Bryan D. Cowan

Cytokine Expression by Models of Human Trophoblast as Assessed by a Semiquantitative Reverse Transcription‐Polymerase Chain Reaction Technique

PROBLEM: Cytokines form an important communication network between the mother and fetus. Defining the significance of these factors requires an understanding of their constitutive expression by maternal and fetal tissues. This study examines cytokine expression by human trophoblast.

First‐Trimester Human Chorionic Villi Express Both Immunoregulatory and Inflammatory Cytokines: A Role for Interleukin‐10 in Regulating the Cytokine Network of Pregnancy

PROBLEM: T‐helper 2 (TH2)‐type cytokines [i.e., interleukin (IL)‐6. IL‐10, and IL‐13] and transforming growth factor (TGF)‐β are expressed by the murine decidua and/or placenta and are likely to suppress inflammatory cytokine [i.e., IL‐2, interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, IL‐1α, and IL‐1β] production at the maternal‐fetal interface. In addition, class I IFNs may protect the fetus from immunologic rejection and viral infections. This study examines the expression of inflammatory/immunoregulatory cytokines and IL‐10 production by first‐trimester chorionic villi.

Intrapartum Detection of a Maerosomie Fetus: Clinieal Versus 8 Sonographic Models

Summary: The purpose of this study was to determine whether clinical or sonographic models have 1) the highest accuracy in differentiating newborns with birth‐weights ≥ 4,000 g (macrosomia) versus ≤ 3,999 g, and 2) among macrosomics which method of predicting birth‐weight has the lowest percentage error. Prospectively, 602 consecutive parturients at term had a clinical estimate of birth‐weight followed by sonographic measurement of fetal parts. The sonographic prediction of birth‐weight was derived using 8 different models that utilize either 1 measurement or a combination of 2 to 4 parameters. The incidence of macrosomia was 11.1% (67 of 602). Analysis of ROC curves indicated that clinical predictions (w = 0.85) were significantly better than 4 of the 8 sonographic models. The mean standardized absolute error among maerosomie newborns is significantly lower when predictions are derived clinically (99 ± 70 g/kg) than using 1 or 2 fetal parts. Sonographic assessment of birth‐weight is not significantly more accurate in the detection of a maerosomie fetus than clinical predictions.

Life-threatening neutropenia following methotrexate treatment of ectopic pregnancy: A report of two cases*

Background Medical treatment of ectopic pregnancy with methotrexate is an increasingly common alternative to surgical management. Initial reports of methotrexate therapy described a very low incidence of complications. We report our experience with two patients who developed profound toxicity following methotrexate treatment of ectopic pregnancy. Case The first patient received a single dose of methotrexate (50 Mg/M2 intramuscularly) for a confirmed ectopic pregnancy. The second patient received three doses of methotrexate (1 mg/kg). Both patients developed life-threatening neutropenia and febrile morbidity requiring hospitalization and supportive care. Conclusion To our knowledge, this is the first description of significant morbidity secondary to bone marrow suppression following methotrexate treatment of ectopic pregnancy. Most patients with ectopic pregnancy who are treated with methotrexate can expect resolution of their symptoms and a low risk of mild complications. However, serious complications after this therapy are possible and may occur even with the single-dose regimen.

Parturitional factors associated with membrane stripping.

OBJECTIVE Our purpose was to determine what factors occurring after digital separation of the chorionic membranes from the lower uterine segment (membrane stripping) are involved in observed clinical changes compared with patients not so treated. STUDY DESIGN Thirty patients were randomly divided among a study population and two control groups to assess uterine contractions and microbiologic, histologic, and biochemical markers associated with parturitional events over a 7-hour time frame. RESULTS Clinically, an increased frequency of uterine contractile activity was observed among patients in the membrane-stripped group (p < 0.03). There was a significant increase in plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha (p < 0.001) and endocervical phospholipase A2 activity (p < 0.04) among those who underwent membrane stripping. Blood leukocyte counts, sedimentation rates, prostaglandin E2 metabolite concentrations, and fibronectin levels revealed no significant change during the 7-hour study session. CONCLUSION Membrane stripping was associated with increases in phospholipase A2 activity and prostaglandin F2 alpha concentrations, indicating a possible correlation with initiation of the cascade of parturitional events.

Management of abnormal genital bleeding in girls and women.

Management of abnormal genital bleeding in girls, adolescents and women, in pregnancy, and in postmenopausal women is reviewed under the headings of evaluation and treatment. In childhood all genital bleeding is clinically significant: it is due to acute infection, foreign bodies, trauma, prolapsed urethra or precocious puberty, rarely to tumors. Bleeding in adolescents and adults is most often due to anovulation, usually estrogen-breakthrough bleeding. Other causes are submucosal leiomyomas, cervical or endometrial polyps, lacerations, uterine or cervical cancer, or systemic disorders such as hypothyroidism or bleeding disorders. Evaluation of bleeding in children requires skill and often general anesthesia, especially if peritoneal laceration is suspected. The 1st step in adolescents and adults is to rule out pregnancy. Pap smears are insufficient: biopsies are advised, especially endometrial biopsies in women 40. Hemoglobin, hematocrit and thyroid status, should also be ordered. Specific treatments involve antibiotics for infection, correction of anemia and orthostatic hypotension, reversal of unopposed estrogen, and medical treatment of menorrhagia and dysfunctional bleeding that does not involve hemodynamic instability. Sometimes curettage, endometrial ablation or hysterectomy is needed. Medical management of breakthrough bleeding caused by unopposed estrogen is high dose estrogen followed by progestin therapy to bring about withdrawal, curettage if necessary, then cyclic combined therapy. In young women 4 birth control pills per day for 5-7 days are often prescribed, with cyclic therapy after withdrawal bleeding is obtained. Prostaglandin inhibitors reduce menstrual loss 50%. Endometrial atrophy in post-menopausal women is treated with cyclic conjugated estrogens and then medroxyprogesterone acetate for 10-13 days per month, or continuous combined therapy for those who can tolerate it.

Receiver-operator characteristic, efficiency analysis, and predictive value of serum progesterone concentration as a test for abnormal gestations

OBJECTIVE Our objective was to determine if a discriminatory progesterone concentration could be established that confidently predicted abnormal early gestations. STUDY DESIGN We analyzed differences in progesterone concentrations between normal (n = 40) and abnormal (n = 34) pregnancies during the first 49 days of gestation. The receiver-operator characteristic curve, test efficiency, and predictive value of serum progesterone to discriminate between an abnormal and normal first-trimester gestation were calculated for progesterone concentrations between 5 and 25 ng/ml. RESULTS Receiver-operator characteristic curve analysis indicated that the best discriminatory progesterone concentration was 10 ng/ml. Test efficiency was maximum between serum progesterone concentration of 9 to 14 ng/ml (80%). When progesterone was less than 10 ng/ml, the predictive value of the abnormal test result was greater than 90%. CONCLUSION Receiver-operator characteristic analysis, test efficiency, and the predictive value of an abnormal test result suggest that the best progesterone cut off point that predicts abnormal early pregnancies is 10 ng/ml.

Ovarian endometriomas do not adversely affect pregnancy success following treatment with in vitro fertilization.

Purpose: Ovarian endometriomas have an uncertain impact on outcome following in vitro fertilization (IVF). Some authors describe a poor response to ovulation induction, and others observe decreased pregnancy success rates. Conversely, IVF outcomes similar to those of patients undergoing IVF for tubal-factor infertility have also been reported. To determine the impact of ovarian endometriomas on pregnancy success in our IVF program, we identified patients with endometriosis and compared outcomes that were stratified by the presence or absence of an endometrioma at the time of follicular aspiration.Methods: One hundred eight patients with a diagnosis of endometriosis treated with IVF were identified, retrospectively. In this group, 24 patients completed 29 cycles in which an ovarian endometrioma was aspirated at the time of oocyte retrieval, and 84 patients without endometriomas completed 147 cycles. The cycles from these two groups were compared for differences in peak estradiol, number of mature follicles, number of oocytes, number of embryos transferred, and clinical pregnancies.Results: There were no significant differences between the two groups with respect to peak estradiol, mature follicles, number of oocytes, number of embryos transferred, or clinical pregnancies.Conclusions: From this retrospective observational analysis it appears that aspiration of an endometrioma at the time of oocyte retrieval has no adverse effect on outcome. This information may prove helpful when faced with the decision to cancel an IVF treatment cycle in patients with this uncommon complication.

Cytokine Expression by First‐Trimester Human Chorionic Villi

PROBLEM: Communication at the human maternal‐fetal interface occurs by an intricate cytokine network. This study examines cytokine expression by normal first‐trimester human chorionic villi.

Treatment of persistent ectopic pregnancy with methotrexate and leukovorum rescue: a case report

&NA; The incidence of ectopic pregnancy is increasing in the Western world, and this reproductive complication has had an adverse impact on subsequent fertility. Advances in the surgical treatment of ectopic pregnancies have been designed to preserve future reproductive potential, but conservative tubal surgery may fail to completely remove the trophoblast. Described is a case of persistent ectopic pregnancy successfully treated with methotrexate. (Obstet Gynecol 67:50S, 1986)