Fayek N. Shamma

Infection and labor: VI. Prevalence, microbiology, and clinical significance of intraamniotic infection in twin gestations with preterm labor

The purpose of this study was to establish the prevalence, microbiology, and outcome of microbial invasion of the amniotic cavity in twin gestation presenting with preterm labor and intact membranes. Amniocenteses were performed on both sacs of 46 women with twin gestations, preterm labor, and intact membranes. Indigo carmine was injected to ensure sampling of both amniotic sacs. Amniotic fluid was cultured for aerobic and anaerobic bacteria, Mycoplasma hominis, and Ureaplasma urealyticum. A positive amniotic fluid culture of at least one sac was noted in 10.8% (5/46) of patients admitted in preterm labor and in 11.9% (5/42) of women delivered of preterm neonates. Of the five patients with microbial invasion of the amniotic cavity, three had microorganisms isolated from both sacs. The presenting sac was involved in all cases, supporting an ascending route for microbial invasion of the amniotic cavity in twin gestation. Polymicrobial infection was found in three of the eight amniotic sacs with positive cultures. In two cases different organisms were isolated from each sac. All patients with positive amniotic fluid cultures were delivered of preterm infants within 48 hours of amniocentesis. Patients with positive amniotic fluid cultures presented with preterm labor at an earlier gestational age and with more advanced cervical dilatation than did women with negative amniotic fluid cultures. Clinical evidence of chorioamnionitis subsequently developed in two of five women with positive amniotic fluid cultures. The interval between amniocentesis and delivery was shorter in women with positive amniotic fluid cultures than in women with negative amniotic fluid cultures (median: 3.5 vs 168 hours, p less than 0.0001). Infants born to women with microbial invasion of the amniotic cavity had a lower median birth weight and a higher incidence of respiratory distress syndrome than those born to women with negative amniotic fluid cultures (birth weight: 1085 vs 1975 gm, p = 0.024; respiratory distress syndrome: 37.5% vs 8.3%, p = 0.04).

The role of office hysteroscopy in in vitro fertilization

Twenty-eight patients participated prospectively in a study to evaluate the impact of hysteroscopically detected uterine and cervical anomalies on the success rate of ET in an IVF-ET program. All participants had a normal intrauterine cavity by standard HSG. All the patients had a diagnostic office hysteroscopy under paracervical block before commencing COH. Because our IVF program does not include hysteroscopy as a requirement before undergoing IVF and because the significance of mild intrauterine abnormalities is not yet known, the hysteroscopic findings were not relayed to the personnel involved in the IVF-ET procedure. Sixteen patients (group I) had a normal hysteroscopic evaluation. Twelve patients (group II) had abnormal hysteroscopic findings including small uterine septa, small submucous fibroids, uterine hypoplasia and cervical ridges. Although no difference in patients or cycle characteristics was present, there was a significant difference in the clinical PR between patients in groups I and II. In conclusion, in an IVF-ET program patients with normal hysterography but abnormal hysteroscopic findings had a significantly lower clinical PR, demonstrating the importance of performing hysteroscopy before IVF-ET.

Middle cerebral artery blood velocity during controlled ovarian hyperstimulation

OBJECTIVE To measure cerebral blood flow velocities using transcranial Doppler during ovulation induction after pituitary suppression. DESIGN Women undergoing controlled ovarian hyperstimulation after pituitary suppression were prospectively studied. SETTING Tertiary institution. PATIENTS A microprocessor-controlled directional pulsed-wave adjustable hand held probe (2 MHz) was used to measure blood flow velocities and pulsatility indices in the right and left middle cerebral arteries (middle cerebral artery) in nine patients. Measurements of peak middle cerebral artery velocities (cm/s) and pulsatility index were obtained after achieving pituitary suppression with leuprolide acetate and repeated over several days after treatment with human menopausal gonadotropin (225 IU/d). RESULTS There was a significant increase in the peak middle cerebral artery velocities (cm/s) of the patients measured at the time of pituitary suppression when compared with those obtained at the time of maximal estradiol (E2) (98 +/- 12 versus 105 +/- 12, P less than 0.03). The pulsatility index also showed a significant increase from 0.72 +/- 0.08 at the time of pituitary suppression to 0.82 +/- 0.04 at the time of maximal hyperestrogenism, P less than 0.002. Estradiol values obtained at the time of the transcranial Doppler examinations were normalized by transformation to their natural logarithms (LnE2). The middle cerebral artery velocities were significantly correlated with LnE2 levels (P less than 0.0001 and r = 0.93). CONCLUSION Estrogen levels appear to be directly correlated with cerebral blood flow velocity and pulsatility index, implying an effect of ovarian steroids on cerebrovascular hemodynamics.

Primary ovarian pregnancy successfully treated with methotrexate

Abstract We describe a case of laparoscopically documented unruptured primary ovarian pregnancy successfully treated with intramuscular methotrexate.

The effect of Norplant on glucose metabolism under hyperglycemic hyperinsulinemic conditions.

OBJECTIVES To assess the impact of a levonorgestrel-releasing implant contraceptive (Norplant; Wyeth-Ayerst Laboratories, Philadelphia, PA) on glucose metabolism. DESIGN Prospective evaluation of insulin action and secretion in women under hyperglycemic hyperinsulinemic clamp conditions in the midfollicular phase before and 8 weeks after Norplant placement. SETTING Yale University Clinical Research Center. PARTICIPANTS Seven previously normally cycling, nonobese, nondiabetic women participated in the study. INTERVENTIONS Norplant insertion. MAIN OUTCOME MEASURES Basal levels of glucose and insulin, as well as glucose-mediated insulin secretion, glucose uptake, and tissue sensitivity to insulin were assessed using the hyperglycemic hyperinsulinemic clamp technique before and after Norplant insertion. RESULTS Norplant placement did not alter the fasting glucose or insulin levels. However, it was associated with a significant 37% increase in the first phase insulin response from a control level of 51 +/- 8 to 70 +/- 10 microU/mL (conversion factor to SI unit, 7.175), and a significant 48% increase in the second phase insulin response from 60 +/- 5 to 89 +/- 8 microU/mL. In association with this increase in insulin levels after Norplant insertion, total mean body glucose uptake (M) increased from 8.08 +/- 0.91 to 9.53 +/- 0.95 mg/kg per minute. However, when expressed as the total body glucose uptake per unit of insulin, the M:I ratio (a measure of tissue sensitivity to insulin) decreased significantly from a mean of 0.12 +/- 0.02 to 0.10 +/- 0.01 mg/kg per minute per microU/mL. CONCLUSION Although Norplant insertion does not alter basal glucose and insulin levels, tissue sensitivity to insulin under hyperglycemic hyperinsulinemic conditions is decreased after Norplant insertion.

Aberrant estradiol flare despite gonadotropin-releasing hormone-agonist-induced suppression is associated with impaired implantation*

Our results confirm the previous report that rapid suppression by GnRH-a is favorable relative to delayed suppression (1). They further indicate that the pattern of E2 production during GnRH-a-induced ovarian suppression may be predictive of cycle outcome. We suggest that imperfect pituitary suppression of bioactive LH as indicated by an aberrant rise in E2 during GnRH-a down-regulation may compromise oocyte quality and ultimately impair implantation. Further study of follicular phase E2 response to GnRH-a suppression may provide a prognostic marker for implantation.

Preliminary evidence that GnRH has the properties of a growth hormone-releasing factor in vivo in the rat.

Objective: We investigated whether GnRH has the properties of a growth hormone-releasing factor in vivo in a mammalian species. Methods: Sexually mature female Sprague-Dawley rats were prepared for in vivo dynamic hormone testing. The rats were assigned to one of four groups: I) GnRH, II) apomorphine and GnRH, III) somatostatin and GnRH, or IV) saline control. Blood samples were drawn at 0, 30, 60, 90, and 120 minutes after treatment. Growth hormone (GH) and LH were measured by radioimmunoassay. Results were analyzed using repeated-measures analysis of variance, Student t test, and comparisons of the area under the curve where appropriate. Results: Gonadotropin-releasing hormone caused a marked rise in both GH and LH levels as a function of time. Apomorphine caused a significant blunting of the LH response to GnRH but did not blunt the GnRH-induced rise in GH. Somatostatin blocked the GnRH-induced rise in GH but did not block the increase in LH. In saline-treated controls, neither the GH nor LH levels exhibited a statistically significant variance over the 2-hour test period. Conclusions: Gonadotropin-releasing hormone appears to have the properties of a growth hormone-releasing factor.

Luteinizing response to human chorionic gonadotropin does not predict outcome in gonadotropin releasing hormone agonist-suppressed/human menopausal gonadotropin-stimulated in vitro fertilization (IVF) cycles.

ObjectiveThe purpose of this study was to determine if early luteinizing potential in gonadotropin releasing hormone agonist (GnRH-a)-suppressed/human menopausal gonadotropin (hMG)-stimulated IVF cycles is predictive of cycle outcome.Design, PatientsThe study was a prospective evaluation of 41 women beginning a GnRH-a-suppressed/hMG-stimulated IVF cycle.SettingThe in vitro fertilization program of a tertiary care institution was the study setting.Main Outcome MeasuresThe main outcome measures were (1) estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration and the following day and (2) the ovarian response to ovulation induction and clinical outcome.ResultsTen of the 41 women achieved a clinical pregnancy (24.4%). There was no significant difference in progesterone (P) levels on the day of or the day following hCG administration between the pregnant and the nonpregnant groups. Both groups exhibited a significant rise in P level in response to hCG. There was no significant difference in E2 levels on the day of hCG between the two groups. The serum E2 did not rise significantly in response to hCG in either group. Patients who became pregnant had significantly more oocytes retrieved, fertilized, cleaved, and transferred.ConclusionsClinical response and outcome in GnRH-a-suppressed/hMG-stimulated IVF cycles are not predicted by early luteinizing potential as indicated by the response of E2 or P to hCG.

Corpus luteum function in successful in vitro fertilization cycles

The function of the corpus luteum in early pregnancy has been subject to some controversy. The purpose of our study was to determine the life span of the corpus luteum in early pregnancy after successful GnRH-a/hMG stimulation in IVF-ET. The study consisted of a retrospective analysis of patients after 12 successful singleton intrauterine IVF-ET cycles. Serum samples were obtained during early pregnancy beginning 14 days after hCG administration. The levels of 17 alpha-OHP, hCG, P, and E2 were measured in each sample. A significant negative correlation was noted between 17 alpha-OHP and date from hCG. The x-intercept of the regression line allowed estimation of the life span of the corpus luteum to be 72 +/- 25 days. In conclusion, in GnRH-a/hMG-stimulated IVF-ET cycles that result in a singleton pregnancy, the functional life span of the corpus luteum averages 72 days.

HLA-DQβ57 in Hispanic patients with insulin-dependent diabetes mellitus

Abstract OBJECTIVE: The purpose of our study was to investigate the distribution of HLA-DQ β-chain amino acid residue 57 (HLA-DQβ57) as a genetic marker of susceptibility for insulin-dependent diabetes mellitus in the Hispanic population. STUDY DESIGN: Fifteen patients of Puerto Rican descent with juvenile-onset insulin-dependent diabetes mellitus underwent human leukocyte antigen typing for HLA-DQβ57 by polymerase chain reaction amplification of the target genomic DQ sequence followed by hybridization of the polymerase chain reaction product to phosphorus 32-labeled allele-specific oligonucleotide probes. A control group of 44 Hispanic adults without diabetes who were undergoing human leukocyte antigen typing for tissue donation were concurrently typed for comparison. RESULTS: The Hispanic insulin-dependent diabetes mellitus group showed a significant increase in homozygosity for a non-aspartate amino acid ( p = 0.023) over a control group of Hispanic subjects without diabetes. A high rate of heterozygosity for aspartate (53.3%) is found in Hispanic subjects with insulin-dependent diabetes mellitus as well. CONCLUSIONS: HLA-DQβ57 in the Hispanic population has a distribution distinct from HLA-DQβ57 in the Caucasian population. A single aspartate is not protective against insulin-dependent diabetes mellitus in Hispanic subjects. (AM J OBSTET GYNECOL 1992;167:1565-70.)