Gynecology and Reproductive Medicine

Saint-Étienne, France

Gynecology and Reproductive Medicine

Saint-Étienne, France
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Gardner T.J.,Mount Sinai School of Medicine | Bolovan-Fritts C.,Gladstone | Teng M.W.,Gladstone | Redmann V.,Mount Sinai School of Medicine | And 7 more authors.
Clinical and Vaccine Immunology | Year: 2013

Infection by human cytomegalovirus (CMV) elicits a strong humoral immune response and robust anti-CMV antibody production. Diagnosis of virus infection can be carried out by using a variety of serological assays; however, quantification of serum antibodies against CMV may not present an accurate measure of a patient's ability to control a virus infection. CMV strains that express green fluorescent protein (GFP) fusion proteins can be used as screening tools for evaluating characteristics of CMV infection in vitro. In this study, we employed a CMV virus strain, AD169, that ectopically expresses a yellow fluorescent protein (YFP) fused to the immediate-early 2 (IE2) protein product (AD169IE2-YFP) to quantify a CMV infection in human cells. We created a high-throughput cell-based assay that requires minimal amounts of material and provides a platform for rapid analysis of the initial phase of virus infection, including virus attachment, fusion, and immediate-early viral gene expression. The AD169IE2-YFP cell infection system was utilized to develop a neutralization assay with a monoclonal antibody against the viral surface glycoprotein gH. The high-throughput assay was extended to measure the neutralization capacity of serum from CMV-positive subjects. These findings describe a sensitive and specific assay for the quantification of a key immunological response that plays a role in limiting CMV dissemination and transmission. Collectively, we have demonstrated that a robust high-throughput infection assay can analyze the early steps of the CMV life cycle and quantify the potency of biological reagents to attenuate a virus infection. © 2013, American Society for Microbiology. All Rights Reserved.


Smith J.A.,Gynecology and Reproductive Medicine | Smith J.A.,Memorial Hermann Hospital Texas Medical Center | Donepudi R.V.,Gynecology and Reproductive Medicine | Argoti P.S.,Gynecology and Reproductive Medicine | And 5 more authors.
Frontiers in Pharmacology | Year: 2017

Background: Indications for surgery during pregnancy have increased. Specifically fetal interventions have increased from conditions that were considered lethal like twin-twin transfusion syndrome and severe fetal anemia to non-lethal conditions like myelomeningocele. The optimal anesthetic agent for in utero surgery is yet to be determined. Success of the procedure is often dictated by the efficacy of the anesthetic to immobilize the fetus without over-sedating mom. Remifentanil is used as preferred agent due to its short half-life however pharmacokinetics in pregnancy is unknown. Objective: To determine the pharmacokinetic parameters of remifentanil in a mid-trimester pregnant patient population undergoing fetal intervention. Study Design: A validated liquid chromatography assay with ultraviolet absorbance was employed to estimate maternal serum remifentanil levels. Blood samples were obtained at baseline and at selected time points: 5, 15, 30, 45, 60 min after the beginning of the remifentanil infusion and at 15, 30, and 60 min post end of infusion. Results: Ten pregnant patients were enrolled in the study however only eight patients had sampling obtained at all time points. The mean gestational age was 22.2 (±2.7) weeks, maternal age was 27.8 (±5.1) years and body mass index was 29.6 (±6.3). After receiving a continuous infusion of remifentanil, mean total dose was 975.3 μg, Cmin was 2.0 ng/mL and Cmax was 8.4 ng/mL. A two-compartment model best described the plasma remifentanil data. Mean pharmacokinetic parameters were: volume of distribution (Vdc) = 124.6 L (16.2-530.8 L), maternal remifentanil total clearance (Clt) = 170.7 L/h (17.7-486.9 L/h), and half-life (t1/2) = 0.6 h (0.2-0.9 h). The maternal remifentanil area under the curve (AUC) ranged from 2.7 to 21.7 μg/L*h. The mean alpha-acidic glycoprotein was 124.8 mg/dL (81.3-149.8). Conclusion: The pharmacokinetic profile of remifentanil in pregnant women is similar to previously reported general population profiles. This data did provide potential rationale for the clinical observations why when remifentanil is dosed based on non-pregnant guidelines, it did not uniformly provide adequate fetal immobilization as per anecdotal perception of operating fetal surgeons. These findings are important for the development of further clinical studies to optimize dosing for surgery during pregnancy including the estimation of placental transfer and total fetal exposure. © 2017 Smith, Donepudi, Argoti, Giezentanner, Jain, Boring, Garcia and Moise.


Lima S.,Gynecology and Reproductive Medicine | Clemenson A.,CHU Nord | Trombert B.,CHU Nord | Lecointre R.,Lyon Sud Hospital | And 3 more authors.
Archives of Gynecology and Obstetrics | Year: 2014

Purpose: Ovarian and tubal dysplasia may be precursors to ovarian cancer. The goal of this study was to check whether these histopathological lesions would be found after ovulation induction using tamoxifen, clomiphene citrate and letrozole. Methods: Seventy-two rats were divided into four groups. In the first group, 24 rats received normal saline. The second group (16 rats) received clomiphene citrate for six cycles. The third group, divided into two sub-groups of eight rats each, were stimulated with tamoxifen for six cycles, with a dosage, respectively, of 0.4 and 0.8 mg/kg/day. In the last group, eight rats received letrozole 0.1 mg/kg/day and eight other rats received letrozole 0.5 mg/kg/day, for six cycles. Once the six cycles had been completed the rats were killed in order to remove ovaries and tubes for histopathological analysis (morphological, p53 and Ki67 immunohistochemical assessment). Results: Histopathological lesions were found in both ovaries and tubes. The mean ovarian dysplasia score was significantly higher in the tamoxifen group whatever the dosage (p = 0.006 and 0.0002) and in the letrozole group with 0.5 mg/kg/day (p = 0.0002) compared with the control group. The mean tubal dysplasia score was significantly higher in all groups that received drug treatment compared with the control group, whatever the dosage used. The proliferation index (Ki67) was significantly higher in the tamoxifen and letrozole groups while no significant difference was found for apoptosis marker p53. Conclusions: Ovulation induction may induce histopathological abnormalities in ovaries and tubes with a different immunohistochemical profile in comparison with salpingo-oophorectomies for genetic risk. © 2014 Springer-Verlag.


Lacoste C.R.,Gynecology and Reproductive Medicine | Clemenson A.,CHU Nord | Lima S.,Gynecology and Reproductive Medicine | Lecointre R.,Lyon Sud Hospital | And 2 more authors.
Fertility and Sterility | Year: 2013

Objective: To assess tubo-ovarian dysplasia via morphologic and immunohistochemical study of rats exposed to ovulation stimulation protocols. Design: Animal experimental study. Setting: Academic research hospital. Animal(s): 72 female Wistar rats divided into three groups. Intervention(s): Stimulation protocols using follicle-stimulating hormone (FSH) or clomiphene citrate for 3, 6, or 12 cycles, after which the animals were killed. Main Outcome Measure(s): Ovarian and tubal dysplasia score and immunohistochemical assessment using p53 and Ki67. Result(s): The ovarian dysplasia score was statistically significantly higher after 12 stimulation cycles in the groups receiving FSH (group B) or clomiphene citrate (group C) compared with control (group A). The tubal dysplasia score was statistically significantly increased after only three stimulation cycles in groups B and C. The Ki67 proliferation marker was statistically significantly expressed in the ovaries from group C, and in the fallopian tubes from groups B and C. P53 was constantly low in all three groups. Conclusion(s): Ovulation stimulation may induce tubal and ovarian histopathologic and immunohistochemical abnormalities with a dose effect. The role of the fallopian tubes and their interaction with the ovaries require further study. © 2013 American Society for Reproductive Medicine.


Pastore L.M.,Gynecology and Reproductive Medicine | Manichaikul A.,University of Virginia | Wang X.Q.,University of Virginia | Finkelstein J.S.,Massachusetts General Hospital
Reproductive Sciences | Year: 2016

FMR1 premutation carriers (55-199 CGG repeats), and potentially women with high normal (35-44) or low normal (<28) CGG repeats, are at risk of premature ovarian aging. The scarcity of population data on CGG repeats <45 CGG, and variation in race-ethnicity, makes it difficult to determine true associations. DNA was analyzed for FMR1 CGG repeat lengths from 803 women (386 caucasians, 219 African Americans, 102 Japanese, and 96 Chinese) from the US-based Study of Women's Health Across the Nation (SWAN). Participants had ≥1 menses in the 3 months before enrollment, ≥1 pregnancy, no history of infertility or hormonal therapy, and menopause ≥46 years. Statistical analyses used Fisher exact tests. Among these women with normal reproductive histories, significant FMR1 repeat length differences were found across race-ethnicity for both the longer (P =.0002) and the shorter (P <.0001) alleles. The trinucleotide length variance was greater for non-Asian than Asian women (P <.0001), despite identical median values. Our data indicate that short allele lengths <25 CGG on one or both alleles are more common in non-Asian than Asian women. We confirm the minor allele in the 35 to 39 CGG range among Asians as reported previously. Only 2 (0.3%) premutation carriers were identified. These data demonstrate that FMR1 distributions do vary by race-ethnicity, even within the "normal" range. This study indicates the need to control for race-ethnicity in FMR1 ovarian aging research and provides race-ethnic population data for females separated by allele. © The Author(s) 2016.


PubMed | University of Virginia, Gynecology and Reproductive Medicine and Massachusetts General Hospital
Type: Journal Article | Journal: Reproductive sciences (Thousand Oaks, Calif.) | Year: 2016

FMR1 premutation carriers (55-199 CGG repeats), and potentially women with high normal (35-44) or low normal (<28) CGG repeats, are at risk of premature ovarian aging. The scarcity of population data on CGG repeats <45 CGG, and variation in race-ethnicity, makes it difficult to determine true associations. DNA was analyzed for FMR1 CGG repeat lengths from 803 women (386 caucasians, 219 African Americans, 102 Japanese, and 96 Chinese) from the US-based Study of Womens Health Across the Nation (SWAN). Participants had 1 menses in the 3 months before enrollment, 1 pregnancy, no history of infertility or hormonal therapy, and menopause 46 years. Statistical analyses used Fisher exact tests. Among these women with normal reproductive histories, significant FMR1 repeat length differences were found across race-ethnicity for both the longer (P = .0002) and the shorter (P < .0001) alleles. The trinucleotide length variance was greater for non-Asian than Asian women (P < .0001), despite identical median values. Our data indicate that short allele lengths <25 CGG on one or both alleles are more common in non-Asian than Asian women. We confirm the minor allele in the 35 to 39 CGG range among Asians as reported previously. Only 2 (0.3%) premutation carriers were identified. These data demonstrate that FMR1 distributions do vary by race-ethnicity, even within the normal range. This study indicates the need to control for race-ethnicity in FMR1 ovarian aging research and provides race-ethnic population data for females separated by allele.


Senzel L.,University Hospital | Avila C.,Gynecology and Reproductive Medicine | Ahmed T.,University Hospital | Hue-Roye K.,Laboratory of Immunohematology | And 2 more authors.
Immunohematology | Year: 2012

Plasma from a 35-year-old, D- woman was found to have anti-D, -C, and -G at 5 weeks' gestation and again at 8 weeks' gestation, when she presented with a nonviable intrauterine pregnancy. The anti-D titer increased with a pattern that suggested it was stimulated by the 8-week pregnancy. Six years before this admission, the patient's blood type changed from group O, D+ to group O, D- after a bone marrow transplant for aplastic anemia. Three years after transplant, the antibody screen was negative. After the patient was admitted for the nonviable pregnancy, the products of con-ception were found to be D+ by DNA testing for RHD. There were no documented transfusions or pregnancies during the interval in which anti-D appeared. The timing of the alloimmunization was unusual. In a subsequent pregnancy, fetal D typing was performed by molecular methods.


Veringa I.,University of Amsterdam | Buitendijk S.,Gynecology and Reproductive Medicine | De Miranda E.,Gynecology and Reproductive Medicine | De Wolf S.,University of Amsterdam | Spinhoven P.,Institute of Psychology
Journal of Psychosomatic Obstetrics and Gynecology | Year: 2011

Background: It is thought that pain cognitions determine coping behavior and success in adapting to labor. The aim of this study was to examine whether pain cognitions assessed by the labor pain coping and cognition list (LPCCL) predict the request for pain relief during the first stage of labor and which pain cognition is the strongest predictor of a request for pain relief over and above, and independent of, other pain cognitions. Methods: Participants in this prospective study were 177 low-risk nulliparous pregnant women. Data were collected on two different occasions. The numerical pain intensity scale (NPS)-anticipated and the LPCCL were administered at 3436 weeks' gestation followed by the NPS-during labor. Results: Catastrophizing and external pain control predicted the request for pain relief during labor after adjustment for relevant demographic and clinical characteristics, respectively (adjusted odds ratio [OR] 2.61 [95% CI 1.454.68] and adjusted OR 1.90 [95% CI 1.163.10]). Catastrophizing was found to be the strongest and independent predictor among the pain cognitions while controlling for significant background variables (adjusted OR 2.61 p-value < 0.001). Conclusion: Catastrophizing seems to have a substantial impact on the request for pain relief in low-risk pregnant women. © 2011 Informa UK, Ltd.


PubMed | Gynecology and Reproductive Medicine
Type: Journal Article | Journal: Fertility and sterility | Year: 2013

To assess tubo-ovarian dysplasia via morphologic and immunohistochemical study of rats exposed to ovulation stimulation protocols.Animal experimental study.Academic research hospital.72 female Wistar rats divided into three groups.Stimulation protocols using follicle-stimulating hormone (FSH) or clomiphene citrate for 3, 6, or 12 cycles, after which the animals were killed.Ovarian and tubal dysplasia score and immunohistochemical assessment using p53 and Ki67.The ovarian dysplasia score was statistically significantly higher after 12 stimulation cycles in the groups receiving FSH (group B) or clomiphene citrate (group C) compared with control (group A). The tubal dysplasia score was statistically significantly increased after only three stimulation cycles in groups B and C. The Ki67 proliferation marker was statistically significantly expressed in the ovaries from group C, and in the fallopian tubes from groups B and C. P53 was constantly low in all three groups.Ovulation stimulation may induce tubal and ovarian histopathologic and immunohistochemical abnormalities with a dose effect. The role of the fallopian tubes and their interaction with the ovaries require further study.

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