Travelling with tea: a Tuckerella's tale.

Tuckerella japonica Ehara appears strongly associated with tea (Camellia sinensis (L.) Kuntze, Theaceae) and, due to certain cultural practices in tea production, has in fact become a world traveller, accompanying the greatly coveted tea plant as it spread across the planet. The history of tea production and culture, and its arrival in the USA, provides the backdrop for this traveller's tale. Tuckerella japonica is morphologically similar to T. flabellifera Miller, described from Tasmania in Australia from Bedfordia salicina (Labill.) D.G. (Asteraceae). These two species have historically been misidentified as each other, creating inaccuracies in the collection records. The implications of this in terms of host plant lists and world distribution are discussed further, along with their morphological separation. The male and immature stages of T. japonica are described for the first time. Tuckerella xinglongensis Lin and Fu, from tea in China, is considered a junior synonym of T. japonica. The loss of the ancestral prostigmatan condition of three nymphal stages during ontogeny is confirmed for males of T. flabellifera, which do not retain a tritonymphal stage.

Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2.

The erbB2 oncogene encodes a 185-kilodalton transmembrane protein whose sequence is similar to the epidermal growth factor receptor (EGFR). A 30-kilodalton factor (gp30) secreted from MDA-MB-231 human breast cancer cells was shown to be a ligand for p185erbB2. An antibody to EGFR abolished the tyrosine phosphorylation induced by EGF and transforming growth factor-alpha (TGF-alpha) but only partially blocked that produced by gp30 in SK-BR-3 breast cancer cells. In two cell lines that overexpress erbB2 but do not expresss EGFR (MDA-MB-453 breast cancer cells and a Chinese hamster ovary cell line that had been transfected with erbB2), phosphorylation of p185erbB2 was induced only by gp30. The gp30 specifically inhibited the growth of cells that overexpressed p185erbB2. An antibody to EGFR had no effect on the inhibition of SK-BR-3 cell colony formation obtained with gp30. Thus, it appeared that gp30 interacted directly with the EGFR and erbB2. Direct binding of gp30 to p185erbB2 was confirmed by binding competition experiments, where gp30 was found to displace the p185erbB2 binding of a specific antibody to p185erbB2. The evidence described here suggests that gp30 is a ligand for p185erbB2.

Hemoglobins A and A2 in New World primates: comparative variation and its evolutionary implications.

Hemoglobin A(2) (alpha(2)delta(2)) in New World primates represents about 1/160 to 1/16 of total hemoglobin and, by virtue of this low proportion, is presumed to be functionally unimportant. Nonetheless, A(2) exhibits genetic polymorphism by electrophoresis in three out of five genera, whereas the major component, hemoglobin A (alpha(2)beta(2)), is electrophoretically invariant. Moreover, in four genera, including man, the evolutionary accumulation of mutations has been greater in delta than in beta Such findings suggest that both polymorphism and evolutionary changes can accrue to an effectively functionless and thus selectively nearly netutral gene.

Radiolabeled antibody targeting of the HER-2/neu oncoprotein.

The HER-2/neu oncogene encodes a Mr 185,000 transmembrane phosphoglycoprotein which is overexpressed in 25-35% of breast and ovarian neoplasms and portends a poor prognosis. We have studied the feasibility of targeting this oncoprotein, designated p185, with radioiodinated murine monoclonal antibodies (muMABs) 4D5 and 7C2, which recognize distinct epitopes on its extracellular domain. The rates of internalization and catabolism of these antibodies were analyzed by cellular radioimmunoassay and electron microscopy. After binding to NIH3T3 HER-2/neu cells, which show high surface expression of p185, the muMABs were endocytosed via coated pits, routed to lysosomes, and degraded. Approximately 44% of 125I-4D5 and 39% of 125I-7C2 were catabolized by tumor cells after 24 h. The biodistribution of radiolabeled 4D5 and 7C2 were evaluated in beige/nude mice bearing s.c. NIH3T3 HER-2/neu grafts. A high specificity of localization was seen with tumor:organ ratios of activity generally ranging from 5:1 to 30:1. However, the percentage injected dose of radioactivity per gram of tumor declined sharply from 25% at 24 h to 5% at 120 h postinjection. Treating the animals with 400-700 muCi 131I-4D5 caused a marked inhibition of tumor growth, although no mice were cured. Unlabeled 4D5 had no effect on tumor progression in this model, but administering 400-700 muCi of 131I-DA4-4, an isotype-matched irrelevant muMAB, resulted in an intermediate degree of growth retardation. Analysis of kinetic blood data and whole-body time-activity curves indicated that the irrelevant conjugate remained in the body 2-3 times longer than 131I-4D5. Radioiodinated anti-HER-2/neu muMABs are attractive agents for radioimmunodiagnosis and radioimmunotherapy of aggressive HER-2/neu-positive breast and ovarian carcinomas, but effective strategies for retarding intratumoral catabolism may be necessary to optimize their clinical utility.

The kinetics of sulfobromophthalein uptake by rat liver sinusoidal vesicles.

The kinetics of bromo[35S]sulfophthalein (35S-BSP) binding by and uptake across the hepatocyte sinusoidal membrane were investigated using isolated rat liver sinusoidal membrane vesicles containing K+ as the principal internal inorganic cation. Uptake of 35S-BSP into vesicles was found to be temperature dependent, with maximum uptake between 35 and 40 degrees C; only binding occurred at or below 15 degrees C. Uptake at 37 degrees C was saturable and resolvable by Eadee-Hofstee analysis into two components: one with high affinity (Km = 53.1 microM) but low capacity, and the second of low affinity (Km = 1150 microM) but high capacity. By pre- or post-incubation, respectively, with unlabelled BSP, trans-stimulation and counter transport of 35S-BSP could also be demonstrated in these vesicles. Uptake was inhibited competitively using 5 microM Rose bengal and 10 microM indocyanine green, and non-competitively using 10 microM DIDS. Taurocholate did not inhibit uptake, and actually enhanced transport at concentrations greater than or equal to 250 microM. Imposition of inwardly directed inorganic ion gradients resulted in the enhancement of 35S-BSP transport when chloride ions were part of this gradient, irrespective of the cation employed whereas there was no apparent cation effect. However, substitution of 10 mM Na+ for 10 mM K+ as the internal cation resulted in a significant increase in uptake in the presence of external K+ as compared to Na+ gradients. This effect was not observed when 10 mM Tris+ was employed as the internal cation. The kinetics of 35S-BSP uptake by isolated sinusoidal membrane vesicles are indicative of facilitated transport. While the observed inorganic ion effects suggest a possible electrogenic component, the driving forces for hepatic BSP uptake remain uncertain. Isolated sinusoidal membrane vesicles provide a useful technique for studying hepatic uptake processes independent of circulatory or subsequent cellular phenomena.

Polycystic ovary syndrome is associated with endothelial dysfunction.

BACKGROUND: We recently reported endothelial dysfunction as a novel cardiovascular risk factor associated with insulin resistance/obesity. Here, we tested whether hyperandrogenic insulin-resistant women with polycystic ovary syndrome (PCOS) who are at increased risk of macrovascular disease display impaired endothelium-dependent vasodilation and whether endothelial function in PCOS is associated with particular metabolic and/or hormonal characteristics. METHODS AND RESULTS: We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) and to euglycemic hyperinsulinemia in 12 obese women with PCOS and in 13 healthy age- and weight-matched control subjects (OBW). LBF increments in response to MCh were 50% lower in the PCOS group than in the OBW group (P:<0.01). Euglycemic hyperinsulinemia increased LBF above baseline by 30% in the PCOS and 60% in OBW group (P:<0.05 between groups). Across all subjects, the maximal LBF response to MCh exhibited a strong inverse correlation with free testosterone levels (r=-0.52, P:<0.007). This relationship was stronger than with any other parameter, including insulin sensitivity. CONCLUSIONS: PCOS is characterized by (1) endothelial dysfunction and (2) resistance to the vasodilating action of insulin. This endothelial dysfunction appears to be associated with both elevated androgen levels and insulin resistance. Given the central vasoprotective role of endothelium, these findings could explain, at least in part, the increased risk for macrovascular disease in women with PCOS.

Recombinant murine interferon-gamma inhibits the fusion of mouse alveolar macrophages in vitro but stimulates the formation of osteoclastlike cells on implanted syngeneic bone particles in mice in vivo.

Osteoclasts are multinucleated cells that originate from the fusion of mononuclear precursors and are responsible for bone resorption. Indirect evidence from in vitro studies suggests that IFN-gamma and TNF-alpha inhibit and stimulate bone resorption, respectively, but contradictory results have emerged from the literature regarding the effects of IFN-gamma on macrophage multinucleation. Using highly sensitive model systems, the present work demonstrates that, in mice, rMuIFN-gamma inhibits the fusion of alveolar macrophages in vitro but augments the number of osteoclastlike cells on implanted syngeneic bone particles in vivo. Although rMuTNF-alpha fails to stimulate macrophage multinucleation in either system, treatment of implanted animals with rMuIFN-gamma appears to limit the inflammatory reaction and favor tissue repair.

Faster clearance of sustained release verapamil in men versus women: continuing observations on sex-specific differences after oral administration of verapamil.

Pharmacokinetic studies after administration of 120 mg oral sustained- and regular-release racemic verapamil were performed in 13 healthy subjects (seven men, age 74 +/- 4 years [mean +/- SD], weight 69.9 +/- 5.4 kg, and body mass index 24.6 +/- 2.2]; and six women, age 65 +/- 13 years, weight 65 +/- 9.9 kg, and body mass index 25.3 +/- 3). Verapamil was measured by HPLC, concentration versus time data analyzed by noncompartmental models, and statistical analyses performed by ANOVA for repeated measurements. The area under the concentration versus time curve (AUC) after administration of sustained-release verapamil was 48,951 +/- 18,079 ng/mL x min(-1) in women compared with 25,595 +/- 10,245 in men and lower than after administration of regular-release verapamil (63,055 +/- 24,411 for women and 34,686 +/- 25,279 in men; P = .05 for sex-related effect and P < .02 for formulation effect). AUC ratios of norverapamil (N-demethylated metabolite) to verapamil after administration of sustained-release verapamil were 1.43 +/- 0.26 in women compared with 1.74 +/- 0.41 in men and 1.43 +/- 0.26 in women compared with 1.78 +/- 0.37 in men after administration of regular-release verapamil (P = .1 for sex-related effect and P = .9 for formulation effect). Apparent oral clearance was 43 +/- 15 mL/min/kg in women compared with 75 +/- 29 in men after administration of sustained-release verapamil and 35 +/- 16 mL/min/kg in women compared with 65 +/- 31 in men after administration of regular-release verapamil (P < .05 for sex-related effect and P < .02 for formulation effect). Apparent oral clearance of both regular- and sustained-release formulations of verapamil was faster in men compared with women in contrast to findings after intravenous administration of verapamil, suggesting that intestinal processes are a factor in sex-specific difference in drug clearance. Greater verapamil and norverapamil bioavailability after administration of regular- compared with sustained-release verapamil also suggests saturable processes at the intestinal level.

Race and sex influence clearance of nifedipine: results of a population study.

OBJECTIVE: To estimate oral clearance of nifedipine and to determine demographic and clinical covariates that affect nifedipine clearance in a clinical population. METHODS: Apparent oral clearance of nifedipine and protein binding were measured in 226 patients receiving sustained-release nifedipine formulations for hypertension and coronary artery disease (black men, n = 111; black women, n = 27; white men, n = 64; white women, n = 24). Mean age +/- SD was 71 +/- 11 years, and mean weight was 86 +/- 17 kg. Nifedipine concentrations were analyzed by HPLC, protein binding was measured by equilibrium dialysis, clearance and covariate effects were estimated by a nonlinear mixed effects population model, and statistical analyses were performed by a nonlinear mixed-effects model (clearance) and ANOVA (protein binding). RESULTS: Clearance was significantly slower in black subjects (8.9 +/- 0.7 mL/min/kg; mean +/- SE) compared with white subjects (11.6 +/- 0.8 mL/min/kg; P = .00004) and in men compared with women (9.3 +/- 0.6 versus 12.1 +/- 1.5 mL/min/kg; P = .0021). Reported alcohol use (alcohol, 8.6 +/- 1.1 versus no alcohol, 10.8 +/- 0.6 mL/min/kg; P = .0002) and smoking status (smoker, 8.8 +/- 2.0 versus nonsmoker, 10.2 +/- 0.6 mL/min/kg; P = .0362) also affected nifedipine clearance. Race and sex had no effect on protein binding of nifedipine (P = .29 and P = .44, respectively). No effects of age, stable coronary artery disease, or reported intake of beta-blockers on nifedipine clearance were detected in this primarily elderly population with hypertension. CONCLUSIONS: The data suggest that race, sex, and environmental factors are identifiable sources of interindividual variation in the oral clearance of nifedipine, a CYP3A substrate. Our experience also suggests that data from clinical populations may be biased with regard to age, sex, and formulation selection, and covariates may not be independently distributed, which can limit analyses.

In vivo comparison of putative probes of CYP3A4/5 activity: erythromycin, dextromethorphan, and verapamil.

OBJECTIVES: Multiple in vivo CYP3A4/5 probes have been proposed. We compared verapamil clearance measures (CYP3A4/5 substrate) to the erythromycin breath test (ERBT) and the cumulative urinary dextromethorphan/3-methoxymorphinan test. METHODS: Clearance of intravenous and oral racemic verapamil and the area under the plasma concentration versus time curve (AUC) ratio of norverapamil (N-demethylated metabolite) to verapamil after oral verapamil dosing, the ERBT, and the dextromethorphan urinary metabolite ratios were measured in 84 healthy nonsmoking subjects (42 men and 42 women; age, 47 +/- 23 (mean +/- SD) years; weight, 69 +/- 11 kg). Relationships between putative CYP3A4/5 probes were assessed by linear regression. RESULTS: The strongest correlation was between intravenous and oral verapamil clearance (r2 = 0.26; P = .0001). Relationships between cumulative urinary dextromethorphan/3-methoxymorphinan and (1) intravenous verapamil clearance (r2 = 0.073; P = .024), (2) oral verapamil clearance (r2 = 0.144; P = .001), and (3) plasma AUC(norverapamil)/AUC(verapamil) after oral verapamil (r2 = 0.10; P = .01) were also detected. The ERBT and intravenous verapamil clearance were weakly related (r2 = 0.04; P = .067). No relationship was detected between ERBT and dextromethorphan/3-methoxymorphinan ratios (r2 = 0.00006; P = .945), oral verapamil clearance (r2 = 0.00006; P = .94), or plasma AUC(norverapamil)/AUC(verapamil) after oral verapamil (r2 = 0.0002; P = .9). CONCLUSIONS: Intravenous and oral verapamil clearance values were significantly correlated, and cumulative dextromethorphan/3-methoxymorphinan urinary ratios correlated with both plasma AUC(norverapamil)/AUC(verapamil) after oral verapamil dosing and with oral and intravenous verapamil clearance. The ERBT correlated only weakly with intravenous verapamil clearance. Results with verapamil are comparable to results with other intravenous and oral CYP3A4/5 probes. Lack of correlation between putative CYP3A4/5 probe results may be attributable to the route of administration; probe characteristics; and intersubject, intrasubject, between-day, and testing measurement variability.

ELISA for quantitation of the extracellular domain of p185HER2 in biological fluids.

The HER2/neu proto-oncogene encodes a receptor that belong to the tyrosine-specific protein kinase family. Amplification of the HER2 gene in patients with breast and ovarian cancer has been shown to predict poorer survival rates. In order to understand the role of HER2 in malignant and normal cells, it is necessary to devise assays that can quantitate expression levels of the HER2 gene product (p185HER2) in production samples, biopsy specimens and biological fluids. We have developed a simple, quantitative ELISA that uses two monoclonal antibodies directed against the extracellular domain of the HER2 gene product, p185HER2 (HER2 ECD). The assay has a detection range of 0.25-120 ng/ml, is precise and sensitive. The ability of this assay to detect biologically active rHER2 ECD is demonstrated by its correlation to a growth inhibitory bioassay (r = 0.92). The sandwich ELISA can also accurately quantitate rHER2 ECD in mouse and monkey serum. This assay should be useful for quantitating low levels of circulating rHER2 ECD in animals in which rHER2 ECD is being used as antigen for immunotherapy and in patients which 'shed' receptor.

Radiation therapy for gliomas of the optic nerve and chiasm.

Thirty-three patients with optic glioma seen over a 30-year period were reviewed. Five patients (15%) had tumor confined to the optic nerve, 8 patients (24%) had optic nerve and chiasmal involvement, and the remaining 20 patients (61%) had invasion of contiguous structures as well as chiasmal involvement. Eleven patients (33%) had a history of neurofibromatosis. Two-thirds of the patients had either a biopsy or a partial resection of the tumor, with the remaining one-third being clinically diagnosed. All patients received irradiation to local fields. The median dose was 5040 cGy in 160 cGy fractions. Of patients alive at last follow-up, the median time of follow-up was 12.3 years. The 5-, 10-, and 15-year overall actuarial survivals were 94, 81, and 74%, respectively. Univariate and multivariate analysis were performed on the following clinical variables: extent of primary tumor, extent of surgery, dose of radiation, gender, race, age, and presence or absence of neurofibromatosis. Extension of the primary lesion to the optic chiasm and age less than or equal to 15 years were the only two variables to have statistically significantly inferior 15-year progression free survivals by multivariate analysis. Eighteen (55%) patients had treatment related complications with most involving the pituitary gland. We conclude that postoperative radiotherapy is beneficial in patients with chiasmal involvement and those with incomplete resections. A minimum tumor dose of 4000 cGy is recommended.

Cardiopulmonary resuscitation in long-term care facilities: a survey of do-not-resuscitate orders in nursing homes.

Growing public debate regarding no cardiopulmonary resuscitation (no-CPR) policies in acute care hospitals, together with recent changes in the patient population of long-term care facilities, has led nursing homes to examine their need for resuscitation policies. To determine current cardiopulmonary resuscitation policies and procedures in nursing homes, medical directors and directors of nursing service in long-term care facilities in Portland, Oregon, were surveyed. Seventy-five percent responded; of these, only 41% reported having a resuscitation policy. Of those with no policy, 70% thought one was needed. Most nursing homes reported that resuscitation was infrequently discussed with patients and families. When a no-CPR determination was made, it was usually documented in the patient's chart. Training in basic life support was required for registered nurses in two thirds of the facilities. Few homes had equipment necessary for advanced life support. It is recommended that: a) nursing homes develop cardiopulmonary resuscitation policies; b) resuscitation orders be made part of the medical record; and c) nursing home personnel increase their ability to perform basic life support.

Müllerian agenesis: an update.

Recently, many advances have been made in the study of sexual differentiation, including the discoveries of the gene for antimüllerian hormone as well as the gene for its receptor. However, the etiology of the clinical syndrome of müllerian agenesis remains elusive. We hypothesize that activating mutations of either the antimüllerian hormone gene or its receptor gene may cause müllerian duct regression in a genetic female during embryogenesis. This clinical commentary discusses the current management of the syndrome including the Abbe-McIndoe procedure, the most commonly used method of surgical correction, and the Frank vaginal dilation method, the most common nonsurgical method of correction.

Clinical evaluations of the Wellcolex Colour Shigella and Salmonella tests.

The Wellcolex Colour Salmonella and Shigella tests are rapid latex agglutination procedures for grouping Salmonella and Shigella using an antibody attached to multicolored latex particles. The tests correctly grouped 46 (100%) of 46 Salmonella clinical isolates in groups A through E and G, 42 (100%) of 42 Shigella clinical isolates, and seven (88%) of eight Shigella stock cultures. The stock culture missed had been passed through many transfers and may have lost some of its antigenicity. The Wellcolex Colour Salmonella test was also found useful in detecting and grouping Salmonella spp. directly from blood culture bottles.

Gender-specific effects on verapamil pharmacokinetics and pharmacodynamics in humans.

Pharmacokinetic studies of i.v. and oral racemic verapamil and 14C-erythromycin breath tests (ERBT) were performed in 84 healthy men (n = 42) and women (n = 42). Verapamil was measured by HPLC, concentration versus time data were analyzed by noncompartmental models, protein binding was measured by equilibrium dialysis, and statistical analyses were performed by ANOVA. Clearance of i.v. and p.o. verapamil was 13.7 +/- 4.3 and 58.4 +/- 35 ml/min/kg (mean +/- SD) in women compared to 12.6 +/- 3.4 and 82.6 +/- 70 ml/min/kg in men (p = 0.076). Bioavailability was higher in women (0.25 +/- 0.09) compared to men (0.20 +/- 0.09, p = 0.019) with a significant Gender x Formulation interaction (p = 0.04). ERBT were higher in women (p < 0.0001). Verapamil (i.v. and p.o.) decreased blood pressure in all subjects with greater heart rate increases after p.o. verapamil in women compared to men (p = 0.041). The findings suggest that sex-specific differences in drug metabolism may occur in both the gut and the liver and involve multiple metabolic pathways and that pharmacokinetic differences will alter pharmacodynamic responses.

Recovery of Chlamydia trachomatis from endometrial and fallopian tube biopsies in women with infertility of tubal origin.

In order to examine the role of chronic active chlamydial infection in tubal infertility, cultures for Chlamydia trachomatis were performed on endometrial biopsies from 38, and fallopian tube biopsies from all, of 52 women undergoing tubal surgery for infertility. C. trachomatis was recovered from one or both sites in 8 of 52 (15%). Five of 6 women with positive fallopian tube cultures had endometrial cultures performed, and of these, 4 (80%) were positive. Three culture-positive women had been treated with tetracycline or doxycycline. Multiple blind passage in tissue culture was required for recovery of all six fallopian tube and four of the six endometrial isolates. No specific anatomic lesion was associated with documented infection. Chronic active chlamydial infection is frequently associated with tubal infertility, may persist despite therapy, and often can be detected by endometrial biopsy culture.

Comparison of serum progesterone and endometrial biopsy for confirmation of ovulation and evaluation of luteal function.

An endometrial biopsy and a blood sample for progesterone determination obtained simultaneously in the midluteal phase of the cycles of 55 infertile women were compared for reliability for confirmation of presumptive ovulation and evaluation of luteal function. Progesterone levels of 3 ng/ml or greater were found in 90.5% of the cycles. Secretory endometrium was identified in 81% of the cycles. Thirty-three cycles yielded sufficient information to compare the two methods for evaluation of luteal function. Histology and progesterone levels were consistent with each other and the presumed time of ovulation in only 11 cycles. Histology was inconsistent with the presumed time of ovulation in 20 cycles, while progesterone was inconsistent in only two cycles. Additional samples for progesterone determinations were obtained during the biopsy cycles of 15 patients who presented adequate data for evaluation of luteal function. A single, well-timed progesterone determination appeared adequately to reflect the data obtained from serial samples in the same cycle. These results support the thesis that a single, well-timed serum progesterone determination is superior to a single endometrial biopsy as a screening method for confirmation of presumptive ovulation and for evaluation of luteal function.

PIP: An attempt to determine how accurate serum progesterone as compared with endometrial biopsy is in confirming that ovualtion has taken place, and what is the value of each method for assessing luteal function in infertile women is presented. Subjects were 55 women who were undergoing evaluation for infertility. Only patients who were presumed to be ovulatory were included. The maximum duration of infertility had been 10 years, with a mean of 3.9 years. Blood samples were obtained at the time of biopsy. Some additional blood samples were taken during the presumed luteal cycles. Progesterone serum levels of 3 ng/ml or higher were found in 90.5% of cycles. Secretory endometrium was found in 81% of cycles. There was a positive correlation between biopsy findings and serum progesteone in only 75% of cases. Only 33 cycles in 32 patients were suitable for luteal function determination. Retarded endometrial histology did not necessarily reflect insufficient progesterone secretion but low serum values during expected periods of peak progesterone secretion usually showed retarded endometrium. These findings had little prognostic value regarding future fertility. A single progesterone sample was as accurate as endometrial histology in confirming presumptive ovulation and was superior as an indication of corpus luteum function. In some cases a combination of well-timed biopsy and 3 or 4 serial progesterone values might be better to evaluate the interaction between corpus luteum function and histologic response.

The effects of baseline ovarian cysts on cycle fecundity in controlled ovarian hyperstimulation.

Patients undergoing COH were prospectively studied in 174 cycles for the presence of baseline ovarian cysts. In 37.4% of all cycles, a baseline cyst > 10 mm mean diameter was found, but a cyst was more common in subsequent cycles than on the first (41.5% versus 15.8%). Cycle fecundity as determined by life table analysis was significantly higher if no baseline cyst were present (0.25 versus 0.06, P > 0.01). These findings suggest that baseline ovarian cysts may adversely affect the chances for pregnancy in COH not associated with IVF or GIFT.