Aberrant gene promoter methylation is a critical event in tumorigenesis. The aim of this study was to explore the promoter hypermethylation of p16 and DAPK1 during the progression of cervical ...precancerous lesions.
A series of 98 cervical neoplasms (72 cervical intraepithelial neoplasia and 26 cervical carcinomas) were evaluated. The promoter methylation status of p16 and DAPK1 was assessed from cervical scrapings by methylation-specific polymerase chain reaction.
For p16, the frequency of promoter hypermethylation showed an increasing trend from normal to dysplastic to invasive squamous cancer specimens, and this increase reached statistical significance (P < 0.0001). However, there was no significant difference in the promoter methylation state of DAPK1 with regard to the various grades of cervical lesions (P = 0.077). Specifically, methylation of p16 was a frequent event in the cervical carcinoma samples, and these figures were statistically significant compared with the normal and cervical intraepithelial neoplasia I cases (P = 0.015 and P = 0.021, respectively).
These results imply that promoter hypermethylation of p16 occurs at an early stage of cervical neoplastic progression. This early event may play an initiating role in the malignant transformation of low-grade dysplasia into high-grade dysplasia and invasive carcinoma. We suggest that aberrant promoter methylation of p16 may serve as a useful biomarker during the follow-up of low-grade dysplasia.
Abstract Objective The standard dose of depot gonadotropin releasing hormone agonist (GnRHa) may be too much to prevent premature luteinizing hormone (LH) surge in controlled ovarian stimulation ...(COS). The purpose of this study was to find out the minimal effective dose of Leuplin depot to prevent premature LH surge in patients undergoing intrauterine insemination (IUI). Materials and Methods From January 2006 to December 2007, unexplained infertile patients who were going to undergo IUI were recruited into the study. They were assigned sequentially to one of the following treatment groups. The first 50 patients received the 1/3-dose of Leuplin depot in the midluteal phase of the cycle preceding COS. If no premature LH surge occurred in the 50 patients, the study was continued with 1/4-dose of Leuplin depot in the subsequent 50 patients. Similarly, if no premature LH surge occurred with 1/4 dose, the study was continued with 1/5-dose of Leuplin depot in the following 50 patients. Ovarian stimulation was started with human menopausal gonadotropin (hMG) at 112.5 IU/d after downregulation, then IUI was performed 36 hours after human chorionic gonadotropin (hCG) injection. Results Premature LH surge was effectively prevented with 1/3-dose and 1/4-dose of Leuplin depot. Premature LH surge occurred in three of the 50 patients (6%) in the 1/5-dose group. The patients in the 1/4-dose group received a significantly lower amount of hMG and fewer days of COS, compared with the 1/3-dose group. Conclusion The 1/4 dose of Leuplin depot is the minimal effective dose to prevent premature LH surge. Further trial is worthwhile to compare the reducing dose Leuplin depot and daily low-dose leuprolide in in vitro fertilization (IVF) programs.
To compare the efficacy of laminaria tents and orally administered misoprostol in priming the cervix before operative hysteroscopy.
Randomized, controlled study (Canadian Task Force classification ...I).
Tertiary medical center.
One hundred twenty premenopausal women who underwent operative hysteroscopy between March 2005 and January 2007.
The women were randomized to receive a laminaria tent or misoprostol for cervical priming.
The primary outcomes were postpriming cervical width insofar as size of Hegar dilators and need for cervical dilation. The secondary outcomes were adverse effects from the priming methods. Postpriming cervical width was greater in the laminaria group but not significantly different from that in the misoprostol group. However, cervical dilation before hysteroscopy was required in more patients in the misoprostol group. Nausea, vomiting, diarrhea, and bleeding were more common in the misoprostol group, and the incidences of chills and headache were similar between the 2 groups.
Laminaria tents are superior to oral misoprostol insofar as less need for cervical dilation and fewer adverse effects.
BACKGROUND: This study compares the fertilization rate and embryonic development of oocytes randomly inseminated by conventional IVF or ICSI in patients with polycystic ovarian syndrome (PCOS) and ...normozoospermic semen during IVF cycles. METHODS: Sibling oocytes were randomized to be inseminated either by ICSI or IVF. Fertilization rate (two pronuclei/COC), day 2 embryonic morphology and rate of development were assessed. RESULTS: A total of 1089 cumulus–oocyte complexes (COC) were collected in 60 cycles (mean±SD, 18.2±7.2). Totals of 541 and 548 COC were inseminated by IVF and ICSI respectively, with a significantly higher fertilization rate in the ICSI group (ICSI versus IVF, 72.3±15.5 versus 44.8±25.1%). No fertilization failure occurred in the group of oocytes inseminated by ICSI, whereas the COC in nine patients (15%) inseminated by IVF had complete fertilization failure. The day 2 embryonic morphology and rate of development were not different regardless of the insemination method. CONCLUSIONS: Our results suggested that another randomized controlled study, randomizing patients instead of sibling oocytes, should be undertaken to compare the pregnancy rate per started cycle and to see whether ICSI should be performed on all, or at least on a portion of, oocytes for patients with PCOS undergoing IVF cycles.
Abstract Cabergoline, a dopamine receptor-2 agonist, is suggested to prevent ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. The aim of this study was to evaluate the influence ...of different timing of cabergoline administration on clinical outcome among patients at risk of developing OHSS. Among infertile women undergoing IVF treatment at risk of developing OHSS, 206 were enrolled in this study. The subjects were randomly allocated into two groups, i.e. the study group ( n = 100) receiving cabergoline beginning on the day of human chorionic gonadotrophin (HCG) injection and the control group ( n = 100) receiving cabergoline starting on the day of oocyte retrieval. Oocyte metaphase-II rate, fertilization rate, clinical outcome and incidence of severe OHSS were compared between the two groups. There were no significant differences in oocyte metaphase-II rate (0.86 ± 0.16 versus 0.85 ± 0.15) or fertilization rate (0.79 ± 0.22 versus 0.76 ± 0.20) or in the incidence of OHSS between two groups. Similarly, there were no significant differences in implantation or clinical pregnancy rate between the two groups. Cabergoline can be administered as soon as HCG injection to prevent early OHSS, without adverse effects on oocyte maturation, fertilization rate and clinical outcome. Cabergoline, a dopamine receptor-2 agonist, is suggested to prevent ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. Nevertheless, the most suitable timing of cabergoline administration has not yet been studied. The aim of this study was to evaluate the influence of different timing of cabergoline administration on final oocyte maturation, fertilization rate and clinical outcome among patients at risk of developing OHSS. Among infertile women undergoing IVF treatment at risk of developing OHSS, 206 were enrolled in this study. The subjects were randomly allocated into two groups, i.e. the study group ( n = 100) receiving cabergoline beginning on the day of human chorionic gonadotrophin (HCG) injection and the control group ( n = 100) receiving cabergoline starting on the day of oocyte retrieval. Oocyte metaphase II rate, fertilization rate, clinical outcome and incidence of severe OHSS were compared between the two groups. There were no significant differences in oocyte metaphase II rate (0.86 ± 0.16 versus 0.85 ± 0.15) or fertilization rate (0.79 ± 0.22 versus 0.76 ± 0.20) or in the incidence of OHSS (3/100 versus 1/100) between the control and study groups. Similarly, there were no significant differences in implantation rate (36.6% versus 34.0%) or clinical pregnancy rate (54.0% versus 51.0%) between the two groups. Among women at high risk of OHSS, cabergoline can be administered as soon as the HCG injection to prevent early OHSS, without adverse effects on oocyte maturation, fertilization rate and clinical outcome.
Abstract Objective: To determine whether a low initial dosage of cetrorelix acetate could prevent a premature luteinizing hormone (LH) surge in women undergoing controlled ovarian stimulation. ...Method: Treatment with a recombinant follicle stimulating hormone was started on Day 3 of the menstrual cycle, and 0.125 mg of cetrorelix was injected daily from Day 5 of the ovarian stimulation until the diameter of the dominant follicle reached at least 16 mm. The dosage was then doubled and maintained at 0.250 mg/day until the day before the injection of human chorionic gonadotropin. Result: There was a significant decrease in serum LH concentration 1 day after doubling the cetrorelix dosage, and the LH concentration remained low during the follicular phase. Clinical pregnancy occurred in 18 women (42.8%), with 2 intrauterine fetal deaths before the 12th week. Conclusion: Increasing the cetrorelix dosage from 0.125 to 0.250 mg/day when the follicular size is appropriate can prevent a premature LH surge.
To investigate if the combination of clomiphene citrate, hMG, and cetrorelix (CC/hMG/cetrorelix protocol) can be applied to patients who had excessive response to GnRHa long protocol.
Fifty patients ...who coasted and failed to conceive in their first cycles stimulated with GnRHa long protocol were stimulated with CC/hMG/cetrorelix protocol. The peak serum estradiol levels, the need of coasting and prolonged coasting (>/=4 days), and the incidences of OHSS were compared.
The peak estradiol level was significantly lower with CC/hMG/cetrorelix protocol compared to GnRHa long protocol. With CC/hMG/cetrorelix protocol, only four patients (8%) needed coasting and no one coasted >/=4 days. In contrast, in the first cycles, 11 patients (22%) needed coasting >/=4 days. The incidence of moderate OHSS was significantly lower with CC/hMG/cetrorelix protocol.
The CC/hMG/cetrorelix protocol is an acceptable alternative protocol for patients who had excessive response to GnRHa long protocol.
This study was performed to evaluate whether a lower dose (0.2 mg) of cetrorelix would prevent premature LH surge in patients undergoing controlled ovarian hyperstimulation.
Controlled ovarian ...hyperstimulation was carried out in 45 patients, starting on menstrual cycle day 3 with recombinant FSH (r-FSH), and a cetrorelix of 0.2 mg was administered from day 5 evening of ovarian stimulation until the day before hCG injection.
There was a statistically significant decrease in serum LH level one day after the first cetrorelix injection and on the day of hCG administration. Serum LH concentrations were maintained constantly low during the follicular phase with no premature LH surge occurring in any of the patients. Clinical pregnancy was achieved for 18 women (40%), with one of these experiencing intrauterine fetal death before 12 week' gestation.
This study demonstrates that a daily dose of cetrorelix 0.2 mg is able to prevent premature LH surge.
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