OBJECTIVE:The objective of the study was to determine whether the route of administration of estrogen therapy in women with metabolic syndrome (MBS) influences inflammation and coagulation parameters.STUDY DESIGN:Fifty symptomatic postmenopausal women with MBS were randomized to receive 1 mg oral estradiol (oE(2)) or 0.05 mg transdermal E(2) (tE(2)) for 3 months. Measurements were compared with those of 20 healthy premenopausal women and 74 normal postmenopausal women.RESULTS:Compared with both control groups, women with MBS had significantly higher levels of certain inflammation and coagulation markers, which cannot be accounted for based on weight alone. After oE(2), antithrombin III decreased from 104% to 96% (P < .01), the metalloproteinase-9/ tissue inhibitor of metalloproteinase-1 ratio increased (P < .02), and E-selectin decreased from 60 +/- 4.4 to 55 +/- 4.6 ng/mL (P < .05). With tE(2), there were no major changes noted.CONCLUSION:Postmenopausal women with MBS have higher levels of certain coagulation and inflammation markers and different responses to oral compared with transdermal estradiol.

Objective: Metabolic syndrome (MBS) is a significant health care problem in postmenopausal women and is driven largely by obesity. We wished to assess the prevalence of insulin resistance (IR), diagnosed using practical methods, and whether several adipocyte factors (adiponectin, leptin, resistin) or the gastric peptide ghrelin, associated with cardiovascular risk, might be abnormal and may relate to IR.Study design: We evaluated 37 obese postmenopausal women with MBS and 34 matched obese premenopausal controls, as well as 14 non-obese premenopausal controls. We measured fasting glucose and insulin, performed 75g 2 hr oral glucose tolerance and intravenous insulin tolerance tests to assess IR, and measured fasting lipids, adiponectin, leptin, resistin and ghrelin.Results: The kinetic decline in glucose after insulin (k(1TT)) as a marker of IR was the most frequently abnormal test (abnormal in 81%), with QUICKI, HOMA, and a modification of the Matsuda-DeFronzo index (ISIM) abnormal in 76, 73, and 68%, respectively. The GIR was abnormal in only 35% of subjects. Leptin and resistin were elevated and adiponectin and ghrelin were decreased in the postmenopausal women, compared to both groups of premenopausal controls. BMI correlated strongly with markers of insulin resistance as well as adipocytokine values. After controlling for BMI, only leptin was predictive of ISIM.Conclusion: Being overweight after menopause results in worsening IR and elevations in adipocytokine levels. While BMI is the most important factor, abnormal adipocytokine secretion may enhance IR and increase cardiovascular risk in postmenopausal women. (c) 2006 Mosby, Inc. All rights reserved.

Objective: To investigate Mullerian inhibiting substance (MIS) levels in women with polycystic ovary syndrome (PCOS)as well as relationships to ovarian morphology; levels of inhibin B, and other reproductive hormones.Design: Prospective clinical study.Setting: Academic endocrinology centers in Palermo, Italy and New York.Patient(s): Forty-six women with PCOS, recruited on the basis of the classic criteria of chronic anovulation and hyperandrogenism, and 25 age-matched ovulatory controls.Intervention(s): Fasting blood was obtained in all subjects in the early follicular phase (days 5-6) after spontaneous or induced menses (in PCOS), and transvaginal ultrasounds were performed.Main Outcome Measure(s): Assessment of values for luteinizing hormone (LH), testosterone (T), androstenedione (A), estradiol (E-2), inhibin B, MIS, fasting insulin, and the calculated quantitative sensitivity check index (QUICKI), as well as assessments of ovarian volume and blood flow.Result(s): Women with PCOS had higher LH, T; and A; higher insulin and lower QUICKI; and higher ovarian volume and lower pulsatility index. Inhibin B concentrations were statistically significantly higher in PCOS patients (70 +/- 8.0 vs. 40 +/- 3.4 pg/mL), as was MIS (6.7 +/- 0.9 vs. 4.6 +/- 0.5 ng/mL). Inhibin B had a statistically significant direct correlation with levels of MIS (r = 0.351). However, MIS, but; not inhibin B, had a statistically significant positive correlation with ovarian size (r = 0.350); the reproductive hormones LH, T, A, and E-2: and insulin (r = 0.249), independent of body mass index. Women with PCOS with the highest levels of MIS had higher ovarian volumes and values of LH, T, A, and insulin.Concluslon(s): Measurements of MIS reflect ovarian findings in PCOS better than levels of inhibin B and are more frequently elevated. However, MIS lacks sensitivity for use as a diagnostic tool in PCOS.

The purpose of this study was to evaluate the treatment efficacy of using IVF-intracytoplasmic sperm injection (ICSI) in HIV serodiscordant couples interested in having children while minimizing the risk of viral transmission. This study reviews the cases of HIV serodiscordant couples (n = 142) seeking fertility treatment at an assisted reproductive centre. The main outcome measures were successful pregnancy rate and HIV seroconversion rate. In calculating crude pregnancy rates, only patients who were actually treated were taken into account. To compensate for cancelled patients, and patient drop-out, lifetable analysis was performed. Life-table analysis demonstrated that 37.0 +/- 5.0% of couples attain a successful pregnancy after one completed IVF-ICSI with embryo transfer (IVF-embryo transfer) cycle. Following two and three IVF-embryo transfer cycles, the pregnancy rates rose to 56.8 +/- 6.0 and 73.4 +/- 6.9% respectively. Overall pregnancy rates were inversely related to age. There were no HIV seroconversions in treated patients or in delivered babies. It is concluded that the use of IVF-ICSI to avoid disease transmission in HIV-1 serodiscordant couples desiring children appears to be safe and yields high rates of pregnancy. However, success is influenced by the woman's age.

In hyperandrogenic women, several phenotypes may be observed. This includes women with classic polycystic ovary syndrome (C-PCOS), those with ovulatory (OV) PCOS, and women with idiopathic hyperandrogenism (IHA), which occurs in women with normal ovaries. Where other causes have been excluded, we categorized 290 hyperandrogenic women who were seen consecutively for this complaint between 1993 and 2004 into these three subgroups. The aim was to compare the prevalence of obesity, insulin resistance, and dyslipidemia as well as increases in C-reactive protein and homocysteine in these different phenotypes with age-matched ovulatory controls of normal weight (n = 85) and others matched for body mass index (BMI) with women with C-PCOS (n = 42). Although BMI affected fasting serum insulin and the Quantitative Insulin-Sensitivity Check Index, these markers of insulin resistance were greatest in C-PCOS (n = 204), followed by OV-PCOS (n = 50) and then IHA (n = 33). Androgen levels were similar in OV-PCOS and IHA but were higher in C-PCOS, whereas gonadotropins were similar in all groups. Lipid abnormalities were highest in C-PCOS and OV-PCOS and were normal in IHA. C-reactive protein was elevated in C-PCOS and OV-PCOS but not IHA. Homocysteine was elevated only in C-PCOS. Overall, the prevalence of obesity (BMI > 30) was 29% in C-PCOS, 8% in OV-PCOS, and 15% in IHA and insulin resistance (Quantitative Insulin-Sensitivity Check Index < 0.33) was 68% in C-PCOS, 36% in OV-PCOS, and 26% in IHA. The prevalence of having at least one elevated cardiovascular risk marker was 45% in C-PCOS 38% in OV-PCOS and was not increased on IHA (6%). These results suggest that among hyperandrogenic women the prevalence of abnormal metabolic and cardiovascular risk parameters is greatest in C-PCOS, followed by OV-PCOS and then women with IHA. Moreover, in that in OV-PCOS and IHA, ages and weights were similar yet the prevalence of metabolic and cardiovascular risk was greater in OV-PCOS, the finding of polycystic ovaries may be a significant modifying factor.

ObjectivePrevious studies have suggested that an increase and redistribution of body fat during menopause predisposes women to cardiovascular disease and metabolic syndrome. The pathophysiologic features of the metabolic syndrome include increased visceral or abdominal fat accumulation, insulin resistance, hypertension, and dyslipidemia (hypertriglyceridemia, reduced HDL, and small dense LDL particles). The prevalence of metabolic syndrome in postmenopausal women aged 50 to 59 is 35% (NHANES III). We wished to determine whether the oral or transdermal route of estrogen administration would be preferable for symptomatic postmenopausal women with a focus on their insulin resistant state.DesignWe randomized 50 symptomatic postmenopausal women, between the ages of 40 and 60, with metabolic syndrome to receive either 1 mg oral micronized estradiol or 50 μg transdermal estradiol (Vivelle-Dot, Novartis Pharmaceuticals, NJ).Materials and methodsWe measured fasting glucose and insulin as well as fasting lipid profiles and performed 75g 2 hr oral glucose tolerance (OGTT) and intravenous insulin tolerance (ITT) tests to assess insulin resistance before and after 12 weeks of oral estradiol or transdermal estradiol. We also measured 2 hr insulin levels after OGTT. The following indices of insulin sensitivity were calculated based on fasting glucose and insulin values: glucose/insulin ratio (GIR), quantitative insulin sensitivity check index (QUICKI), and homeostasis model assessment (HOMA). Insulin sensitivity index as defined by Matsuda and deFronzo (ISIM) and AUCglu were calculated based on the results of the 2hr OGTT; and kITT, defined as the response to insulin infusion, was derived from the results of the ITT.ResultsThere was no change in body weight after 12 weeks of estrogen therapy. After oral estrogen therapy, there was significant worsening of insulin resistance markers; GIR decreased (7.68 ± 0.60 vs. 5.52 ± 0.45, p < 0.01), baseline insulin increased (15.28 ± 1.27 vs. 22.02 ± 2.40 μU/ml, p < 0.01), QUICKI decreased (0.3177 ± 0.0043 vs. 0.2977 ± 0.0057, p < 0.01), and HOMA increased (3.96 ± 0.38 vs. 8.59 ± 2.08, p < 0.05). The only significant change in the lipid profile was an increase in HDL (50.46 ± 2.34 vs. 55.08 ± 2.51 mg/dl, p < 0.01), with no significant change in triglycerides or LDL. After transdermal estrogen therapy, no significant changes occurred, except a decrease in GIR (7.13 ± 0.63 vs. 5.77 ± 0.43, p < 0.05). And there were no changes in lipid parameters, except for a decrease in ApoA1 (219.12 ± 4.52 vs. 199.52 ± 6.31 mg/dl, p < 0.01).ConclusionOur data suggest that in this short term study, oral estradiol may worsen insulin resistance while transdermal estradiol exerts neutral effects. These data may not reflect alterations which occur with estrogen therapy in more metabolically normal postmenopausal women. ObjectivePrevious studies have suggested that an increase and redistribution of body fat during menopause predisposes women to cardiovascular disease and metabolic syndrome. The pathophysiologic features of the metabolic syndrome include increased visceral or abdominal fat accumulation, insulin resistance, hypertension, and dyslipidemia (hypertriglyceridemia, reduced HDL, and small dense LDL particles). The prevalence of metabolic syndrome in postmenopausal women aged 50 to 59 is 35% (NHANES III). We wished to determine whether the oral or transdermal route of estrogen administration would be preferable for symptomatic postmenopausal women with a focus on their insulin resistant state. Previous studies have suggested that an increase and redistribution of body fat during menopause predisposes women to cardiovascular disease and metabolic syndrome. The pathophysiologic features of the metabolic syndrome include increased visceral or abdominal fat accumulation, insulin resistance, hypertension, and dyslipidemia (hypertriglyceridemia, reduced HDL, and small dense LDL particles). The prevalence of metabolic syndrome in postmenopausal women aged 50 to 59 is 35% (NHANES III). We wished to determine whether the oral or transdermal route of estrogen administration would be preferable for symptomatic postmenopausal women with a focus on their insulin resistant state. DesignWe randomized 50 symptomatic postmenopausal women, between the ages of 40 and 60, with metabolic syndrome to receive either 1 mg oral micronized estradiol or 50 μg transdermal estradiol (Vivelle-Dot, Novartis Pharmaceuticals, NJ). We randomized 50 symptomatic postmenopausal women, between the ages of 40 and 60, with metabolic syndrome to receive either 1 mg oral micronized estradiol or 50 μg transdermal estradiol (Vivelle-Dot, Novartis Pharmaceuticals, NJ). Materials and methodsWe measured fasting glucose and insulin as well as fasting lipid profiles and performed 75g 2 hr oral glucose tolerance (OGTT) and intravenous insulin tolerance (ITT) tests to assess insulin resistance before and after 12 weeks of oral estradiol or transdermal estradiol. We also measured 2 hr insulin levels after OGTT. The following indices of insulin sensitivity were calculated based on fasting glucose and insulin values: glucose/insulin ratio (GIR), quantitative insulin sensitivity check index (QUICKI), and homeostasis model assessment (HOMA). Insulin sensitivity index as defined by Matsuda and deFronzo (ISIM) and AUCglu were calculated based on the results of the 2hr OGTT; and kITT, defined as the response to insulin infusion, was derived from the results of the ITT. We measured fasting glucose and insulin as well as fasting lipid profiles and performed 75g 2 hr oral glucose tolerance (OGTT) and intravenous insulin tolerance (ITT) tests to assess insulin resistance before and after 12 weeks of oral estradiol or transdermal estradiol. We also measured 2 hr insulin levels after OGTT. The following indices of insulin sensitivity were calculated based on fasting glucose and insulin values: glucose/insulin ratio (GIR), quantitative insulin sensitivity check index (QUICKI), and homeostasis model assessment (HOMA). Insulin sensitivity index as defined by Matsuda and deFronzo (ISIM) and AUCglu were calculated based on the results of the 2hr OGTT; and kITT, defined as the response to insulin infusion, was derived from the results of the ITT. ResultsThere was no change in body weight after 12 weeks of estrogen therapy. After oral estrogen therapy, there was significant worsening of insulin resistance markers; GIR decreased (7.68 ± 0.60 vs. 5.52 ± 0.45, p < 0.01), baseline insulin increased (15.28 ± 1.27 vs. 22.02 ± 2.40 μU/ml, p < 0.01), QUICKI decreased (0.3177 ± 0.0043 vs. 0.2977 ± 0.0057, p < 0.01), and HOMA increased (3.96 ± 0.38 vs. 8.59 ± 2.08, p < 0.05). The only significant change in the lipid profile was an increase in HDL (50.46 ± 2.34 vs. 55.08 ± 2.51 mg/dl, p < 0.01), with no significant change in triglycerides or LDL. After transdermal estrogen therapy, no significant changes occurred, except a decrease in GIR (7.13 ± 0.63 vs. 5.77 ± 0.43, p < 0.05). And there were no changes in lipid parameters, except for a decrease in ApoA1 (219.12 ± 4.52 vs. 199.52 ± 6.31 mg/dl, p < 0.01). There was no change in body weight after 12 weeks of estrogen therapy. After oral estrogen therapy, there was significant worsening of insulin resistance markers; GIR decreased (7.68 ± 0.60 vs. 5.52 ± 0.45, p < 0.01), baseline insulin increased (15.28 ± 1.27 vs. 22.02 ± 2.40 μU/ml, p < 0.01), QUICKI decreased (0.3177 ± 0.0043 vs. 0.2977 ± 0.0057, p < 0.01), and HOMA increased (3.96 ± 0.38 vs. 8.59 ± 2.08, p < 0.05). The only significant change in the lipid profile was an increase in HDL (50.46 ± 2.34 vs. 55.08 ± 2.51 mg/dl, p < 0.01), with no significant change in triglycerides or LDL. After transdermal estrogen therapy, no significant changes occurred, except a decrease in GIR (7.13 ± 0.63 vs. 5.77 ± 0.43, p < 0.05). And there were no changes in lipid parameters, except for a decrease in ApoA1 (219.12 ± 4.52 vs. 199.52 ± 6.31 mg/dl, p < 0.01). ConclusionOur data suggest that in this short term study, oral estradiol may worsen insulin resistance while transdermal estradiol exerts neutral effects. These data may not reflect alterations which occur with estrogen therapy in more metabolically normal postmenopausal women. Our data suggest that in this short term study, oral estradiol may worsen insulin resistance while transdermal estradiol exerts neutral effects. These data may not reflect alterations which occur with estrogen therapy in more metabolically normal postmenopausal women.

ObjectiveHIV sero-discordant couples may safely conceive with IVF-ICSI. At the time of initial consultation for assisted reproduction, most HIV+ men are on antiretroviral medication. As many of these medications are designed to inhibit replication of DNA, it is theoretically possible that spermatogenesis may be affected. A greater number of medications may potentially produce a cumulative effect. To study the effects of antiretroviral therapies on sperm populations, we compared the initial semen analyses (SA) of HIV+ men on no therapy, monotherapy, or high activity antiretroviral therapy (HAART).DesignRetrospective cohort analysisMaterials and methodsPatients (pts) were categorized as those on no therapy, monotherapy, or HAART (2 or more medications). Combination formulations were included in the HAART data. Only specimens obtained after 2–3 days of abstinence by masturbation for initial evaluation were included in the analyses. Primary parameters analyzed were concentration, motility, modified Kruger morphology, and number of round cells.ResultsSeventy-six semen analyses met criteria for evaluation. Mean age of the pts was 37.8 yrs(±0.6; 22–50) (±SE;range). Mean duration of infection at presentation was 8.3 yrs (±0.6; 0.4–21). Co-morbidities: 49 none, 4 Hep B, 5 Hep C, 1 DM, 1 h/o PCP, 1 NHL, 4 w/more than 1 condition. Eight pts were on no medications, 6 were on monotherapy, and 62 were on HAART. Medications of monotherapy pts: 1 protease inhibitor (PI), 0 nucleoside/nucleotide analog reverse transcriptase inhibitor (NARI), 5 nonnucleoside reverse transcriptase inhibitor (NNRI). Of pts on HAART: 7 PI+NNRI, 20 PI+NARI, 7 PI+NARI+NNRI, 15 combo NNRI, 13 NNRI+NARI. Comparing pts on no therapy, monotherapy, or HAART, there were no statistically significant differences in motility, or morphology. Pts on monotherapy had a significantly lower concentration than the no therapy or HAART groups, but this is likely due to small sample size of the monotherapy group. Pts on no therapy had statistically fewer round cells than those on HAART (1.83±.65 v 3.25±.33). Those on no therapy also had a statistically higher viral load than those on monotherapy and HAART, and a higher CD4 than those on HAART (but not monotherapy). Pt's w/ low VL (<50) had more round cells than those with high VL (>1000), but no other parameters were independently affected by VL or CD4.ConclusionWhile reverse transcriptase inhibitors work by preventing viral DNA replication, there is no detrimental effect to spermatogenesis as assessed by semen analysis. Fewer round cells in the non-treated groups may be significant for fewer immature spermatozoa, or a lesser degree of bacterial infection. Although other variables deserve attention, such as fertilization rate, and pregnancy outcome, antiretroviral therapy should not be withheld from HIV+ men participating in assisted reproduction. ObjectiveHIV sero-discordant couples may safely conceive with IVF-ICSI. At the time of initial consultation for assisted reproduction, most HIV+ men are on antiretroviral medication. As many of these medications are designed to inhibit replication of DNA, it is theoretically possible that spermatogenesis may be affected. A greater number of medications may potentially produce a cumulative effect. To study the effects of antiretroviral therapies on sperm populations, we compared the initial semen analyses (SA) of HIV+ men on no therapy, monotherapy, or high activity antiretroviral therapy (HAART). HIV sero-discordant couples may safely conceive with IVF-ICSI. At the time of initial consultation for assisted reproduction, most HIV+ men are on antiretroviral medication. As many of these medications are designed to inhibit replication of DNA, it is theoretically possible that spermatogenesis may be affected. A greater number of medications may potentially produce a cumulative effect. To study the effects of antiretroviral therapies on sperm populations, we compared the initial semen analyses (SA) of HIV+ men on no therapy, monotherapy, or high activity antiretroviral therapy (HAART). DesignRetrospective cohort analysis Retrospective cohort analysis Materials and methodsPatients (pts) were categorized as those on no therapy, monotherapy, or HAART (2 or more medications). Combination formulations were included in the HAART data. Only specimens obtained after 2–3 days of abstinence by masturbation for initial evaluation were included in the analyses. Primary parameters analyzed were concentration, motility, modified Kruger morphology, and number of round cells. Patients (pts) were categorized as those on no therapy, monotherapy, or HAART (2 or more medications). Combination formulations were included in the HAART data. Only specimens obtained after 2–3 days of abstinence by masturbation for initial evaluation were included in the analyses. Primary parameters analyzed were concentration, motility, modified Kruger morphology, and number of round cells. ResultsSeventy-six semen analyses met criteria for evaluation. Mean age of the pts was 37.8 yrs(±0.6; 22–50) (±SE;range). Mean duration of infection at presentation was 8.3 yrs (±0.6; 0.4–21). Co-morbidities: 49 none, 4 Hep B, 5 Hep C, 1 DM, 1 h/o PCP, 1 NHL, 4 w/more than 1 condition. Eight pts were on no medications, 6 were on monotherapy, and 62 were on HAART. Medications of monotherapy pts: 1 protease inhibitor (PI), 0 nucleoside/nucleotide analog reverse transcriptase inhibitor (NARI), 5 nonnucleoside reverse transcriptase inhibitor (NNRI). Of pts on HAART: 7 PI+NNRI, 20 PI+NARI, 7 PI+NARI+NNRI, 15 combo NNRI, 13 NNRI+NARI. Comparing pts on no therapy, monotherapy, or HAART, there were no statistically significant differences in motility, or morphology. Pts on monotherapy had a significantly lower concentration than the no therapy or HAART groups, but this is likely due to small sample size of the monotherapy group. Pts on no therapy had statistically fewer round cells than those on HAART (1.83±.65 v 3.25±.33). Those on no therapy also had a statistically higher viral load than those on monotherapy and HAART, and a higher CD4 than those on HAART (but not monotherapy). Pt's w/ low VL (<50) had more round cells than those with high VL (>1000), but no other parameters were independently affected by VL or CD4. Seventy-six semen analyses met criteria for evaluation. Mean age of the pts was 37.8 yrs(±0.6; 22–50) (±SE;range). Mean duration of infection at presentation was 8.3 yrs (±0.6; 0.4–21). Co-morbidities: 49 none, 4 Hep B, 5 Hep C, 1 DM, 1 h/o PCP, 1 NHL, 4 w/more than 1 condition. Eight pts were on no medications, 6 were on monotherapy, and 62 were on HAART. Medications of monotherapy pts: 1 protease inhibitor (PI), 0 nucleoside/nucleotide analog reverse transcriptase inhibitor (NARI), 5 nonnucleoside reverse transcriptase inhibitor (NNRI). Of pts on HAART: 7 PI+NNRI, 20 PI+NARI, 7 PI+NARI+NNRI, 15 combo NNRI, 13 NNRI+NARI. Comparing pts on no therapy, monotherapy, or HAART, there were no statistically significant differences in motility, or morphology. Pts on monotherapy had a significantly lower concentration than the no therapy or HAART groups, but this is likely due to small sample size of the monotherapy group. Pts on no therapy had statistically fewer round cells than those on HAART (1.83±.65 v 3.25±.33). Those on no therapy also had a statistically higher viral load than those on monotherapy and HAART, and a higher CD4 than those on HAART (but not monotherapy). Pt's w/ low VL (<50) had more round cells than those with high VL (>1000), but no other parameters were independently affected by VL or CD4. ConclusionWhile reverse transcriptase inhibitors work by preventing viral DNA replication, there is no detrimental effect to spermatogenesis as assessed by semen analysis. Fewer round cells in the non-treated groups may be significant for fewer immature spermatozoa, or a lesser degree of bacterial infection. Although other variables deserve attention, such as fertilization rate, and pregnancy outcome, antiretroviral therapy should not be withheld from HIV+ men participating in assisted reproduction. While reverse transcriptase inhibitors work by preventing viral DNA replication, there is no detrimental effect to spermatogenesis as assessed by semen analysis. Fewer round cells in the non-treated groups may be significant for fewer immature spermatozoa, or a lesser degree of bacterial infection. Although other variables deserve attention, such as fertilization rate, and pregnancy outcome, antiretroviral therapy should not be withheld from HIV+ men participating in assisted reproduction.

In-vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) has been offered to human immunodeficiency virus (HIV) serodiscordant couples where the man is infected and the woman seronegative to achieve pregnancy while minimizing the risk of HIV transmission. We assess the efficacy of IVF-ICSI in HIV-1 serodiscordant couples in terms of number of IVF cycles typically needed to achieve a successful pregnancy. A retrospective review of HIV-1 serodiscordant couples undergoing IVF-ICSI at a university-based program. Between 7/1997 − 4/2003, couples known to be HIV-1 serodiscordant (male HIV-1 seropositive) were screened for assisted reproduction. 108 of 142 (76%) were deemed suitable for enrollment. Male partners were aged (mean±SD, (range)) 37.1±5.4 years (22–48 years); females aged 33.4±4.5 years (21–43 years). Women were prescribed ovarian hyperstimulation, and IVF-ICSI was performed on retrieved oocytes. Main outcome measures were successful pregnancy (live birth or ongoing pregnancy) rate per IVF-ICSI cycle with embryo transfer (ET) and HIV seroconversion rate. Life table analysis was performed to estimate number of IVF-ICSI cycles needed to obtain a successful pregnancy. Data was further stratified by female age (Group 1: age under 34, Group 2: age 34–37, and Group 3: age 38–43). Fresh ET cycles were included for analysis as well as cumulative rates for cycles including frozen ET. 98 women underwent at least one IVF-ICSI cycle (156 oocyte retrievals) with 92 women undergoing embryo transfer (146 IVF-ET cycles). 10 ET were cancelled post-retrieval either due to no fertilization/poor embryo quality (n=5) or risk of severe ovarian hyperstimulation syndrome (n = 5). There were 54 successful pregnancies after IVF-ICSI. Six additional pregnancies resulted from FET cycles. Life table analysis illustrates that overall 28.2±4.2% of couples could expect a successful pregnancy after one completed fresh IVF-ET cycle, with 48.0±5.7% and 64.8±7.3% expected pregnancy rates after 2 and 3 fresh IVF-ET cycles, respectively. 36.3% of IVF-ET cycles produced enough embryos for fresh transfer and cryopreservation. The cumulative successful pregnancy rate (fresh IVF-ET and FET cycles) after one completed IVF-ET cycle was estimated to be 30.1±4.2%, with 52.7±5.6%, and 67.5±6.7% expected pregnancy rates after 2 and 3 IVF-ET cycles, respectively. Again, success rate was inversely related to age group. There were no seroconversions in treated patients or in delivered babies. The use of IVF-ICSI to avoid disease transmission in HIV-1 serodiscordant couples desiring children yields high rates of success and appears to be safe. Best candidates appear to be women of younger age.

The physiology of normal androgen production in women has been poorly understood. Defining an androgen insufficiency state in women, in the absence of adrenal suppression and/or bilateral oophorectomy, has been difficult. Nevertheless, beneficial effects of androgen on many organ systems, including bone and the brain, are well documented. This review discusses the definition of androgen insufficiency, anticipated effects of androgen treatment on several factors of health, and treatment options for women with androgen insufficiency.

ObjectiveIn-vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) has been offered to human immunodeficiency virus (HIV) serodiscordant couples where the man is infected and the woman seronegative to achieve pregnancy while minimizing the risk of HIV transmission. We describe successive pregnancies resulting in healthy infants in six HIV-discordant couples who underwent in vitro fertilization with intracytoplasmic sperm injection.DesignA retrospective case series.Materials and methodsBetween 7/1997 − 3/2004, couples known to be HIV serodiscordant (male HIV-1 seropositive) were screened for assisted reproduction using IVF-ICSI. 108 of 142 (76%) HIV serodiscordant couples were deemed suitable for enrollment during this time. 64 women have either delivered or have currently ongoing pregnancies. Of these, six couples (9.4%) desired and achieved successive pregnancies following IVF-ICSI. Husbands aged 37.7±6.7 (30–47) (mean ± SD, (range)) years were asymptomatic HIV seropositive men with viral loads of 129.5±181.8 (50–500) copies/ml and CD4 counts of 343±254 (96–704) per mm3, having been diagnosed with the disease 5.2±3.4 (2–10) years. Female partners were aged 31.6±2.2 (28–33) years, with day 3 FSH values of 6.3±1.8 (3.6–8.5). All six women were childless prior to initiating IVF-ICSI treatment. Women were prescribed standard ovarian hyperstimulation, and IVF-ICSI performed on retrieved oocytes. Main outcome measures were IVF outcome, pregnancy outcome, and seroconversion rate.ResultsSix HIV serodiscordant couples who achieved successive pregnancies through the use of IVF-ICSI underwent 2–4 IVF retrieval cycles/couple. Two of six couples had successive pregnancies with two IVF cycles, resulting in singleton and twin pregnancies. Three of the six couples had successive pregnancies after 3 IVF cycles, resulting in singleton-twins (two couples) and singleton-singleton pregnancies. The remaining couple underwent four cycles of IVF to achieve successive pregnancies (two singleton pregnancies). All female recipients tested HIV-EIA negative 3 and 6 months post-embryo transfer, and at delivery. All babies (n=13) tested HIV-DNA negative at birth and 3 months postpartum (two pregnancies are ongoing). There were no major complications experienced during IVF-ICSI and delivery. The babies and the couples are all in general good health. The six couples had expressed prior to initial treatment an interest in having more than one child. Most of these couples returned 1–2 years post-partum to achieve this.ConclusionAdvances in assisted reproduction (i.e. sperm washing techniques, IVF-ICSI) coupled with improvements in HIV care, now allow couples an opportunity to have a family and remain healthy. They often will return for a second child to fulfill this dream and experience good success. ObjectiveIn-vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) has been offered to human immunodeficiency virus (HIV) serodiscordant couples where the man is infected and the woman seronegative to achieve pregnancy while minimizing the risk of HIV transmission. We describe successive pregnancies resulting in healthy infants in six HIV-discordant couples who underwent in vitro fertilization with intracytoplasmic sperm injection. In-vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) has been offered to human immunodeficiency virus (HIV) serodiscordant couples where the man is infected and the woman seronegative to achieve pregnancy while minimizing the risk of HIV transmission. We describe successive pregnancies resulting in healthy infants in six HIV-discordant couples who underwent in vitro fertilization with intracytoplasmic sperm injection. DesignA retrospective case series. A retrospective case series. Materials and methodsBetween 7/1997 − 3/2004, couples known to be HIV serodiscordant (male HIV-1 seropositive) were screened for assisted reproduction using IVF-ICSI. 108 of 142 (76%) HIV serodiscordant couples were deemed suitable for enrollment during this time. 64 women have either delivered or have currently ongoing pregnancies. Of these, six couples (9.4%) desired and achieved successive pregnancies following IVF-ICSI. Husbands aged 37.7±6.7 (30–47) (mean ± SD, (range)) years were asymptomatic HIV seropositive men with viral loads of 129.5±181.8 (50–500) copies/ml and CD4 counts of 343±254 (96–704) per mm3, having been diagnosed with the disease 5.2±3.4 (2–10) years. Female partners were aged 31.6±2.2 (28–33) years, with day 3 FSH values of 6.3±1.8 (3.6–8.5). All six women were childless prior to initiating IVF-ICSI treatment. Women were prescribed standard ovarian hyperstimulation, and IVF-ICSI performed on retrieved oocytes. Main outcome measures were IVF outcome, pregnancy outcome, and seroconversion rate. Between 7/1997 − 3/2004, couples known to be HIV serodiscordant (male HIV-1 seropositive) were screened for assisted reproduction using IVF-ICSI. 108 of 142 (76%) HIV serodiscordant couples were deemed suitable for enrollment during this time. 64 women have either delivered or have currently ongoing pregnancies. Of these, six couples (9.4%) desired and achieved successive pregnancies following IVF-ICSI. Husbands aged 37.7±6.7 (30–47) (mean ± SD, (range)) years were asymptomatic HIV seropositive men with viral loads of 129.5±181.8 (50–500) copies/ml and CD4 counts of 343±254 (96–704) per mm3, having been diagnosed with the disease 5.2±3.4 (2–10) years. Female partners were aged 31.6±2.2 (28–33) years, with day 3 FSH values of 6.3±1.8 (3.6–8.5). All six women were childless prior to initiating IVF-ICSI treatment. Women were prescribed standard ovarian hyperstimulation, and IVF-ICSI performed on retrieved oocytes. Main outcome measures were IVF outcome, pregnancy outcome, and seroconversion rate. ResultsSix HIV serodiscordant couples who achieved successive pregnancies through the use of IVF-ICSI underwent 2–4 IVF retrieval cycles/couple. Two of six couples had successive pregnancies with two IVF cycles, resulting in singleton and twin pregnancies. Three of the six couples had successive pregnancies after 3 IVF cycles, resulting in singleton-twins (two couples) and singleton-singleton pregnancies. The remaining couple underwent four cycles of IVF to achieve successive pregnancies (two singleton pregnancies). All female recipients tested HIV-EIA negative 3 and 6 months post-embryo transfer, and at delivery. All babies (n=13) tested HIV-DNA negative at birth and 3 months postpartum (two pregnancies are ongoing). There were no major complications experienced during IVF-ICSI and delivery. The babies and the couples are all in general good health. The six couples had expressed prior to initial treatment an interest in having more than one child. Most of these couples returned 1–2 years post-partum to achieve this. Six HIV serodiscordant couples who achieved successive pregnancies through the use of IVF-ICSI underwent 2–4 IVF retrieval cycles/couple. Two of six couples had successive pregnancies with two IVF cycles, resulting in singleton and twin pregnancies. Three of the six couples had successive pregnancies after 3 IVF cycles, resulting in singleton-twins (two couples) and singleton-singleton pregnancies. The remaining couple underwent four cycles of IVF to achieve successive pregnancies (two singleton pregnancies). All female recipients tested HIV-EIA negative 3 and 6 months post-embryo transfer, and at delivery. All babies (n=13) tested HIV-DNA negative at birth and 3 months postpartum (two pregnancies are ongoing). There were no major complications experienced during IVF-ICSI and delivery. The babies and the couples are all in general good health. The six couples had expressed prior to initial treatment an interest in having more than one child. Most of these couples returned 1–2 years post-partum to achieve this. ConclusionAdvances in assisted reproduction (i.e. sperm washing techniques, IVF-ICSI) coupled with improvements in HIV care, now allow couples an opportunity to have a family and remain healthy. They often will return for a second child to fulfill this dream and experience good success. Advances in assisted reproduction (i.e. sperm washing techniques, IVF-ICSI) coupled with improvements in HIV care, now allow couples an opportunity to have a family and remain healthy. They often will return for a second child to fulfill this dream and experience good success.

Objective: Normal pregnancy requires an intricate interplay between ovary, uterus, and products of conception (embryo and placenta). Components of this interplay common to all three elements are angiogenesis and vasculogenesis. A major regulator of vasculogenesis, angiogenesis, and endothelial cell survival is VEGF acting through the VEGF receptor 2 (VEGFR-2). We hypothesized that administering a single dose of blocking antibody against VEGFR-2 on embryonic day (ED) 6.5 would disrupt normal embryonic development by interfering with function and development of one or more of these systems.Design: Prospective.Materials and Methods: Adult pregnant female CD1 mice were randomized into four groups: control: saline injection on ED 6.5; treatment: anti-VEGF-R2 antibody DC101 injection (66 mg/kg; ImClone Inc., New York) on ED 6.5; replacement control: Subcutaneous placement of four 10 mg/pellet 21-day release progesterone (P4) tabs (Innovative Research of America) on ED 5.5, oophorectomy and saline injection on ED 6.5; replacement treatment: four P4 tabs ED 5.5, oophorectomy, and anti-VEGF-R2 antibody ED 6.5. Animals were sacrificed on ED 13.5 (n = 7 per group). Outcome parameters included: animal and uterine weights, number of implantation sites, embryonic development, uterine histology, ovarian histology, and maternal serum P4 levels. The Wilcoxon rank test was used for statistical analysis.Results: Animal and uterine weights increased in control, replacement control, and replacement treatment group animals with the progression of pregnancy, whereas they remained unchanged in treatment group animals (p < 0.01). Implantation sites were absent on embryonic day 13.5 in the treatment group. Histological evaluation of the uterus revealed an absence of embryonic tissue on day 13.5 in the treatment group. In the control and both replacement groups ED 13.5 appropriate embryonic and placental structures were observed. Endothelial cell staining with PECAM in the control group showed that luteal vascular density was around 30% on ED 6.5 and ED 13.5. In contrast a six-fold decrease in vasculature was observed in treatment group corpora lutea on ED 13.5 (p<0.01). Caspase-3 staining, a marker for apoptosis, was significantly increased in the treatment group corpora lutea on ED 7.5 and 13.5 when compared to control. Progesterone levels in the treatment group decreased to baseline levels on ED 13.5, while P4 levels fluctuated around 25 ng/mL in the control group on ED 13.5. Progesterone levels in the replacement groups mirrored those of the control group. Preliminary data also suggest that embryonic development is compromised in replacement animals, when the antibody is given after ED 6.5.Conclusion: Anti-VEGFR-2 antibody interfered with postimplantation in vivo pregnancy development. The antibody prevented survival of luteal endothelial cells. Corpora lutea became dysfunctional, ovarian progesterone production and secretion was disrupted, and the products of conception failed to continue in their development. Interestingly, progesterone replacement seems to reverse the effects of the antibody, and the pregnancy develops normally. It appears that a single dose of antibody given on ED 6.5 does not disrupt pregnancy development or uterine function in the presence of pregnancy appropriate P4 levels; however these are areas of continued investigation. Potential clinical applications of this work include treatment of ectopic pregnancy and termination of abnormal intrauterine pregnancies. Objective: Normal pregnancy requires an intricate interplay between ovary, uterus, and products of conception (embryo and placenta). Components of this interplay common to all three elements are angiogenesis and vasculogenesis. A major regulator of vasculogenesis, angiogenesis, and endothelial cell survival is VEGF acting through the VEGF receptor 2 (VEGFR-2). We hypothesized that administering a single dose of blocking antibody against VEGFR-2 on embryonic day (ED) 6.5 would disrupt normal embryonic development by interfering with function and development of one or more of these systems. Design: Prospective. Materials and Methods: Adult pregnant female CD1 mice were randomized into four groups: control: saline injection on ED 6.5; treatment: anti-VEGF-R2 antibody DC101 injection (66 mg/kg; ImClone Inc., New York) on ED 6.5; replacement control: Subcutaneous placement of four 10 mg/pellet 21-day release progesterone (P4) tabs (Innovative Research of America) on ED 5.5, oophorectomy and saline injection on ED 6.5; replacement treatment: four P4 tabs ED 5.5, oophorectomy, and anti-VEGF-R2 antibody ED 6.5. Animals were sacrificed on ED 13.5 (n = 7 per group). Outcome parameters included: animal and uterine weights, number of implantation sites, embryonic development, uterine histology, ovarian histology, and maternal serum P4 levels. The Wilcoxon rank test was used for statistical analysis. Results: Animal and uterine weights increased in control, replacement control, and replacement treatment group animals with the progression of pregnancy, whereas they remained unchanged in treatment group animals (p < 0.01). Implantation sites were absent on embryonic day 13.5 in the treatment group. Histological evaluation of the uterus revealed an absence of embryonic tissue on day 13.5 in the treatment group. In the control and both replacement groups ED 13.5 appropriate embryonic and placental structures were observed. Endothelial cell staining with PECAM in the control group showed that luteal vascular density was around 30% on ED 6.5 and ED 13.5. In contrast a six-fold decrease in vasculature was observed in treatment group corpora lutea on ED 13.5 (p<0.01). Caspase-3 staining, a marker for apoptosis, was significantly increased in the treatment group corpora lutea on ED 7.5 and 13.5 when compared to control. Progesterone levels in the treatment group decreased to baseline levels on ED 13.5, while P4 levels fluctuated around 25 ng/mL in the control group on ED 13.5. Progesterone levels in the replacement groups mirrored those of the control group. Preliminary data also suggest that embryonic development is compromised in replacement animals, when the antibody is given after ED 6.5. Conclusion: Anti-VEGFR-2 antibody interfered with postimplantation in vivo pregnancy development. The antibody prevented survival of luteal endothelial cells. Corpora lutea became dysfunctional, ovarian progesterone production and secretion was disrupted, and the products of conception failed to continue in their development. Interestingly, progesterone replacement seems to reverse the effects of the antibody, and the pregnancy develops normally. It appears that a single dose of antibody given on ED 6.5 does not disrupt pregnancy development or uterine function in the presence of pregnancy appropriate P4 levels; however these are areas of continued investigation. Potential clinical applications of this work include treatment of ectopic pregnancy and termination of abnormal intrauterine pregnancies.

Microstructures of a metallocene-based polyethylene (mPE1) with an ethyl branching content of 10.4 mol% have been systematically investigated here. Crystallization and melting behavior are studied using differential scanning calorimetry (DSC). A broad distribution of crystal perfection, revealed by the melting endotherm with a plateau-like shape, is observed due to a dense and equal population distribution of short chain branching. Based on the DSC stepwise fractionation method, the length of the crystallizable ethylene sequence is estimated to be insufficiently long to develop a fold as normally observed in the lamellar crystals, which is consistent with results obtained by the temperature-rising elution fractionation (TREF) technique. Thus, characteristics of fringed-micelle-like crystals of this particular mPE1 are expected owing to the high level of butene comonomer content. When samples are crystallized for a prolonged time, thickening of less perfect crystals takes place but the crystals with more perfection remain intact. A linear relation with a slope of unity between the apparent melting peak temperature, T-m, of the less perfect crystals and the crystallization temperature, T-c, is found, i.e. T-m (degreesC) = T-c + 5.1, at an extremely low level of crystallinity. The determination of equilibrium melting temperature of this unique mPE1, based on the Hoffman-Weeks approach, becomes unfeasible due to the absence of a feature attributable to lamellar microstructures.To characterize the dimensions of fringed-micelle-like crystals, the long period and the crystalline thickness of mPE1 crystallized slowly from the molten state to room temperature have been determined by small-angle X-ray scattering. Although the two-phase model does not seem appropriate for this highly branched mPE1, one-dimensional correlation function approach has tentatively been applied. The deduced thickness of the crystallites is significantly small, ca. 2.6 nm, which is in good agreement with results obtained from DSC fractionation and TREF. Based on the measured elastic modulus of mPE1 and the Guth theory for composites, the aspect ratio of the fringed-micelle-like crystals is estimated as well to be ca. 30 which is relatively small, compared to that for lamellar crystals, ca. 100-1000. (C) 2000 Elsevier Science Ltd. All rights reserved.

Experiments for 140nm and 160nm contacts were optimized through simulation on an 18 percent transmitting phase shift mask for KrF lithography. A transmission of 18 percent is shown to have the most linear aerial image behavior through focus. The simulations were run using a primitive positive photoresist model in order to predict trends in resolution and to predict when side lobes begin printing. Experiments show that the 140nm and 160nm contact holes resolve without side lobe printing through focus and through exposure. Reticle SEMs verify that a ternary contact hole mask is capable of manufacture. By adding both opaque and clear sub- resolution assist features, the experiments show contacts as small as 140nm resolve with 0.50 micrometers focus latitude with 10 percent exposure latitude through pitch. Cross sectional SEMs verify that contact holes are larger due to the addition of zero order light as suggested by theory and show that side lobes begin to print. Experiments also prove that NA has the largest impact on resolution and exposure latitude and that (sigma) has the largest impact on depth of focus.