Public health infection prevention: An analysis of existing training during the COVID-19 pandemic.

OBJECTIVES: In response to the COVID-19 pandemic, agencies and organizations required trainings to support the needs of the public health workforce. To better understand the training resources available, this study identified, organized, and classified infection prevention and control (IPC) training and educational opportunities. STUDY DESIGN: Environmental scan. METHODS: A total of 306 IPC training resources were compiled between January and April 2021. Key themes and topics were identified and compared to the Healthcare Infection Control Practices Advisory Committee's (HICPAC) core IPC practices. RESULTS: Three hundred and six training resources, including webinars, fact sheets, module-based learning activities, infographics, and professional practice guidance materials, were identified. Common themes included proper use of personal protective equipment (e.g., masks, gloves), community reopening guidance, and mass vaccination resources. A large proportion (74.9%) of trainings were under 60 min. Using the HICPAC framework, the most frequently addressed content included standard precautions (40%), leadership support (31.6%), and transmission-based precautions (25.8%). Few trainings addressed performance monitoring and feedback (17.1%). CONCLUSIONS: A wide range of organizations developed IPC-specific content during the pandemic. However, these resources did not address the breadth of knowledge required to implement IPC concepts effectively. The creation of universally applicable IPC core competencies and the development of high-quality IPC education and trainings for public health and the overall responder workforces should be prioritized. Accessible high-quality online and just-in-time trainings are critical for future pandemic and disaster preparedness.

Urinary tract infections in very low birthweight infants: A two-center analysis of microbiology, imaging and heart rate characteristics.

BACKGROUND: Increased understanding of characteristics of urinary tract infection (UTI) among very low birthweight infants (VLBW) might lead to improvement in detection and treatment. Continuous monitoring for abnormal heart rate characteristics (HRC) could provide early warning of UTIs. OBJECTIVE: Describe the characteristics of UTI, including HRC, in VLBW infants. METHODS: We reviewed records of VLBW infants admitted from 2005-2010 at two academic centers participating in a randomized clinical trial of HRC monitoring. Results of all urine cultures, renal ultrasounds (RUS), and voiding cystourethrograms (VCUG) were assessed. Change in the HRC index was analyzed before and after UTI. RESULTS: Of 823 VLBW infants (27.7±2.9 weeks GA, 53% male), 378 had > / = 1 urine culture obtained. A UTI (≥10,000 CFU and >five days of antibiotics) was diagnosed in 80 infants, (10% prevalence, mean GA 25.8±2.0 weeks, 76% male). Prophylactic antibiotics were administered to 29 (36%) infants after UTI, of whom four (14%) had another UTI. Recurrent UTI also occurred in 7/51 (14%) of infants not on uroprophylaxis after their first UTI. RUS was performed after UTI in 78%, and hydronephrosis and other major anomalies were found in 19%. A VCUG was performed in 48% of infants and 18% demonstrated vesicoureteral reflux (VUR). The mean HRC rose and fell significantly in the two days before and after diagnosis of UTI. CONCLUSIONS: UTI was diagnosed in 10% of VLBW infants, and the HRC index increased prior to diagnosis, suggesting that continuous HRC monitoring in the NICU might allow earlier diagnosis and treatment of UTI.

Alveolar heparan sulfate shedding impedes recovery from bleomycin-induced lung injury.

The pulmonary epithelial glycocalyx, an anionic cell surface layer enriched in glycosaminoglycans such as heparan sulfate and chondroitin sulfate, contributes to the alveolar barrier. Direct injury to the pulmonary epithelium induces shedding of heparan sulfate into the air space; the impact of this shedding on recovery after lung injury is unknown. Using mass spectrometry, we found that heparan sulfate was shed into the air space for up to 3 wk after intratracheal bleomycin-induced lung injury and coincided with induction of matrix metalloproteinases (MMPs), including MMP2. Delayed inhibition of metalloproteinases, beginning 7 days after bleomycin using the nonspecific MMP inhibitor doxycycline, attenuated heparan sulfate shedding and improved lung function, suggesting that heparan sulfate shedding may impair lung recovery. While we also observed an increase in air space heparanase activity after bleomycin, pharmacological and transgenic inhibition of heparanase in vivo failed to attenuate heparan sulfate shedding or protect against bleomycin-induced lung injury. However, experimental augmentation of airway heparanase activity significantly worsened post-bleomycin outcomes, confirming the importance of epithelial glycocalyx integrity to lung recovery. We hypothesized that MMP-associated heparan sulfate shedding contributed to delayed lung recovery, in part, by the release of large, highly sulfated fragments that sequestered lung-reparative growth factors such as hepatocyte growth factor. In vitro, heparan sulfate bound hepatocyte growth factor and attenuated growth factor signaling, suggesting that heparan sulfate shed into the air space after injury may directly impair lung repair. Accordingly, administration of exogenous heparan sulfate to mice after bleomycin injury increased the likelihood of death due to severe lung dysfunction. Together, our findings demonstrate that alveolar epithelial heparan sulfate shedding impedes lung recovery after bleomycin.

Shifted inferior frontal laterality in women with major depressive disorder is related to emotion-processing deficits.

BACKGROUND: Facial emotion perception (FEP) is a critical human skill for successful social interaction, and a substantial body of literature suggests that explicit FEP is disrupted in major depressive disorder (MDD). Prior research suggests that weakness in FEP may be an important phenomenon underlying patterns of emotion-processing challenges in MDD and the disproportionate frequency of MDD in women. Method Women with (n = 24) and without (n = 22) MDD, equivalent in age and education, completed a FEP task during functional magnetic resonance imaging. RESULTS: The MDD group exhibited greater extents of frontal, parietal and subcortical activation compared with the control group during FEP. Activation in the inferior frontal gyrus (IFG) appeared shifted from a left >right pattern observed in healthy women to a bilateral pattern in MDD women. The ratio of left to right suprathreshold IFG voxels in healthy controls was nearly 3:1, whereas in the MDD group, there was a greater percentage of suprathreshold IFG voxels bilaterally, with no leftward bias. In MDD, relatively greater activation in right IFG compared with left IFG (ratio score) was present and predicted FEP accuracy (r = 0.56, p < 0.004), with an inverse relationship observed between FEP and subgenual cingulate activation (r = - 0.46, p = 0.02). CONCLUSIONS: This study links, for the first time, disrupted IFG activation laterality and increased subgenual cingulate activation with deficient FEP in women with MDD, providing an avenue for imaging-to-assessment translational applications in MDD.

Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis.

Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (P=1.59 × 10(-11)) was the strongest predisposing allele, whereas DRB1*11 (P=1.42 × 10(-10)) was protective. Additionally, DRB1*14 and the DPB1 association (DPB1*03:01; P=9.18 × 10(-7)) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC.

Evidence for malaria selection of a CR1 haplotype in Sardinia.

Complement receptor 1 (CR1) levels have been associated with malarial susceptibility and/or severity of the disease in different population groups, and CR1 is a receptor for Plasmodium falciparum. In this study, multiple CR1 single-nucleotide polymorphisms (SNPs) showed strong evidence of population differentiation between Sardinian and other European ethnic groups. Cross population algorithms comparing haplotype structure and differences in haplotype and allele frequency distribution provided additional support for natural selection of CR1 in Sardinia. The predominant Sardinian CR1 haplotype included SNPs that are associated with decreased CR1 levels in Europeans and other population groups. Previous studies have shown that the SNPs within the dominant Sardinian haplotype have a significantly higher frequency in a malaria endemic compared with non-endemic regions in India. Together with the historical evidence of the prevalence of malaria in Sardinia, these data support the role of malaria leading to positive selection of this CR1 haplotype in Sardinia.

Amerindian ancestry in Argentina is associated with increased risk for systemic lupus erythematosus.

Previous studies have demonstrated that in admixed populations, West African ancestry is associated with an increased prevalence of systemic lupus erythematosus (SLE). In the current study, the effect of Amerindian ancestry in SLE was examined in an admixed population in Argentina. The Argentine population is predominantly European with approximately 20% Amerindian admixture, and a very small (<2%) contribution from West Africa. The results indicate that Amerindian admixture in this population is associated with a substantial increase in SLE susceptibility risk (Odds Ratio=7.94, P=0.00006). This difference was not due to known demographic factors, including site of collection, age and gender. In addition, there were trends towards significance for Amerindian ancestry influencing renal disease, age of onset and anti-SSA antibodies. These studies suggest that populations with Amerindian admixture, like those with West African admixture, should be considered in future studies to identify additional allelic variants that predispose to SLE.

In situ stabilization of soil lead using phosphorus.

In situ stabilization of Pb-contaminated soils can be accomplished by adding phosphorus. The standard remediation procedure of soil removal and replacement currently used in residential areas is costly and disruptive. This study was carried out to evaluate the influence of P and other soil amendments on five metal-contaminated soils and mine wastes. Seven treatments were used: unamended control; 2,500 mg of P/kg as triple superphosphate (TSP), phosphate rock (PR), acetic acid followed by TSP, and phosphoric acid (PA); and 5,000 mg of P/kg as TSP or PR. A significant reduction in bioavailable Pb, as determined by the physiologically based extraction test (PBET), compared with the control upon addition of P was observed in all materials tested. Increasing the amount of P added from 2,500 to 5,000 mg/kg also resulted in a significantly greater reduction in bioavailable Pb. Phosphate rock was equally or more effective than TSP or PA in reducing bioavailable Pb in four out of five soils tested. Preacidification produced significantly lower bioavailable Pb compared with the same amount of P from TSP or PR in only one material. Reductions in Pb bioavailability as measured by PBET were evident 3 d after treatment, and it may indicate that the reactions between soil Pb and P occurred in situ or during the PBET. No further reductions were noted over 365 d. X-ray diffraction data suggested the formation of pyromorphite-like minerals induced by P additions. This study suggests that P addition reduced bioavailable Pb by PBET and has potential for in situ remediation of Pb-contaminated soils.

Addition of an N-terminal dimerization domain promotes assembly of hCG analogs: implications for subunit combination and structure-function analysis.

Human chorionic gonadotropin (hCG) is a heterodimeric placental glycoprotein hormone that acts through ovarian lutropin receptors (LHR) to maintain early pregnancy. Its ability to distinguish LHR and follitropin receptors (FSHR) is controlled by 20 beta-subunit 'seatbelt' residues that surround alpha-subunit loop 2. Positively charged amino acids between residues 93-100, a small loop within the seatbelt, have been postulated to make essential LH receptor contacts. Previous studies showed that analogs containing negatively charged amino acids in this small loop had 5-10% the activity of hCG and 1-10% the lutropin activities of hCG/hFSH chimeric analogs capable of binding LHR and FSHR. These effects might be due to the influence of these residues on receptor contacts or on hormone conformation. During efforts to distinguish these possibilities, we increased and decreased the number of residues in this loop, mutations we anticipated would distort its conformation. Consistent with this supposition, these changes inhibited dimer formation, precluding assessment of these mutations on hormone activity. Addition of Fos and Jun dimerization domains to the N-termini of hCGalpha- and hCG/hFSHbeta-subunit chimeras overcame the effects of the seatbelt mutations on subunit combination and enabled preparation of heterodimers containing six, seven, or nine residues in their seatbelt loops. These had 0.1-10% the lutropin and 3-60% the follitropin activities of bifunctional chimeras containing 8 residues derived from hCG in the seatbelt loop. The abilities of N-terminal dimerization domains to promote subunit combination may permit structure/function analysis of other residues that influence heterodimer formation.

The New Zealand Socioeconomic Index: developing and validating an occupationally-derived indicator of socio-economic status.

OBJECTIVE: Following revision of the international standard classification (ISCO88), to update and validate on health data an occupationally derived indicator of socio-economic status (SES) adapted to changing occupational and demographic conditions. METHOD: The development of the New Zealand Socioeconomic Index (NZSEI) is based on a 'returns to human capital' model of the stratification process and uses data from the 1991 New Zealand Census (n = 1,051, 926) to generate scores for 97 occupational groups. The construct validation of the scale is carried out on data from the 1992-93 nationwide Household Health Survey (n = 3,000) using three health indicators (self-assessed health, cigarette smoking, general practitioner visits). RESULTS: In general, the results are consistent with expected socio-economic patterns drawn from the literature for the three indicators. CONCLUSIONS: While further work is required on a number of methodological and conceptual issues, the NZSEI provides a robust, standardised and internationally comparable occupational scale of SES for both males and females in either full- or part-time employment. IMPLICATIONS: The NZSEI can be used on routinely collected occupational data. It has a clear conceptual rationale, updates existing SES scales, and provides a link to international standards in SES and occupational classification.

Surgical management of cornual-isthmic tubal obstruction.

OBJECTIVE: To examine the efficacy of microsurgical tubal anastomosis among patients having failed attempts to correct cornual-isthmic tubal obstruction by hysteroscopic tubal catheterization. DESIGN: An open observational trial. SETTING: A tertiary referral reproductive medicine practice. PATIENT(S): Forty-three patients with laparoscopically confirmed bilateral cornual-isthmic obstruction and otherwise normal fallopian tubes. Thirty-three control patients with a history of elective sterilization presenting for tubal anastomosis. INTERVENTION(S): All patients with bilateral cornual-isthmic obstruction underwent attempted hysteroscopic tubal cannulation. Those unsuccessfully catheterized proceeded with microsurgical resection and anastomosis. Candidates for reversal of sterilization underwent microsurgical repair in standard layered technique. MAIN OUTCOME MEASURE(S): Mean time to achieve pregnancy, as well as cumulative pregnancy rates for all three groups using life-table analysis, were calculated. RESULT(S): Cumulative pregnancy rates for patients with successful tubal catheterization, for those requiring microsurgical repair, and for reversal of elective sterilization were 0.68%, 0.56%, and 0.29%, respectively, at 12 months. Mean duration to achieve pregnancy was similar for both cornual-isthmic blockage-treated groups and was shorter than that for the sterilization-reversal group. CONCLUSION(S): Patients with cornual-isthmic obstruction and otherwise normal fallopian tubes who are treated successfully by either tubal catheterization or resection and microsurgical anastomosis demonstrate high pregnancy rates, short interval to achieve pregnancy, and similar obstetric outcome. If no pregnancy is achieved within 1 year of surgery, reevaluation and consideration for possible IVF and ET is indicated.

The effect of hypertonic sodium and dantrolene on propranolol cardiotoxicity.

OBJECTIVE: To evaluate whether measures that lower cytosolic calcium (Ca) can reverse propranolol (PROP) toxicity in the isolated, perfused rat heart. METHODS: Isolated rat hearts were perfused on a Langendorff apparatus with Krebs-Henseleit-bicarbonate (KHB) buffer solution. Toxicity was produced by perfusing the hearts with PROP (5 micrograms/mL) for 30 minutes. Subsequently, the hearts were treated for 30 minutes with buffer containing PROP plus experimental treatment. Three treatments were chosen: hypertonic sodium (Na) (160 mmol), to stimulate Na-Ca exchange, dantrolene (DAN) (10 mumol), to inhibit Ca release from sarcoplasmic reticulum, and combined hypertonic Na and DAN. The hearts were paced after 20 minutes of treatment. Heart rate (HR), left ventricular peak systolic pressure (LVP), the first derivative of LVP (dP/dt), and coronary flow were measured. RESULTS: PROP decreased HR and rendered the hearts refractory to pacing. PROP did not alter dP/dt. PROP increased LVP consistent with increased cytosolic Ca. Combined hypertonic Na and DAN treatment restored the ability to pace PROP-toxic hearts to the basal HR. Individually, hypertonic Na or DAN treatment partially restored the ability to pace toxic hearts. As experimental treatments increased HR, dP/dt and LVP decreased, consistent with decreased cytosolic Ca availability. CONCLUSION: These data are consistent with the hypothesis that bradycardia during beta-blocker cardiotoxicity is mediated by altered Ca homeostasis.

Direct gamete uterine transfer in patients with tubal absence or occlusion.

PURPOSE: Our aim was to examine the potential of the uterine cavity to affect fertilization and early embryo development. DESIGN: A prospective IRB-approved protocol for patients fulfilling study eligibility criteria was used. METHODS: Patients studied included those with primary or secondary infertility, aged less than 38 years, with no history of severe male-factor infertility, and with hysterosalpingogram- and laparoscopic-confirmed bilateral proximal tubal occlusion. Superovulation induction was accomplished with a combination of GnRH agonist and menotropins, with serum hormonal and sonographic monitoring. Within 24 hr prior to, and again at the time of, ovulatory hCG administration, progesterone (P4) was given. Sonographic-guided transvaginal retrieval was performed 35 hr after hCG. Between four and six oocytes were returned to the uterine cavity, admixed with sperm, immediately following retrieval. Luteal support consisted of daily P4 administration. RESULTS: Of the 20 patients recruited for the study, all completed the retrieval and transfer procedure. A total of four clinical pregnancies was achieved, with one early first-trimester loss, one late first-trimester loss (Trisomy 14), and two healthy term infants delivered. IVF of surplus oocytes demonstrated a 82.5% fertilization rate and 66.7% cleavage following cryopreservation. CONCLUSIONS: Human fertilization can be achieved through direct uterine transfer of gametes. Furthermore, administration of P4 prior to the ovulatory dose of hCG is compatible with in vitro or in vivo fertilization and implantation.

Effect of ethanol, haloperidol, and lorazepam on cardiac conduction and contraction.

Haloperidol and lorazepam are commonly used to sedate ethanol (E)-intoxicated patients in emergency departments. This study was conducted to explore the role of ethanol in altering the potency of haloperidol and lorazepam with respect to cardiac conduction and contraction. For mechanical studies, isolated rat hearts were studied under isovolumetric conditions by using standard Langendorff technique. Hearts were perfused with Krebs-Heinseleit-Bicarbonate buffer containing haloperidol or lorazepam in concentrations ranging from 100 to 750 ng/ml (one heart per drug concentration). For both haloperidol and lorazepam individually, significant reductions in Left ventricular-generated pressure (LVGP) were observed at a concentration of 750 ng/ml (haloperidol = 2,250 nM and lorazepam = 2,000 nM). The addition of 20 and 65 mM ethanol shifted the concentration-response effect of haloperidol such that LVGP was significantly reduced at haloperidol = 500 and 300 ng/ml, respectively (p < 0.05 vs. basal control; paired t test). Ethanol produced no observable shift on the lorazepam concentration-response for LVGP. For electrophysiologic studies, hearts were perfused with haloperidol and lorazepam (300 ng/ml) +/- 65 mM ethanol. Compared with basal control, E + H significantly decreased heart rate (-74 +/- 12 beats/min) and increased His-ventricular conduction time (+7.6 +/- 1.5 ms vs. +1.7 +/- 0.6 ms for control hearts). Both haloperidol and EH significantly increased atrioventricular (AV) effective refractory period and the atrioventricular-His (AH) conduction interval. No significant changes in any electrophysiologic parameter were observed with ethanol or lorazepam perfused individually or with the combination of ethanol and lorazepam. Ethanol potentiates haloperidol-induced electromechanical depression of isolated rat hearts. Ethanol had no such effect on lorazepam.

Menotropins alone are superior to a clomiphene citrate and menotropin combination for superovulation induction among clomiphene citrate failures.

OBJECTIVE: To examine the difference in efficacy between two protocols of superovulation induction with IUI among infertile couples. DESIGN: A prospective randomized trial. SETTING: Normal human volunteers in an infertility clinic. PATIENTS: Consecutively treated patients attending our infertility clinic for superovulation induction with IUI who had been unsuccessfully treated by clomiphene citrate (CC). INTERVENTIONS: Infertile couples were randomized to undergo one of two controlled ovarian hyperstimulation protocols. Group A patients received daily hMG beginning on cycle day 3, whereas group B patients were administered CC days 3 through 7, followed by hMG from day 7 onward. Randomization was performed using a random numbers table. In both groups, ovulation was triggered by 5,000 IU hCG and IUI was performed by 36 hours. MAIN OUTCOME MEASURES: Studied cycle performance parameters included peak E2, number of dominant and intermediate-sized follicles recruited, endometrial thickness and pattern, and frequency of monitoring. RESULTS: Data analysis demonstrated no significant difference between the two groups with respect to patient age, parity, weight, indication for superovulation and IUI, number of dominant follicles recruited, peak E2, or mean number of total motile sperm inseminated. Endometrial thickness and pattern differed between treatments, however, with group A demonstrating relatively thicker and proportionately more trilaminar patterns than group B. Group A had significantly more serum E2 measurements, as well as transvaginal sonograms performed, when compared with group B. Pregnancy rates for groups A and B were 0.192 and 0.091, respectively. Of 25 pregnancies in group A, 7 (0.28) were multiples, whereas there were no multiple gestations in group B. CONCLUSION: For patients undergoing superovulation with IUI, a menotropin-alone protocol yields significantly higher pregnancy rates than one using a combination of menotropin with CC. These differences could not be explained by patient characteristics. Among cycle performance parameters, endometrial thickness and pattern differed significantly between the two groups.

The effects of extracellular ions on beta-blocker cardiotoxicity.

The mechanism of beta-blocker induced cardiotoxicity is poorly understood. One possible explanation is that beta-blockers induce ion dyshomeostasis, resulting in cardiac hyperpolarization. The intent of this study was to determine if modifying extracellular ions would reverse cardiotoxicity from two beta-blockers: propranolol (PROP) and atenolol (ATEN). Two treatments were studied: low extracellular K+ and high extracellular Na+. Isolated rat hearts were perfused on a Langendorff apparatus with Krebs-Henseleit- Bicarbonate buffer (KHB) solution. Toxicity (Tox) was induced by perfusing hearts for 30 min with KHB + PROP [5 microgram/ml] or KHB + ATEN [2.5 mg/ml]. Subsequently, hearts were perfused with KHB containing either PROP or ATEN, but modified by lowering K+ [2.3 mM] or raising Na+ [160 mM] for a 30-min treatment (Tx) period. Hearts were paced near the end of treatment. Cardiodynamics were monitored via a balloon-tipped catheter in the left ventricle. The first derivative of LV pressure (dP/dt) with respect to time served as our index of myocardial performance. Tx groups were as follows: (1) KHB only, (2) PROP only, (3) PROP + K, (4) PROP + Na, (5) ATEN only, (6) ATEN 4 K, and (7) ATEN + Na. PROP induced negative chronotropic effects and rendered the hearts refractory to pacing. ATEN demonstrated similar chronotropic toxicity plus decreased myocardial contractility. Tx with low extracellular K+ and high extracellular Na+ increased HR and restored the ability to pace, thereby reversing toxicity. These data suggest that beta-blocker toxicity is mediated via hyperpolarization.

Identification of hormonal parameters for successful systemic single-dose methotrexate therapy in ectopic pregnancy.

Single-dose methotrexate is an alternative to surgery in treating ectopic pregnancy. Because success rates vary, we sought to identify factors which predict treatment outcome. A total of 44 women with ectopic gestation were treated. The non-laparoscopic diagnosis of ectopic pregnancy was made following history, physical examination, ultrasound, endometrial biopsy and the measurement of serial beta-human chorionic gonadotrophin (HCG) and progesterone concentrations. Methotrexate (50 mg/m2 i.m.) was administered, with a second dose given 1 week later in patients with plateauing or rising beta-HCG concentrations. Of 44 patients, 23 (52.3%) were successfully treated with one dose. An additional 10 women (22.7%) were also successfully managed but required a second dose, giving an overall success rate of 75.0%. In all, 11 women (25.0%) required surgery, four of whom experienced tubal rupture. Receiver operator curves were constructed to optimally select pretreatment beta-HCG and progesterone cut-off concentrations for successful treatment. Using beta-HCG < 1500 IU/l or progesterone < 7.0 ng/ml (22.3 nmol/l) as a cut-off concentration produced a diagnostic test with a sensitivity of 87.5%, a specificity of 90.0%, a positive predictive value of 96.6% and a negative predictive value of 69.2%. Conversely, this model predicts that patients with serum beta-HCG concentrations > or = 1500 IU/l and progesterone concentrations > or = 7.0 ng/ml are at far greater risk of failing single-dose methotrexate therapy.

Serum progesterone as a predictor of methotrexate success in the treatment of ectopic pregnancy.

OBJECTIVE: To determine the prognostic value of a single serum progesterone measurement for resolution of ectopic pregnancy following methotrexate therapy. METHODS: All patients attending our infertility clinic had quantitative beta-hCG and serum progesterone measured prospectively within the first week of missed menses. Ectopic pregnancy was diagnosed nonsurgically by poorly rising beta-hCG levels and lack of evidence of intrauterine gestation by transvaginal sonography. Once diagnosed, candidates received a single intramuscular injection of methotrexate, 50 mg/m2. Treatment outcome was categorized as either resolved or requiring surgery, and interpreted with respect to serum progesterone measured within 24 hours of methotrexate administration. RESULTS: Twenty-one patients were treated for ectopic pregnancy. Eleven had serum progesterone levels greater than 10 ng/mL and ten patients had levels of 10 ng/mL or less. The two groups did not differ significantly with respect to age, weight, hCG at the time of methotrexate administration, or amount of methotrexate administered. Of the 11 patients with serum progesterone levels above 10 ng/mL, only five had pregnancies that resolved following methotrexate. All ten patients with levels less than 10 ng/mL had resolution. This difference is significant (P = .009, 95% confidence interval 0.26-0.84). There was no improvement in the prediction of outcome when either the absolute or daily percentage increase of hCG was determined before methotrexate administration. CONCLUSION: A single serum progesterone measurement above or below 10 ng/mL is useful for predicting resolution of tubal pregnancy with methotrexate treatment.

Does increasing frequency of intrauterine insemination improve pregnancy rates significantly during superovulation cycles?

OBJECTIVE: To compare pregnancy rates (PR) per treatment cycle of controlled ovarian hyperstimulation (COH) patients receiving a single IUI with COH patients receiving two IUIs. DESIGN: A prospective randomized trial of consecutively treated patients attending our infertility clinic for COH and IUI. METHODS: Patients undergoing COH by hMG and hCG were randomized to receive either one (group A) or two (group B) IUIs. Randomization was performed using a random number table. Group A IUIs were timed 35 hours after ovulatory hCG, whereas group B IUIs were performed 19 and 43 hours after hCG. RESULTS: A total of 120 patients during 169 cycles were randomized between group A (90 cycles) and group B (79 cycles). Data analysis demonstrated no significant differences between groups A and B with respect to age, indications for COH, duration of hMG treatment, total amount of hMG administered, peak E2 levels, number of dominant follicles recruited, or mean number of total motile sperm inseminated. Pregnancy rates for groups A and B were 0.11 and 0.14, respectively. The size of our study population permits a conclusion that a 300%, 200%, or 100% difference in PR between the two groups does not exist (power 0.97, 0.80, or 0.61, respectively). CONCLUSION: Among patients undergoing COH and IUI, increasing the frequency of insemination does not provide a significant increase in cycle pregnancy rate.