486 research outputs found
Successful induction of ovulation and completed pregnancy using recombinant human luteinizing hormone and follicle stimulating hormone in a woman with Kallmann's syndrome
The induction of ovulation in women with hypogonado-trophic hypogonadism requires follicle stimulating hormone (FSH) for follicular growth and both FSH and luteinizing hormone (LH) to induce optimal follicular steroidogenesis. The development of human recombinant FSH and LH means that individually tailored doses of both hormones can be used with the aim of inducing unifollicular ovulation. This report describes the use of recombinant human FSH and LH for the induction of ovulation and conception in the second cycle of treatment, and subsequently a successfully completed pregnancy in a woman with Kallmann's syndrom
Tumour-derived leukaemia inhibitory factor is a major driver of cancer cachexia and morbidity in C26 tumour-bearing mice
BACKGROUND: Cancer cachexia is a metabolic wasting syndrome that is strongly associated with a poor prognosis. The initiating factors causing fat and muscle loss are largely unknown. Previously, we found that leukaemia inhibitory factor (LIF) secreted by C26 colon carcinoma cells was responsible for atrophy in treated myotubes. In the present study, we tested whether C26 tumourâderived LIF is required for cancer cachexia in mice by knockout of Lif in C26 cells.
METHODS: A C26 Lif null tumour cell line was made using CRISPRâCas9. Measurements of cachexia were compared in mice inoculated with C26 vs. C26^Lifâ/â tumour cells, and atrophy was compared in myotubes treated with medium from C26 vs. C26^Lifâ/â tumour cells. Levels of 25 cytokines/chemokines were compared in serum of mice bearing C26 vs. C26^Lifâ/â tumours and in the medium from these tumour cell lines.
RESULTS: At study endpoint, C26 mice showed outward signs of sickness while mice with C26^Lifâ/â tumours appeared healthy. Mice with C26^Lifâ/â tumours showed a 55â75% amelioration of body weight loss, muscle loss, fat loss, and splenomegaly compared with mice with C26 tumours (P < 0.05). The heart was not affected by LIF levels because the loss of cardiac mass was the same in C26 and C^26Lifâ/â tumourâbearing mice. LIF levels in mouse serum was entirely dependent on secretion from the tumour cells. Serum levels of interleukinâ6 and GâCSF were increased by 79âfold and 68âfold, respectively, in C26 mice but only by fiveâfold and twoâfold, respectively, in C26^Lifâ/â mice, suggesting that interleukinâ6 and GâCSF increases are dependent on tumourâderived LIF.
CONCLUSIONS: This study shows the first use of CRISPRâCas9 knockout of a candidate cachexia factor in tumour cells. The results provide direct evidence for LIF as a major cachexia initiating factor for the C26 tumour in vivo. Tumourâderived LIF was also a regulator of multiple cytokines in C26 tumour cells and in C26 tumourâbearing mice. The identification of tumourâderived factors such as LIF that initiate the cachectic process is immediately applicable to the development of therapeutics to treat cachexia. This is a proof of principle for studies that when carried out in human cells, will make possible an understanding of the factors causing cachexia in a patientâspecific manner.This work was supported by NIAMS R01AR060217 to S. C. K. and R. W. J. and NIAMS R01 R01AR060209 to A. R. J., and by the Dudley Allen Sargent Research Fund. The authors certify that they comply with the ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2017.40 (R01AR060217 - NIAMS; R01 R01AR060209 - NIAMS; Dudley Allen Sargent Research Fund)Published versio
Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment
Replacing GnRH agonist cotreatment for the prevention of a premature rise
in LH during ovarian stimulation for in vitro fertilization (IVF) by the
late follicular phase administration of GnRH antagonist may render
supplementation of the luteal phase redundant, because of the known rapid
recovery of pituitary function after antagonist cessation. This randomized
two-center study was performed to compare nonsupplemented luteal phase
characteristics after three different strategies for inducing final oocyte
maturation. Forty patients underwent ovarian stimulation using recombinant
(r-)FSH (150 IU/d, fixed) combined with a GnRH antagonist (antide; 1 mg/d)
during the late follicular phase. When at least one follicle above 18 mm
was observed, patients were randomized to induce oocyte maturation by a
single injection of either r-human (h)CG (250 microg) (n = 11), r-LH (1
mg) (n = 13), or GnRH agonist (triptorelin; 0.2 mg) (n = 15). Retrieved
oocytes were fertilized by either IVF or intracytoplasmatic sperm
injection, depending on sperm quality. Embryo transfer was performed 3-4 d
after oocyte retrieval. No luteal support was provided. Serum
concentrations of FSH, LH, estradiol (E(2)), progesterone (P), and hCG
were assessed at fixed intervals during the follicular and luteal phase.
The median duration of the luteal phase was 13, 10, and 9 d for the r-hCG,
the r-LH, and the GnRH agonist group, respectively (P = 0.005). The median
area under the curve per day (from 4 d post randomization until the onset
of menses) for LH was 0.50, 2.34, and 1.07 for the r-hCG, the r-LH, and
the GnRH agonist group, respectively (P = 0.001). The median area under
the curve per day for P was 269 vs. 41 and 16 for the r-hCG, the r-LH, and
the GnRH agonist group, respectively (P < 0.001). Low pregnancy rates
(overall, 7.5%; range, 0-18% per started cycle) were observed in all
groups. In conclusion, the nonsupplemented luteal phase was insufficient
in all three groups. In the patients receiving r-hCG, the luteal phase was
less disturbed, compared with both other groups, presumably because of
prolonged clearance of hCG from the circulation and the resulting extended
support of the corpus luteum. Despite high P and E(2) concentrations
during the early luteal phase in all three groups, luteolysis started
prematurely, presumably because of excessive negative steroid feedback
resulting in suppressed pituitary LH release. Hence, support of corpus
luteum function remains mandatory after ovarian stimulation for IVF with
GnRH antagonist cotreatment
Long-term treatment of uterine fibroids with ulipristal acetate
Objective:
To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.<p></p>
Design:
Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo.<p></p>
Setting:
European clinical gynecology centers.<p></p>
Patient(s):
Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding.<p></p>
Intervention(s):
Patients received up to four 3-month courses of UPA 10Â mg daily, immediately followed by 10-day double-blind treatment with NETA (10Â mg daily) or placebo.<p></p>
Main Outcome Measure(s):
Amenorrhea, fibroid volume, endometrial histology.<p></p>
Result(s):
After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4Â days (interquartile range, 2â6Â days). Median fibroid volume change was â45% (interquartile range, â66%; â25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3Â days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were â63%, â67%, and â72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology.<p></p>
Conclusion(s):
Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids
Discontinuation of rLH two days before hCG may increase the number of oocytes retrieved in IVF
<p>Abstract</p> <p>Background</p> <p>Administration of recombinant luteinizing hormone (rLH) in controlled ovarian hyperstimulation may benefit a subpopulation of patients. However, late follicular phase administration of high doses of rLH may also reduce the size of the follicular cohort and promote monofollicular development.</p> <p>Methods</p> <p>To determine if rLH in late follicular development had a negative impact on follicular growth and oocyte yield, IVF patients in our practice who received rFSH and rLH for the entire stimulation were retrospectively compared with those that had the rLH discontinued at least two days prior to hCG trigger.</p> <p>Results</p> <p>The two groups had similar baseline characteristics before stimulation with respect to age, FSH level and antral follicle count. However, the group which had the rLH discontinued at least two days prior to their hCG shot, had a significantly higher number of oocytes retrieved, including a higher number of MII oocytes and number of 2PN embryos.</p> <p>Conclusions</p> <p>When using rLH for controlled ovarian hyperstimulation, administering it from the start of stimulation and stopping it in the late follicular phase, at least two days prior to hCG trigger, may increase oocyte and embryo yield.</p
Living in a hot redox soup: antioxidant defences of the hydrothermal worm Alvinella pompejana
Kinetic studies of peroxiredoxin 6 from Arenicola marina: Rapid oxidation by 3 hydrogen peroxide and peroxynitrite but lack of reduction by hydrogen sulfide
, respectively, at pH 7.4 and 25°C. Reduction of tert-butyl hydroperoxide was slower. 34 The pK a of the peroxidatic thiol of AmPrx6 was determined as 5
Comparison of Clinical Efficacy between a Single Administration of Long-Acting Gonadotrophin-Releasing Hormone Agonist (GnRHa) and Daily Administrations of Short-Acting GnRHa in In Vitro Fertilization-Embryo Transfer Cycles
This study was aimed to evaluate the efficacy of a single administration of long-acting gonadotrophin-releasing hormone agonist (GnRHa) as compared with daily administrations of short-acting GnRHa in controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) cycles. The mean dosage of recombinant follicle-stimulating hormone (rFSH) required for COH (2,354.5±244.2 vs. 2,012.5±626.1 IU) and the rFSH dosage per retrieved oocyte (336.7±230.4 vs. 292.1±540.4 IU) were significantly higher in the long-acting GnRHa group (N=22) than those in the short-acting GnRHa group (N=28) (p<0.05). However, the mean number of visit to the hospital that was required before ovum pick-up (3.3±0.5 vs. 22.2±2.0) and the frequency of injecting GnRHa and rFSH (12.8±1.2 vs. 33.5±3.5) were significantly decreased in the long-acting GnRHa group (p<0.0001). The clinical pregnancy rate, implantation rate, and early pregnancy loss rate were not significantly different between the 2 groups. So, we suggest that a single administration of long-acting GnRHa is a useful alternative for improving patient's convenience with clinical outcomes comparable to daily administrations of short-acting GnRHa in COH for IVF-ET cycles
Absence of aromatase protein and mRNA expression in endometriosis.
BACKGROUND: Aromatase has been reported to be involved in estrogen biosynthesis and expressed in eutopic and ectopic endometrium of endometriosis patients. The objective of the present study was to investigate its expression and localization in three distinct types of endometriosis. METHODS: Human peritoneal, ovarian and rectovaginal endometriotic lesions and matched eutopic endometrium were collected from patients during laparoscopy. Aromatase protein localization (immunohistochemistry, n = 63) and mRNA expression [quantitative polymerase chain reaction (Q-PCR), n = 64] were assessed. RESULTS: No aromatase protein was detected by immunohistochemistry in either the glandular or stromal compartment of endometriotic lesions or eutopic endometrium, while it was strong in placental syncytiotrophoblasts, granulosa and internal theca cells from pre-ovulatory follicles, and luteal cells from corpus luteum. By Q-PCR, low but discernible levels of aromatase expression were found in endometriomas, probably due to follicular expression. Transcripts for aromatase were barely detectable in only a few peritoneal and rectovaginal endometriotic lesions, and a few eutopic endometrium samples, probably due to contaminating surrounding tissues (adipose tissue, intact peritoneum). CONCLUSIONS: Unlike previous studies, we observed no aromatase protein in any of the endometriosis types, and barely detectable aromatase mRNA expression, suggesting that locally produced aromatase (within endometriotic lesions) may be less implicated in endometriosis development than previously postulated. Potential factors responsible for these discrepancies are discussed
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