OBJECTIVE: To study the effectiveness of a new intrauterine degradable polymer film (Womed Leaf) in the management of moderate to severe intrauterine adhesions (IUA). DESIGN: PREG-2 study was a multicenter, double-blind, randomized, controlled, stratified, two-arm superiority clinical trial conducted in 16 centers in seven countries. SETTING: Not applicable. PATIENT(S): Patients ≥18 years scheduled for hysteroscopic adhesiolysis because of symptomatic severe or moderate adhesions (according to American Fertility Society [AFS] IUA score) were considered eligible for the study. INTERVENTION(S): After adhesiolysis, patients were randomized at a 1:1 ratio to either have a Womed Leaf film inserted (intervention group) or not (control group). MAIN OUTCOME MEASURE(S): The primary effectiveness endpoint of the study was the change in AFS IUA score on second-look hysteroscopy (SLH), assessed by an independent evaluator, and compared with baseline. Information on the rate of no IUA and responder rate was collected as secondary effectiveness outcomes, while reported adverse events and patient-reported outcomes as safety and tolerability measures. RESULT(S): Between October 26, 2021, and September 28, 2023, a total of 160 women were randomized (Womed Leaf: n = 75 and controls: n = 85). The reduction in IUA AFS score on SLH was significantly higher in the intervention compared with the control group (mean 5.2 ± 2.8 vs. 4.2 ± 3.2). Similarly, the absence of adhesions on SLH was significantly higher in the intervention group (41% vs. 24%; odds ratio, 2.44; confidence interval, 1.161-5.116). None of the reported adverse events were serious or considered related to the device. CONCLUSION(S): Womed Leaf is effective and safe in the management of symptomatic severe or moderate IUAs. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier: NCT04963179.
- MeSH
- adheze tkání MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- hysteroskopie * metody škodlivé účinky MeSH
- lidé MeSH
- nemoci dělohy * diagnóza MeSH
- polymery MeSH
- stupeň závažnosti nemoci MeSH
- vstřebatelné implantáty MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: To explore whether maternal baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) affect pregnancy outcomes particularly in normotensive women (SBP, 90-139 mm Hg; DBP, 60-89 mm Hg) and hypertensive women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective cohort study. SETTING: Maximum care hospital for reproductive medicine. PATIENT(S): This study included 73,462 patients who underwent IVF/ICSI at the Reproductive and Genetic Hospital of CITIC-Xiangya between January 1, 2016, and November 30, 2020, selected on the basis of pre-established criteria. Analysis was limited to the first transfer cycle of the first stimulation cycle. INTERVENTION: Baseline SBP and DBP. MAIN OUTCOME MEASURE(S): The primary outcome focused on the live birth rate (LBR), with the secondary outcomes including clinical pregnancy rate, ectopic pregnancy rate, first-trimester miscarriage rate, second- or third-trimester fetal loss, and delivery/neonatal/maternal outcomes. Analytic methods included Poisson regression, linear regression, linear mixed-effect model, and restricted cubic spline analysis as appropriate. RESULT(S): For normotensive women, a 10-mm Hg increase in SBP was associated with an adjusted relative risk of 0.988 (95% confidence interval, 0.981-0.995) for live birth likelihood. However, DBP was not significantly associated with LBR after adjustments. The secondary outcomes indicated that increases in SBP and DBP were associated with higher risks of first-trimester miscarriage, gestational diabetes mellitus, and gestational hypertension in the normotensive subset. Sensitivity analyses confirmed these associations between SBP/DBP and LBR, consistent with the main findings even under stricter guidelines and after adjusting for multiple confounders. Subgroup analyses showed variation in the impact of blood pressure on LBR across different demographics and conditions. Consistent with earlier studies on blood pressure and birth outcomes, we found a 10-mm Hg increase in SBP was associated with a 5.4% (adjusted relative risk per 10 mm Hg, 0.946; 95% confidence interval, 0.907-0.986) reduction in LBR in the hypertensive subgroup. CONCLUSION(S): Systolic blood pressure impacted LBR outcomes in normotensive women who underwent IVF/ICSI, which suggests the need for reconsidering blood pressure management guidelines for reproductive-age women, focusing on reproductive health in addition to cardiovascular risk.
- MeSH
- dospělí MeSH
- fertilizace in vitro * MeSH
- intracytoplazmatické injekce spermie * škodlivé účinky MeSH
- kohortové studie MeSH
- krevní tlak * fyziologie MeSH
- lidé MeSH
- narození živého dítěte * MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- úhrn těhotenství na počet žen v reprodukčním věku MeSH
- výsledek těhotenství epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach. DESIGN: Genome-wide association study. SETTING: Not applicable. PATIENTS: A discovery cohort of adult female childhood cancer survivors from the pan-European PanCareLIFE cohort (n = 743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, central nervous system or total body irradiation, or stem cell transplantation. Replication was attempted in the US-based St. Jude Lifetime Cohort (n = 391; median age: 31.3 years). EXPOSURE: Female childhood cancer survivors are at risk of therapy-related gonadal impairment. Alkylating agents are well-established risk factors, and the interindividual variability in gonadotoxicity may be explained by genetic polymorphisms. Data were collected in real-life conditions, and cyclophosphamide equivalent doses were used to quantify alkylation agent exposure. MAIN OUTCOME MEASURE: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function, and the findings were combined in a meta-analysis. RESULTS: Three genome-wide significant (<5.0 × 10-8) and 16 genome-wide suggestive (<5.0 × 10-6) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. On the basis of the effect allele frequency (EAF) (>0.01 if not genome-wide significant), and biologic relevance, 15 single nucleotide polymorphisms were selected for replication. None of the single nucleotide polymorphisms were statistically significantly associated with AMH levels. A meta-analysis indicated that rs78861946 was associated with borderline genome-wide statistical significance (reference/effect allele: C/T; effect allele frequency: 0.04, beta (SE): -0.484 (0.091). CONCLUSION: This study found no genetic variants associated with a lower ovarian reserve after gonadotoxic treatment because the findings of this genome-wide association study were not statistically significant replicated in the replication cohort. Suggestive evidence for the potential importance of 1 variant is briefly discussed, but the lack of statistical significance calls for larger cohort sizes. Because the population of childhood cancer survivors is increasing, large-scale and systematic research is needed to identify genetic variants that could aid predictive risk models of gonadotoxicity as well as fertility preservation options for childhood cancer survivors.
- MeSH
- alkylační protinádorové látky škodlivé účinky MeSH
- antimülleriánský hormon * krev genetika MeSH
- celogenomová asociační studie * MeSH
- dítě MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory genetika farmakoterapie MeSH
- ovariální rezerva * genetika účinky léků účinky záření MeSH
- přežívající onkologičtí pacienti * MeSH
- rizikové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVE: To demonstrate the use of a single-stapler technique during rectosigmoid resection in women with deep infiltrating endometriosis (DIE). DESIGN: A step-by-step video demonstration of rectosigmoid resection and end-to-end anastomosis using two circularly placed sutures and one circular stapler. SETTING: Institute for the Care of Mother and Child, Prague, Czech Republic. PATIENT(S): A 39-year-old woman presented with primary sterility and deep infiltrating endometriosis, and an EZIAN score of A2,B2,C3. A nodule was located 9 cm from the anus and was 38 × 9 mm in size. This included an intramural fibroma of 6 cm and a left-sided ovarian endometriotic cyst of 6 cm. Her pain on the visual analogue scale were dysmenorea 6, dyspareunia 5-6, dyschezie 7, dysuria 0, and acyclic pain 5. INTERVENTIONS: The primary objective was to replace the linear-stapler resection with two simple, strictly circularly placed sutures, to cut the intestinal wall between them, and to form the end-to-end anastomosis with a circular stapler. The one-stapler technique consisted of the following steps: intestinal wall cleansing as in the limited segmental resection; placement of one strictly circular suture just below the DIE nodule, without fixation; placement of the first circular suture just below the DIE nodule, ideally with at least three full-thickness "bites" of the intestinal wall; placement of the second circular stitch approximately 2 cm below the first one in a similar manner (three full-thickness "bites"); interruption of the intestinal wall with a harmonic scalpel; end-to-end intestinal anastomosis with a circular stapler; and airtightness test of the anastomosis. This results in only one incision line and therefore a lower risk of leakage. Intestinal resection time was on average 10 minutes longer compared to that for the linear stapler technique. So far, we have successfully performed the procedure in 25 women. Perioperative leakage was observed in two of these 25 patients in the classical procedure group and in none of the 25 patients in the group with the one-stapler technique. There were no differences in C-reactive protein (CRP) on third and fifth postoperative days or in other complications such as bleeding and pyrexia). The cost of procedure is lowered by the decrease in the number of staplers from 3 to 1. The patients' postoperative follow-up was uneventful, and they were discharged from the hospital at the same time as the women in whom the classical stapler technique was performed. MAIN OUTCOME MEASURES(S): The primary outcome was the development of a new surgical approach to resection rectosigmoid endometriotic nodules that would decrease the number of incision lines on the intestine. The secondary outcome measures were peri- and postoperative complications (i.e., bleeding, intestinal leakage, postoperative infection, CRP), length of the surgery and hospitalization, and cost of the procedure. CONCLUSION: Multiple incision lines following resection of the rectosigmoid colon and end-to-end anastomosis are risk factors for postoperative intestinal leakage. Therefore, a single incision line formed with two circular sutures, and one circular stapler may reduce the risk of postoperative complications and also financial expenses of the procedure. We believe that this method is suitable and easiest for nodules located less than 6 cm from the anal verge because of possible complications with angulation of linear stapler.
- MeSH
- colon sigmoideum diagnostické zobrazování chirurgie MeSH
- dospělí MeSH
- endometrióza diagnostické zobrazování chirurgie MeSH
- laparoskopie metody MeSH
- lidé MeSH
- rektum diagnostické zobrazování chirurgie MeSH
- šicí techniky * MeSH
- sutura * MeSH
- video-asistovaná chirurgie metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- kazuistiky MeSH
OBJECTIVE: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. DESIGN: Double-blind, randomized administration of four 12-week courses of ulipristal acetate. SETTING: Gynecology centers. PATIENT(S): Four hundred fifty-one subjects with symptomatic uterine fibroid(s) and heavy menstrual bleeding. INTERVENTION(S): Four repeated 12-week treatment courses of daily 5 or 10 mg ulipristal acetate. MAIN OUTCOME MEASURE(S): Endometrial safety and general safety, laboratory parameters, amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), and pain. RESULT(S): Efficacy results, such as bleeding control and fibroid volume reduction, were in line with previously published data. Pain and QoL showed marked improvements from screening, even during the off-treatment intervals. The safety profile of ulipristal acetate was confirmed, and repeated treatment courses did not increase the occurrence of adverse reactions. There were no significant changes in laboratory parameters during the study. The percentage of subjects with endometrial thickness ≥ 16 mm was 7.4% (all subjects) after the first treatment course and returned to below screening levels (4.9%) in subsequent treatment courses. As in previous studies, ulipristal acetate did not increase the occurrence of endometrial features of concern. The frequency of nonphysiological changes did not increase with repeated treatment. They were observed in 17.8% and 13.3% of biopsies after treatment courses 2 and 4, respectively, and were reversible after treatment cessation. CONCLUSION(S): The results of this study demonstrate the efficacy and further support the safety profile of repeated intermittent treatment of symptomatic fibroids with ulipristal acetate. CLINICAL TRIAL REGISTRATION NUMBER: NCT01629563.
- MeSH
- biopsie MeSH
- časové faktory MeSH
- děložní krvácení diagnóza farmakoterapie etiologie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- kvalita života MeSH
- leiomyom komplikace diagnóza farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření bolesti MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory dělohy komplikace diagnóza farmakoterapie MeSH
- norpregnadieny aplikace a dávkování škodlivé účinky MeSH
- pánevní bolest diagnóza farmakoterapie etiologie MeSH
- protinádorové látky aplikace a dávkování škodlivé účinky MeSH
- průzkumy a dotazníky MeSH
- rozvrh dávkování léků MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVE: To study pregnancies in a large group of patients with growth hormone deficiency and hypopituitarism; and to investigate potential factors determining pregnancy outcomes and pregnancy complications. DESIGN: We analyzed pregnancies reported in KIMS, the Pfizer International Metabolic Database, of adult patients with growth hormone deficiency treated with growth hormone. SETTING: Outpatient clinics. PATIENT(S): A total of 201 pregnancies were reported: 173 in female patients and 28 in partners of male patients. INTERVENTION(S): Growth hormone replacement therapy (GHRT) was prescribed according to the local clinical practice. MAIN OUTCOME MEASURE(S): Pregnancy outcomes (live births, gestational week at delivery, and birth weight), pregnancy complications, and their relationship to use of GHRT during pregnancy were analyzed with regression models. RESULT(S): Two-thirds of women underwent fertility treatment to achieve pregnancy. Growth hormone replacement therapy was stopped before pregnancy in 7.5% of the female patients, as soon as pregnancy was confirmed in 40.1%, and at the end of the second trimester in 24.7% of the patients, whereas 27.6% continued GHRT throughout pregnancy. Birth of a healthy child was reported in 79% of the female pregnancies, nonelective abortions occurred mainly in the first trimester, and one fetal malformation (cystic hygroma) was diagnosed in the second trimester. Pregnancy outcomes and pregnancy complications were not related to GHRT treatment patterns, method of conception, or number of additional pituitary deficiencies. CONCLUSION(S): These data on pregnancy outcomes in a large group of women with hypopituitarism revealed no relationship between GHRT regimens and pregnancy outcomes.
- MeSH
- asistovaná reprodukce MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- databáze faktografické MeSH
- dospělí MeSH
- gestační stáří MeSH
- hormonální substituční terapie škodlivé účinky MeSH
- hypopituitarismus krev komplikace diagnóza farmakoterapie MeSH
- komplikace těhotenství etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidský růstový hormon aplikace a dávkování škodlivé účinky krev nedostatek MeSH
- mladiství MeSH
- mladý dospělý MeSH
- narození živého dítěte MeSH
- porodní hmotnost MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- rozvrh dávkování léků MeSH
- těhotenství MeSH
- výsledek těhotenství * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- Spojené státy americké MeSH
OBJECTIVE: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. DESIGN: Double-blind, randomized administration of two 12-week courses of ulipristal acetate. SETTING: Gynecology centers. PATIENT(S): A total of 451 patients with symptomatic uterine fibroid(s) and heavy bleeding. INTERVENTION(S): Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate. MAIN OUTCOME MEASURE(S): Amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), pain. RESULT(S): In the 5- and 10-mg treatment groups (62% and 73% of patients, respectively) achieved amenorrhea during both treatment courses. Proportions of patients achieving controlled bleeding during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10 mg of ulipristal acetate, respectively. Pain and QoL improved in both groups. Ulipristal acetate was well tolerated with less than 5% of patients discontinuing treatment due to adverse events. CONCLUSION(S): Repeated 12-week courses of daily oral ulipristal acetate (5 and 10 mg) effectively control bleeding and pain, reduce fibroid volume, and restore QoL in patients with symptomatic fibroids. CLINICAL TRIAL REGISTRATION NUMBER: NCT01629563 (PEARL IV).
- MeSH
- amenorea diagnóza farmakoterapie MeSH
- aplikace orální MeSH
- bolest diagnóza farmakoterapie MeSH
- bolesti hlavy chemicky indukované diagnóza MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- kvalita života * MeSH
- leiomyom diagnóza farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory dělohy diagnóza farmakoterapie MeSH
- nauzea chemicky indukované diagnóza MeSH
- norpregnadieny aplikace a dávkování škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: To study the incidence of monozygotic twinning (MZT) in patients using in vitro fertilization, relative to their age, genetic background, ovarian function, and assisted reproductive techniques used. DESIGN: Analysis of a collected database. SETTING: Infertility treatment center. PATIENT(S): A total of 1,876 patients receiving infertility treatment between 2000 and 2012. Pregnancies with monozygotic twins (A: 23) were compared with deliveries of dizygotic twins (B: 423), singleton pregnancies (C: 880), and aborted pregnancies (D: 389). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A genetic survey on multiple pregnancies in the extended family. Measures were micromanipulation technique, the length of embryo cultivation, type of cultivation media, basal follicle-stimulating hormone level, estradiol level on the day of human chorionic gonadotropin administration, number of oocytes, total consumption of gonadotropins, and consumption of gonadotropins needed for recovery of 1 oocyte. RESULT(S): No differences were found between the incidence of MZT in cycles that did vs. did not use micromanipulation techniques. In addition, the length of embryo cultivation or type of cultivation media used did not affect the results. Estradiol levels and implantation rates were significantly higher in group A. The incidence of MZT in families in group A was significantly higher than that in groups B and C. CONCLUSION(S): We propose that the high incidence of MZT in infertility-clinic patients is conditioned by hereditary factors, and good ovarian function only facilitates the expression. The resulting recommendation is that young women with a positive family history and good ovarian function undergo elective single-embryo transfer, and proper counseling is advisable.
- MeSH
- asistovaná reprodukce statistika a číselné údaje MeSH
- dospělí MeSH
- dvojčata monozygotní * genetika statistika a číselné údaje MeSH
- incidence MeSH
- lidé MeSH
- novorozenec MeSH
- přenos embrya metody statistika a číselné údaje MeSH
- rozdělení zygoty * genetika MeSH
- těhotenství s dvojčaty genetika statistika a číselné údaje MeSH
- těhotenství MeSH
- úhrn těhotenství na počet žen v reprodukčním věku MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrations. DESIGN: Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0-14.9 pmol/L [0.7-<2.1 ng/mL]; high: 15.0-44.9 pmol/L [2.1-6.3 ng/mL]) trial. SETTING: Seven infertility centers in four countries. PATIENT(S): Two hundred sixty-five women aged ≤37 years. INTERVENTION(S): Controlled ovarian stimulation with either 5.2, 6.9, 8.6, 10.3, or 12.1 μg of rhFSH, or 11 μg (150 IU) of follitropin alfa in a GnRH antagonist cycle. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved. RESULT(S): The number of oocytes retrieved increased in an rhFSH dose-dependent manner, from 5.2 ± 3.3 oocytes with 5.2 μg/d to 12.2 ± 5.9 with 12.1 μg/d. The slopes of the rhFSH dose-response curves differed significantly between the two AMH strata, demonstrating that a 10% increase in dose resulted in 0.5 (95% confidence interval 0.2-0.7) and 1.0 (95% confidence interval 0.7-1.3) more oocytes in the low and high AMH stratum, respectively. Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata. No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata. Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum. CONCLUSION(S): Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner. The availability of blastocysts is less influenced by the rhFSH dose and AMH level. CLINICAL TRIAL REGISTRATION NUMBER: NCT01426386.
- MeSH
- antimülleriánský hormon aplikace a dávkování MeSH
- dospělí MeSH
- fertilizace in vitro metody MeSH
- folikuly stimulující hormon lidský aplikace a dávkování MeSH
- indukce ovulace metody MeSH
- intracytoplazmatické injekce spermie metody MeSH
- lidé MeSH
- odběr oocytu * MeSH
- rekombinantní proteiny aplikace a dávkování MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: To determine whether inhibition of epidermal growth factor (EGF) receptor tyrosine kinase with lapatinib affects oocyte maturation, expression of the cumulus expansion-associated genes such as tumor necrosis factor alpha-induced protein 6 (TNFAIP6) and prostaglandin-endoperoxide synthase 2 (PTGS2), and synthesis of hyaluronan (HA) and progesterone (P) by porcine oocyte cumulus complexes (OCC). DESIGN: Our work focuses on lapatinib, an orally active small molecule that selectively inhibits the tyrosine kinase domain of both EGF receptor and human EGF receptor 2, and downstream signaling. SETTING: A reproductive biology laboratory. PATIENT(S): Not applicable. INTERVENTION(S): Porcine OCC were cultured in vitro in a medium with FSH/LH in the presence/absence of lapatinib. MAIN OUTCOME MEASURE(S): Methods performed: real-time reverse transcriptase-polymerase chain reaction (PCR), immunofluorescence, RIA. RESULT(S): In FSH/LH-stimulated and expanded cumulus oophorus extracellular matrix, HA was detected with biotinylated HA-binding proteins. However, weaker HA- and weaker cytoplasmic TNFAIP6 were detected were detected in lapatinib-pretreated OCC. The expression of the two cumulus expansion-associated gene transcripts was significantly decreased and synthesis of HA by cumulus cells was reduced. Lapatinib (10 μM) inhibited FSH/LH-induced oocyte meiotic maturation. Progesterone production increased after OCC stimulation with FSH/LH and was significantly decreased by lapatinib (10 μM). CONCLUSION(S): Lapatinib inhibits oocyte maturation and reduces expression of cumulus expansion-associated transcripts, and synthesis of HA and P in OCC cultured in vitro in FSH/LH-supplemented medium.
- MeSH
- buněčná diferenciace účinky léků fyziologie MeSH
- chinazoliny farmakologie MeSH
- folikuly stimulující hormon farmakologie MeSH
- inhibitory růstu farmakologie MeSH
- kultivované buňky MeSH
- kumulární buňky cytologie účinky léků MeSH
- meióza účinky léků fyziologie MeSH
- oocyty cytologie účinky léků MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH