Priming with human chorionic gonadotropin before retrieval of immature oocytes in women with infertility due to the polycystic ovary syndrome.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
S L Tan
Publications and source records attributed to S L Tan.
NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-dependent manner and perturbs mitogenic signaling.
Although hepatitis C virus (HCV) infection is an emerging global epidemic causing severe liver disorders, the molecular mechanisms of HCV pathogenesis remain elusive. The NS5A nonstructural protein of HCV contains several proline-rich sequences consistent with Src homology (SH) 3-binding sites found in cellular signaling molecules. Here, we demonstrate that NS5A specifically bound to growth factor receptor-bound protein 2 (Grb2) adaptor protein. Immunoblot analysis of anti-Grb2 immune complexes derived from HeLa S3 cells infected with a recombinant vaccinia virus (VV) expressing NS5A revealed an interaction between NS5A and Grb2 in vivo. An inactivating point mutation in the N-terminal SH3 domain, but not in the C-terminal SH3 domain, of Grb2 displayed significant diminished binding to NS5A. However, the same mutation in both SH3 regions completely abrogated Grb2 binding to NS5A, implying that the two SH3 domains bind in cooperative fashion to NS5A. Further, mutational analysis of NS5A assigned the SH3-binding region to a proline-rich motif that is highly conserved among HCV genotypes. Importantly, phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) was inhibited in HeLa S3 cells infected with NS5A-expressing recombinant VV but not recombinant VV control. Additionally, HeLa cells stably expressing NS5A were refractory to ERK1/2 phosphorylation induced by exogenous epidermal growth factor. Moreover, the coupling of NS5A to Grb2 in these cells was induced by epidermal growth factor stimulation. Therefore, NS5A may function to perturb Grb2-mediated signaling pathways by selectively targeting the adaptor. These findings highlight a viral interceptor of cellular signaling with potential implications for HCV pathogenesis.
Adaptor Proteins, Signal Transducing↗
The cellular inhibitor of the PKR protein kinase, P58(IPK), is an influenza virus-activated co-chaperone that modulates heat shock protein 70 activity.
P58(IPK), a member of the tetratricopeptide repeat and J-domain protein families, was first recognized for its ability to inhibit the double-stranded RNA-activated protein kinase, PKR. PKR is part of the interferon-induced host defense against viral infection, and down-regulates translation initiation via phosphorylation of eukaryotic initiation factor 2 on the alpha-subunit. P58(IPK) is activated in response to infection by influenza virus, and inhibits PKR through direct protein-protein interaction. Previously, we demonstrated that the molecular chaperone heat shock protein 40 (hsp40) was a negative regulator of P58(IPK). We could now report that influenza virus activates the P58(IPK) pathway by promoting the dissociation of hsp40 from P58(IPK) during infection. We also found that the P58(IPK)-hsp40 association was disrupted during recovery from heat shock, which suggested a regulatory role for P58(IPK) in the absence of virus infection. The PKR pathway is even more complex as we show in this report that the molecular chaperone, hsp/Hsc70, was a component of a trimeric complex with hsp40 and P58(IPK). Moreover, like other J-domain proteins, P58(IPK) stimulated the ATPase activity of Hsc70. Taken together, our data suggest that P58(IPK) is a co-chaperone, possibly directing hsp/Hsc70 to refold, and thus inhibit kinase function.
Adenosine Triphosphatases↗
Progestogen therapy during pituitary desensitization with gonadotropin-releasing hormone agonist prevents functional ovarian cyst formation: a prospective, randomized study.
OBJECTIVES: We sought to assess whether the use of norethindrone and gonadotropin-releasing hormone agonist therapy in the early follicular phase reduces the occurrence of functional ovarian cysts and shortens the duration of pituitary desensitization. We also assessed whether the use of norethindrone impairs implantation rates after in vitro fertilization treatment. STUDY DESIGN: We performed a prospective, randomized, single-blind study involving 117 patients who were randomized to receive norethindrone 24 hours before gonadotropin-releasing hormone agonist therapy (n = 63, treatment group) or gonadotropin-releasing hormone agonist alone (n = 54, control group) for pituitary desensitization. RESULTS: The incidence of functional ovarian cyst formation after 1 week of gonadotropin-releasing hormone agonist therapy was significantly lower in the treatment group compared with the control group. Furthermore, the duration of pituitary suppression was significantly shorter in the treatment group than in the control group. There were no significant differences between the 2 groups in the follicular response and embryo quality. Adjusted for age, the implantation rate (22% vs 9%, P =.02) and clinical pregnancy rate (34% vs 18%, P =.04) were significantly higher in the treatment group than in the control group. CONCLUSION: A combination of norethindrone and gonadotropin-releasing hormone agonist therapy is therefore more effective in achieving prompt pituitary suppression and should be considered for routine use during in vitro fertilization cycles.
Adolescent↗
Value of ovarian stromal blood flow velocity measurement after pituitary suppression in the prediction of ovarian responsiveness and outcome of in vitro fertilization treatment.
OBJECTIVE: To evaluate whether ovarian stromal blood flow velocity after pituitary suppression is predictive of ovarian response and the outcome of IVF treatment in patients with normal basal serum FSH levels and to compare the predictive value of this test with age, early follicular phase serum FSH level, E2 level, and FSH:LH ratio. DESIGN: Prospective observational study of women undergoing IVF treatment. SETTING: A tertiary referral center for assisted reproduction. PATIENT(S): Eighty-eight women who received the long buserelin acetate treatment protocol. INTERVENTION(S): Transvaginal color and pulsed Doppler measurement of the ovarian stromal peak systolic velocity (PSV) after pituitary suppression and measurement of the basal serum FSH level, E2 level, and FSH:LH ratio. MAIN OUTCOME MEASURE(S): Number of mature oocytes retrieved and pregnancy rate. RESULT(S): Ovarian stromal PSV was the most important single independent predictor of ovarian response in patients with a normal basal serum FSH level, when compared with age, basal FSH level, E2 level, or FSH:LH ratio. Patients in group 2 (PSV > or = 10 cm/s) had a significantly higher median number of mature oocytes retrieved (11 versus 5.5) and a higher clinical pregnancy rate (35.3% versus 11.3%) than patients in group 1 (PSV <10 cm/s), even after controlling for age. CONCLUSION(S): Ovarian stromal blood flow velocity, after pituitary suppression is confirmed, is predictive of ovarian responsiveness and the outcome of IVF treatment.
Adult↗
Production of steroids from human cumulus cells treated with different concentrations of gonadotropins during culture in vitro.
OBJECTIVE: To evaluate the output of E2 and progesterone produced by cumulus cells, derived from mature and immature oocytes, in culture medium. DESIGN: Prospective randomized study. SETTING: McGill Reproductive Center, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada. PATIENT(S): Twenty-one women, <38 years of age and with normal menstrual cycles, who were undergoing intracytoplasmic sperm injection for assisted reproduction. INTERVENTION(S): Culture medium with or without fetal bovine serum (FBS) supplemented with either a physiologic (75 mIU/mL) or a supraphysiologic (7,500 mIU/mL) concentration of gonadotropins. MAIN OUTCOME MEASURE(S): Comparison of steroid levels in culture medium. RESULT(S): Estradiol secretion was significantly increased in the culture medium with FBS supplemented with both concentrations of FSH alone compared with control. However, E2 secretion was inhibited by both concentrations of FSH with LH. The level of E2 was undetectable in the medium without FBS even after supplementation with both concentrations of FSH alone, hCG alone, and FSH with LH. Progesterone production was increased in the medium with FBS supplemented with FSH alone, hCG alone, and FSH with LH compared with control. There was no difference in progesterone levels in the culture medium without FBS supplemented with both concentrations of FSH alone and hCG alone compared with control. However, progesterone secretion was increased in the medium without FBS supplemented with a physiologic concentration of FSH with LH. CONCLUSION(S): Culture medium with FBS supplemented with a physiologic and a supraphysiologic concentration of FSH stimulates E2 secretion from cumulus cells derived from mature and immature oocytes. This suggests that it may be not necessary to add E2 to the culture medium for maturation in vitro of immature human oocytes retrieved from patients undergoing stimulated cycles.
Adult↗
Serum vascular endothelial growth factor concentrations in in vitro fertilization cycles predict the risk of ovarian hyperstimulation syndrome.
OBJECTIVE: To explore the value of serum vascular endothelial growth factor (VEGF) concentrations during IVF cycles in predicting the risk of ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective study. SETTING: London Women's Clinic. PATIENT(S): One hundred seven women undergoing IVF. Mild OHSS developed in 10 women, moderate OHSS in 7, and severe OHSS in 3. INTERVENTION(S): Serum VEGF concentrations were measured before treatment, after pituitary desensitization, and on the days of hCG administration, oocyte collection, and ET. MAIN OUTCOME MEASURE(S): Serum VEGF concentrations. RESULT(S): Serum VEGF concentrations were higher in women in whom OHSS developed. The increase in the VEGF concentration that occurred between the day of hCG administration and the day of oocyte collection (the "VEGF rise") was an important marker of OHSS. The VEGF rise was higher in women in whom OHSS developed. A higher VEGF rise predicted all cases of OHSS and moderate/severe cases of OHSS with a sensitivity of 100% and a specificity of 60%. A likelihood ratio test showed that adding the VEGF rise or the VEGF concentration on the day of oocyte collection to a regression model as a continuous variable to the number of follicles, the E2 concentration, and the presence of polycystic ovaries significantly contributed to predicting the risk of OHSS. CONCLUSION(S): The results support the role of VEGF as an important nonsteroidal index of ovarian response. The VEGF rise may have an advantage over the E2 concentration, the number of follicles, and the number of oocytes, which individually predict only 15%-25% of cases of OHSS.
Adult↗
Prospective randomized double-blind trial of the correlation between time of administration and antiestrogenic effects of clomiphene citrate on reproductive end organs.
OBJECTIVE: To investigate whether the timing of administration of clomiphene citrate (CC) affects hormone levels, follicular recruitment, reproductive end organs, and pregnancy rates. DESIGN: Prospective, randomized, double-blind trial. SETTING: Academic center. PATIENT(S): Twenty-three patients with unexplained infertility. INTERVENTION(S): Twenty-three patients with unexplained infertility underwent 45 cycles of CC and IUI. For each cycle, patients were randomized either to receive 100 mg of CC on days 1-5 and placebo on days 5-9 (study group), or placebo on days 1-5 and CC on days 5-9 (control group). MAIN OUTCOME MEASURE(S): The difference in uterine artery PI, number of follicles, endometrial thickness, and pregnancy rates. RESULT(S): Gonadotropins and E2 levels, as well as uterine artery pulsatility index, were significantly higher in the study group on day 5. In addition, in the study group, a longer time interval existed between finishing CC and IUI (8 versus 6 days; MD = 2 days; 95% CI = 1-3) and the pregnancy rate was higher than in the control group (6 versus 0; OR = 15.1; 95% CI = 1.1-72.4). CONCLUSION(S): Clomiphene citrate commenced on day 1 of the menstrual cycle, rather than day 5, results in more rapid follicular growth, a longer CC-free period before IUI, and higher pregnancy rates. Although methodologically sound, our results should be taken with some degree of caution because they are based on a relatively small number of patients.
Adult↗
In vitro fertilization and intracytoplasmic sperm injection pregnancies after successful transport of oocytes by airplane.
OBJECTIVE: To determine the feasibility of a transport IVF program involving air transportation of oocytes. DESIGN: Prospective cohort study. SETTING: Regional hospital (Hôpital de Chicoutimi) and University Infertility Center (McGill Reproductive Center, Montreal). PATIENT(S): The first series of patients referred for IVF or IVF and ICSI, for a variety of indications, who opted for inclusion in the transport IVF program. INTERVENTION(S): The IVF-ET with ovarian stimulation and oocyte collection at the peripheral unit and transport of the oocytes by airplane to the McGill Reproductive Center where IVF or ICSI was performed. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Seven couples, in the first series, underwent nine cycles of transport IVF treatment. Two also underwent ICSI. There were two clinical pregnancies. CONCLUSION(S): Transport IVF using air travel is possible and opens the possibility for this type of program to be implemented in large countries with scattered populations, such as the United States, Canada, and Australia.
Adult↗
Ovarian stromal echogenicity in women with clomiphene citrate-sensitive and clomiphene citrate-resistant polycystic ovary syndrome.
OBJECTIVE: To compare stromal echogenicity in women with clomiphene citrate (CC)-sensitive and CC-resistant polycystic ovary syndrome (PCOS), and to compare stromal echogenicity before and after laparoscopic ovarian drilling in women with CC-resistant PCOS. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENT(S): Twenty-two infertile women. INTERVENTION(S): Transvaginal ultrasound examination and laparoscopic ovarian drilling. MAIN OUTCOME MEASURE(S): Ovarian stromal index (ratio of mean ovarian stromal echogenicity to mean echogenicity of the entire ovary). RESULT(S): The mean (+/- SD) ovarian stromal index was 1.26+/-0.27 in the women with CC-sensitive PCOS and 1.22+/-0.11 in the women with CC-resistant PCOS. The ovarian stromal index and ovarian volume of the women with CC-resistant PCOS before and after ovarian drilling were not significantly different. CONCLUSION(S): There was no difference in the stromal index and ovarian volume between women with CC-sensitive PCOS and women with CC-resistant PCOS. There was no overall difference in the stromal index and ovarian volume in women with CC-resistant PCOS before and after ovarian drilling.
Adult↗
Pregnancies resulting from in vitro matured oocytes retrieved from patients with polycystic ovary syndrome after priming with human chorionic gonadotropin.
OBJECTIVE: To describe pregnancies that resulted from in vitro matured oocytes derived from two unstimulated, anovulatory patients with polycystic ovary syndrome after priming with hCG before oocyte retrieval. DESIGN: Case series. SETTING: McGill Reproductive Center, Royal Victoria Hospital, McGill University. PATIENT(S): Two women with polycystic ovary syndrome. INTERVENTION(S): Progesterone induction of a withdrawal bleeding episode. The administration of subcutaneous hCG 36 hours before oocyte retrieval in a natural menstrual cycle. In vitro maturation of immature oocytes, fertilization, and ET. Luteal support with oral estrogen and progesterone. MAIN OUTCOME MEASURE(S): Pregnancy outcome. RESULT(S): Two clinical pregnancies were confirmed after oocyte maturation in vitro, fertilization with intracytoplasmic sperm injection, and ET. CONCLUSION(S): The administration of hCG 36 hours before harvesting of immature oocytes may improve the maturational and developmental competence of the oocytes and the pregnancy rates of unstimulated patients with polycystic ovary syndrome.
Adult↗
Protein phosphorylation in bovine oocytes following fertilisation and parthenogenetic activation in vitro.
This study examined the event of protein phosphorylation in bovine oocytes in response to sperm penetration and parthenogenetic activation. In vitro matured oocytes were labelled with [32P]orthophosphate at 3 h intervals from 3 h to 18 h or from 0 h to 12 h following in vitro fertilisation and parthenogenetic activation, respectively. The level of protein dephosphorylation, at approximately 43 kDa, was similar in fertilised and parthenogenetically activated bovine oocytes. However, the level of protein phosphorylation at 40 kDa, 23 kDa and 18 kDa was different between these two samples. There were no such changes of protein phosphorylation and dephosphorylation in the control oocytes. Further, by two-dimensional gel electrophoresis there is a difference in the level of protein phosphorylation at 18 kDa between the fertilised and activated oocytes. These results suggest that this protein phosphorylation may be related to the formation of the male pronucleus in bovine oocytes.
Animals↗
Effects of hydrosalpingeal fluid on murine embryo development and implantation.
PURPOSE: Our purpose was to evaluate the effects of various concentrations of hydrosalpingeal fluid (HSF) on the preimplantation development and implantation of murine embryos. METHODS: One-cell mouse embryos were cultured in KSOM culture medium with 0.1, 1.0, 10, or 50% HSF, without and with lactate supplementation. Late-stage embryos were transferred into the uteri of pseudopregnant CD-1 females to determine implantation rates. The embryo transfer technique used was developed by our group and its effectiveness was evaluated during this experiment. RESULTS: Blastocyst development in the 0.1, 1.0, 10, and 50% group was 45, 55.0, 12.5, and 17.5%, respectively, with lactate supplementation, and 35.0, 52.5, 12.5, and 5.0%, respectively, without lactate supplementation, while in the KSOM (control) group it was 63.8%. Blastocyst development was reduced compared to controls in the 10% HSF and 50% HSF groups. Implantation rates for the 0.1 and 1.0% groups with lactate supplementation were 43.0 and 25.0%, respectively, and those with lactate supplementation were 50.6 and 61.8%, respectively, while in the KSOM group the implantation rate was 65.5%. None of the implantation rates were significantly different. CONCLUSIONS: Hydrosalpingeal fluid has a concentration-dependent inhibitory effect on in vitro murine embryo development, but it has minimal effects on implantation rates.
Animals↗
Serum vascular endothelial growth factor (VEGF) in the normal menstrual cycle: association with changes in ovarian and uterine Doppler blood flow.
OBJECTIVE: To investigate whether changes in circulating serum vascular endothelial growth factor (VEGF) concentrations during the menstrual cycle are associated with changes in blood flow within the ovaries and uterus. PATIENTS AND MEASUREMENTS: Serum VEGF concentrations were measured and pulsed and colour Doppler blood flow waveforms recorded within the ovarian stroma and uterine arteries during the early follicular, the immediate preovulatory and the mid-luteal phases of the menstrual cycle of 14 healthy women. RESULTS: Mean (+/- SD) serum VEGF concentrations rose from 2.44 +/- 0.1 ng/ml in the early follicular phase to 3 +/- 0.8 ng/ml in the pre-ovulatory phase and to 4.4 +/- 0.9 ng/ml in the mid-luteal phase (P < 0.0001) of the menstrual cycle. Mean peak systolic blood flow velocity (PSV) and time-averaged maximum flow velocity (TAMXV) were higher within the ovarian stroma of the ovary bearing the dominant follicle and the uterine arteries in the pre-ovulatory and mid-luteal phase than in the same sites during the early follicular phase of the menstrual cycle. PSV rose significantly from the early follicular phase (11 +/- 6 cm/s) to 14 +/- 4 cm/s in the pre-ovulatory phase and further in the mid-luteal phase (26 +/- 7 cm/s, P = 0.0001). Within the uterine arteries, mean PSV rose significantly from 28 +/- 9 cm/s in the early follicular phase to 31 +/- 8 cm/s in the pre-ovulatory phase and further in the mid-luteal phase (44 +/- 11 cm/s, P < 0.005). Serum VEGF correlated with serum progesterone concentrations in the luteal phase (r = 0.85, P < 0.001), with serum oestradiol concentrations in the early follicular (r = 0.67, P = 0.009), pre-ovulatory (r = 0.57, P = 0.03) and luteal phases (r = 0.68, P < 0.005) and with serum testosterone in the early follicular phase (r = 0.63, P = 0.01). CONCLUSIONS: Cyclical changes in serum vascular endothelial growth factor concentrations are associated with coincident changes in ovarian and uterine blood flow.
Adult↗
The pattern of changes in ovarian stromal and uterine artery blood flow velocities during in vitro fertilization treatment and its relationship with outcome of the cycle.
OBJECTIVES: To assess the effect of short-term (2-3 weeks) pituitary suppression and controlled ovarian stimulation on ovarian and uterine artery Doppler measurements during the in vitro fertilization (IVF) treatment cycle and to compare the pattern of these changes between conception and non-conception cycles as well as between patients with normal and those with polycystic ovaries. DESIGN: Prospective observational study of women undergoing IVF treatment. SUBJECTS: Women using the long-treatment buserelin protocol who did not have uterine fibroids, ovarian cysts or endometrioma. METHODS: Serial transvaginal color and pulsed Doppler measurements of ovarian stromal and uterine artery blood flow velocity were carried out in the early follicular phase of the menstrual cycle, on the day of pituitary suppression and on the day of administration of human chorionic gonadotropin (hCG). The main outcome measures were the ovarian stromal and uterine artery blood flow peak systolic velocity (PSV) and pulsatility index (PI). RESULTS: A total of 105 patients were recruited but six patients were excluded from the analysis because they had only one stage of the measurements performed. There was a significant decline in mean ovarian stromal artery PSV after 2-3 weeks of gonadotropin releasing hormone (GnRH) agonist therapy but no effect on ovarian stromal artery PI. The mean uterine artery PSV or PI did not change significantly after 2-3 weeks of GnRH agonist therapy. There was a significantly higher mean ovarian stromal artery PSV in conception cycles compared to non-conception cycles in the early follicular phase and on the day of pituitary suppression, but not on the day of hCG administration. There were no differences between conception and non-conception cycles in the mean uterine artery PSV or PI. Women with polycystic ovaries had a higher mean ovarian artery PSV on all the three occasions of measurement. CONCLUSION: These data suggest that assessment of ovarian blood flow before commencement of gonadotropin stimulation may play a role in assessing cycles likely to result in pregnancy.
Adult↗
Clinical applications of Doppler and three-dimensional ultrasound in assisted reproductive technology.
Explore the source record for details and available documents.
Blood Flow Velocity↗
The emerging role of the interferon-induced PKR protein kinase as an apoptotic effector: a new face of death?
Recent research has thrown a spotlight on the interferon (IFN)-induced PKR protein kinase, implicating it as an important effector of apoptosis induced by several cellular stress conditions, including viral infection, cytokine treatment, and growth factor deprivation. In this review, we summarize the evidence for the role of PKR as a death accomplice and discuss how PKR might promote cell demise in light of current knowledge of the molecular mechanisms of apoptosis. Given its new found role and its established antiviral function, it is no wonder that PKR is a popular target for viral evasion of the host defense. PKR-dependent apoptosis may offer a novel cell-death pathway for specific manipulation in therapeutic strategies against apoptosis-related diseases.
Animals↗
The outcome of in-vitro fertilization treatment in women with sonographic evidence of polycystic ovarian morphology.
This study compared the outcome of a course of up to three cycles of in-vitro fertilization (IVF) treatment in 46 women (97 cycles) who had polycystic ovaries (PCO) seen on ultrasound scan, but who had no clinical symptomatology associated with polycystic ovary syndrome, with that of 145 women (332 cycles) who had normal ovarian morphology on ultrasound examination. All 191 women had normal early follicular phase serum follicle stimulating hormone (FSH) concentrations, were less than 40 years of age and used the long protocol of pituitary suppression with gonadotrophin-releasing hormone agonist therapy. On average, the women with PCO produced more follicles, oocytes and embryos than the women with normal ovaries, but the fertilization, cleavage and miscarriage rates were similar. Adjusted for age, the odds of achieving a pregnancy within three cycles of treatment in a woman with PCO were 69% higher than those of a woman with normal ovaries [odds ratio (OR): 1.69, 95% confidence interval (CI) 0.99-2.90, P = 0.05)] and the odds of achieving a live birth were 82% higher (OR: 1.82, 95% CI 1.05-3.16, P = 0.03). There is, therefore, evidence that outcome of IVF treatment for women with PCO seen on ultrasound examination may be better than that for women with normal ovaries.
Abortion, Spontaneous↗