- Email: [email protected]
Spotlight on obstetrics
SPOTLIGHT ON OBSTETRICS
noted between groups with respect to the other outcomes studied. Level I.
smoking status, and socioeconomic status. Level II-3.
● ● ●
● ● ●
Commentary: The authors of this study recognized the fact that serious maternal morbidity was slightly increased in their study in the planned cesarean delivery group. They also acknowledged that a policy of planned cesarean delivery might affect future childbearing because of the complications associated with repeat cesarean delivery, such as infection, bleeding, thromboembolic problems, and surgical trauma, and because of the physical effects that cesarean delivery might have on reproductive organs. However, they did demonstrate that at 3 months postpartum there was little difference in outcome between women in the planned cesarean group and those in the vaginal delivery group, and that both groups were satisfied with their type of delivery. It is therefore likely that the choice of type of delivery for a breech presentation will probably continue to depend on the perceived safety of the fetus. The results of this study favored planned cesarean delivery and the trend worldwide is in that direction, although it is not yet known if this is the best choice for mother and fetus.
Commentary: This large and carefully performed study clearly demonstrated that the risk of obstetric complications, neonatal morbidity, and perinatal mortality are greatest in nulliparous women and women of gravida 4 and greater. Previously, grand-multiparity and its attendant risks were considered to begin with para 5. The authors dispelled this notion and demonstrated that the risks of multigravity begin with para 4. Whereas couples in most developed countries have tended to have smaller families, it is still important for ob/ gyns to realize that different risks arise with increased parity and to anticipate the problems that may occur.
Morton A. Stenchever, MD Editor
Maternal Outcome 3 Months After Breech Birth Hannah ME, Hannah WJ, Hodnett ED, et al, for the Term Breech Trial 3-Month Follow-up Collaborative Group. Outcomes at 3 months after planned cesarean vs planned vaginal delivery for breech presentation at term. JAMA 2002;287:1822–31.
Synopsis: This study was a follow-up of the Term Breech Trial that was carried out between 1997 and 2000 on 2088 women with a breech presentation who were randomized to either planned cesarean delivery or planned vaginal birth. The Term Breech Trial was carried out in 121 centers in 26 countries; about half of these were developed nations and about half were developing nations. The studies originally found a significant reduction in adverse perinatal outcomes with planned cesarean delivery compared with planned vaginal delivery. However, maternal morbidity increased during the first 6 weeks in the cesarean group. The current study looked at 1940 women enrolled at 110 centers who were followed up at 3 months postpartum and were asked to complete a questionnaire. The questionnaire was returned by 82.3% of the women; 798 of these had been randomized to planned cesarean delivery and 798 to planned vaginal delivery. The study investigated the women’s responses to breast-feeding; infant health; ease of caring for the infant and adjusting to being a new mother; sexual relations and relationships with the husband/partner; pain; urinary, flatal, and fecal incontinence; depression; and views regarding the childbirth experience and study participation. Women in the planned cesarean delivery group were less likely to report urinary incontinence than were respondents in the planned vaginal delivery group (4.5% versus 7.3%). Incontinence of flatus was not different between the two groups but was less of a problem in the planned cesarean delivery group when it occurred. Otherwise, no other differences were ©2002 by the American College of Obstetricians and Gynecologists Published by Elsevier Science Inc. 1085-6862/02/$6.00
Parity and Pregnancy Outcomes Bai J, Wong FWS, Bauman A, Mohsin M. Parity and pregnancy outcomes. Am J Obstet Gynecol 2002;186:274 – 8.
Synopsis: The authors performed a cross-sectional analysis of 510,989 women who delivered in New South Wales, Australia between 1992– 1997. Pregnancy outcomes were compared by parity with attention to obstetric complications, neonatal morbidity, and perinatal mortality. Nulliparous women and grand-multipara women had significantly more obstetric complications, neonatal morbidity, and perinatal mortality than did women of parity 1, 2, or 3. By evaluating each parity separately, the authors demonstrated that grandmultiparity should begin at 4, not 5, as has been previously taught. All their data were corrected for potential confounders, including age, maternal
Outcome After Elective Labor Induction in Nulliparas Cammu H, Martens G, Ruyssinck G, Amy JJ. Outcome after elective labor induction in nulliparous women: A matched cohort study. Am J Obstet Gynecol 2002;186: 240 – 4.
Synopsis: The authors performed a matched cohort study comparing 7683 nulliparous women undergoing elective labor induction in 80 labor services in northern Belgium with 7683 matched controls who delivered spontaneously. They found a cesarean delivery rate of 9.9% versus 6.5%, instrumental delivery rate of 31.6% versus 29.1%, epidural anesthesia use of 80% versus 58%, and transfer of the infant to the neonatal ward of 10.7% compared with 9.4%, for the study and control groups, respectively. All these differences were statistically significant. In most cases cesarean delivery was necessary because of failure to progress in the first stage of labor. The difference in the neonatal ward admission rate was attributed to the higher admission rate for maternal convenience when the woman had had a cesarean delivery, and reflected the rates of cesarean delivery in the two groups. The number of infants with congenital anomalies and the number of neonatal deaths were equal in the two groups. Academic teaching
October 2002
●
ACOG CLINICAL REVIEW
●
3
hospitals and referral hospitals recorded higher rates of elective induction than community hospitals. Level II-2. ● ● ●
Commentary: The authors demonstrated in a carefully performed, matched cohort study that elective induction of labor carried a higher risk of cesarean and instrument delivery. Although the patients were low-risk nulliparous women at term and most of the inductions were performed for convenience, selection bias is unavoidable when comparing elective induction with spontaneous labor. Within the cohort of women who underwent elective induction, there were bound to be some who may have had difficulty either initiating labor or having a normal labor. This difficulty was probably less likely in women who presented in spontaneous labor. Likewise, women having an elective induction, as the authors showed, were more likely to have epidural anesthesia. It is not known if the epidural anesthesia changed the management of labor in these women, but it may have been a factor. The authors showed that 1 in 29 induced labors ended in an additional cesarean over what could have been expected had labor begun spontaneously. The greater likelihood of admission to the neonatal intensive care unit also led to a potential increase in the total cost associated with the practice of induced labor. The question must be asked: Is the convenience worth the increased cost?
Metformin Reduces GDM in Women With PCOS Glueck CJ, Wang P, Kobayashi S, Phillips H, Sieve-Smith L. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril 2002;77:520 –5.
Synopsis: Metformin is an oral antihyperglycemic drug used worldwide for the treatment of type 2 diabetes that has recently been found to facilitate ovulation in some women with polycystic ovary syndrome (PCOS). The authors performed a prospective study on 33 nondiabetic women with PCOS who conceived while taking 4
●
ACOG CLINICAL REVIEW
●
metformin and delivered live infants (this group had had 12 previous pregnancies without metformin). Of 33, 28 took the drug through delivery. They also studied retrospectively 39 nondiabetic women with PCOS who had live birth pregnancies without metformin therapy. In the study group, 1 of 33 (3%) developed gestational diabetes, compared with 8 of 12 (67%) during the previous pregnancies without metformin therapy. Of the 39 patients who did not take metformin, gestational diabetes occurred in 14 of 60 pregnancies. Most of the patients in both groups were very obese with body mass index (BMI) of 33.5 kg/m2 and 33.6 kg/m2 in the prospective and retrospective cohorts, respectively. Fasting insulin levels, insulin resistance, and insulin secretion were also high in both groups. In 21 of 33 patients in the study group who conceived while taking metformin, complete data were available for weight, BMI, insulin resistance, and insulin secretion. These patients showed a median weight decrease from 94 to 88 kg, a BMI decrease from 33.6 kg/m2 to 29.6 kg/m2, and a decrease in insulin levels, insulin resistance, and insulin secretion, all of which were statistically significant after metformin therapy. There were no major fetal malformations or fetal hypoglycemia in the 34 live births of the 33 patients who were treated. Level II-2.
PCOS will decrease the risk of subsequent development of type 2 diabetes, but the benefits of preventing gestational diabetes appear to be real, and this therapy should be considered, particularly in obese women with PCOS.
Risk of Birth Defects After Intracytoplasmic Sperm Injection and IVF Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 2002;346:725–30.
Synopsis: The authors in this western Australian study assessed the prevalence of major birth defects diagnosed by 1 year of age in 4000 randomly selected infants conceived naturally, 301 infants conceived with intracytoplasmic sperm injection, and 837 infants conceived with in vitro fertilization (IVF). Major birth defects were recorded in 8.6% of the infants conceived by intracytoplasmic sperm injection, 9.0% conceived with IVF, and 4.2% conceived naturally. After adjustment for maternal age, parity, sex of the infant, and correlations between siblings, the odds ratio (OR) for having a major birth defect was still 2.0 for infants conceived by intracytoplasmic sperm injection or IVF compared with controls. Level II-2.
● ● ●
● ● ●
Commentary: As PCOS affects 5–10% of women and is considered a risk factor for gestational diabetes, it is exciting to find a strategy that may prevent gestational diabetes from occurring in women with polycystic ovary disease. Metformin has previously been shown to reduce the spontaneous miscarriage rate in diabetic women, women with gestational diabetes, and women with PCOS who are not diabetic by as much as 10-fold, and to date the drug has not been shown to be teratogenic. The ability of metformin to reduce weight, BMI, insulin levels, insulin resistance, and insulin secretion before conception as shown in the 21 women in this study also offers a considerable benefit. It is not yet known if metformin treatment for women with
Commentary: The data presented in this study were of interest, especially since the OR for the development of major birth defects was double for infants conceived by assisted reproductive technology compared with controls. Nevertheless, most infants conceived by assisted reproductive technology did not have major birth defects. Many factors can probably account for the increased risk, including older parental age, the reason for assisted reproductive technology, and the effects of the biological manipulation associated with assisted reproductive technology. The information presented should be given to couples who are contemplating the use of assisted reproductive technology as they attempt to make an informed judgment about their course of action.
October 2002
©2002 by the American College of Obstetricians and Gynecologists Published by Elsevier Science Inc. 1085-6862/02/$6.00
Erythromycin Not a Risk Factor for Newborn Pyloric Stenosis Louik C, Werler MM, Mitchell AA. Erythromycin use during pregnancy in relation to pyloric stenosis. Am J Obstet Gynecol 2002;186:288 –90.
Synopsis: A recent investigation by the US Centers for Disease Control and Prevention concluded that neonates who received erythromycin might be at increased risk for pyloric stenosis. The authors therefore carried out a study using the database of the Slone Epidemiology Unit at Boston University, which contained information on 1044 infants with pyloric stenosis. They compared these infants with two control groups composed of 1704 infants without malformations and 15,356 infants with a wide range of other malformations. They found no relationship between maternal ingestion of erythromycin during weeks 1–24, 25– 40, or 32– 40 and the development of pyloric stenosis when compared with the control groups. Level II-2. ● ● ●
Commentary: The authors were correct in attempting to identify a relationship between erythromycin use during pregnancy and the development of pyloric stenosis in the infant, in light of the CDC finding that erythromycin treatment of neonates may have led to the development of pyloric stenosis. Erythromycin is used routinely in pregnancy for treating many maternal infections and does cross the placenta. Therefore, the finding that maternal ingestion of erythromycin any time during pregnancy was not associated with infant development of pyloric stenosis is somewhat reassuring, although not conclusive.
Q Fever During Pregnancy Raoult D, Fenollar F, Stein A. Q fever during pregnancy: Diagnosis, treatment, and follow-up. Arch Intern Med 2002;162: 701– 4.
Synopsis: Q fever is caused by an intracellular bacterium Coxiella burnetii, an infection that occurs worldwide. The organism infects mammals, birds, domestic animals, and pets, and ©2002 by the American College of Obstetricians and Gynecologists Published by Elsevier Science Inc. 1085-6862/02/$6.00
is generally acquired by inhalation of aerosols from the amniotic fluid or placenta of infected animals. In female animals, infection with this agent is associated with abortions, infertility, and low birth weight (LBW) offspring. During acute infection, granuloma formation occurs in infected viscera and IgM and IgG antibodies develop. The authors noted from the sparse literature on the topic that 38% of human pregnancies in which Q fever was contracted ended in abortions or neonatal death, and 33% in premature births with LBW infants; no abnormalities occurred in only 29% of pregnancies. The authors added data on 17 patients and noted that the outcome of pregnancy depended on the trimester of infection. Abortion occurred in 100% of seven patients who were infected during the first trimester. They noted that the only effective bacteriocidal regimen in vitro is concurrent doxycycline and chloroquine use, but since doxycycline is not advised during pregnancy, they used co-trimoxazole and continued it throughout pregnancy. As C burnetii is excreted in milk, patients were advised against breast-feeding. Level III. ● ● ●
Commentary: Q fever during pregnancy is probably rare in the United States, but it is reasonable for ob/gyns to acquaint themselves with this disease and the severe effect that it can have on gestation. Q fever has been associated with endocarditis and with chronic infection, and the information that the authors offered is a useful review of this condition.
Cocaine Exposure and Preterm Birth Savitz DA, Henderson L, Dole N, Herring A, Wilkins DG, Rollins D, et al. Indicators of cocaine exposure and preterm birth. Obstet Gynecol 2002;99:458 – 65.
Synopsis: The authors performed a nested case-control study in a cohort of 2611 black and white women enrolled in prenatal care in North Carolina. Cocaine exposure was ascertained by self-report in 263 cases and 612 controls, by urine assay at 24 –29 weeks’ gestation in 226 cases and 564
controls, and postpartum in 160 cases and 408 controls. Postpartum hair assays were positive in 169 cases and 435 controls. In this study, cases were women who delivered preterm and controls delivered at term. The authors found that cocaine exposure was identified in 2% based on self-report, 5– 6% based on urine assay, and 13– 15% based on hair assays. Black ethnicity, lower education levels, and poverty were strongly predictive of positive hair assays. Hair cocaine and benzoylecgonine levels were not associated with preterm birth, except for a somewhat stronger association in births occurring before 34 weeks’ gestation compared with those occurring before 37 weeks’ gestation. Level II-2. ● ● ●
Commentary: As the authors correctly pointed out, self-reporting of the use of an illegal drug was probably not accurate. Searching for evidence of cocaine and its metabolite in urine is probably useful only if the drug has been used within 3 days of the test. However, hair assays may be accurate after several months and provide a more complete assessment. The authors did not determine with certainty if cocaine is damaging to the fetus or the pregnancy, but the data from this study may suggest some association between current use and early prematurity. The study did point out strong demographic predictors of exposure that suggest areas in which intervention efforts can be targeted.
Birth Weight in Infants Conceived by Use of Assisted Reproductive Technology Schieve LA, Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS. Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med 2002;346:731–7.
Synopsis: The authors used population-based data to compare the rates of low birth weight (LBW) (ⱕ 2500 g) and very low birth weight (VLBW) (⬍ 1500 g) among infants who were conceived with assisted reproductive technology with the rates of LBW and VLBW among infants born in the general population. They
October 2002
●
ACOG CLINICAL REVIEW
●
5
compared 42,463 infants born in 1996 –1997 and conceived with assisted reproductive technology with 3,389,098 infants born in the United States in 1997; births to women 20 years of age and older were considered. The risk of LBW in infants conceived with assisted reproductive technology was found to be 2.6 times greater than that of the general population (95% confidence interval 2.4, 2.7). Although only 0.6% of infants born to women over the age of 20 in 1997 were conceived with assisted reproductive technology, these infants accounted for 3.5% of LBW and 4.3% of VLBW infants. No difference in rate of LBW was noted between twins conceived by assisted reproductive technology and those conceived spontaneously. The risk of term LBW infants remained elevated even when the authors corrected for various factors, but the risk of preterm LBW was no longer increased in analyses restricted to study infants who had been carried by presumably healthy women. The authors concluded that assisted reproductive technologies accounted for a disproportionate number of LBW and VLBW infants in the United States, in part because of the increase in multiple gestations, but also because of the higher rates of LBW among singleton infants conceived with this technology. Level II-2.
Sonographic Assessment of Cervical Length Soriano D, Weisz B, Seidman DS, Chetrit A, Schiff E, Lipitz S, et al. The role of sonographic assessment of cervical length in the prediction of preterm birth in primigravidae with twin gestation conceived after infertility treatment. Acta Obstet Gynecol Scand 2002;81:39 – 43.
Synopsis: In an attempt to evaluate the risk factors for preterm birth in primigravidae with twin gestations, the authors used transvaginal ultrasound between 18 and 24 weeks’ gestation to measure the length of the cervix in 54 prospectively enrolled twin pregnancies. Maternal age was 30.9 ⫾ 5.3 years (range 22– 46 years). Nine patients (20.5%) delivered before 34 weeks’ gestation and had a mean cervical length in the second trimester of 30.1 ⫾ 6.1 mm. Women who delivered after 34 weeks had a cervical length of 42.2 ⫾ 6.2 mm (P⬍.001). The authors concluded that cervical length longer than 35 mm predicted delivery after 34 weeks’ gestation with sensitivity of 88.5%, specificity of 88.9%, and positive and negative predictive values of 96.9% and 66.7%, respectively. There were no differences with respect to maternal age, body mass index, weight gain in pregnancy, smoking, or work during pregnancy between the two groups. Level III. ● ● ●
● ● ●
Commentary: The authors observed that women who conceived by assisted reproductive technology gave birth to an increased number of LBW and VLBW infants, both at term and preterm. Many factors affect a woman’s decision to undergo assisted reproductive techniques, including medical conditions that prevent couples from conceiving under normal circumstances. In addition, as the authors noted in their discussion, conception using assisted reproductive techniques involves a number of hormonal and other modifications of normal conception. The role of each of these factors is not known, but the cumulative effect is not surprising. Although most of these couples had serious reproductive problems, when conception occurred most had reasonable reproductive success. 6
●
ACOG CLINICAL REVIEW
●
Commentary: The information provided by this study is useful in assisting physicians to anticipate which patients with twin gestations may be at risk for premature delivery. However, the information may not assist the physician to determine what therapeutic course to follow. As the authors pointed out, 77.8% of patients who delivered prematurely had previously experienced premature contractions leading to cervical change, and had required treatment by tocolysis. In the group that delivered later, only two patients (5.7%) had had premature contractions. Therefore, the problem was unclear. Was premature delivery caused by premature labor due to the effect of cervical length or due to another factor, such as intrauterine infection? The data presented will probably not answer this question, and therefore it will still be necessary to
October 2002
determine management for patients with shortened cervical length on an individual basis.
Surgically Obtained Sperm Increases Risk of Gestational Hypertension and Preeclampsia Wang JX, Knottnerus AM, Schuit G, Norman RJ, Chan A, Dekker GA. Surgically obtained sperm, and risk of gestational hypertension and pre-eclampsia. Lancet 2002; 359:673– 4.
Synopsis: The authors compared the rates of preeclampsia and gestational hypertension in women who conceived by intracytoplasmic sperm injection using sperm that was surgically obtained from the epididymis with women who conceived by in vitro fertilization (IVF) or intracytoplasmic sperm injection with ejaculated sperm and who had been exposed to their partner’s sperm in seminal fluid. There were 1075 women in the IVF with ejaculated sperm group, 464 in the intracytoplasmic sperm injection with ejaculated sperm group, and 82 in the intracytoplasmic sperm injection with surgically obtained sperm group. Whereas the incidence of preeclampsia in the IVF with ejaculated sperm group and the intracytoplasmic sperm injection with ejaculated sperm group was the same (4%), the incidence was 11% in the group with intracytoplasmic sperm injection with surgically obtained sperm, an odds ratio (OR) of 3.10 (95% confidence interval [CI] 1.59, 6.73). For gestational hypertension, the OR in the group with intracytoplasmic sperm injection with surgically obtained sperm was 2.10 (95% CI 1.30, 3.62). The authors suggested that there is a protective effect of semen exposure to the later development of gestational hypertension and preeclampsia, and that these conditions may be associated with exposure to sperm cells or a factor in the ejaculate that is closely related to sperm. Level II-2. ● ● ●
Commentary: The cause of pregnancy-induced hypertension or preeclampsia is not known, but several different circumstances seem to be related to its development. The authors ©2002 by the American College of Obstetricians and Gynecologists Published by Elsevier Science Inc. 1085-6862/02/$6.00
presented yet another possibility: they found that gestational hypertension and preeclampsia were more common among women implanted with an oocyte fertilized with surgically obtained sperm, rather than ejaculated sperm. This study implied that sperm may be in some way responsible for the problem and that semen or seminal fluid may in some way be protective. Immunologic factors undoubtedly play at least some part in the development of pregnancy-induced hypertension and preeclampsia. The challenge now seems to lie in properly sorting out these factors.
SPOTLIGHT ON GYNECOLOGY
circulating tumor cells, respectively. Level II-2. ● ● ●
Commentary: The findings of this study implied that epithelial carcinoma cells metastasized early via the blood and were probably present at distant sites, at least on a microscopic basis, early in the natural history of the disease. Therefore, detecting them in the blood or bone marrow, which relates to factors such as when cells are excreted into the blood and to sampling considerations, had little effect on the prognosis of the disease. Treatment modalities must be able to affect cells at distant areas of the body; local treatment, no matter how complete, will probably not be enough in most cases to affect a cure.
Morton A. Stenchever, MD Editor
Ovarian Carcinoma Cells in Peripheral Blood and Bone Marrow Marth C, Kisic J, Kærn J, Trope´ C, Fodstad Ø. Circulating tumor cells in the peripheral blood and bone marrow of patients with ovarian carcinoma do not predict prognosis. Cancer 2002;94:707–12.
Synopsis: The authors studied 90 patients with histologically proven epithelial ovarian carcinoma for the presence of tumor cells in blood and in bone marrow. Blood was obtained from all 90 patients and bone marrow from 73 patients. Tumor cells were identified by a microbead coated with antibody MOC-31 that recognizes an epitope that is regularly expressed by ovarian carcinoma cells. Carcinoma cells were detected in the bone marrow in 21% of patients and in the peripheral blood of 12% of the patients. All patients with peripheral blood that was positive for tumor cells also had bone marrow-positive cells, but the reverse was not always the case. Detection was not related to stage, type of histology, grade, residual disease, or CA 125 tumor marker concentration. Detection of tumor cells in peripheral blood and/or bone marrow was also not related to overall prognosis, as the overall survival rate was 25 and 28 months for patients with and without ©2002 by the American College of Obstetricians and Gynecologists Published by Elsevier Science Inc. 1085-6862/02/$6.00
Race Differences Associated With Estrogen Receptor Isoform Profiles in Breast Tumors Poola I, Clarke R, DeWitty R, Leffall LD. Functionally active estrogen receptor isoform profiles in the breast tumors of African American women are different from the profiles in breast tumors of Caucasian women. Cancer 2002;94:615–23.
Synopsis: Because black women seem to develop highly aggressive breast tumors and experience a mortality rate that is approximately three times higher than other populations, the authors wanted to determine if aggressive tumor biology could be related to distinct alterations in the estrogen receptor (ER) isoforms, specifically ER isoform mRNA, ER␣ wild type, ER wild type, ER␣ exon 3⌬ and ER␣ exon 5⌬. They compared the expression of these isoforms in both tumor tissue and matched normal tissue from 24 patients. They found that the ER isoform, which is thought to be protective, was decreased significantly compared with matched normal tissue, and that active ER␣ exon 5⌬ and the dominant negative ER␣ exon 3⌬ mRNA levels were higher in tumor tissue than in matched normal tissue. They noted that these changes were distinct from the alterations that had been observed previously in tumors
from white patients and believed that these differences demonstrated a biological reason for the increased tumor aggressiveness and associated mortality of breast cancer seen in black women. Level II-1. ● ● ●
Commentary: The authors of this study offered an interesting observation. Studies that have considered the higher mortality rate from breast cancer in black women compared with white and Hispanic women and have corrected for the late-stage of the disease at the time of diagnosis frequently seen in black women, low socioeconomic status, and limited access to medical facilities and services, still found a noncontrollable difference in tumor aggressiveness and mortality rates. These findings suggested that there were also biological implications, some of which the authors of the current study appeared to have demonstrated. Tumors in black women seem to be characterized by an elevated level of constitutively active ER ␣ exon 5⌬ dominant negative ER␣ exon 3⌬ mRNA and an increased ER␣-to-ER ratio due to a decrease in the ER mRNA levels. These findings were different from those in white women and should be helpful to clinicians as they plan management for black women with breast cancer. It should also be useful information for individuals who plan surveillance programs in order to facilitate the diagnosis of breast cancer as early as possible in black women.
GnRH Agonist and Add-Back Therapy for Endometriosis Surrey ES, Hornstein MD, for the Add-Back Study Group. Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: Long-term follow-up. Obstet Gynecol 2002;99:709 –19.
Synopsis: This study was a posttreatment follow-up analysis of a randomized, double-masked, placebo-controlled 1-year trial in which four groups of patients with endometriosis were treated with the GnRH agonist
October 2002
●
ACOG CLINICAL REVIEW
●
7
noted between groups with respect to the other outcomes studied. Level I.
smoking status, and socioeconomic status. Level II-3.
● ● ●
● ● ●
Commentary: The authors of this study recognized the fact that serious maternal morbidity was slightly increased in their study in the planned cesarean delivery group. They also acknowledged that a policy of planned cesarean delivery might affect future childbearing because of the complications associated with repeat cesarean delivery, such as infection, bleeding, thromboembolic problems, and surgical trauma, and because of the physical effects that cesarean delivery might have on reproductive organs. However, they did demonstrate that at 3 months postpartum there was little difference in outcome between women in the planned cesarean group and those in the vaginal delivery group, and that both groups were satisfied with their type of delivery. It is therefore likely that the choice of type of delivery for a breech presentation will probably continue to depend on the perceived safety of the fetus. The results of this study favored planned cesarean delivery and the trend worldwide is in that direction, although it is not yet known if this is the best choice for mother and fetus.
Commentary: This large and carefully performed study clearly demonstrated that the risk of obstetric complications, neonatal morbidity, and perinatal mortality are greatest in nulliparous women and women of gravida 4 and greater. Previously, grand-multiparity and its attendant risks were considered to begin with para 5. The authors dispelled this notion and demonstrated that the risks of multigravity begin with para 4. Whereas couples in most developed countries have tended to have smaller families, it is still important for ob/ gyns to realize that different risks arise with increased parity and to anticipate the problems that may occur.
Morton A. Stenchever, MD Editor
Maternal Outcome 3 Months After Breech Birth Hannah ME, Hannah WJ, Hodnett ED, et al, for the Term Breech Trial 3-Month Follow-up Collaborative Group. Outcomes at 3 months after planned cesarean vs planned vaginal delivery for breech presentation at term. JAMA 2002;287:1822–31.
Synopsis: This study was a follow-up of the Term Breech Trial that was carried out between 1997 and 2000 on 2088 women with a breech presentation who were randomized to either planned cesarean delivery or planned vaginal birth. The Term Breech Trial was carried out in 121 centers in 26 countries; about half of these were developed nations and about half were developing nations. The studies originally found a significant reduction in adverse perinatal outcomes with planned cesarean delivery compared with planned vaginal delivery. However, maternal morbidity increased during the first 6 weeks in the cesarean group. The current study looked at 1940 women enrolled at 110 centers who were followed up at 3 months postpartum and were asked to complete a questionnaire. The questionnaire was returned by 82.3% of the women; 798 of these had been randomized to planned cesarean delivery and 798 to planned vaginal delivery. The study investigated the women’s responses to breast-feeding; infant health; ease of caring for the infant and adjusting to being a new mother; sexual relations and relationships with the husband/partner; pain; urinary, flatal, and fecal incontinence; depression; and views regarding the childbirth experience and study participation. Women in the planned cesarean delivery group were less likely to report urinary incontinence than were respondents in the planned vaginal delivery group (4.5% versus 7.3%). Incontinence of flatus was not different between the two groups but was less of a problem in the planned cesarean delivery group when it occurred. Otherwise, no other differences were ©2002 by the American College of Obstetricians and Gynecologists Published by Elsevier Science Inc. 1085-6862/02/$6.00
Parity and Pregnancy Outcomes Bai J, Wong FWS, Bauman A, Mohsin M. Parity and pregnancy outcomes. Am J Obstet Gynecol 2002;186:274 – 8.
Synopsis: The authors performed a cross-sectional analysis of 510,989 women who delivered in New South Wales, Australia between 1992– 1997. Pregnancy outcomes were compared by parity with attention to obstetric complications, neonatal morbidity, and perinatal mortality. Nulliparous women and grand-multipara women had significantly more obstetric complications, neonatal morbidity, and perinatal mortality than did women of parity 1, 2, or 3. By evaluating each parity separately, the authors demonstrated that grandmultiparity should begin at 4, not 5, as has been previously taught. All their data were corrected for potential confounders, including age, maternal
Outcome After Elective Labor Induction in Nulliparas Cammu H, Martens G, Ruyssinck G, Amy JJ. Outcome after elective labor induction in nulliparous women: A matched cohort study. Am J Obstet Gynecol 2002;186: 240 – 4.
Synopsis: The authors performed a matched cohort study comparing 7683 nulliparous women undergoing elective labor induction in 80 labor services in northern Belgium with 7683 matched controls who delivered spontaneously. They found a cesarean delivery rate of 9.9% versus 6.5%, instrumental delivery rate of 31.6% versus 29.1%, epidural anesthesia use of 80% versus 58%, and transfer of the infant to the neonatal ward of 10.7% compared with 9.4%, for the study and control groups, respectively. All these differences were statistically significant. In most cases cesarean delivery was necessary because of failure to progress in the first stage of labor. The difference in the neonatal ward admission rate was attributed to the higher admission rate for maternal convenience when the woman had had a cesarean delivery, and reflected the rates of cesarean delivery in the two groups. The number of infants with congenital anomalies and the number of neonatal deaths were equal in the two groups. Academic teaching
October 2002
●
ACOG CLINICAL REVIEW
●
3
hospitals and referral hospitals recorded higher rates of elective induction than community hospitals. Level II-2. ● ● ●
Commentary: The authors demonstrated in a carefully performed, matched cohort study that elective induction of labor carried a higher risk of cesarean and instrument delivery. Although the patients were low-risk nulliparous women at term and most of the inductions were performed for convenience, selection bias is unavoidable when comparing elective induction with spontaneous labor. Within the cohort of women who underwent elective induction, there were bound to be some who may have had difficulty either initiating labor or having a normal labor. This difficulty was probably less likely in women who presented in spontaneous labor. Likewise, women having an elective induction, as the authors showed, were more likely to have epidural anesthesia. It is not known if the epidural anesthesia changed the management of labor in these women, but it may have been a factor. The authors showed that 1 in 29 induced labors ended in an additional cesarean over what could have been expected had labor begun spontaneously. The greater likelihood of admission to the neonatal intensive care unit also led to a potential increase in the total cost associated with the practice of induced labor. The question must be asked: Is the convenience worth the increased cost?
Metformin Reduces GDM in Women With PCOS Glueck CJ, Wang P, Kobayashi S, Phillips H, Sieve-Smith L. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril 2002;77:520 –5.
Synopsis: Metformin is an oral antihyperglycemic drug used worldwide for the treatment of type 2 diabetes that has recently been found to facilitate ovulation in some women with polycystic ovary syndrome (PCOS). The authors performed a prospective study on 33 nondiabetic women with PCOS who conceived while taking 4
●
ACOG CLINICAL REVIEW
●
metformin and delivered live infants (this group had had 12 previous pregnancies without metformin). Of 33, 28 took the drug through delivery. They also studied retrospectively 39 nondiabetic women with PCOS who had live birth pregnancies without metformin therapy. In the study group, 1 of 33 (3%) developed gestational diabetes, compared with 8 of 12 (67%) during the previous pregnancies without metformin therapy. Of the 39 patients who did not take metformin, gestational diabetes occurred in 14 of 60 pregnancies. Most of the patients in both groups were very obese with body mass index (BMI) of 33.5 kg/m2 and 33.6 kg/m2 in the prospective and retrospective cohorts, respectively. Fasting insulin levels, insulin resistance, and insulin secretion were also high in both groups. In 21 of 33 patients in the study group who conceived while taking metformin, complete data were available for weight, BMI, insulin resistance, and insulin secretion. These patients showed a median weight decrease from 94 to 88 kg, a BMI decrease from 33.6 kg/m2 to 29.6 kg/m2, and a decrease in insulin levels, insulin resistance, and insulin secretion, all of which were statistically significant after metformin therapy. There were no major fetal malformations or fetal hypoglycemia in the 34 live births of the 33 patients who were treated. Level II-2.
PCOS will decrease the risk of subsequent development of type 2 diabetes, but the benefits of preventing gestational diabetes appear to be real, and this therapy should be considered, particularly in obese women with PCOS.
Risk of Birth Defects After Intracytoplasmic Sperm Injection and IVF Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 2002;346:725–30.
Synopsis: The authors in this western Australian study assessed the prevalence of major birth defects diagnosed by 1 year of age in 4000 randomly selected infants conceived naturally, 301 infants conceived with intracytoplasmic sperm injection, and 837 infants conceived with in vitro fertilization (IVF). Major birth defects were recorded in 8.6% of the infants conceived by intracytoplasmic sperm injection, 9.0% conceived with IVF, and 4.2% conceived naturally. After adjustment for maternal age, parity, sex of the infant, and correlations between siblings, the odds ratio (OR) for having a major birth defect was still 2.0 for infants conceived by intracytoplasmic sperm injection or IVF compared with controls. Level II-2.
● ● ●
● ● ●
Commentary: As PCOS affects 5–10% of women and is considered a risk factor for gestational diabetes, it is exciting to find a strategy that may prevent gestational diabetes from occurring in women with polycystic ovary disease. Metformin has previously been shown to reduce the spontaneous miscarriage rate in diabetic women, women with gestational diabetes, and women with PCOS who are not diabetic by as much as 10-fold, and to date the drug has not been shown to be teratogenic. The ability of metformin to reduce weight, BMI, insulin levels, insulin resistance, and insulin secretion before conception as shown in the 21 women in this study also offers a considerable benefit. It is not yet known if metformin treatment for women with
Commentary: The data presented in this study were of interest, especially since the OR for the development of major birth defects was double for infants conceived by assisted reproductive technology compared with controls. Nevertheless, most infants conceived by assisted reproductive technology did not have major birth defects. Many factors can probably account for the increased risk, including older parental age, the reason for assisted reproductive technology, and the effects of the biological manipulation associated with assisted reproductive technology. The information presented should be given to couples who are contemplating the use of assisted reproductive technology as they attempt to make an informed judgment about their course of action.
October 2002
©2002 by the American College of Obstetricians and Gynecologists Published by Elsevier Science Inc. 1085-6862/02/$6.00
Erythromycin Not a Risk Factor for Newborn Pyloric Stenosis Louik C, Werler MM, Mitchell AA. Erythromycin use during pregnancy in relation to pyloric stenosis. Am J Obstet Gynecol 2002;186:288 –90.
Synopsis: A recent investigation by the US Centers for Disease Control and Prevention concluded that neonates who received erythromycin might be at increased risk for pyloric stenosis. The authors therefore carried out a study using the database of the Slone Epidemiology Unit at Boston University, which contained information on 1044 infants with pyloric stenosis. They compared these infants with two control groups composed of 1704 infants without malformations and 15,356 infants with a wide range of other malformations. They found no relationship between maternal ingestion of erythromycin during weeks 1–24, 25– 40, or 32– 40 and the development of pyloric stenosis when compared with the control groups. Level II-2. ● ● ●
Commentary: The authors were correct in attempting to identify a relationship between erythromycin use during pregnancy and the development of pyloric stenosis in the infant, in light of the CDC finding that erythromycin treatment of neonates may have led to the development of pyloric stenosis. Erythromycin is used routinely in pregnancy for treating many maternal infections and does cross the placenta. Therefore, the finding that maternal ingestion of erythromycin any time during pregnancy was not associated with infant development of pyloric stenosis is somewhat reassuring, although not conclusive.
Q Fever During Pregnancy Raoult D, Fenollar F, Stein A. Q fever during pregnancy: Diagnosis, treatment, and follow-up. Arch Intern Med 2002;162: 701– 4.
Synopsis: Q fever is caused by an intracellular bacterium Coxiella burnetii, an infection that occurs worldwide. The organism infects mammals, birds, domestic animals, and pets, and ©2002 by the American College of Obstetricians and Gynecologists Published by Elsevier Science Inc. 1085-6862/02/$6.00
is generally acquired by inhalation of aerosols from the amniotic fluid or placenta of infected animals. In female animals, infection with this agent is associated with abortions, infertility, and low birth weight (LBW) offspring. During acute infection, granuloma formation occurs in infected viscera and IgM and IgG antibodies develop. The authors noted from the sparse literature on the topic that 38% of human pregnancies in which Q fever was contracted ended in abortions or neonatal death, and 33% in premature births with LBW infants; no abnormalities occurred in only 29% of pregnancies. The authors added data on 17 patients and noted that the outcome of pregnancy depended on the trimester of infection. Abortion occurred in 100% of seven patients who were infected during the first trimester. They noted that the only effective bacteriocidal regimen in vitro is concurrent doxycycline and chloroquine use, but since doxycycline is not advised during pregnancy, they used co-trimoxazole and continued it throughout pregnancy. As C burnetii is excreted in milk, patients were advised against breast-feeding. Level III. ● ● ●
Commentary: Q fever during pregnancy is probably rare in the United States, but it is reasonable for ob/gyns to acquaint themselves with this disease and the severe effect that it can have on gestation. Q fever has been associated with endocarditis and with chronic infection, and the information that the authors offered is a useful review of this condition.
Cocaine Exposure and Preterm Birth Savitz DA, Henderson L, Dole N, Herring A, Wilkins DG, Rollins D, et al. Indicators of cocaine exposure and preterm birth. Obstet Gynecol 2002;99:458 – 65.
Synopsis: The authors performed a nested case-control study in a cohort of 2611 black and white women enrolled in prenatal care in North Carolina. Cocaine exposure was ascertained by self-report in 263 cases and 612 controls, by urine assay at 24 –29 weeks’ gestation in 226 cases and 564
controls, and postpartum in 160 cases and 408 controls. Postpartum hair assays were positive in 169 cases and 435 controls. In this study, cases were women who delivered preterm and controls delivered at term. The authors found that cocaine exposure was identified in 2% based on self-report, 5– 6% based on urine assay, and 13– 15% based on hair assays. Black ethnicity, lower education levels, and poverty were strongly predictive of positive hair assays. Hair cocaine and benzoylecgonine levels were not associated with preterm birth, except for a somewhat stronger association in births occurring before 34 weeks’ gestation compared with those occurring before 37 weeks’ gestation. Level II-2. ● ● ●
Commentary: As the authors correctly pointed out, self-reporting of the use of an illegal drug was probably not accurate. Searching for evidence of cocaine and its metabolite in urine is probably useful only if the drug has been used within 3 days of the test. However, hair assays may be accurate after several months and provide a more complete assessment. The authors did not determine with certainty if cocaine is damaging to the fetus or the pregnancy, but the data from this study may suggest some association between current use and early prematurity. The study did point out strong demographic predictors of exposure that suggest areas in which intervention efforts can be targeted.
Birth Weight in Infants Conceived by Use of Assisted Reproductive Technology Schieve LA, Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS. Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med 2002;346:731–7.
Synopsis: The authors used population-based data to compare the rates of low birth weight (LBW) (ⱕ 2500 g) and very low birth weight (VLBW) (⬍ 1500 g) among infants who were conceived with assisted reproductive technology with the rates of LBW and VLBW among infants born in the general population. They
October 2002
●
ACOG CLINICAL REVIEW
●
5
compared 42,463 infants born in 1996 –1997 and conceived with assisted reproductive technology with 3,389,098 infants born in the United States in 1997; births to women 20 years of age and older were considered. The risk of LBW in infants conceived with assisted reproductive technology was found to be 2.6 times greater than that of the general population (95% confidence interval 2.4, 2.7). Although only 0.6% of infants born to women over the age of 20 in 1997 were conceived with assisted reproductive technology, these infants accounted for 3.5% of LBW and 4.3% of VLBW infants. No difference in rate of LBW was noted between twins conceived by assisted reproductive technology and those conceived spontaneously. The risk of term LBW infants remained elevated even when the authors corrected for various factors, but the risk of preterm LBW was no longer increased in analyses restricted to study infants who had been carried by presumably healthy women. The authors concluded that assisted reproductive technologies accounted for a disproportionate number of LBW and VLBW infants in the United States, in part because of the increase in multiple gestations, but also because of the higher rates of LBW among singleton infants conceived with this technology. Level II-2.
Sonographic Assessment of Cervical Length Soriano D, Weisz B, Seidman DS, Chetrit A, Schiff E, Lipitz S, et al. The role of sonographic assessment of cervical length in the prediction of preterm birth in primigravidae with twin gestation conceived after infertility treatment. Acta Obstet Gynecol Scand 2002;81:39 – 43.
Synopsis: In an attempt to evaluate the risk factors for preterm birth in primigravidae with twin gestations, the authors used transvaginal ultrasound between 18 and 24 weeks’ gestation to measure the length of the cervix in 54 prospectively enrolled twin pregnancies. Maternal age was 30.9 ⫾ 5.3 years (range 22– 46 years). Nine patients (20.5%) delivered before 34 weeks’ gestation and had a mean cervical length in the second trimester of 30.1 ⫾ 6.1 mm. Women who delivered after 34 weeks had a cervical length of 42.2 ⫾ 6.2 mm (P⬍.001). The authors concluded that cervical length longer than 35 mm predicted delivery after 34 weeks’ gestation with sensitivity of 88.5%, specificity of 88.9%, and positive and negative predictive values of 96.9% and 66.7%, respectively. There were no differences with respect to maternal age, body mass index, weight gain in pregnancy, smoking, or work during pregnancy between the two groups. Level III. ● ● ●
● ● ●
Commentary: The authors observed that women who conceived by assisted reproductive technology gave birth to an increased number of LBW and VLBW infants, both at term and preterm. Many factors affect a woman’s decision to undergo assisted reproductive techniques, including medical conditions that prevent couples from conceiving under normal circumstances. In addition, as the authors noted in their discussion, conception using assisted reproductive techniques involves a number of hormonal and other modifications of normal conception. The role of each of these factors is not known, but the cumulative effect is not surprising. Although most of these couples had serious reproductive problems, when conception occurred most had reasonable reproductive success. 6
●
ACOG CLINICAL REVIEW
●
Commentary: The information provided by this study is useful in assisting physicians to anticipate which patients with twin gestations may be at risk for premature delivery. However, the information may not assist the physician to determine what therapeutic course to follow. As the authors pointed out, 77.8% of patients who delivered prematurely had previously experienced premature contractions leading to cervical change, and had required treatment by tocolysis. In the group that delivered later, only two patients (5.7%) had had premature contractions. Therefore, the problem was unclear. Was premature delivery caused by premature labor due to the effect of cervical length or due to another factor, such as intrauterine infection? The data presented will probably not answer this question, and therefore it will still be necessary to
October 2002
determine management for patients with shortened cervical length on an individual basis.
Surgically Obtained Sperm Increases Risk of Gestational Hypertension and Preeclampsia Wang JX, Knottnerus AM, Schuit G, Norman RJ, Chan A, Dekker GA. Surgically obtained sperm, and risk of gestational hypertension and pre-eclampsia. Lancet 2002; 359:673– 4.
Synopsis: The authors compared the rates of preeclampsia and gestational hypertension in women who conceived by intracytoplasmic sperm injection using sperm that was surgically obtained from the epididymis with women who conceived by in vitro fertilization (IVF) or intracytoplasmic sperm injection with ejaculated sperm and who had been exposed to their partner’s sperm in seminal fluid. There were 1075 women in the IVF with ejaculated sperm group, 464 in the intracytoplasmic sperm injection with ejaculated sperm group, and 82 in the intracytoplasmic sperm injection with surgically obtained sperm group. Whereas the incidence of preeclampsia in the IVF with ejaculated sperm group and the intracytoplasmic sperm injection with ejaculated sperm group was the same (4%), the incidence was 11% in the group with intracytoplasmic sperm injection with surgically obtained sperm, an odds ratio (OR) of 3.10 (95% confidence interval [CI] 1.59, 6.73). For gestational hypertension, the OR in the group with intracytoplasmic sperm injection with surgically obtained sperm was 2.10 (95% CI 1.30, 3.62). The authors suggested that there is a protective effect of semen exposure to the later development of gestational hypertension and preeclampsia, and that these conditions may be associated with exposure to sperm cells or a factor in the ejaculate that is closely related to sperm. Level II-2. ● ● ●
Commentary: The cause of pregnancy-induced hypertension or preeclampsia is not known, but several different circumstances seem to be related to its development. The authors ©2002 by the American College of Obstetricians and Gynecologists Published by Elsevier Science Inc. 1085-6862/02/$6.00
presented yet another possibility: they found that gestational hypertension and preeclampsia were more common among women implanted with an oocyte fertilized with surgically obtained sperm, rather than ejaculated sperm. This study implied that sperm may be in some way responsible for the problem and that semen or seminal fluid may in some way be protective. Immunologic factors undoubtedly play at least some part in the development of pregnancy-induced hypertension and preeclampsia. The challenge now seems to lie in properly sorting out these factors.
SPOTLIGHT ON GYNECOLOGY
circulating tumor cells, respectively. Level II-2. ● ● ●
Commentary: The findings of this study implied that epithelial carcinoma cells metastasized early via the blood and were probably present at distant sites, at least on a microscopic basis, early in the natural history of the disease. Therefore, detecting them in the blood or bone marrow, which relates to factors such as when cells are excreted into the blood and to sampling considerations, had little effect on the prognosis of the disease. Treatment modalities must be able to affect cells at distant areas of the body; local treatment, no matter how complete, will probably not be enough in most cases to affect a cure.
Morton A. Stenchever, MD Editor
Ovarian Carcinoma Cells in Peripheral Blood and Bone Marrow Marth C, Kisic J, Kærn J, Trope´ C, Fodstad Ø. Circulating tumor cells in the peripheral blood and bone marrow of patients with ovarian carcinoma do not predict prognosis. Cancer 2002;94:707–12.
Synopsis: The authors studied 90 patients with histologically proven epithelial ovarian carcinoma for the presence of tumor cells in blood and in bone marrow. Blood was obtained from all 90 patients and bone marrow from 73 patients. Tumor cells were identified by a microbead coated with antibody MOC-31 that recognizes an epitope that is regularly expressed by ovarian carcinoma cells. Carcinoma cells were detected in the bone marrow in 21% of patients and in the peripheral blood of 12% of the patients. All patients with peripheral blood that was positive for tumor cells also had bone marrow-positive cells, but the reverse was not always the case. Detection was not related to stage, type of histology, grade, residual disease, or CA 125 tumor marker concentration. Detection of tumor cells in peripheral blood and/or bone marrow was also not related to overall prognosis, as the overall survival rate was 25 and 28 months for patients with and without ©2002 by the American College of Obstetricians and Gynecologists Published by Elsevier Science Inc. 1085-6862/02/$6.00
Race Differences Associated With Estrogen Receptor Isoform Profiles in Breast Tumors Poola I, Clarke R, DeWitty R, Leffall LD. Functionally active estrogen receptor isoform profiles in the breast tumors of African American women are different from the profiles in breast tumors of Caucasian women. Cancer 2002;94:615–23.
Synopsis: Because black women seem to develop highly aggressive breast tumors and experience a mortality rate that is approximately three times higher than other populations, the authors wanted to determine if aggressive tumor biology could be related to distinct alterations in the estrogen receptor (ER) isoforms, specifically ER isoform mRNA, ER␣ wild type, ER wild type, ER␣ exon 3⌬ and ER␣ exon 5⌬. They compared the expression of these isoforms in both tumor tissue and matched normal tissue from 24 patients. They found that the ER isoform, which is thought to be protective, was decreased significantly compared with matched normal tissue, and that active ER␣ exon 5⌬ and the dominant negative ER␣ exon 3⌬ mRNA levels were higher in tumor tissue than in matched normal tissue. They noted that these changes were distinct from the alterations that had been observed previously in tumors
from white patients and believed that these differences demonstrated a biological reason for the increased tumor aggressiveness and associated mortality of breast cancer seen in black women. Level II-1. ● ● ●
Commentary: The authors of this study offered an interesting observation. Studies that have considered the higher mortality rate from breast cancer in black women compared with white and Hispanic women and have corrected for the late-stage of the disease at the time of diagnosis frequently seen in black women, low socioeconomic status, and limited access to medical facilities and services, still found a noncontrollable difference in tumor aggressiveness and mortality rates. These findings suggested that there were also biological implications, some of which the authors of the current study appeared to have demonstrated. Tumors in black women seem to be characterized by an elevated level of constitutively active ER ␣ exon 5⌬ dominant negative ER␣ exon 3⌬ mRNA and an increased ER␣-to-ER ratio due to a decrease in the ER mRNA levels. These findings were different from those in white women and should be helpful to clinicians as they plan management for black women with breast cancer. It should also be useful information for individuals who plan surveillance programs in order to facilitate the diagnosis of breast cancer as early as possible in black women.
GnRH Agonist and Add-Back Therapy for Endometriosis Surrey ES, Hornstein MD, for the Add-Back Study Group. Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: Long-term follow-up. Obstet Gynecol 2002;99:709 –19.
Synopsis: This study was a posttreatment follow-up analysis of a randomized, double-masked, placebo-controlled 1-year trial in which four groups of patients with endometriosis were treated with the GnRH agonist
October 2002
●
ACOG CLINICAL REVIEW
●
7