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1.
Stratton P Hartog B Hajizadeh N Piquion J Sutherland D Merino M Lee YJ Nieman LK 《Human reproduction (Oxford, England)》2000,15(5):1092-1099
Previous studies in women have shown that the antiprogestin mifepristone delays or inhibits folliculogenesis. The purpose of this study was to explore whether a new analogue, CDB-2914, has similar effects on folliculogenesis, ovulation, or on subsequent luteal phase endometrial maturation. Forty-four normally cycling, healthy women recorded urine LH and vaginal bleeding during pre-treatment, treatment, and post-treatment cycles. At a lead follicle diameter of 14-16 mm, a single oral dose (10, 50, 100 mg) of CDB-2914 or placebo was given, and daily ultrasound, oestradiol and progesterone were obtained until follicular collapse; an endometrial biopsy was obtained 5-7 days later. Single doses of CDB-2914 were well tolerated. Mid-follicular CDB-2914 suppressed lead follicle growth, causing a dose-dependent delay in folliculogenesis and suppression of plasma oestradiol. At higher doses, a new lead follicle was often recruited. Although luteinized unruptured follicles were observed at the 100 mg dose, all women had follicular collapse. There was a significant delay in endometrial maturation after CDB-2914 at all doses. The treatment cycle was lengthened by 1-2 weeks in 30% at 100, 27% at 50 and 9% at 10 mg. CDB-2914 altered ovarian and endometrial physiology without major effects on menstrual cyclicity and may have therapeutic utility. 相似文献
2.
Our goal was to determine the endocrine and post-coital anti-fertility activity of CDB-2914. Concurrent administration of progesterone to rats on day 4 post-mating blocked the anti-fertility activity of a single oral 2 mg dose of CDB-2914. CDB-2914 did not exhibit progestational activity in the oestradiol-primed immature female rabbit at doses that exhibited anti-progestational activity. CDB-2914 antagonized exogenous and endogenous progesterone-stimulated uterine haptoglobin synthesis and secretion in immature and adult mated rabbits respectively. Neither CDB-2914 nor mifepristone exhibited glucocorticoid activity as determined by thymus involution in rats; mifepristone was twice as potent as CDB-2914 in antagonizing glucocorticoid action. Post-coital CDB-2914 treatment resulted in a dose-dependent reduction in implantation sites and pregnancy rates in rabbits. CDB-2914-induced inhibition of uterine weight increase, endometrial glandular arborization and uterine haptoglobin synthesis/secretion correlated with inhibition of pregnancy in mated rabbits. A single oral dose of 64 mg CDB-2914/rabbit was effective at blocking pregnancy when administered on day 4, 5, or 6 post-mating, whereas 32 mg/rabbit was only partially effective in this regard. These data demonstrate that CDB-2914 is a potent, orally active anti-progestin with weak anti-glucocorticoid activity. CDB-2914 inhibited implantation in adult rats and rabbits demonstrating its potential as a post-coital contraceptive drug. 相似文献
3.
Xu Q Ohara N Liu J Amano M Sitruk-Ware R Yoshida S Maruo T 《Molecular human reproduction》2008,14(3):181-191
Effects of progesterone receptor modulator CDB-2914 on the expression of the extracellular matrix (ECM) components were examined in cultured human uterine leiomyoma and myometrial cells. ECM metalloproteinase inducer (EMMPRIN), matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs) and collagen levels were assessed by Western blot analysis, MMP activity assay and real-time RT-PCR. RNA interference (RNAi) of EMMPRIN was performed using small interfering mRNA. In cultured leiomyoma cells, CDB-2914 treatment at concentrations greater than or equal to 10(-8) M significantly increased EMMPRIN, MMP-1 and MMP-8 protein contents and MMP-1, MMP-2, MMP-3 and MMP-9 mRNA levels, and activity of MMP-1, MMP-2, MMP-3 and MMP-9 in the medium. TIMP-1 and TIMP-2 were significantly decreased at mRNA and protein levels by CDB-2914 treatment at concentrations > or =10(-7) M in these cells. CDB-2914 treatment decreased types I and III collagen protein contents. However, CDB-2914 treatment did not affect the ECM component expression in cultured myometrial cells. RNAi of EMMPRIN abrogated CDB-2914-mediated both induction of MMPs and reduction of TIMPs and collagens in cultured leiomyoma cells. These results suggest that CDB-2914 modulates the expression of EMMPRIN, MMPs, TIMPs and collagens in cultured leiomyoma cells without comparable effects on myometrial cells. 相似文献
4.
Xu Q Ohara N Chen W Liu J Sasaki H Morikawa A Sitruk-Ware R Johansson ED Maruo T 《Human reproduction (Oxford, England)》2006,21(9):2408-2416
BACKGROUND: This study was conducted to evaluate the effects of graded concentrations (10(-8), 10(-7) and 10(-6) M) of progesterone receptor (PR) modulator CDB-2914 on the protein contents of PR, of vascular endothelial growth factor (VEGF), adrenomedullin (ADM) and their receptors in cultured human uterine leiomyoma and matching myometrial cells. METHODS: PR-A, PR-B, VEGF-A, VEGF-B, VEGF receptor (VEGFR)-1, VEGFR-2, ADM and ADM receptor (ADMR) contents were assessed by Western blot analysis. RESULTS: Treatment with 100 ng/ml progesterone increased VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells and normal myometrial cells. The concomitant treatment with 10(-6) M CDB-2914 significantly decreased the progesterone-induced VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment alone decreased VEGFR-1, VEGFR-2 and ADMR contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment increased PR-A and decreased PR-B contents in cultured leiomyoma cells in a dose-dependent manner compared with untreated cultures, whereas no significant changes in PR isoform contents were observed in normal myometrial cells. CONCLUSIONS: These results suggest that CDB-2914 down-regulates VEGF, ADM and their receptor contents and modulates PR isoform contents in cultured leiomyoma cells in a cell-type-specific manner. 相似文献
5.
The overall aim of these studies was to investigate the oral and i.m. bioavailability of CDB-2914 in intact female rhesus monkeys, and to compare the serum concentrations of CDB-2914 with that of mifepristone following oral administration. In the first study, a 50 mg bolus of CDB-2914 per monkey was administered intravenously, orally or intramuscularly. The area under the serum concentration-time curve for 72 h (AUC(0-72)) following i.v. injection was 18 320 +/- 2718 ng/ml*h, and that for oral administration was 10 464 +/- 3248 ng/ml*h. Thus, the oral bioavailability of CDB-2914 equivalents was 56%. The AUC(0-168 h) following i.m. injection was 11 226 +/- 1130 ng/ml*h. Therefore, the i.m. bioavailability of CDB-2914 equivalents was 62%. In the second study, the serum concentrations of CDB-2914 and mifepristone equivalents were compared following an oral bolus dose in two different formulations. When administered at 5 mg/kg in aqueous suspending vehicle (ASV), the mean peak serum concentration (C(max)) of CDB-2914 equivalents (192 +/- 64 ng/ml) occurred at 5 +/- 1 h, whereas the C(max) of mifepristone equivalents (82 +/- 25 ng/ml) occurred at 3 +/- 1 h. Following administration in gelatin capsules (35 mg/monkey), the C(max) of CDB-2914 equivalents (129 +/- 24 ng/ml) occurred at 5 +/- 1 h, while the C(max) of mifepristone equivalents (31 +/- 8 ng/ml) occurred at 3 +/- 1 h. The serum concentration (AUC(0-120 h)) of CDB-2914 equivalents was 4.7- or 5. 3-fold greater than that of mifepristone equivalents when administered orally in ASV or gelatin capsules respectively. The serum protein binding characteristics of CDB-2914 were also studied. CDB-2914 bound to human alpha(1)-acid glycoprotein (AAG), but not with as high an affinity as mifepristone. In contrast, neither CDB-2914 nor mifepristone bound with high affinity to AAG, corticosteroid binding globulin or sex hormone binding globulin in monkey serum. Collectively, these results indicated that CDB-2914 was more efficiently absorbed than mifepristone following oral administration to female rhesus monkeys. 相似文献
6.
The effects of 1-month administration of asoprisnil (J867), a selective progesterone receptor modulator, in healthy premenopausal women 总被引:3,自引:0,他引:3
Chwalisz K Elger W Stickler T Mattia-Goldberg C Larsen L 《Human reproduction (Oxford, England)》2005,20(4):1090-1099
BACKGROUND: Asoprisnil (J867) is a novel selective progesterone receptor modulator (SPRM) that exhibits partial agonist and antagonist activities and tissue selective effects. This double-blind, dose-escalation study was conducted to evaluate the effects of asoprisnil in 60 regularly cycling premenopausal women. METHODS: Asoprisnil or placebo was administered orally for 28 days starting at the beginning of the menstrual cycle in doses of 5 mg once daily (QD), 5 mg twice daily (BID), 10 mg QD, 25 mg QD, 25 mg BID and 50 mg BID. Within each dose group, two women were randomized to placebo and eight to asoprisnil. Progesterone concentrations indicative of luteinization were defined as at least one progesterone measurement during the luteal phase exceeding 3.5 ng/ml. RESULTS: Asoprisnil consistently prolonged the menstrual cycle at doses > or = 10 mg QD. However, the effects on luteal phase progesterone indicative of luteinization were inconsistent and lacked dose dependency. Asoprisnil suppressed periovulatory estradiol but not below follicular phase levels. No significant changes were observed in cortisol and prolactin. Asoprisnil was well tolerated. CONCLUSIONS: Asoprisnil reversibly suppressed menstruation at doses > or = 10 mg QD irrespective of the effect on luteal phase progesterone concentrations indicative of luteinization. It induces amenorrhea primarily by targeting the endometrium in the absence of estrogen deprivation. 相似文献
7.
Clinical and endometrial effects of oestradiol and progesterone in post-menopausal women 总被引:1,自引:0,他引:1
This study reports the clinical effects in a group of post-menopausal women after 4 months of treatment with 2 mg micronized 17 beta-oestradiol (E2) in combination with different doses of micronized progesterone (50, 100 or 200 mg) for 25 days each month. The 30 participants were divided into three groups. All of the subjects tolerated the preparation well and obtained relief from their climacteric complaints. None dropped out because of side effects and no changes were observed in blood pressure, weight or Papanicolaou cytology. Breakthrough bleeding was noted in the first cycle, mainly in the group receiving the lowest dose of progesterone. Endometrial biopsies performed before and after 4 months of treatment showed an atrophic endometrium in most of the women who received 100 mg progesterone and in all of the women on 200 mg progesterone. The results showed that this new combination of 2 mg E2 and micronized progesterone in different doses was both effective and well accepted. 相似文献
8.
Thirty women with climacteric symptoms were treated for 4 months with 2 mg 17β-oestradiol and different doses of progesterone (50, 100 or 200 mg). The concentrations of total and free cholesterol, phospholipids, triglycerides (TG), apoprotein A1 and apoprotein B were determined in high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) fractions and in serum. HDL levels increased and LDL levels decreased, while TG levels in VLDL remained unchanged, which indicates that the lipoprotein pattern is oestrogen-induced and that progesterone exerts little or no influence. 相似文献
9.
Considerable progress has been made in elucidating the mechanism of action of antiprogestins. The biological response to a progesterone antagonist depends on many factors. The usual effect is that of an antagonist, but progesterone agnostic or even antioestrogenic or oestrogenic effects have also been observed. The present review focuses on the clinical applications of antiprogestins in the non-pregnant uterus. Whereas high doses of antiprogestins block ovulation, low doses impair endometrial development without affecting ovulation, hormonal levels or bleeding patterns Indeed, the endometrium is the tissue which is the most sensitive to antiprogestins. The effect of antiprogestins is to produce a delay in endometrial maturation and to postpone the appearance of the implantation window. This concept of 'endometrial contraception' requires further testing in humans, although the principle has been proven in monkeys. In contrast to the low doses of mifepristone which delay endometrial maturation, a minimum dose of 50 mg is required to produce endometrial bleeding. Late luteal phase antiprogestin administration does not disturb ovulation, hormonal levels or bleeding patterns. This has clinical application, and mifepristone has been used together with prostaglandins in women with delayed menses to successfully prevent implantation. Mifepristone has also been shown to be an effective post-coital agent. However, when used on a regular basis once monthly at the end of the cycle as a potential contraceptive, the results are disappointing. Because of their antiproliferative and anti-oestrogenic effects on the endometrium, antiprogestins are also used in the treatment of oestrogen-dependent conditions such as endometriosis and fibromyomas. In humans, chronic administration of high doses of antiprogestins has on rare occasions been associated with endometrial hyperplasia, presumably a consequence of unopposed oestrogen activity. This does not occur with low doses (1 mg daily for 5 months). 相似文献
10.
Mifepristone (RU 486) is a potent antigestagen and antiglucocorticoid which when given at a dose of 25-600 mg disrupts folliculogenesis, inhibits ovulation and induces menses in healthy women. This study reports the effects of much lower doses of mifepristone than used previously, given for the duration of a complete menstrual cycle. Healthy female volunteers (n = 11) with regular menstrual cycles were given mifepristone at a daily dose of 5 mg (n = 6) or 2 mg (n = 5) for 30 days, beginning immediately after an ovulatory placebo cycle. Mifepristone prevented menstruation for the duration of the treatment period, with recurrence of menses 15-29 days after replacement of mifepristone with placebo. Daily mifepristone given in either 5 mg or 2 mg doses inhibited ovulation, as indicated by the lack of a rise in urinary pregnanediol excretion. The excretion of oestrone glucuronide in urine rose during treatment, suggesting ovarian follicular development. Inhibition of ovulation appeared to result from a failure of the positive feedback effect of oestradiol on the hypothalamo-pituitary axis, as no surges of luteinizing hormone were seen despite pre-ovulatory levels of oestrone glucuronide being measured during exposure to mifepristone. The cycle immediately following treatment was shorter than the pre-treatment cycle, with lower peak levels of pregnanediol glucuronide, suggesting an inadequate luteal phase. Recovery from the effects of mifepristone treatment was more rapid after 2 mg than after 5 mg and one subject conceived in the immediate post-treatment phase, indicating adequate ovulation and luteinization.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
11.
Baird DT Brown A Critchley HO Williams AR Lin S Cheng L 《Human reproduction (Oxford, England)》2003,18(1):61-68
BACKGROUND: Mifepristone in low daily doses has contraceptive potential by inhibiting ovulation and menstruation. Because follicular development is maintained, the endometrium is exposed to estrogen for prolonged periods unopposed by progesterone. METHODS: Endometrial biopsies were collected from 90 women in Edinburgh and Shanghai before (late proliferative) and 60 and 120 days after taking 2 or 5 mg mifepristone per day for 120 days. RESULTS: Ovulation and menstruation were inhibited in >90% of cycles and estrogen production was similar to that observed during the follicular phase of the control cycle. By 120 days, endometrial thickness increased significantly in women in Edinburgh but decreased in Shanghai. Endometrial histology showed inactive proliferative or cystic changes with dense stroma. There was a significant decrease in markers of proliferation, i.e. mitotic index and Ki67 staining. There were no pregnancies in a total of 200 women-months in 50 sexually active women who used no other method of contraception. CONCLUSIONS: We confirm that ovulation and menstruation were suppressed in the majority of cycles and there was asynchrony between ovarian activity and endometrial histology, which showed no signs of hyperplasia or atypia. These preliminary data suggest that daily low-dose mifepristone is potentially a safe estrogen-free contraceptive pill which has the added health benefit of amenorrhoea. 相似文献
12.
Croxatto Horacio B.; Salvatierra Ana M.; Fuentealba Blanca; Zurth Christian; Beier Sybille 《Human reproduction (Oxford, England)》1994,9(8):1442-1447
The effects of the antiprogestion onapristone on the menstrualcycle were assessed in surgically sterilized volunteer women.The steroid was given orally at the dose of 5, 15 or 50 mg/day,from day 5 to day 11 of the cycle. Ovarian ultrasonography andhormonal determinations in plasma and urine were used to monitorthe pre-treatment, treated and post-treatment cycles. Onapristone,given at a dose of 5 mg/day, arrested follicular growth andinconsistently. The dose of 15 or 50 mg/day arrested folliculargrowth and oestradiol increase and delayed gonadotrophin surge,extending the length of the follicular phase in five of sevenwomen in each group. After discontinuation of treatment theleading follicle resumed its growth and ovulation occurred asjudged by the elevation of plasma progesterone, preceded inmost but not all cases by an echographic image of follicularcollapse. The ensuing luteal phases were not significantly alteredin length or plasma progesterone concentration. Cortisol concentrationswere unaffected and no serious side-effects were recorded. Theantifolliculotrophic effect of onapristone demonstrated here,together with previous reports of similar activity of mifepristonein women, indicate that this may be a general property of compoundsthat interfere with progesterone receptor function. 相似文献
13.
Day 14 maternal serum progesterone levels predict pregnancy outcome in IVF/ICSI treatment cycles: a prospective study 总被引:1,自引:0,他引:1
Ioannidis G Sacks G Reddy N Seyani L Margara R Lavery S Trew G 《Human reproduction (Oxford, England)》2005,20(3):741-746
BACKGROUND: Serum progesterone has been advocated as a tool in the diagnosis of early pregnancy failure. We conducted this prospective study in order to investigate the potential value of early (14 days after oocyte recovery) serum progesterone measurement, in women undergoing IVF/ICSI and receiving rectal progesterone supplements, in relation to pregnancy outcome. METHODS: 442 women consecutively treated by IVF or ICSI had serum progesterone and bhCG levels prospectively measured 14 days after oocyte retrieval (day 0). All women received natural progesterone 400 mg rectally until the pregnancy test on day 14. Pregnant women were followed up by serial transvaginal ultrasound scans to 8 weeks gestation. RESULTS: 115 women (26%) had a viable intra-uterine pregnancy at 8 weeks gestation, 80 (18.1%) had an abnormal pregnancy (biochemical, ectopic, miscarriage) and 247 (55.9%) failed to conceive. Women with on-going pregnancies had significantly higher serum progesterone levels (median: 430, 95%CI: 390-500 nmol/l) compared to those who had either an abnormal pregnancy (72, 48-96 nmol/l; P < 0.001) or failed to conceive (33, 28-37 nmol/l; P < 0.001). Receiver-operator curve analysis demonstrated that a single serum progesterone on day 14 post-oocyte retrieval, could highly differentiate between normal and abnormal pregnancies (area under the curve = 0.927, 95%CI = 0.89-0.96; P < 0.0001). CONCLUSIONS: In spite of exogenous progesterone supplementation, serum progesterone levels, from as early as 4 weeks gestation (day 14 post-oocyte retrieval) were significantly elevated and predicted women destined to have viable intra-uterine pregnancies. These high levels are suggestive that endogenous progesterone is already sufficient in viable pregnancies and that exogenous progesterone administration will not rescue a pregnancy destined to result in a miscarriage. Single serum progesterone measurement could be a useful indicator of pregnancy outcome in women undergoing IVF or ICSI treatment. 相似文献
14.
Elkind-Hirsch KE Phillips K Bello SM McNicho M de Ziegler D 《Human reproduction (Oxford, England)》2002,17(2):295-298
BACKGROUND: We investigated the possibility of correcting the endometrial alterations induced with clomiphene citrate (CC) by vaginal hormonal supplementation (HS) with estradiol (E2) and progesterone gel. METHODS: Oligo-ovulatory women were prospectively randomized into four groups receiving either 50 mg (groups 1 and 2) or 100 mg (groups 3 and 4) of CC from cycle day 3-8. Groups 2 and 4 also received vaginal E2 cream 0.1 mg twice daily from day 8 until the LH surge and vaginal progesterone gel, starting 3 days after ovulation. All participants had an endometrial biopsy performed 10 +/- 1 days after ovulation. RESULTS: All biopsies in the HS groups (2 and 4) showed complete predecidual changes, and were 'in-phase' with findings normally made 10 days post-ovulation (+/- 2 days of clinical dating). However, without HS (groups 1 and 3), only 4/6 and 3/6 biopsies showed predecidual changes in women receiving 50 and 100 mg of CC. CONCLUSION: The addition of vaginal E2 and progesterone to CC ovulation induction regimens normalizes the alterations in endometrial morphology. Hormonal treatment combining vaginal E2 and progesterone may improve endometrial receptivity in CC cycles and ultimately yield higher pregnancy rates. 相似文献
15.
Effects of ospemifene (FC-1271a) on uterine endometrium,vaginal maturation index,and hormonal status in healthy postmenopausal women 总被引:2,自引:0,他引:2
OBJECTIVE: Selective estrogen receptor modulators (SERMs) are drugs that exhibit both estrogen agonistic and antagonistic effects that are tissue-specific. Ospemifene (FC-1271a) is a novel SERM compound, which has been shown in animal models to have estrogen-like effects on bone and the cardiovascular system, while having antiestrogen-like effects in uterus and breast. In this study, we investigated the effects of ospemifene on the uterine endometrium, vaginal maturation index and hormonal status in healthy postmenopausal women. METHODS: The study was conducted as a double-blind, placebo-controlled phase I study, where 40 healthy postmenopausal women volunteers were randomized to receive daily oral doses of ospemifene either 25, 50, 100 or 200 mg or placebo for 12 weeks. Vaginal ultrasonography and endometrial biopsy were performed and vaginal maturation index determined at baseline and at 12 weeks' visit. Serum concentrations of estradiol, luteinizing hormone, follicle stimulating hormone (FSH), sex-hormone binding globulin (SHBG), parathyroid hormone and prolactin were determined from samples taken at baseline, at 4 days and at 4, 12, and 16 weeks' visits. Climacteric symptoms were assessed using 12 visual analogue scales (VAS) at baseline and at the end of the study. RESULTS: No clinically significant changes were seen in endometrial thickness at any dose level. Ospemifene exerted a very weak estrogenic effect on endometrial histology. On the other hand, it induced a clear estrogenic effect on vaginal epithelium. Among the endocrine parameters only FSH and SHBG showed significant dose dependent changes; FSH decreased and SHBG increased during the treatment. In general, ospemifene was well tolerated. The 25 and 50 mg doses tended to reduce climacteric symptoms, but no statistically significant differences were observed between different doses of ospemifene and placebo. The highest dose level (200 mg) induced more subjective adverse reactions, especially hot flushes, than lower doses. CONCLUSION: Our study suggests that a safe and well tolerated dose of ospemifene for potential clinical use may be between 25 and 100 mg. Further studies are needed to substantiate the results of this Phase I pilot study. 相似文献
16.
J Smitz P Devroey B Faguer C Bourgain M Camus A C Van Steirteghem 《Human reproduction (Oxford, England)》1992,7(2):168-175
A luteal phase defect has been demonstrated in cycles stimulated using a protocol including a gonadotrophin releasing hormone agonist (GnRHa). We have conducted a randomized prospective study of luteal and early pregnancy supplementation in 262 women selected for in-vitro fertilization (IVF), gamete intra-Fallopian transfer (GIFT) or zygote intra-Fallopian transfer (ZIFT). Either intramuscular progesterone in oil (50 mg/day) or intravaginal micronized progesterone (600 mg/day) was used as luteal supplement. In association with oestradiol valerate, progesterone administration was initiated from the day before oocyte retrieval until the 12th week of pregnancy. The implantation rate just failed to reach statistical significance (P = 0.07) in favour of the group receiving intravaginal progesterone. In the latter group, we observed a higher clinical pregnancy rate (33.6 versus 26.7%, not significant). Despite lower plasma progesterone levels, a lower first trimester abortion rate (P less than 0.05) was found in the intravaginally treated group. Intravaginal micronized progesterone was well tolerated by all patients and appeared more effective than intramuscular progesterone in improving the implantation rate, and in decreasing the incidence of abortions in stimulated cycles including GnRHa. 相似文献
17.
We have recently demonstrated the efficacy of paracervical block (PCB) used in conjunction with conscious sedation during egg collection. The dosage of lignocaine used in various studies ranges from 50 mg to 200 mg. There are, however, no studies evaluating the efficacy of different doses of local anaesthetic agents used in PCB. In this prospective, double-blind and placebo-controlled study, 150 women undergoing egg collection in their first IVF cycle were randomized to receive 200 mg and 150 mg lignocaine in PCB. No differences were seen in the demographic data, the ovarian responses, the duration of egg collection and the number of follicles punctured. The fertilization, implantation and pregnancy rates were similar when either 150 mg or 200 mg lignocaine was employed. The median pain levels during vaginal punctures were 14.0 (2.5th-97.5th centiles: 0-75.4) and 14.0 (2.5th-97.5th centiles: 0-86.5) in patients receiving 200 mg and 150 mg lignocaine respectively, whereas the corresponding median abdominal pain levels were 14.0 (2.5th-97.5th centiles: 0-85.6) and 14.0 (2.5th-97.5th centiles: 0-99.1). These pain levels during egg collection were not significantly different between the two groups. The use of 200 mg lignocaine in PCB is not justified, even in the absence of toxic effects. 相似文献
18.
Swahn M.-L.; Bygdeman M.; Seppala M.; Johannisson E.; Cekan S. 《Human reproduction (Oxford, England)》1993,8(2):193-200
The effects of RU 486 combined with tamoxifen and tamoxifenalone on hormonal parameters and endometrial development atthe time of implantation were studied. Measurements of cytosolicoestrogen and progesterone receptors in endometrium and placentalprotein 14 (PP14) in plasma were also included. Three dosageschedules were used: single oral dose of 40 mg tamoxifen aloneand in combination with 200 mg RU 486, and 40 mg tamoxifen forthree consecutive days starting on the first day after the luteinizinghormone (LH) surge. The combined treatment prolonged the lutealphase (P < 0.05) and increased the plasma levels of progesterone.A single dose of tamoxifen did not affect the bleeding patternand plasma hormone levels, but raised plasma oestradiol andLH with the 3-day treatment. The endometrium was retarded afterthe combined and the 3-day treatment with tamoxifen. Concentrationsof cytosolic progesterone receptors were higher after the combinedtherapy, but were unaffected after tamoxifen only. PP14 levelswere higher (P < 0.05) after repeated tamoxifen doses thanin controls, but were lower with combined treatment. Progesteroneand oestrogen are evidently necessary for endometrial maturationduring the secretory phase of the menstrual cycle. PP14 levelsin plasma cannot be used for clinical assessments of endometrialfunction because high levels coincide with disturbed endometrialdevelopment. 相似文献
19.
Ricci G Tamaro G Simeone R Giolo E Nucera G De Seta F Guaschino S 《Human reproduction (Oxford, England)》2001,16(3):449-456
This prospective, randomized, controlled study compared the effects of recombinant human FSH (r-hFSH) and highly purified urinary FSH (u-hFSH HP) on lipoprotein(a) [Lp(a)] concentrations in women undergoing ovarian stimulation. Fifty infertile women were randomly allocated into two equally sized treatment groups (n = 25 per group). Thirty normal ovulation women were recruited as controls. The infertile women received u-hFSH or r-hFSH 150 IU/day starting on cycle day 2. From cycle day 6 the dose was adjusted according to ovarian response. Human chorionic gonadotrophin 10,000 IU was administered once there was at least one follicle > or =18 mm in diameter. The luteal phase was supported with progesterone 50 mg/day for at least 15 days. Repeated measurements of Lp(a) concentrations were performed during both stimulated and natural cycles. A significant increase in luteal phase Lp(a) concentrations was detected in the stimulated cycles, whereas no significant changes in serum Lp(a) concentrations were observed during natural cycles. There were no significant differences between the urinary and recombinant FSH effects on serum Lp(a). The luteal Lp(a) increase was transitory because after 1 month Lp(a) concentrations returned to baseline values if pregnancy failed to occur; in pregnant women persistent increased Lp(a) concentrations were found at the 8th week. The percentage changes in serum Lp(a) were positively correlated with the luteal progesterone increase (r = 0.40, P < 0.05), but not with follicular or luteal oestradiol increase. The women with low baseline Lp(a) (< or =5 mg/dl) had a greater increase of the Lp(a) concentrations at midluteal phase than women with baseline Lp(a) >5 mg/dl. In conclusion, the recombinant or urinary hFSH administration does not directly influence Lp(a) concentrations. The luteal Lp(a) increase in stimulated cycles is not related to gonadotrophin treatment per se, but appears to be related to the high luteal progesterone concentrations, physiologically or pharmacologically determined. Our results also suggest that the sensitivity to the progesterone changes could be related to apolipoprotein(a) phenotype. 相似文献
20.
Termination of early pregnancy with ZK 98, 734: pharmacokinetic behaviour and clinical effect 总被引:1,自引:0,他引:1
Swahn Marja-Liisa; Kovacs Laszlo; Cekan Sten Z.; Aedo Ana-Rosa; Westlund Par 《Human reproduction (Oxford, England)》1994,9(1):57-63
The antiprogestin RU 486 (mifepristone) is highly effectivein inducing early abortion in women only if the compound iscombined with a prostaglandin analogue. A new related antiprogestin,ZK 98, 734, has been reported in animal studies to be much morepotent as an abortifacient than mifepristone, concomitant withless antiglucocorticoid activity. The aim of the present two-centrestudy was to explore the abortifacient efficacy and plasma concentrationsof ZK 98, 734 in women seeking abortion. A total of 96 pregnantwomen with amenorrhoea of <49 days were treated with oraldoses of 12.5, 25, 50 or 100 mg ZK 98, 734 twice daily for 4days. The overall rate of complete abortion and continuing livepregnancies was 68 and 20% respectively, i.e. results comparablewith treatment with mifepristone alone. No dose-response relationshipwas noted. In patients with complete abortion, signs of lutealsysfunction in terms of oestradiol and progesterone productionwere evident on the fourth treatment day, in contrast to patientswith failures. Increased amounts of cortisol and prolactin werefound during treatment both in successfully treated patientsand failures, whereas aldosterone values remained unaffected.The effect on cortisol may indicate some antiglucocorticoidactivity in the human. The concentrations of ZK 98, 734 in peripheralblood after 25, 50 and 100 mg twice daily for 4 days were similar.The values were slightly above 0.5µmol/l on the secondday of treatment. Maximal concentrations of 0.7 µmol/lwere seen on treatment day 4. Plasma concentrations of ZK 98,734 did not differ in cases of complete abortion and failures.In conclusion, the abortifacient efficacy in relation to doseof the new antigestaged ZK 98, 734 does not essentially differfrom that of mifepristone treatment alone. 相似文献