2002 Annual Meeting
ABSTRACT 1
Expression of a Retinol Dehydrogenase (hRoDH-4), a Member of the Retinol/Steroid Dehydrogenase Family Implicated in Retinoic Acid Biosynthesis, in Normal and Neoplastic EndometriaBy Invitation
Joanna M. Cain, MD
Richard Zaino, MD
Debra Shearer, BS
R. Alan Bennett, MD
George Olt, MD
Judith Weisz, MB, BChir.
OBJECTIVE: Retinoic acid (RA) plays an essential role in epithelial differentiation and retinoid homeostasis is disrupted in cancers of epithelial origin. The goal of this study was to determine whether hRoDH-4, an enzyme that can catalyze the first and rate-limiting step in RA biosynthesis, is expressed in normal endometrium and, if so, whether its expression is altered in endometrial cancer.
STUDY DESIGN: Proliferative, secretory, hyperplastic and neoplastic endometria were examined by immunocytochemistry for hRoDH-4 protein and by RT/PCR for hRoDH-4 transcript.
RESULTS: In proliferative and secretory glandular epithelium immunoreactive hRoDH-4 was uniformly present. In endometrial cancers hRoDH-4 immunoreactivity was markedly reduced in many neoplastic epithelial cells. Expression of hRoDH-4 in normal and neoplastic endometrium was confirmed by RT/PCR.
CONCLUSION: These findings are consistent with the hypothesis that altered expression of enzymes important for in situ RA biosynthesis is an important phenotypic change associated with the development of endometrial cancer.
DISCUSSANT: Carolyn D. Runowicz, MD
ABSTRACT 2
Prevention of Neonatal Group B Streptococcal Disease: A Combined Intraparum and Neonatal ProtocolBy Invitation
George D. Wendel, Jr., MD
Kenneth J. Leveno, MD
Pablo J. Sánchez, MD
Gregory L. Jackson, MD
Donald D. McIntire, PhD
Jane D. Siegel, MD
OBJECTIVE: We sought to assess the efficacy of a clinical protocol to reduce the incidence of early-onset neonatal Group B Streptococcus (GBS) sepsis.
STUDY DESIGN: We assessed neonatal sepsis from GBS and other organisms using a before-after study design to evaluate the effects of implementation of combined intrapartum antimicrobial prophylaxis given selectively to mothers with GBS risks and penicillin G given to all neonates.
RESULTS: In 1994, 31 of 13, 887 livebirths developed early-onset GBS sepsis (2.2 per 1000); 13 preterm and 18 term cases. After implementation of the prophylaxis protocol (1995), 6 of 13,527 livebirths had early-onset GBS (0.4 per 1000) (P < 0.001). There were no preterm GBS (P = .0004) and 6 term cases (P = 0.02). The efficacy continued through 1999 (0.5 per 1000) without an increase in neonatal infections due to other bacteria.
CONCLUSION: Combined maternal and infant antimicrobial prophylaxis can significantly and safely reduce rates of early-onset GBS sepsis in both preterm and term infants.
DISCUSSANT: David E. Soper, MD
ABSTRACT 3
Establishing a Clinical Program for HIV-1 Seropositive Males to Father Healthy Children Using IVF-ICSIBy Invitation
Mark V. Sauer, MD
Peter L. Chang, MD
OBJECTIVE: We assessed the safety and efficacy of providing men seropositive for human immunodeficiency virus type 1 (HIV-1) assisted reproduction.
STUDY DESIGN: HIV-1 serodiscordant couples underwent in-vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI). To determine safety, patients were screened for HIV-1 three and six months after embryo transfer (ET). Infants and mothers were tested at delivery and three months postpartum. To measure efficacy, clinical outcomes were compared to matched IVF-ICSI controls.
RESULTS: There were no seroconversions in women (n = 34) or offspring (n = 13) following 55 ETs. Treatment efficacy was similar to controls; retrieved eggs (15.8 ± 1.3 vs. 12.3 ± 0.8); fertilization rate (64.9% vs. 68.0%); embryos cryopreserved (1.1 ± 0.3 vs. 0.3 ± 0.1, p < 0.05); clinical pregnancies/ET (45.5% vs. 35.4%); ongoing/ delivered pregnancies/ET (30.9% vs. 25.0%).
CONCLUSION: Although preliminary, IVF-ICSI provides HIV-1 serodiscordant couples a reasonably safe alternative to have children, as their assisted reproduction performance is similar to conventional patients.
DISCUSSANT: Richard L. Sweet, MD
ABSTRACT 4
Impact of Cerclage on Obstetrical Outcome in Twin Gestations with a Shortened Cervical LengthBy Invitation
Roger B. Newman, MD
R. Stephen Krombach, MS
Mary C. Myers, CNM
Daniel L. McGee, PhD
OBJECTIVE: To determine the impact of cerclage placement on obstetrical outcome in twin gestations with a shortened cervical length.
STUDY DESIGN: A prospective cohort study of 147 consecutive twin pregnancies (July 1994 to March 2001) who underwent transvaginal ultrasonographic cervical length measurement between 18 and 26 weeks gestation. Cerclage was offered to women with cervical lengths <= 25 mm. Patients without cerclage were segregated into quartiles by cervical length. Regression analysis and Chi-square tests were used to determine the impact of cervical length and cerclage on parameters of prematurity.
RESULTS: One hundred twenty-eight twin gestations met inclusion criteria including 21 (16.4%) who underwent cerclage for a cervical length <= 25 mm. Decreasing cervical length was significantly associated with a shorter length of gestation, lower combined birthweight, delivery < 34 weeks, preterm PROM, and very low birthweight. None of these outcomes was altered by cerclage placement.
CONCLUSION: Mid-trimester cerclage does not alter the risks of prematurity associated with a shortened cervical length in twin gestations.
DISCUSSANT: Jay D. Iams, MD
ABSTRACT 5
A Time-Based Analysis of Fetal Pulmonary Phospholipid Production in Normal and Diabetic PregnancyBy Invitation
Thomas R. Moore, MD
OBJECTIVE: To determine if there are time-based differences in the production of various fetal pulmonary phospholipids in diabetics and normal controls
STUDY DESIGN: A 2:1 case-control study of 295 diabetics and 590 controls was performed utilizing gestation-matched amniocentesis specimens analyzed for lecithin/ sphingomyelin (LS) ratio, phosphatidylinositol (PI) and phosphatidylglycerol (PG) composition. Diabetic subjects were stratified according to type of diabetes, degree of blood sugar control and birth centile of the neonate.
RESULTS: There was no difference in LS ratios over gestational age by type of diabetes or quality of glycemic control. Women with preexisting diabetes had significantly higher PI levels at 33 - 35 weeks gestation, which became similar to controls after 36 weeks, whereas GDM patients and controls had similar PI levels throughout. In diabetic subjects, the onset of production of PG was delayed from 35.9 ± 1.1 weeks (controls), to 38.7 ± .9 weeks (overt diabetics) and 37.3 ± 1.0 weeks for GDM (p < .001). The delay in PG synthesis was not related to infant gender, level of maternal glucose control or fetal macrosomia.
CONCLUSIONS: Fetal pulmonary maturation, as evidenced by the onset of PG production in the amniotic fluid, is delayed in diabetic pregnancy by 1 - 1.5 weeks. This delay appears to be associated with an early and sustained elevation in amniotic fluid PI levels at 32 - 34 weeks.
DISCUSSANT: Oded Langer, MD
ABSTRACT 6
Intrauterine Progesterone Treatment of Early Endometrial CancerBy Invitation
Frederic J. Montz, MD
Robert E. Bristow, MD
Alessandro Bovicelli, MD
Rafael Tomacruz, MD
Robert J. Kurman, MD
OBJECTIVE: To assess the feasibility of using a progesterone-containing intrauterine device (IUD) to treat presumed FIGO stage I A, grade 1 endometrioid cancer in women at high risk for peri-operative complications.
STUDY DESIGN: Candidates were American Society of Anesthesiologists Class III or IV women with grade 1 endometrioid cancer and no imaging evidence of myometrial invasion. Subjects underwent hysteroscopy, D and C, and IUD placement followed by endometrial biopsy every three months for one year. The records of similar patients treated surgically during the three years before protocol initiation were reviewed for comparison.
RESULTS: Sixteen patients fulfilled study criteria. Fourteen consented to participation; one was excluded at time of IUD placement (grade 2 disease identified) and one was lost to follow-up. Twelve subjects have been followed up to 36 months; biopsies were negative in seven of 11 at six months and six of eight at 12 months. No IUD related complications, except for expulsion, occurred. Sixteen complications (one fatal) occurred in nine of the 15 controls.
CONCLUSION: Intrauterine progesterone appears to eradicate some cases of presumed stage I A grade 1 endometrioid cancer in high-risk women.
DISCUSSANT: William T. Creasman, MD
ABSTRACT 7
Evaluation of Endometrial PolypsBy Invitation
Steven R. Goldstein, MD
Ana Monteagudo, MD
Dorota Popiolek, MD
Pat Mayberry, RDMS
Ilan Timor-Tritsch, MD
INTRODUCTION: Endometrial polyps are relatively common in all groups of women. More polyps are being diagnosed with widespread use of transvaginal ultrasound and sonohysterography. The reported incidence of malignancy is low. The potential benefit of a non-invasive technique to distinguish benign from malignant polyps is obvious. This study was undertaken to evaluate endometrial polyps by color flow Doppler ultrasound and histopathology.
MATERIALS AND METHODS: This was an observational study of patients with an endometrial polyp on sonohysterography who had interrogation of their polyp with color Doppler ultrasound and subsequently polypectomy. Polyp volume, resistive index (R.I.), pulsatility index (P.I.), indication for scan (bleeding versus incidental), and patient age were correlated with histopathologic type of the polyp (non-functional, proliferative, secretory, hyperplastic, or malignant).
RESULTS: Of 61 patients studied 42 (68.9%) were scanned for abnormal bleeding and 19 (31.1%) had their polyps discovered incidentally. There were no statistically significant differences between histologic categories and the R.I., P.I., or size of the polyp. The age of patients with non-functional polyps was significantly greater than any other group (p < .001). Ninety-four percent of the functional polyps presented with abnormal bleeding while 38% of the non-functional group were discovered incidentally (p < .001).
CONCLUSION: The data suggest that objective assessment of blood flow impedance (R.I., P.I.) in endometrial polyps, as well as size of these polyps, cannot replace surgical removal and pathologic evaluation to predict histologic type. Patients with non-functional polyps were older and less likely to present with vaginal bleeding.
DISCUSSANT: Robert S. Neuwirth, MD
ABSTRACT 8
Effect of Hypoxia on Calcium influx and Calcium/Calmodulin-Dependent Kinase Activity in Neuronal Nuclei of the Guinea Pig Fetus during DevelopmentBy Invitation
Dev Maulik, MD, PhD
Qazi M. Ashraf, MD
Om P. Mishra, PhD
Maria Delivoria-Papadopoulos, MD
OBJECTIVE: To investigate the effect of hypoxia on neuronal nuclear Ca++ influx and CaM kinase activity in the guinea pig fetal brain during development. STUDY DESIGN: Preterm and term pregnant guinea pigs (n = 61) were exposed to either 21% or 7% oxygen for 60 min.
METHOD: Hypoxia in the fetal cerebral cortical tissue was documented by determining the tissue concentrations of ATP and phosphocreatine. Fetal cerebral cortical neuronal nuclei were isolated and purified, and ATP-dependent Ca++-influx and CaM kinase activity were determined.
RESULTS: Hypoxia resulted in increased neuronal intranuclear 45Ca++-influx from 6.65 ± 1.29 pmoles/mg protein to 9.07 ± 1.98 pmoles/mg protein (p < 0.05) in preterm, and from 6.65 ± 1.63 pmoles/mg protein to 11.26 ± 1.79 pmoles/mg protein (p < 0.05) in term fetuses. The hypoxia induced 45Ca++-influx was significantly higher (p < 0.05) in the term than in the preterm fetuses. Hypoxia resulted in increased CaM kinase activity from 383.7 ± 53.3 pmoles/mg/min protein to 451.6 ± 59.5 pmoles/mg/min protein (p < 0.05) in the preterm, and from 364.6 ± 109.7 pmoles/mg/min protein to 487.0 ± 43.3 pmoles/mg/min protein (p < 0.05) in term fetuses. No significant difference was observed in the CaM kinase activity between the preterm and the term groups.
CONCLUSION: Cerebral hypoxia alters neuronal nuclear calcium influx and calcium-dependent phosphorylating mechanisms in the guinea pig fetal brain during development.
DISCUSSANT: Mark Phillippe, MD
ABSTRACT 9
In-Vitro Maturation and Fertilization of Oocytes from Unstimulated Ovaries: Predicting the Number of Immature Oocytes Retrieved by Early Follicular Phase Ultrasound ScanBy Invitation
Seang Lin Tan, MD
Timothy J. Child, MD
Bulent Gulekli, MD
OBJECTIVE: In order to select women who will benefit most from in-vitro maturation of oocytes treatment, this study was undertaken to examine the ability of a transvaginal ultrasound scan to predict the number of immature oocytes collected from unstimulated ovaries.
STUDY DESIGN: The relationship between the number of immature oocytes retrieved and the pregnancy rate was assessed in 189 IVM treatment cycles. In 96 consecutive cycles, an early follicular phase transvaginal ultrasound measurement of the antral follicle count (AFC), ovarian volume and peak ovarian stromal blood flow velocity (Vmax) was performed and the results correlated with the number of immature oocytes.
RESULTS: The clinical pregnancy rate increased significantly with the number of oocytes retrieved (P = 0.02) and was 26.8% (15/56) in those with > 10 immature oocytes. The AFC, ovarian volume and ovarian stromal Vmax were all predictive of the number of oocytes retrieved but when the other factors were controlled by multiple regression analysis, the AFC was the only significant predictor (P < 0.001).
CONCLUSIONS: Pregnancy rates after IVM correlate with the number of immature oocytes retrieved. This is best predicted by an ultrasound assessment of the antral follicle count.
DISCUSSANT: Michael R. Soules, MD
ABSTRACT 10
Adenosine A2A Receptors Trigger Hypoxic
Inhibition of Fetal Breathing in Sheep
By Invitation
Brian J. Koos, MD, DPhil
Takatsugu Maeda, MD
Calvin Jan
Grace Lopez, MD
OBJECTIVE: Hypoxia inhibits fetal breathing through activation of central adenosine (ADO) receptors that modulate fetal behavioral state. This study was designed to determine whether ADO A1 and/or A2A receptor subtypes mediate the depressant effects of hypoxia.
STUDY DESIGN: In 14 chronically catheterized fetal sheep (> 0.8 term), hypoxemia was induced by having the ewe breathe a gas mixture of 9% O2 for one hour. During hypoxia, the fetus was infused intra-arterially with a vehicle or an antagonist for ADO A1 or A2A receptors. Statistical analysis was performed using ANOVA with Tukey's LSD criterion.
RESULTS: Fetal isocapnic hypoxemia [(PaO2: ~24 Torr (control), ~14 Torr (hypoxia)] virtually eliminated rapid eye movements (REM) and breathing when the fetus was infused with vehicle or the A1 receptor antagonist. In contrast, ADO A2A receptor blockade abolished the hypoxia-induced arrest of REM and breathing.
CONCLUSION: Hypoxic inhibition of REM and breathing depends critically upon activation of adenosine A2A receptors.
DISCUSSANT: Frank A. Manning, MD