Oral Administration of Pentoxifylline Reduces Endometriosis-Like Lesions in a Nude Mouse Model.

INTRODUCTION: Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. STUDY DESIGN: Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. RESULTS: Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm3 vs 276.75 ± 94.30 mm3 and 145.33 ± 38.20 mm3, respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm2) versus group 2 (1.35 ± 0.43 mm2) and control (2.84 ± 0.60 mm2; P = .001). Vascularization and cytokine levels were also reduced posttreatment. CONCLUSION: Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

Markers of deep infiltrating endometriosis in patients with ovarian endometrioma: a predictive model.

OBJECTIVE: The purpose of the study was to develop an easily applicable predictive model to predict deep infiltrating endometriosis in patients with ovarian endometrioma. STUDY DESIGN: We performed a retrospective analysis of 178 consecutive women with ovarian endometrioma who underwent surgery, with histological confirmation and complete removal of endometriosis in the Hospital Clinic of Barcelona. Several markers were prospectively obtained and compared between the group of patients presenting deep infiltrating endometriosis associated with ovarian endometrioma and women with only ovarian endometrioma. Multiple logistic regression analysis was performed to create a model to predict the presence of deep infiltrating endometriosis and internal validation was later performed. RESULTS: Of the 178 patients studied, 80 (45%) were classified in the ovarian endometrioma group and 98 (55%) in the group of patients presenting deep infiltrating endometriosis associated with ovarian endometrioma. The independent variables to predict deep infiltrating endometriosis were: at least one previous pregnancy, a past history of surgery for endometriosis and the mean endometriosis-associated pelvic pain score. The area under the ROC curve was 0.91 (95% confidence interval: 0.86-0.94), with an optimal cut-off of the predicted probability of 0.54. The sensitivity of the model was 80% and the specificity 84%. CONCLUSIONS: This model predicts the development of deep infiltrating endometriosis in patients with ovarian endometriomas allowing prioritization of women for referral to specialized centers.

The use of inhaled sevoflurane during operative hysteroscopy is associated with increased glycine absorption compared to intravenous propofol for maintenance of anesthesia.

STUDY OBJECTIVE: To compare the effects of anesthesia maintenance drugs (inhaled sevoflurane versus intravenous propofol) used in general anesthesia on the absorption of glycine 1.5% solution during hysteroscopy. DESIGN: Prospective comparative study. SETTING: Tertiary care university hospital. PATIENTS: One hundred fifteen women undergoing hysteroscopy. INTERVENTIONS: Women were assigned to receive general anesthesia with inhaled sevoflurane (n = 77) or intravenous propofol (n = 38) to maintain anesthesia. MEASUREMENTS: The primary endpoint was clinically relevant glycine 1.5% absorption (>1000 mL), while secondary endpoints were the median of glycine absorption, operative time, complications and the incidence of discontinuation of the hysteroscopic procedure due to excessive glycine 1.5% absorption. MAIN RESULTS: Maintenance with sevoflurane produced significantly increased absorption of glycine 1.5% solution compared to intravenous anesthesia (264 vs 202 mL, P = .007). Clinically relevant absorption rates (>1000 mL) were observed in the sevoflurane group (P = .04) while none of the women receiving intravenous anesthesia reached this absorption level. No cases of severe post-operative hyponatremia (Na(1+)<125 mmol/L) or adverse events derived from glycine 1.5% absorption were reported. No major complications (such as perforations, severe hemorrhage or infection) were presented during the interventions. CONCLUSIONS: The results of the present study show that the use of inhaled sevoflurane is associated with significantly increased glycine 1.5% absorption compared to intravenous propofol for the maintenance of anesthesia. However, further randomized controlled trials are needed to assess the possible mechanisms and risk factors involved in the higher absorption induced by sevoflurane.

Long-term satisfaction and tolerability with low-dose flutamide: a 20-year surveillance study on 120 hyperandrogenic women.

OBJECTIVE: To evaluate the long-term safety, satisfaction and tolerability of flutamide therapy for female hyperandrogenism. DESIGN: A 20-year surveillance study. METHODS: Setting: Gynecology Department in a teaching hospital. PATIENTS: Hyperandrogenic women complaining for hirsutism treatment were followed between February 1995 and April 2015. INTERVENTIONS: Women received flutamide 125 or 250 mg/day alone (n = 55) or combined with oral contraceptives (n = 65). MAIN OUTCOME MEASURES: Adverse events, safety, tolerability satisfaction and efficacy were assessed every 6 months during all the follow-up. Lab tests including liver and lipid profiles were also recorded in each control. RESULTS: Patients under flutamide therapy showed significant improvements in hirsutism scores after 6 months of treatment with a maximum effect at 12 months that was maintained during all the therapy time. Satisfaction reported by patients with the efficacy of the drug in a visual scale was also high. A total of 54.2 % women presented one or more adverse effects during the follow-up; 33.3% showed at least one adverse effect possibly related with the study drug; and 24.1% withdrew from the study because of adverse effects. During the follow-up, as many as 89.9 % of patients abandoned flutamide. Reasons include: questions linked to medical problems (50%), attempt pregnancy (4%) and significant improvement in the symptomatology (35.8%). CONCLUSIONS: Flutamide is very effective for hirsutism treatment; however, adverse effects are very frequent and affect compliance.

Increased circulating cell-derived microparticle count is associated with recurrent implantation failure after IVF and embryo transfer.

Cell-derived microparticles (cMPs) are small membrane vesicles that are released from many different cell types in response to cellular activation or apoptosis. Elevated cMP counts have been found in almost all thrombotic diseases and pregnancy wastage, such as recurrent spontaneous abortion and in a number of conditions associated with inflammation, cellular activation and angiogenesis. cMP count was investigated in patients experiencing unexplained recurrent implantation failure (RIF). The study group was composed of 30 women diagnosed with RIF (RIF group). The first control group (IVF group) (n = 30) comprised patients undergoing a first successful IVF cycle. The second control group (FER group) included 30 healthy women who had at least one child born at term and no history of infertility or obstetric complications. cMP count was significantly higher in the RIF group compared with the IVF and FER groups (P < 0.05 and P < 0.01, respectively) (RIF group: 15.8 ± 6.2 nM phosphatidylserine equivalent [PS eq]; IVF group: 10.9 ± 5.3 nM PS eq; FER group: 9.6 ± 4.0 nM PS eq). No statistical difference was found in cMP count between the IVF and FER groups. Increased cMP count is, therefore, associated with RIF after IVF and embryo transfer.

Age, independent from ovarian reserve status, is the main prognostic factor in natural cycle in vitro fertilization.

OBJECTIVE: To analyze natural cycle IVF (NC-IVF) results according to patient age, ovarian reserve status following the Bologna criteria, cause of infertility, and modification of the cycle with the use of GnRH antagonist. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university hospital. PATIENT(S): Nine hundred forty-seven natural cycles carried out in 320 patients. INTERVENTION(S): Analysis of 947 NC-IVF outcomes performed in one single center between January 2010 and December 2014. MAIN OUTCOME MEASURE(S): Pregnancy rates per cycle started, per ET, and per patient, as well as ongoing pregnancy rate at a minimum of 12 weeks of gestation. RESULT(S): Among the three age groups analyzed (≤35 years, 36-39 years, and ≥40 years), pregnancy rates per cycle were significantly lower in the older group of patients (11.4% vs. 11.6% vs. 5.9%). In addition, miscarriage rate (7.7% vs. 34.4% vs. 50%) and ongoing pregnancy rate (10.6% vs. 7.6%vs. 3.0%) were negatively affected by patient age. However, no differences were observed according to patient ovarian reserve status, cause of infertility, or modification of the cycle with GnRH antagonist. The multivariate logistic regression confirmed that patient age was the only variable that could predict pregnancy in NC-IVF cycles (odds ratio, 0.93; 95% confidence interval, 0.88-0.98). CONCLUSION(S): NC-IVF is a feasible and "patient-friendly" option to be offered to young patients, independent of their ovarian reserve status.

Differential effect of mode of conception and infertility treatment on fetal growth and prematurity.

Objectives To examine perinatal outcomes in pregnancies conceived by different methods: fertile women with spontaneous pregnancies, infertile women who achieved pregnancy without treatment, pregnancies achieved by ovulation induction (OI) and in vitro fertilization or intra-cytoplasmic sperm injection (IVF/ICSI). Methods Retrospective single-center cohort study including 200 fertile and 748 infertile women stratified according to infertility treatment. The outcome measurements were preterm delivery (PTD), small-for-gestational-age (SGA), gestational diabetes, placenta previa or preeclampsia. Results The overall rate of pregnancy complications was significantly increased in all infertility groups regardless of the infertility treatment (adjusted odds ratio (OR): infertile without treatment 2.3 versus OI 2.2 versus IVF/ICSI 3.4). While PTD was mainly associated to IVF/ICSI (adjusted OR: infertile without treatment 1.3 versus OI 1.6 versus IVF/ICSI 3.3), SGA was significantly associated to both OI and IVF/ICSI (adjusted OR: infertile without treatment 1.9 versus OI 2.7 versus IVF/ICSI 2.6). All these associations remained statistically significant after adjusting by maternal age and twin pregnancy. Conclusions This study confirms the higher prevalence of pregnancy complications in infertile women irrespectively of receiving infertility treatment or not, and further describes a preferential association of prematurity with IVF/ICSI, and SGA with treated infertility (OI and IVF/ICSI).

Comparison of the effects of calcium carbonate and ossein-hydroxyapatite complex on back and knee pain and quality of life in osteopenic perimenopausal women.

BACKGROUND: Back and knee pain (BP; KP), which often accompanies osteoporosis, is a prevalent health problem affecting quality of life (QoL) in middle-aged women. AIM: To compare the effects of calcium carbonate (CC) and ossein-hydroxyapatite complex (OHC) on BP and KP and QoL in perimenopausal osteopenic women. SUBJECTS: 74 perimenopausal women were randomized to receive 1,200 mg/day of CC (n=38) or 1,660 mg/day of OHC (n=36) for 6 months. METHODS: This was a randomized, open-label, parallel-group, controlled, prospective study. Back and knee basal pain was recorded using a visual analogue scale (VAS) at each control and exercise-induced pain was recorded using a visual rating system (VRS). Changes in QoL were evaluated using the SF-36 questionnaire. RESULTS: In patients treated with OHC, mean VAS and VRS pain scores decreased significantly after 5 and 6 months of treatment, indicating a significant analgesic effect. In the CC group, however, changes were minor and non-significant. Two-way analysis of variance using treatment group and time as independent variables revealed a significantly greater effect of OHC over CC on VAS and VRS scores. SF-36 showed significant improvement for OHC on the physical component summary score and no changes for CC. Responses to items assessing emotional and social aspects of QoL showed only a significant improvement in vitality for OHC and no significant changes for CC in any of the four dominions constituting the SF-36 mental component. CONCLUSION: OHC has a significant analgesic effect and improves the physical component of QoL to a greater extent than CC.

Patient-level analysis of five international cohorts further confirms the efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies.

We performed an individual patient meta-analysis to determine whether aspirin has a significant protective effect on the risk of first thrombosis among patients with antiphospholipid antibodies (aPL). Five international cohort studies with available individual patient-level data, reporting on primary prophylaxis with continuous treatment with low-dose aspirin in patients with aPL were included. The main outcome was the occurrence of a first thrombotic in patients with aPL treated with low-dose aspirin compared to those not treated with low-dose aspirin. Pooled Hazard Ratios (HRs) and 95%CIs were calculated using frailty models. We pooled data from 497 subjects and 79 first thrombotic events (3469 patient-years of follow-up). After adjustment on cardiovascular risk factors, aPL profiles, and treatment with hydroxychloroquine, the HR for the risk of a first thrombosis of any type in aPL carriers treated with low-dose aspirin versus those not treated with aspirin was 0.43 (95%CI 0.25-0.75). Subgroup analysis showed a protective effect of aspirin against arterial (HR: 0.43 [95%CI: 0.20-0.93]) but not venous (HR: 0.49 [95%CI: 0.22-1.11]) thrombosis. Subgroup analysis according to underlying disease revealed a protective effect of aspirin against arterial thrombosis for systemic lupus erythematosus (SLE) (HR: 0.43 [95%CI: 0.20-0.94]) and asymptomatic aPL carriers (HR: 0.43 [95%CI 0.20-0.93]). We found no independent protective effect of hydroxychloroquine. This individual patient data meta-analysis shows that the risk of first thrombotic event as well of first arterial thrombotic event is significantly decreased among SLE patients and asymptomatic aPL individuals treated by low-dose aspirin.

High-throughput sperm differential proteomics suggests that epigenetic alterations contribute to failed assisted reproduction.

STUDY QUESTION: Are there quantitative alterations in the proteome of normozoospermic sperm samples that are able to complete IVF but whose female partner does not achieve pregnancy? SUMMARY ANSWER: Normozoospermic sperm samples with different IVF outcomes (pregnancy versus no pregnancy) differed in the levels of at least 66 proteins. WHAT IS KNOWN ALREADY: The analysis of the proteome of sperm samples with distinct fertilization capacity using low-throughput proteomic techniques resulted in the detection of a few differential proteins. Current high-throughput mass spectrometry approaches allow the identification and quantification of a substantially higher number of proteins. STUDY DESIGN, SIZE, DURATION: This was a case-control study including 31 men with normozoospermic sperm and their partners who underwent IVF with successful fertilization recruited between 2007 and 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: Normozoospermic sperm samples from 15 men whose female partners did not achieve pregnancy after IVF (no pregnancy) and 16 men from couples that did achieve pregnancy after IVF (pregnancy) were included in this study. To perform the differential proteomic experiments, 10 no pregnancy samples and 10 pregnancy samples were separately pooled and subsequently used for tandem mass tags (TMT) protein labelling, sodium dodecyl sulphate-polyacrylamide gel electrophoresis, liquid chromatography tandem mass spectrometry (LC-MS/MS) identification and peak intensity relative protein quantification. Bioinformatic analyses were performed using UniProt Knowledgebase, DAVID and Reactome. Individual samples (n = 5 no pregnancy samples; n = 6 pregnancy samples) and aliquots from the above TMT pools were used for western blotting. MAIN RESULTS AND THE ROLE OF CHANCE: By using TMT labelling and LC-MS/MS, we have detected 31 proteins present at lower abundance (ratio no pregnancy/pregnancy < 0.67) and 35 at higher abundance (ratio no pregnancy/pregnancy > 1.5) in the no pregnancy group. Bioinformatic analyses showed that the proteins with differing abundance are involved in chromatin assembly and lipoprotein metabolism (P values < 0.05). In addition, the differential abundance of one of the proteins (SRSF protein kinase 1) was further validated by western blotting using independent samples (P value < 0.01). LIMITATIONS, REASONS FOR CAUTION: For individual samples the amount of recovered sperm not used for IVF was low and in most of the cases insufficient for MS analysis, therefore pools of samples had to be used to this end. WIDER IMPLICATIONS OF THE FINDINGS: Alterations in the proteins involved in chromatin assembly and metabolism may result in epigenetic errors during spermatogenesis, leading to inaccurate sperm epigenetic signatures, which could ultimately prevent embryonic development. These sperm proteins may thus possibly have clinical relevance. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Spanish Ministry of Economy and Competitiveness (Ministerio de Economia y Competividad; FEDER BFU 2009-07118 and PI13/00699) and Fundación Salud 2000 SERONO13-015. There are no competing interests to declare.

Immune and stress mediators in response to bilateral adnexectomy: comparison of single-port access and conventional laparoscopy in a porcine model.

STUDY OBJECTIVE: To evaluate systemic markers of immune and stress responses after bilateral adnexectomy performed using 2 different laparoscopic techniques in pigs. DESIGN: Prospective comparative study (Canadian Task Force classification II-2). SETTING: University teaching hospital, research hospital, and tertiary care center. ANIMALS: Twenty female Yorkshire pigs undergoing laparoscopic surgery. INTERVENTIONS: Animals underwent bilateral salpingo-oophorectomy (ovary and fallopian tube extraction), performed via conventional laparoscopy (n = 10) or the single-port access approach (n = 10). MEASUREMENTS AND MAIN RESULTS: Injury provokes an acute-phase response, primarily produced by cytokines. The inflammatory response has been well described for major surgery and for conventional laparoscopy; however, little information is currently available for single-port laparoscopy, and none in the gynecologic field. This is the first study to compare serum cytokine interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) concentrations at baseline and in the early postoperative period (2, 4, and 20 hours) after bilateral salpingo-oophorectomy performed via conventional laparoscopy (n = 10) or single-port access (n = 10) in a porcine model. The stress response was measured using glucose and cortisol concentrations and the animals' response to surgery via a 6-category observation-based behavior test. Both IL-6 and TNF-α concentrations peaked at 4 hours after surgery, and were significantly lower in the single-port access group (p = .02) than in the conventional laparoscopy group (p = .02). In addition, in the single-port access group, concentrations of stress markers were slightly lower at all intervals recorded and were statistically significant at 2 hours after the operation for glucose concentration (mean [SD], 164.50 [26.73] mg/dL for conventional laparoscopy vs 86.50 [17.93] mg/dL for single-port access; p = .02). CONCLUSION: Evidence of improved inflammatory and stress responses was recorded in the minimally invasive single-port group. More clinical investigations are needed to further study the applicability of single-port access laparoscopy in gynecologic surgery.

Comparative cytogenetic analysis in two tissues with different lineage in Turner's syndrome patients: correlation with phenotype.

OBJECTIVE: To analyze karyotype of Turner's syndrome (TS) patients in two tissues of different lineage, and to correlate them with phenotype. STUDY DESIGN: An observational study was designed at the Gynaecological Endocrinology Unit of Hospital Clinic in Barcelona. Patients diagnosed with TS by blood karyotype were included, between 20 and 50 years of age. A new 50-cell count blood karyotype and a urethral cell karyotype from urine samples were performed. Data on some TS-related comorbidities were collected. RESULTS: Twenty-seven TS patients were included. Urine cultures of 12 patients were contaminated by microorganisms. With 50-cell count blood karyotype, three cryptic mosaicisms were found. Six patients with mosaicism in blood karyotype showed pure monosomy in urine karyotype. Correlations exist between blood karyotype and phenotype where spontaneous menarche, height, dysmorphology, congenital malformations and hypothyroidism are concerned, whereas they did not appear in urine analysis. CONCLUSIONS: Karyotyping T-lymphocytes in blood samples is the gold standard technique. 50-cell count may be considered if TS or ovarian failure is suspected, in order to detect cryptic mosaicisms. Urethral cell culture from urine samples presents technical difficulties and some limitations, due to the easier lost of abnormal X-chromosome. A partial correlation between blood karyotype and phenotype exists.

Hearing loss in adult women with Turner's syndrome and other congenital hypogonadisms.

OBJECTIVES: To define the patterns and causes of hearing decline associated to Turner's syndrome (TS). METHODS: An observational study with three cohorts was designed: 31 TS patients, 15 women with other congenital hypogonadims (OCH) and 41 healthy age-matched women taking contraception. Microotoscopy, standard pure-tone audiometry brain auditory evoked potentials (BAEP) were performed to study hearing function. RESULTS: Up to 87% of TS subjects suffered from some degree of hearing loss (HL) in the audiograms, compared with 20% OCH and 27% controls. Sensorineural hearing loss (SNHL) was the most frequent type of hypoacusia found in TS group. BAEP study demonstrated that 61% of TS women showed HL compared to 20% in OCH patients. No significant differences in latencies, amplitudes, and interpeaks of waves I, III and V were found between TS and OCH, nor when compared to reference population. Worse results were observed among the oldest TS patients, those with pure monosomy or isochromosome, and those with a history of recurrent otitis. CONCLUSIONS: More than a half of TS females presented HL. SNHL is the most frequent pattern among middle-aged women with TS. Old age, karyotype and recurrent otitis are predisposition factors to produce HL, while oestrogens play a minor role.

Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: an international and collaborative meta-analysis.

We performed a meta-analysis to determine whether aspirin has a significant protective effect on risk of first thrombosis among patients with antiphospholipid antibodies (aPL+). Observational and interventional studies identified from the Medline, Embase and Cochrane databases were selected if they assessed the incidence of first thrombosis in aPL+ patients treated with aspirin versus those without. Pooled effect estimates were obtained using a random-effects model. Of 1211 citation retrieved, 11 primary studies (10 observational and 1 interventional) met inclusion criteria, including a total of 1208 patients and 139 thrombotic events. The pooled odds ratio (OR) for the risk of first thrombosis in patients treated with aspirin (n=601) was 0.50 (95%CI: 0.27 to 0.93) compared to those without aspirin (n=607), with significant heterogeneity across studies (I(2)=46%, p=0.05). Subgroup analysis showed a protective effect of aspirin against arterial (OR: 0.48 [95%CI: 0.28-0.82]) but not venous (OR: 0.58 [95% CI: 0.32-1.06]) thrombosis, as well as in retrospective (OR: 0.23 [0.13-0.42]) but not prospective studies (OR: 0.91 [0.52-1.59]). Subgroup analysis according to underlying disease revealed a significant protective effect of aspirin for asymptomatic aPL+ individuals (OR: 0.50 [0.25-0.99]), for systemic lupus erythematosus (SLE) (OR: 0.55 [0.31-0.98]) and obstetrical antiphospholipid syndrome (APS) (OR: 0.25 [0.10-0.62]). This meta-analysis shows that the risk of first thrombotic event is significantly decreased by low dose aspirin among asymptomatic aPL individuals, patients with SLE or obstetrical APS. Importantly, no significant risk reduction was observed when considering only prospective studies or those with the best methodological quality.

Thromboembolism risk following recurrent miscarriage.

Normal pregnancy is associated with extensive changes in hemostasis such that the procoagulant effect becomes dominant. The evolutionary advantage of this hypercoagulability may be to counteract the inherent instability associated with hemochorial placentation, which is unique to human beings. However, overall, there is a four- to 10-fold increased thrombotic risk throughout gestation and the postpartum period. Certain inherited or acquired thrombophilic factors may predispose to arterial and/or venous thrombosis and have a possible association with pregnancy complications, including recurrent miscarriage (RM), which affects up to 5% of couples with childbearing desire. A subgroup of women with RM has been demonstrated to be in a prothombotic state before and after pregnancy. The long-term health implications of this hypercoagulability may imply an increased risk of ischemic heart disease. Moreover, the presence of antiphospholipid antibodies rather than thrombophilic genetic defects (i.e., factor V Leiden or prothrombin G202010A mutation) in patients with RM is a determinant of thrombotic events later in life, especially among those patients having also cardiovascular risk factors. This article highlights the thromboembolic risk in nonpregnant RM patients in different thrombophilic settings and the need for thromboprophylaxis among these patients.

Assisted reproductive technologies are associated with cardiovascular remodeling in utero that persists postnatally.

BACKGROUND: Assisted reproductive technologies (ARTs) have been shown to be associated with general vascular dysfunction in late childhood. However, it is unknown whether cardiac remodeling is also present and if these changes already manifest in prenatal life. Our aim was to assess fetal and infant (6 months of age) cardiovascular function in ART pregnancies. METHODS AND RESULTS: This prospective cohort study included 100 fetuses conceived by ART and 100 control pregnancies. ART fetuses showed signs of cardiovascular remodeling, including a more globular heart with thicker myocardial walls, decreased longitudinal function (tricuspid ring displacement in controls: median, 6.5 mm [interquartile range, 6.1-7.1 mm]; tricuspid ring displacement in ART: 5.5 mm [interquartile range, 5.1-6.1]; P<0.001), impaired relaxation, and dilated atria (atrial area in controls, 1.46 cm(2) [interquartile range, 1.2-1.5 cm(2)]; atrial area in ART, 1.6 cm(2) [interquartile range, 1.3-1.8 cm(2)]; P<0.001). Additionally, ART infants showed persistence of most cardiac changes and a significant increase in blood pressure and aortic intima-media thickness (systolic blood pressure in controls, 74 mm Hg [interquartile range, 67-83 mm Hg]; systolic blood pressure in ART, 83 mm Hg [interquartile range, 75-94 mm Hg]; P<0.001; aortic intima-media thickness in controls, 0.52 mm [interquartile range, 0.45-0.56 mm]; aortic intima-media thickness in ART, 0.64 mm [interquartile range, 0.62-0.67]; P<0.001). We could not demonstrate that our findings were directly caused by ART because of their association with various confounding factors, including intrauterine growth restriction or factors related to the cause of infertility. CONCLUSIONS: Children conceived by ART manifest cardiac and vascular remodeling that is present in fetal life and persists in postnatal life, suggesting opportunities for early detection and potential intervention. The underlying mechanisms and the effect of potential confounders such as growth restriction or prematurity remain to be elucidated.

Conservative medical treatment of ovarian hyperstimulation syndrome: a single center series and cost analysis study.

OBJECTIVE: To present the results of a large series of patients with ovarian hyperstimulation syndrome treated with a conservative medical approach and to compare the cost of this treatment with outpatient management with paracentesis according to published data. DESIGN: Retrospective case series and cost analysis study using a decision-tree model. SETTING: University hospital. POPULATION: 496 consecutive patients with ovarian hyperstimulation syndrome treated in our center from 1991 to 2010. METHODS: All patients were treated with a conservative medical approach: (a) conservative outpatient approach: bed rest and a low-sodium diet or (b) hospitalized patients: bed rest, low-sodium diet, 20% albumin (60 g/day) and furosemide (20 mg/8 h). MAIN OUTCOME MEASURES: Percentage of admissions, length of hospital stay and readmissions. Total cost of each therapeutic approach. RESULTS: (a) Conservative outpatient approach (n = 377): all cases solved without admission. (b) Hospitalized patients with conservative medical treatment (n = 119): 2.8 days of mean hospital stay, no patient required paracentesis or admission to intensive care unit. Readmissions: Five patients (4.2%) resolved on restarting medical treatment. (c) Cost-analysis comparison: Cost of the outpatient approach with paracentesis: US$980 (range US$519-3557). Cost of conservative medical treatment: US$570 (range US$232-1640). CONCLUSIONS: Ovarian hyperstimulation syndrome can be safely managed with a conservative medical approach, which was not found to be more expensive than outpatient management with paracentesis.

Turner's syndrome and other forms of congenital hypogonadism impair quality of life and sexual function.

OBJECTIVE: We sought to assess the burden of Turner's syndrome (TS) and other congenital hypogonadisms (OCH) on quality of life (QOL) and sexual function. STUDY DESIGN: An observational study was undertaken in a gynecological endocrinology unit of a teaching hospital. Three cohorts of women aged 20-50 years were compared: 26 TS patients, 21 women with OCH and wild-type karyotype, and 41 healthy age-matched women who were included as controls. All subjects filled out the Medical Outcome Study Short Form (SF-36) and the Female Sexual Function Index. RESULTS: TS subjects had significantly worse QOL scores in physical functioning (P = .026) and role physical functioning (P = .032) whereas OCH showed significantly worse scores in physical functioning (P = .027) and bodily pain (P = .025) compared to controls. In all, 80% of OCH and 50% of TS patients declared sexual activity. Sexually active TS patients had poorer arousal outcomes (P = .009) and OCH women showed significantly worse scores in arousal (P = .002), orgasm (P = .007), pain (P = .001), and Female Sexual Function Index total score (P = .004) compared with healthy controls. No differences between sexually active and inactive TS women were found in SF-36 scores, clinical characteristics, or anthropomorphic characteristics. CONCLUSION: TS and OCH subjects presented impaired physical domains in QOL. Women with TS are less likely to be involved in sexual activity, arousal dysfunctions being their main symptom. Conversely, arousal, orgasm, pain, and total score were significantly affected in OCH subjects.

Outcome from consecutive ICSI cycles in patients treated with recombinant human LH and those supplemented with urinary hCG-based LH activity during controlled ovarian stimulation in the long GnRH-agonist protocol.

Clinical results were compared in a well-established, assisted reproduction program during the cross-over from highly purified (HP)-human menopausal gonadotropin (hMG) to rhFSH/rhLH. We included the last 33 patients treated with HP-hMG and the first 33 patients receiving rhFSH/rhLH for ovarian stimulation in their first intracytoplasmic sperm injection cycle. Patient baseline characteristics were almost identical in the two groups. Ovarian stimulation characteristics (days of stimulation, total amount of FSH administered using a modest initial loading dose of 150 IU/d, patients with oocyte retrieval) were similar for the two groups. However, the number of total and leading follicles and E2 serum levels on the human chorionic gonadotropin injection day were significantly higher in the rhFSH/rhLH group. The oocyte yield was significantly higher in the rhFSH/rhLH group as well as the number of metaphase II oocytes, difference almost reaching the statistical significance. The number of oocytes fertilized was also higher in patients receiving rhFSH/rhLH treatment. Implantation and clinical pregnancy rates were similar in both the study groups. It is concluded that in women undergoing controlled ovarian hyperstimulation under pituitary suppression for ART, the recombinant combined product containing FSH and LH in a fixed 2:1 ratio is more effective than HP-hMG in terms of follicle development, oocyte yield and quality, and fertilization rates.

Role of decreased androgens in the ovarian response to stimulation in older women.

Ovarian testosterone increases the response of antral follicles to stimulation, declines with age, and has effects mediated or potentiated by insulin-like growth hormone I (IGF-I). Increased circulating insulin and IGF-I, exogenous testosterone, and increased local ovarian testosterone concentrations due to aromatase inhibition or exogenous luteinizing hormone/human chorionic gonadotropin are all associated with an increased ovarian response to gonadotropins. These factors should be further investigated alone or in combination for enhancing oocyte yield with fertility treatments, particularly in older reproductive-age women.