A comparison of three gonadotrophin-releasing hormone analogues in an in-vitro fertilization programme: a prospective randomized study.
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The use of gonadotrophin-releasing hormone analogues (GnRHa) has resulted in improved pregnancy rates in in-vitro fertilization (IVF) treatment cycles. Traditionally, short-acting analogues have been employed because of concerns over long-acting depot preparations causing profound suppression and luteal phase defects adversely affecting pregnancy and miscarriage rates. We randomized 60 IVF patients to receive a short-acting GnRHa, nafarelin or buserelin, or to receive a depot formulation, leuprorelin, all commenced in the early follicular phase and compared their effects on hormonal suppression and clinical outcome. We found that on day 15 of administration there was a significant difference in the suppression of oestradiol from initial concentrations, when patients on buserelin were compared with patients on nafarelin or leuprorelin (54 versus 72 and 65%; P < 0.05) and also in the number of patients satisfactorily suppressed, (80 versus 90 and 90%; P < 0.05), though there were no differences between the analogues by day 21. Similarly there was no difference in hormonal suppression during the stimulation phase or in implantation, pregnancy or miscarriage rates in comparing the three agonists. We conclude that with nafarelin and leuprorelin, stimulation with gonadotrophins may begin after 2 weeks of suppression and that long-acting GnRHa are as effective as short-acting analogues with no detrimental effects on the luteal phase. (+info)
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.
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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. (+info)
Is there a difference in the function of granulosa-luteal cells in patients undergoing in-vitro fertilization either with gonadotrophin-releasing hormone agonist or gonadotrophin-releasing hormone antagonist?
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Gonadotrophin-releasing hormone (GnRH) regulates gonadotrophin release. It has been shown that GnRH may have a direct effect on the ovary, as the addition of GnRH to granulosa cell cultures inhibits the production of progesterone and oestradiol. Specific GnRH receptors have been found to be present in rat and human granulosa cells. Desensitization of the pituitary by GnRH agonist has become common in in-vitro fertilization (IVF) treatment, usually by a long protocol of 2-3 weeks. With the introduction of GnRH antagonists, which produce an immediate blockage of the GnRH receptors, a much shorter exposure is needed of 3-6 days. The aim of this study was to evaluate the effect of a GnRH agonist (buserelin) and a GnRH antagonist (cetrorelix) on the function of granulosa cells cultured in vitro from IVF patients. Women were treated by IVF randomized either to have buserelin nasal spray from the luteal phase in the previous cycle or cetrorelix from day 6 of the cycle. Both groups had ovarian stimulation with human menopausal gonadotrophin (HMG) 150 IU daily, i.e. HCG was administered when the follicles were larger than 17 mm, and aspirated 36 h later. Granulosa cells, separated and washed from large follicles containing ova, were pooled. After 48 h of pre-incubation, the granulosa cells were cultured for 4 days in medium with either added testosterone or cAMP with or without HCG, with change of medium after 2 days. The progesterone and oestradiol concentrations in the culture medium were measured by immunological assay, and cellular protein was measured by microprotein assay. The results showed that granulosa cells from women treated with GnRH antagonist (cetrorelix) responded earlier to the in-vitro hormone stimulation in terms of progesterone accumulation than women treated with the GnRH agonist (buserelin). This may have been due to difference in time of exposure to the analogue. The results may indicate that the luteal function is less impaired in GnRH antagonist treatment than in GnRH agonist treatment. (+info)
A prospective, randomized, double-blind clinical trial to study the efficacy and efficiency of a fixed dose of recombinant follicle stimulating hormone (Puregon) in women undergoing ovarian stimulation.
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A prospective, randomized, double-blind, multicentre (n = 5) study was conducted to compare the influence of either a 100 or 200 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH) on the number of oocytes retrieved and the total dose used in down-regulated women undergoing ovarian stimulation. Fertilization was done by intracytoplasmic sperm injection or conventional in-vitro fertilization. A total of 199 women were treated with FSH, 101 subjects with 100 IU and 98 subjects with 200 IU. In subjects of the 200 IU treatment group, significantly more oocytes were retrieved compared to the 100 IU group (10.6 versus 6.2 oocytes, P < 0.001). The total dose needed to develop at least three follicles with a diameter of > or = 17 mm was significantly lower in the 100 IU treatment group (1114 IU versus 1931 IU, P < 0.001). In the low-dose group, significantly lower serum concentrations of oestradiol, progesterone and FSH were observed at the day of human chorionic gonadotrophin administration. Although more cycle cancellations due to low response were seen in the 100 IU group (n = 24 versus n = 3), the clinical pregnancy rate per started cycle was similar (24.7% in the 100 IU group versus 23.3% in the 200 IU group). In the high-dose group, more side-effects, in particular more cases of ovarian hyperstimulation syndrome, were noted. It is concluded that compared to 200 IU, the use of a 100 IU fixed dose is less efficacious in terms of the number of oocytes retrieved, but more efficient as indicated by a lower total dose. (+info)
Prevention of premenstrual exacerbation of hereditary coproporphyria by gonadotropin-releasing hormone analogue.
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A 20-year-old Japanese female needed frequent hospitalization due to premenstrual exacerbation of hereditary coproporphyria (HCP). Intranasal buserelin acetate, a gonadotropin-releasing hormone analogue, was given to suppress her menstrual cycles. Her porphyric symptoms subsided dramatically as she became amenorrhoeic. Urinary excretion of porphyrin derivatives fell significantly. She has been free from recurrent attacks, but suffers a minor porphyric attack once in 5 years. However, borderline osteopenia secondary to hypoestrogenism has been noted. Although these analogues are potent in suppressing estrogen-induced porphyric symptoms, due precautions should be taken to avoid bone demineralization in the long-term use. (+info)
Persistent dominant follicle alters pattern of oviductal secretory proteins from cows at estrus.
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The experimental objective was to compare synthesis of oviductal secretory proteins of dairy cows bearing a persistent dominant follicle (PDF) versus a fresh dominant follicle (FDF) at estrus. On Day 7 after synchronized estrus (Day 0), cows received an intravaginal progesterone device and injection of prostaglandin F2alpha (PGF2alpha). On Day 9, cows received an injection of a GnRH agonist (FDF group; n = 3) or received no injection (PDF group, n = 3). On Day 16, all cows received PGF2alpha, and progesterone devices were removed. At slaughter on Day 18 or Day 19, oviducts ipsilateral and contralateral to the dominant follicle were divided into infundibulum, ampulla, and isthmus regions. Explants from oviductal regions were cultured in minimal essential medium supplemented with [3H]leucine for 24 h. Two-dimensional fluorographs of proteins in conditioned media were analyzed by densitometry. Rate of incorporation of [3H]leucine into macromolecules was greater in the infundibulum, ampulla, and isthmus of FDF cows (p < 0.01). Overall, intensities of radiolabeled secretory protein (P) 2 and P13 were greater for FDF than for PDF. In the ampulla, P14 was more intense for FDF while P7 was more intense for PDF. Abundance of P1 in the isthmus was greater for PDF cows. Across regions, P5, P6, P8, P9, and P11 were more intense for PDF than for FDF in the ipsilateral side. In the contralateral side, P19 was more intense for PDF than for FDF, whereas P6, P8, P9, and P11 were more intense for FDF. Differences in biosynthetic activity and in secreted oviductal proteins from cows bearing a PDF may contribute to the decrease in fertility associated with a PDF. (+info)
The effect of smoking on oocyte quality and hormonal parameters of patients undergoing in vitro fertilization-embryo transfer.
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PURPOSE: The aim of the present study was to investigate the influence of smoking on different parameters such as oocyte count, embryo score, and basal hormone values within the scope of in vitro fertilization-embryo transfer (IVF-ET). METHODS: Eight hundred thirty-four women undergoing IVF-ET treatment were classified as smokers or nonsmokers on the basis of questionnaires. Additionally, we divided them into three groups according to their stimulation protocol--"combined stimulation" [I; clomiphene citrate plus human menopausal gonadotropin (hMG)], "ultrashort" [II; gonadotropin releasing hormone agonist (GnRHa) plus hMG or follicle-stimulating hormone (FSH)], and "long downregulation protocol" (III)--and further classified again as smokers or nonsmokers within the groups. RESULTS: In general, smoking patients were significantly (P = 0.0195) younger than nonsmokers and showed a significantly (P = 0.0379) lower embryo score and a tendency (P = 0.0931) to produce fewer oocytes. There was no significant difference concerning the number of normally or pathologically fertilized and transferred oocytes and embryos suitable for cryopreservation. Women who smoked had significantly (P = 0.0112) higher basal 17-beta-estradiol (E2), luteinizing hormone (LH) (P = 0.0001), and dehydroepian-drosteronesulfate (DHEAS) (P = 0.0039) levels, but their basal human prolactin (HPRL) levels were significantly (P = 0.0033) lower than those of nonsmokers. According to the stimulation protocol used, we found the following results. Smoking patients in group I showed a significantly (P = 0.023) lower embryo score and produced fewer oocytes (P = 0.0113), with fewer of them being fertilized (P = 0.0072) and transferred (P = 0.0067). Women who smoked had significantly (P = 0.0002) higher basal LH levels, but their HPRL levels were significantly (P = 0.031) lower than those of nonsmokers. Furthermore, they had a thinner endometrium on the day of embryo transfer (P = 0.0366). In group II we measured significantly elevated basal E2 levels (P = 0.0089) and higher LH values (P = 0.0092) in smokers. Group III showed a trend (P = 0.0565) toward lower HPRL values in smokers. CONCLUSIONS: Although the fertilization rate of oocytes and the pregnancy rate were not significantly different between smokers and nonsmokers, we found significantly alterated hormonal parameters and negatively influenced oocyte parameters, particularly after clomiphene stimulation. So we might consider using only GnRHa protocols for smoking patients. Additionally, we advise our patients to stop smoking before an IVF-ET treatment because of the complex effects of smoking on the reproductive and hormonal system. (+info)
Involvement of parathyroid hormone-related peptide in cell proliferation activity of human uterine leiomyomas.
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Uterine leiomyomas develop from uterine smooth muscle cells, which are known to be regulated by estrogen and other growth factors. The purpose of this study was to investigate the role of expression of parathyroid hormone related-peptide (PTHrP) in the growth of uterine leiomyomas treated or untreated with gonadotropin-releasing hormone agonist (GnRH-a). Thirty-nine leiomyoma tissues were obtained from 36 patients who had been treated with GnRH-a (n=10) or without GnRH-a (n=29). The intensity of PTHrP immunostaining was categorized into three grades; "negative", "weakly positive", and "positive". Leiomyoma cell growth was estimated by the proliferating cell nuclear antigen (PCNA) labeling index (LI) with an image analyser. We also investigated the correlation between PTHrP expression and cell proliferation or histopathological findings. In the GnRH-a-untreated group, LI of the PTHrP "positive" group was significantly higher than that of the PTHrP "negative" group, but the intensity of PTHrP immunostaining did not correlate with LI in the GnRH-a-treated group. PTHrP expression did not correlate with histological findings or clinical parameters (age and phase of menstrual cycle) in either the GnRH-a-treated or the -untreated group. In addition, the expression of mRNA for PTHrP and its receptor was detected in leiomyomas by reverse transcriptase-polymerase chain reaction (RT-PCR). Our results indicate that the expression of PTHrP in leiomyomas correlated positively with cell growth in the GnRH-a-untreated group, suggesting that PTHrP may act as a local cell growth modifier in an autocrine/paracrine fashion on uterine leiomyomas. (+info)