceptable and effective contraceptive for these post-partum and post-abortal teens, who articulated a high motivation to avoid a subsequent unplanned pregnancy. However, it is clearly not the only method teens will choose to use, and more attention must be paid to adequate counseling of those choosing another method.

Obstetrics and gynecology.

Emergency contraception could reduce the number of unintended pregnancies by 1.7 million. The best approach to oral contraception is education and not limitation, but it is unlikely that there will be any increase in contraceptive availability in the near future. Routine ultrasonography in low-risk pregnancies does not appear to be cost-effective.

Comparison of adolescent and adult experiences with Norplant levonorgestrel contraceptive implants.

OBJECTIVE: To compare acceptability, tolerance of side effects, and continuation rates among adolescent and adult Norplant accepters. METHODS: An 18-month observational study was conducted of 136 adolescents and 542 adults who received Norplant at the Francis Scott Key Medical Center in Baltimore, Maryland. Data were collected from the following: a self-administered history form completed at the preinsertion visit, a self-administered follow-up form completed at routine follow-up visits, problem-visit chart review, and telephone contact for patients noncompliant with follow-up appointments. RESULTS: The adolescents ranged in age from 13-18 years (mean 16.4), and adults ranged in age from 19-46 (mean 24.7). The mean parity among teenagers was 1.4; among adults, 3.2. Thirty-nine percent of teenagers and 64% of adults had had one or more therapeutic abortions. Forty percent of adolescents and 47% of adults reported at least one contraceptive failure in the past. Both adolescent and adult Norplant accepters made few telephone calls or problem visits because of complaints or side effects. Compliance with routine annual follow-up was poor for adolescents (24 of 136, 18%) and adults (72 of 542, 13%). Follow-up of noncompliant patients revealed low rates of implant removal. Fifteen adolescents (11%) and 60 adults (11%) had Norplant removed. The most common reasons for removal included irregular bleeding, weight gain, headaches, and desire for pregnancy. CONCLUSIONS: Implant acceptability, continuation, and tolerance of side effects were high and comparable among adolescent and adult accepters. Initial implant users were primarily adolescents or adults who had experienced problems with other forms of reversible contraception. Adherence to scheduled follow-up appointments was poor, regardless of age.

Preliminary experience with Norplant in an inner city population.

Norplant, the five-year subdermal contraceptive system, is the first implantable contraceptive method approved for general use in the United States. We describe the preliminary experiences of 246 U.S. women who accepted Norplant between April, 1991 and September, 1991. Norplant was well accepted among this diverse general population. Intensive counselling about side effects, especially menstrual changes, is crucial for patient satisfaction. Although 48% of acceptors experienced menstrual cycle changes and 70% experienced at least one side effect, phone calls and unscheduled visits for problems were infrequent. Adequate counselling about side effects obviates the need for a routine follow-up visit one month after insertion.

PIP: Between April and October 1991 in Baltimore, Maryland, family planning providers tried to follow 246 13-42 year old women at a clinic at the Francis Scott Key (FSK) Medical Center for 3 months who accepted the levonorgestrel-releasing implant Norplant to evaluate its acceptability and effectiveness among a high-risk population. 56% of the women were Black and 41% White. 69% were single. Most were interval gynecologic patients (109), but many were postabortion patients (97). The providers could only follow 108 women. Reasons for unscheduled visits were insertion site tenderness, amenorrhea, and removal. At 1 month, 70 % had at least 1 side effect. 48% had irregular bleeding 1-2 months after insertion. Other side effects included headache (49%), acne (24%), weight gain (22%), increased appetite (19%), and dizziness (18.5%). The 24-hour telephone hotline had only received 38 problem calls, all of which were from FSK Norplant patients. More than 50% of the calls were about menstruation concerns. Reasons for removal included pressure to receive Norplant, increased acne, headaches and prolonged bleeding, and postinsertion site problems. 1 woman became pregnant, but it occurred before insertion. She underwent an abortion and continued to use Norplant. 78% of the women considered Norplant to be excellent and 14% considered it to be good. 95% would recommend it to others. 69% reported convenience to be the best thing about Norplant and 22% said it was pregnancy prevention. Worst things were irregular bleeding (26%) and progestin-related side effects (e.g., headaches and weight gain) (19%). 35% did not consider anything to be bad about Norplant. 64% had at least some apprehension before insertion, the major reasons being fear of needles (48%) and of pain (37%). Prior to insertion, just 37% were worried about potential side effects. The providers thought that the routine follow-up visit at 1 month was not cost-effective and provided no specific clinical benefit. They advocated adequate counseling about side effects to take the place of the follow-up visit.

Oral contraceptives and breast disease.

Epidemiologic data support the hypothesis that the types of OCs used before the mid-1970s protected against most forms of benign breast disease. It is unclear whether current low-dose progestogen OCs will confer the same protection. Further studies are necessary to clarify this. For breast cancer, the relationship is more complex. It is possible that prolonged use of high-dose OCs exert a small increased risk for breast cancer development in women before age 45. Furthermore, prolonged use before a first term pregnancy may result in a small increase in risk for breast cancer before age 45. Studies evaluating the effect of current low-dose OCs are necessary to elucidate what, if any, effect they may have on breast cancer development. Furthermore, as our population ages, studies will be able to determine what effect, if any, may be present in women over age 60, those women with the highest underlying risk of breast cancer. And finally, more research of basic breast tissue physiology and the effect of endogenous and exogenous hormones on this complex organ is needed.

PIP: This review covers the epidemiology of benign and neoplastic breast disease, the theoretical effects of steroids on the breast, and the effects of oral contraceptives on both. Breast cancer has been increasing since the 1940s in older U.S. women, killing about 44,500 of the 175,000 new cases per year. In addition fibrocystic breast disease may affect up to 50% of premenopausal women, resulting in 500,000 biopsies, of which 10% are cancerous, 33% of those in post-menopausal women. The involvement of steroids in development of the human breast, and in breast cancer, is reviewed. The breast does not complete its development until the end of the 1st pregnancy. The terminal ductal cells, from which breast cancers form, are susceptible to stimulation by progestins in nulliparas. Progestins, at least in the high doses used in early orals, protect against benign breast disease. Inadequate amounts of progesterone, however, as in irregular cycles, seem to predispose to breast cancer. Epidemiologic studies of oral contraceptive use and breast cancer are reviewed under the studies of oral contraceptive use and breast cancer are reviewed under the headings of overall results, age, age 45, parity, use before 1st pregnancy, use at young ages, latent effect, hormone formulation, associated benign breast disease, association with other neoplasms, and receptor status. There are slightly increased risks for cancer before age 45 for long-term use of pills before the 1st term pregnancy, although the data are not wholly consistent, in that the specific sub-groups of women affected differ in different studies. There is no clear evidence for a latent effect, that is, appearance of cancer 20-30 years after stopping the pill. Nor is there evidence of breast cancer linked to any specific pill type, nor with benign breast disease, nor with endometrial cancer. The reason for rising breast cancer rates is still unknown. The absolute number of increased cases related to oral contraceptives is insufficient to affect national rates. It is possible that the inconsistent findings in epidemiological studies reflects use of high-dose pills in the 1960s and early 1970s. The contraceptive and non-contraceptive benefits of the pill are more important for women's health than the potential cases of breast cancer in young women who took them for prolonged durations.

Fertility after contraception or abortion.

There is a very small correlation, if any, between the prior use of OCs and congenital malformations, including Down's syndrome. There are few, if any, recent reports on masculinization of a female fetus born to a mother who took an OC containing 1 mg of a progestogen during early pregnancy. However, patients suspected of being pregnant and who are desirous of continuing that pregnancy should not continue to take OCs, nor should progestogen withdrawal pregnancy tests be used. Concern still exists regarding the occurrence of congenital abnormalities in babies born to such women. The incidence of postoperative infection after first trimester therapeutic abortion in this country is low. However, increasing numbers of women are undergoing repeated pregnancy terminations, and their risk for subsequent pelvic infections may be multiplied with each succeeding abortion. The incidence of prematurity due to cervical incompetence or surgical infertility after first trimester pregnancy terminations is not increased significantly. Asherman's syndrome may occur after septic therapeutic abortion. The pregnancy rate after treatment of this syndrome is low. The return of menses and the achievement of a pregnancy may be slightly delayed after OCs are discontinued, but the fertility rate is within the normal range by 1 year. The incidence of postpill amenorrhea of greater than 6 months' duration is probably less than 1%. The occurrence of the syndrome does not seem to be related to length of use or type of pill. Patients with prior normal menses as well as those with menstrual abnormalities before use of OCs may develop this syndrome. Patients with normal estrogen and gonadotropin levels usually respond with return of menses and ovulation when treated with clomiphene. The rate for achievement of pregnancy is much lower than that for patients with spontaneous return of menses. The criteria for defining PID or for categorizing its severity are diverse. The incidence of PID is higher among IUD users than among patients taking OCs or using a barrier method. The excess risk of PID among IUD users, with the exception of the first few months after insertion, is related to sexually transmitted diseases and not the IUD. Women with no risk factors for sexually transmitted diseases have little increased risk of PID or infertility associated with IUD use. There appears to be no increased risk of congenital anomalies, altered sex ratio, or early pregnancy loss among spermicide users. All present methods of contraception entail some risk to the patient. The risk of imparied future fertility with the use of any method appears to be low.(ABSTRACT TRUNCATED AT 400 WORDS)

PIP: This is a comprehensive review of the risk of infertility or adverse effects on pregnancy outcome, such as chromosomal or congenital birth defects, amenorrhea, pelvic inflammatory disease (PID), or spontaneous abortion, after use of oral contraceptives, IUDs, induced abortion or spermicides. The sequelae reported for orals are chromosomal abnormalities, the VACTERL anomalies, masculinization of female fetus, Down's syndrome and post-pill amenorrhea. Several large studies found no increased risks for birth defects, although the risk of malformations when pregnant women inadvertently take the pill in early pregnancy was high in 1 of 2 such studies. Masculinization was reported with high dose combined hormone treatment and in 2 infants of a woman who took Enovid. the bulk of recent studies on secondary amenorrhea indicate that it is rare, but just as likely to occur in women with prior normal or abnormal menstrual patterns. One study found that amenorrhea is 7.7 times more likely to develop in women who took the pill to regulate menses. It is recommended that women with amenorrhea be screened for pituitary tumors and counseled before prescribing pills, and that those who fail to ovulate after stopping the pill be treated at least 6 months with clomiphene. A massing of all studies on the impact of 1st trimester induced abortion on subsequent fertility, premature delivery and spontaneous abortion, shows all relative risks around 1.0. After multiple abortions, the results are conflicting. In contrast, prior series analyzing illegal abortion have an unquestioned adverse effect on fertility and pregnancy outcome. Asherman's syndrome, a rare disorder of intrauterine adhesions, menstrual abnormalities, infertility and habitual abortion, has been associated with D & C abortion concurrent with pelvic sepsis, or traumatic pregnancy with D & C. This condition can be treated with moderate success. The bulk of IUD studies conclude that there is no overall decrement in fertility, while some disaggregated studies point the Dalkon shield as a higher risk and copper IUDs as a lower risk. PID and its consequences are now considered related to the immediate post-insertion time frame, or specifically to women who are at risk of contracting sexually transmitted disease, i.e., those with multiple partners, those with prior PID and nulliparas. Comprehensive review of current large series on spermicides shows no relationship between their use and spontaneous abortion or congenital malformation.

Contraception.

PIP: The combined progestogen/estrogen oral contraceptive is the most common form of contraception in the US. They contain 1 of 5 synthetic progestogens (derived from 19-nortestosterone) and 1 of 2 estrogens. 3 new progestin compounds are in use in Europe and Asia. They are norgestimate, desogestrel, and gestodene. Estrogen seems to cause vascular complications. Progestin may cause atherosclerosis. Desogestrel and gestodene were studied for 6 months. They have little effect on glucose and lipid metabolism. Triphasal ethinyl estradiol/levonorgestrel and ethinyl estradiol/norethindrone (Ortho Novum 7/7/7) were compared in a 12-month prospective clinical trial. There seems to be no consensus of a pattern of increased breast cancer associated with oral contraceptive use. The UK National Case Control Study Group analyzed women younger than 36 years at the time breast cancer was diagnosed. 91% of their cohort had used pills. A significant trend was found when risk was analyzed with duration of taking pills. Women who had taken the pill for 4 years had no increased risk of breast cancer. However, there was an increased relative risk of 1.7 (P0.001) for women who took pills for more than 8 years. Among women using the pill for 8 years, the relative risk was 2.6 (p0.0001). AMong women using pills with 50 ug. of estrogen, the trend to increased risk was (P0.10). The 1988 National Survey of adolescent males showed that 60% of men never married were active sexually. Among 17- to 19-year-old-men who live in metropolitan areas, condom use has more than doubled, compared with 1979. In 1988, a "new" copper-containing IUD was approved for use in the US by the Food and Drug Administration, the Copper T 380 A. Pregnancy rates are less with this than with older devices. IUDs may cause pelvic inflammatory disease with resulting tubal infertility. However, the risk was overstated earlier. Women who have only 1 sexual partner in their lifetime had no significant risk of tubal infertility. "lost" IUDs continue to be a problem.^ieng