Bleeding and spontaneous abortion after therapy for infertility.

OBJECTIVE: To determine the incidence of early-pregnancy bleeding and spontaneous abortion (SAB) after various treatments for infertility and to assess whether bleeding is predictive of SAB. DESIGN: An historic cohort study of women who conceived after various treatments. SETTING: Hospital-based private practice. PATIENT(S): We studied 418 patients in whom 500 consecutive clinical pregnancies occurred. INTERVENTION(S): Patients were grouped according to the method of conception: ovulation induction, IVF, and other. The latter category included interventions not requiring ovulation induction, such as surgery and insemination. A fourth group of subjects who conceived independently of treatment was used as the control. MAIN OUTCOME MEASURE(S): Bleeding and pregnancy outcome (SAB, ectopic pregnancy, or ongoing pregnancy). RESULT(S): Rates of SAB did not differ among the treatment groups. SAB occurred significantly more often after bleeding than when bleeding did not occur (30.8% versus 19.8%, respectively). Bleeding was predictive of SAB only in patients <35 years old (odds ratio 2.4). CONCLUSION(S): Infertile women who conceive after reproductive therapy are not at increased risk for SAB compared with women who conceive naturally. There appears to be no association between previous diagnosis or treatment and the occurrence of SAB in previously infertile women. Bleeding is associated with a twofold relative risk of SAB.

Ciprofibrate--racemate and enantiomers: effects of a four-week treatment on male inbred Fischer rats. A biochemical and morphological study.

Ciprofibrates (racemate and both enantiomers, Raccip, R- and Scip) were administered orally in doses of 1 and 10 mg/kg once daily over 28 days to male inbred Fischer 344 rats, age 90-110 days at the beginning of the experiment. Body mass gain was observed in all groups. The 1 mg groups showed almost no difference to the control group. The 10 mg groups exhibited less body mass gain, most pronounced in the Scip group. Liver masses were increased in a dose dependent manner up to more than 200%, only the 10 mg Scip group was not significantly different from the 1 mg group which exhibited an increase in liver weight to about 175%. Also the kidney weights increased to 130%, whereas thymus and spleen weights were decreased in the high dose groups. Liver microsomal cytochromes P450 (P450) concentrations were not altered in the 1 mg groups and distinctly lowered in the 10 mg groups. Ethoxyresorufin and ethoxycoumarin O-deethylations were lowered in all experimental groups in a dose dependent manner, after administration of the high doses down to 30% of the control levels or less. Pentoxyresorufin O-depentylation, however, was increased in all 1 mg groups. In the high dose groups it was not altered. Ethylmorphine N-demethylation was decreased after administration of the high doses by about 50%, but only Scip decreased this reaction also after administration of the low dose. NADPH/Fe2+-stimulated microsomal luminol and lucigenin amplified chemiluminescence was increased, whereas hydrogen peroxide formation was depressed even by the low doses to 50% of the normal values, to about 25% by the high doses. Microsomal lipid peroxidation, however, was only slightly or not influenced. Glutathion concentrations (in the reduced and the oxidized form) were increased in a dose dependent manner by about 20 to 30%, the concentration of lipid peroxides was not significantly influenced. Thus, the effects of the enantiomers were not different and were similar to those of the racemate. In serum, cholesterol and triglycerides were only moderately lowered. Albumin concentrations were significantly enhanced in all groups, total proteins after 1 mg/kg Raccip only. Serum bilirubins were not altered, and among the indicator enzymes for liver damage only ALAT, alkaline phosphatase and the dehydrogenases were increased, in no case higher than twofold. Histologically distinct effects were seen after administration of both doses, more pronounced after 10 mg/kg, but with no differences between the enantiomers and Raccip: marked hypertrophy of the hepatocytes, reduced staining of the nuclei, strongly acidophilic granulated cytoplama, no basophilia of the cell bodies, loss of glycogen. These changes were most pronounced around the central veins. Hepatocyte apoptoses also were observed. By immunohistochemistry an increased staining was seen for all P450 isoforms tested (1A1, 2B1, 2E1, 3A2 and 4A1), predominantly perivenously and most pronounced after administration of the high doses without differences between Rcip, Scip or Raccip (preliminary results). By electron microscopy a moderate proliferation of peroxisomes after treatment with 1 mg/kg Cips with a ratio between mitochondria and peroxisomes of about 1:1 (controls: 10:1) was observed, and the peroxisomes were a more heterogeneous population. The relative portions of glycogen and both forms of the ER decreased. Treatment with 10 mg/kg Rcip, Scip or Raccip led to a strong increase in the number of peroxisomes, in some hepatocytes the ratio between mitochondria and peroxisomes was 1:3 with an increased heterogeneity among the peroxisomes evidenced by a broad range of electron densities. Most peroxisomes lacked a nucleoid. Thus, the biochemical effects differed only slightly and the morphological effects of the enantiomers were not different and were similar to those of the racemate.

Quantitative topographical analysis of EEG during nonstandardized and standardized hyperventilation.

The aim of this study was to compare the topographical quantitative EEG (qEEG) changes induced by nonstandardized hyperventilation and those induced by standardized hyperventilation (with the end-tidal PCO2 being maintained at 2 kPa [15 mm Hg]). We examined 18 healthy volunteers during nonstandardized and 20 during standardized hyperventilation. During nonstandardized hyperventilation, the mean spectral power density in this group significantly increased 1.9 fold within the delta-, 2.2 fold within the theta-, 1.8 fold within the alpha-, and 1.9 fold within the beta-frequency band. There was no significant change of the power ratio and was no topographic difference between 4 frequency bands investigated. During standardized hyperventilation, the mean spectral power density in the group significantly increased to 12.9 fold within the delta-, to 7.6 fold within the theta-, to 1.4 fold within the alpha-, and to 2.4 fold within the beta frequency band. The power ratio decreased significantly. Such a pronounced EEG slowing with delta and theta augmentation was never found during nonstandardized hyperventilation. We conclude that a consistent slowing of the qEEG in all leads including a constant topographical maximum can only be induced by standardized, sufficiently pronounced hyperventilation.

Efficacy of intracytoplasmic sperm injection using intentionally cryopreserved epididymal spermatozoa.

Microsurgical epididymal sperm aspiration was a great advance in the therapy of patients with non-reconstructable, obstructive azoospermia, most notably congenital bilateral absence of the vas deferens. Using conventional in-vitro fertilization, pregnancies were rarely achieved because the rate of oocyte fertilization was extremely poor. However, the use of retrieved spermatozoa in conjunction with intracytoplasmic sperm injection (ICSI) has dramatically increased the likelihood of embryo formation. Typically, sperm and oocyte harvesting are performed simultaneously. We have investigated whether frozen-thawed spermatozoa work as well as fresh spermatozoa. When we had concluded from our own population of patients (groups I and II) that they did, we adopted a policy of aspirating spermatozoa, primarily cryopreserving them and using them for ICSI at a later date. We found the fertilization rates of this latter cohort of patients (group III) to be excellent (37% per oocyte), and the ongoing pregnancy rate is quite satisfactory (40% per couple, 29% per cycle). We offer this approach as an alternative to the traditional scheme because it markedly eases the burden of partner scheduling on both the couple and the clinicians involved. In addition, assurance of the availability of male partner spermatozoa can be attained prior to beginning ovulation induction.

The achievement of pregnancies using assisted reproductive technologies for male factor infertility after retroperitoneal lymph node dissection for testicular carcinoma.

OBJECTIVE: To evaluate the success of electroejaculation with assisted reproductive technologies (ART) in anejaculate men after retroperitoneal lymph node dissection (RPLND) for testicular cancer. DESIGN: Retrospective clinical study. SETTING: Tertiary care, university-affiliated IVF program. PATIENTS: Anejaculate men after RPLND, spouses. INTERVENTIONS: Electroejaculation, microsurgical sperm aspiration, various assisted reproductive technologies. MAIN OUTCOME MEASURES: Sperm density and motility, fertilization rate, pregnancy rate (PR). RESULTS: Compared with patients not receiving chemotherapy, patients who received chemotherapy had diminished average sperm densities and motilities (63 x 10(6) and 20% versus 101 x 10(6) 32%, respectively); decreased fertilization rates per cycle for IVF and intracytoplasmic sperm injection (ICSI) (11% versus 26%, respectively); lower PRs per cycle of hMG-IUI and IVF (14% versus 60% and 8% versus 50%, respectively). No pregnancies were achieved with natural cycle-IUI, clomiphene citrate-IUI, or GIFT. Two couples progressed to intracytoplasmic sperm injection with one achieving the successful delivery of healthy twins. The overall PR per cycle was 22%. CONCLUSIONS: Patients receiving chemotherapy had decreased sperm densities, motilities, fertilization, and PRs for each modality used. Rectal probe electroejaculation with ART can help anejaculate men after RPLND achieve biologic paternity. An early move to the more aggressive therapies (hMG-IUI, IVF, ICSI) is supported.

Gonadotropin-releasing hormone antagonist versus agonist administration in women undergoing controlled ovarian hyperstimulation: cycle performance and in vitro steroidogenesis of granulosa-lutein cells.

OBJECTIVES: We sought to determine the effectiveness of a gonadotropin-releasing hormone antagonist compared with an agonist in suppressing a spontaneous luteinizing hormone surge in women undergoing controlled ovarian hyperstimulation for in vitro fertilization and gamete intrafallopian transfer and to examine whether in vivo administration of these analogs effects granulosa-lutein cells steroidogenesis in vitro. STUDY DESIGN: This prospective case-control study included 30 healthy women undergoing ovarian hyperstimulation with human menopausal gonadotropins. Fifteen women received the Nal-Glu antagonist, 5 mg intramuscularly daily, when the lead follicle was > or = 15 mm or serum estradiol level was > or = 500 pg/ml. The control group included 15 women who underwent oocyte retrieval on the same day as the study subjects and were given the agonist leuprolide acetate, 250 micrograms subcutaneously daily, starting on cycle day 1. Granulosa-lutein cells were purified from follicular aspirates from six subjects and six controls and cultured in parallel, evaluating basal progesterone production, progesterone response to follicle-stimulating hormone or luteinizing hormone and aromatase activity. RESULTS: No difference was demonstrated in the total amount of gonadotropins received by the two groups. Overall, the gonadotropin-releasing hormone antagonist was given for only 2.5 +/- 0.2 (mean +/- SEM) days before human chorionic gonadotropin administration. The antagonist group showed significantly lower levels of serum luteinizing hormone than did the agonist group, 1.0 +/- 0.2 versus 4.2 +/- 0.5 mIU/ml (p = 0.0001) on the day of human chorionic gonadotropin administration. Serum estradiol levels were significantly lower in the antagonist than the agonist group, 820 +/- 120 versus 1361 +/- 110 pg/ml (p = 0.003) on the day of human chorionic gonadotropin administration. There was no difference in the number of retrieved oocytes, but the antagonist group had a higher proportion of mature oocytes, 82% +/- 4% versus 62.4% (p = 0.02), and a higher proportion of embryos of good quality, 69.8% +/- 9.8% versus 44.3% +/- 7.2% (p = 0.03) in the agonist group. Granulosa-lutein cells from antagonist-treated women showed significantly lower aromatase activity the first 6 hours after retrieval, 17.6 +/- 1.6 versus 31.3 +/- 7.4 ng/ml per 6 hours estradiol (p = 0.03), whereas basal and gonadotropin-stimulated with progesterone responses were similar. CONCLUSION: Gonadotropin-releasing hormone antagonist administration during the late follicular phase resulted in lower serum luteinizing hormone and estradiol levels and more mature oocytes and embryos of better quality compared with gonadotropin-releasing hormone agonist administration. These results suggest that gonadotropin-releasing hormone antagonist administration in ovarian hyperstimulation has practical advantages over the agonist regimen. Gonadotropin-releasing hormone analogs may have direct action on ovarian function with differential effects on granulosa-lutein cell aromatase activity. This could explain the lower serum estradiol levels routinely observed in women given gonadotropin-releasing hormone antagonist.

Evolving approaches to management of quality in clinical microbiology.

Quality management in clinical microbiology began in the 1960s. Both government and professional societies introduced programs for proficiency testing and laboratory inspection and accreditation. Many laboratory scientists and pathologists were independently active and creative in expanding efforts to monitor and improve practices. The initial emphasis was placed on intralaboratory process. Later, attention was shifted to physician ordering, specimen collection, reporting, and use of information. Quality management in the laboratory depends in large part on the monitoring of indicators that provide some evidence of how laboratory resources are being used and how the information benefits patient care. Continuous quality improvement should be introduced. This consists of a more thorough assessment of doing the right things versus the wrong things in terms of customer demand and satisfaction and studying the cumulative effect of error when responsibility is passed from one person to another. Prevention of error is accomplished more through effective training and continuing education than through surveillance. Also, this system will force more conscious attention to meeting the expectations of the many customers that must be satisfied by laboratory services, including patients, physicians, third-party payers, and managed-care organizations.

The sex ratio of normal and manipulated human sperm quantitated by the polymerase chain reaction.

OBJECTIVE: To establish the primary sex ratio, the relative abundance of X and Y chromosome-bearing sperm, in unselected sperm and in sperm selected by swim-up or Sephadex filtration (SpermPrep column; Fertility Technologies, Inc., Natick, MA). This was done to evaluate the possibility that these semen manipulations change the primary sex ratio. DESIGN: Ninety-eight unmanipulated semen samples were analyzed for sex chromosome content using quantitative polymerase chain reaction (PCR). A smaller number of samples was analyzed before and after either swim-up or Sephadex filtration. RESULTS: The mean percentage of all sex chromosomes identified as a Y chromosome in unmanipulated semen samples ranged from 41.9% to 56.7%, with a mean average of 50.3%. There was no significant change in sex chromosome composition after either swim-up (n = 17) or column filtration (n = 20). CONCLUSIONS: The chromosome compositions of semen samples from a large number of men have equal numbers of X and Y. Swim-up and SpermPrep filtration do not appear to alter the primary sex ratio.

Acute adrenocorticotropin stimulation of postmenopausal cigarette smokers and nonsmokers: effects on steroidogenesis.

Cigarette smoking has been associated with elevated levels of A and DHEAS in postmenopausal women. One possible mechanism postulated for this effect is enzymatic blockage by components of cigarette smoke. In this study, acute ACTH stimulation of postmenopausal cigarette smokers did not result in abnormal elevations of precursor steroids. Other possible mechanisms may be operative in vivo to account for the previously reported findings.

Chronic T-lymphocyte activation in chronic renal failure: a study of hemodialysis, CAPD and pre-dialysis patients.

In this study we measured indices of T-lymphocyte activation in normal volunteers, chronic hemodialysis patients, CAPD patients and chronic renal failure patients not yet on dialysis. Serum IL-2 levels were elevated in patients compared to controls. Soluble IL-2 receptors were elevated in all three patient groups and were highest in CAPD patients. Clearance of IL-2 and soluble interleukin receptors was negligible in dialysis and renal failure patients. Hemodialysis patients had a significantly lower percentage of CD3-positive cells than all other groups. Hemodialysis with a variety of membrane/bath combinations did not significantly affect any of the parameters measured. This study provides some support for the hypothesis that chronic T-cell activation is present in renal failure.

Preoperative uterine artery embolization in cervical pregnancy.

Cervical pregnancy often results in massive hemorrhage following curettage. Performance of uterine artery embolization before curettage is reported in three consecutive cases of cervical pregnancy. All patients had a successful outcome without significant hemorrhage.

Laboratory reports issued on or after discharge date.

The authors of this article discuss the problem of ensuring that physicians are informed of bacteriology test results in a timely manner, a study they undertook, and the steps taken to solve the problem.

Tumor necrosis factor, interleukin-1 and beta 2-microglobulin levels in chronic hemodialysis patients.

We measured tumor necrosis factor (TNF alpha), interleukin-1 (IL1-B), and beta-2 microglobulin (B2M) levels in 10 chronic hemodialysis patients before and during dialysis with six different dialysate/dialyzer combinations. The mean pre-dialysis serum level of B2M was 23.4 +/- 11.1 mg/L (nl less than 3 mg/L). There was no significant effect of hemodialysis with any dialysate/dialyzer combination on intradialytic serum B2M levels. Five patients had detectable pre-dialysis serum levels of TNF alpha (greater than 40 pg/ml) at least once and 2 had detectable levels prior to all dialyses. Six patients had detectable pre-dialysis serum levels of IL1-B (greater than 20 pg/ml) at least once, and 2 had detectable levels prior to all dialyses. Serum TNF alpha, IL1-B and B2M levels were not significantly correlated with one another. Our data do not support the hypothesis that blood-membrane interactions significantly affect circulating levels of TNF alpha, IL1-B or B2M. Chronic high level elevations of plasma IL1-B and TNF alpha are not uniformly observed in hemodialysis patients, arguing against a role for these substances as systemic uremic toxins.

Preoperative angiographic uterine artery embolization in the management of cervical pregnancy.

The diagnosis of a cervical ectopic pregnancy is often made intraoperatively in the presence of extensive hemorrhage during attempted evacuation. In some cases, hysterectomy has been the necessary treatment to control bleeding. We report two cases of cervical pregnancy detected by ultrasound. Before pregnancy termination, the uterine arteries were successfully embolized using angiographic techniques. As a result, surgical evacuation was performed with minimal hemorrhage; hysterectomy was not required and the patients' potential fertility was retained.

Efficacy and safety considerations in women with uterine leiomyomas treated with gonadotropin-releasing hormone agonists: the estrogen threshold hypothesis.

Gonadotropin-releasing hormone agonists induce a reversible hypogonadotropic hypogonadal environment. Leiomyomas are common, estrogen-sensitive, benign neoplasms that decrease in size by 40% to 50% during gonadotropin-releasing hormone agonist treatment. During gonadotropin-releasing hormone agonist therapy most women are amenorrheic. After discontinuation of gonadotropin-releasing hormone agonist treatment, uterine and myoma size increase and a return to pretreatment menstrual patterns often occurs. Concerns about the safety of long-term hypoestrogenism have made long-term gonadotropin-releasing hormone agonist administration an undesirable treatment strategy. This article focuses on the use of gonadotropin-releasing hormone agonists as preoperative therapy in selected women undergoing hysterectomy or myomectomy and the combination of a gonadotropin-releasing hormone agonist with estrogen-progestin "add-back" treatment as a potential long-term medical therapy for women with symptomatic leiomyomas. Finally, an estrogen threshold hypothesis to assess the effects of circulating estrogen concentrations on different tissues, is presented.

Type I diabetes in an adolescent with common variable immunodeficiency.

A male adolescent with common variable immunodeficiency developed type I diabetes approximately 1 year after the initiation of immunoglobulin therapy. Immunologic evaluation revealed decreased numbers of T cells and an intrinsic B cell defect in immunoglobulin production. Lymphocytes from the patient failed to generate normal suppressor activity. There were no insulin or islet cell antibodies present in the patient's serum or in the commercial immunoglobulin preparations he received. The patient's HLA phenotype included HLA-DR3 and 4, placing him genetically at high risk for type I diabetes.

Use of transfer factor in a pediatric AIDS patient with disseminated Mycobacterium avium intracellulare.

An 8-year-old male with AIDS and disseminated Mycobacterium avium intracellulare infection was treated with transfer factor (TF) prepared from maternal lymphocytes. Subsequent lymphocyte stimulation studies and repeat cultures failed to demonstrate improvement during treatment. His overall clinical status remained unchanged. No adverse effects of TF were noted.

Anaphylaxis to human serum albumin.

During her 26th week of pregnancy a 20-year-old woman developed generalized pruritus, urticaria, flushing, tinnitus, and tachycardia during plasmapheresis with 5% human serum albumin (HSA) as adjunctive treatment for anti-Kell isoimmunization. The reaction was controlled with intravenous diphenhydramine. Despite pretreatment with diphenhydramine and betamethasone a subsequent attempt to perform plasmapheresis with infusion of 5% HSA resulted in a more severe reaction which progressed to respiratory distress. Intradermal skin testing with 5% HSA produced a 9 x 11-mm wheal and 17 x 21-mm erythema at 15 minutes. An enzyme-linked immunoassay was positive for IgE antibody to 5% HSA before and after dialysis for removal of Na caprylate. These results are consistent with an IgE-mediated basis for this patient's reaction to HSA.