Increasing the daily dose of recombinant follicle stimulating hormone (Puregon) does not compensate for the age-related decline in retrievable oocytes after ovarian stimulation.
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A prospective, randomized, double-blind, multicentre (n = 6) study was conducted to compare the influence of either a 150 or 250 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH, Puregon) on the number of oocytes retrieved and the total dose used in down-regulated women between 30 and 39 years of age undergoing ovarian stimulation. In all, 138 women were treated with recombinant FSH, 67 with 150 IU and 71 with 250 IU. The number of oocytes retrieved in the low-dose group was 9.1 compared to 10.6 in the high-dose group (not significant). In the 30-33 years of age class receiving the 250 IU dose, a surplus of 4.2 oocytes (14.8 versus 10.6) was found, whereas in the 37-39 age class nearly one oocyte more was retrieved in the 150 IU group (8.1 versus 7.4). The total dose used to reach the criterion for human chorionic gonadotrophin (HCG) administration was 1727 IU for the women treated with 150 IU daily and 2701 IU for the 250 IU treated women (P < 0. 001). No significant relationships were found between serum FSH concentrations as obtained in the early follicular phase and the number of oocytes collected, or the total dose. It is concluded that in women between 30 and 39 years of age, the decline in number of oocytes retrieved with increasing age cannot be overcome by augmenting the daily dose of recombinant FSH from 150 to 250 IU. (+info)
Follicular and luteal phase characteristics following early cessation of gonadotrophin-releasing hormone agonist during ovarian stimulation for in-vitro fertilization.
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Gonadotrophin-releasing hormone agonists (GnRHa) are widely used in in-vitro fertilization (IVF) for the prevention of a premature rise in luteinizing hormone (LH) concentrations. However, the administration of GnRHa during the follicular phase may also impair subsequent luteal function due to retarded recovery of pituitary gonadotrophin secretion. Therefore, luteal supplementation is generally applied. The present study was designed to determine whether a premature LH surge would still be prevented after early cessation of GnRHa during ovarian stimulation and whether subsequent luteal phase LH production would be sufficient to support progesterone synthesis by the corpus luteum. Sixty patients were randomized for three groups: (i) A long GnRHa/human menopausal gonadotrophin (HMG) protocol with luteal support by repeated human chorionic gonadotrophin (HCG) (n = 20), (ii) early follicular phase cessation of GnRHa without luteal support (n = 20), and (iii) a long GnRHa protocol without luteal support (n = 20). Frequent ultrasound and blood sampling was performed during the entire IVF cycle. Forty normo-ovulatory women served as controls. No premature LH surges were found after early cessation of GnRHa. In this group, some pituitary recovery occurred during the late luteal phase, but this did not affect corpus luteum function. Progesterone concentrations were shown to be dependent on disappearance of the pre-ovulatory bolus of HCG. Pregnancies occurred in all three groups. In conclusion, early follicular phase cessation of GnRHa is still effective in the prevention of a premature rise in LH. Although some pituitary recovery was observed thereafter, corpus luteum function is still abnormal due to early luteolysis. (+info)
Ovarian response to repeated controlled stimulation in in-vitro fertilization cycles in patients with ovarian endometriosis.
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In-vitro fertilization (IVF) is an effective infertility treatment for women with endometriosis, but most women need to undergo several cycles of treatment to become pregnant. This case-control study was designed to assess how consistently women with ovarian endometriosis respond to ovarian stimulation in consecutive treatment cycles compared to women with tubal infertility. We compared outcome measures in 40 women with a history of surgically confirmed ovarian endometriosis and 80 women with tubal infertility, all of whom had at least three IVF treatment cycles. The groups were matched for age and early follicular follicle stimulating hormone (FSH) concentration at their first IVF cycle. Outcome measures included number of follicles, number of oocytes, peak oestradiol concentration and number of FSH ampoules required per follicle. Cumulative pregnancy and live birth rates were calculated in both groups. The ovarian endometriosis group had a significantly poorer ovarian response and required significantly more ampoules of FSH per cycle, a difference that became greater with each subsequent cycle. However, cumulative pregnancy (63.3 versus 62.6% by fifth cycle) and live birth (46.8 versus 50.9% by fifth cycle) rates were similar in both groups. In conclusion, despite decreased ovarian response to FSH, ovarian endometriosis does not decrease the chances of successful IVF treatment. (+info)
Quantitative assessment of subendometrial blood flow by three-dimensional-ultrasound is an important predictive factor of implantation in an in-vitro fertilization programme.
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This study was designed to investigate the role of three-dimensional (3D) power Doppler sonography of the (sub-) endometrial area on the first day of ovarian stimulation in predicting the outcome of an in-vitro fertilization (IVF) programme. Among the 75 cycles analysed, the overall pregnancy rate was 20% (15/75) per cycle and 23.8% (15/63) per embryo transfer. Intra-observer variability of the colour histogram was checked in 14 patients with the results demonstrating a high level of agreement. Neither endometrial measurements nor uterine blood flow were correlated with the pregnancy rate. In contrast, all 3D indices were significantly lower in conception compared with non-conception cycles (P < 0.05). Logistic regression analysis found the subendometrial flow index to be the strongest predictive factor of IVF success among the tested sonographic parameters (P = 0.04). In conclusion, quantitative assessment of spiral artery blood flow may be of predictive value for implantation in IVF cycles even before ovarian stimulation therapy is started. (+info)
Clinical efficacy of peritoneovenous shunting for the treatment of severe ovarian hyperstimulation syndrome.
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We investigated prospectively the clinical efficacy of a newly developed continuous autotransfusion system of ascites (CATSA) without protein supplement in patients with severe ovarian hyperstimulation syndrome (OHSS). Peritoneovenous shunting was used to recirculate ascites. The CATSA was performed for 5 h at a rate of 100-200 ml/h once a day. Eighteen patients were treated with the CATSA (CATSA group) and 36 were treated with an intravenous 37.5 g/day of albumin supplement (albumin group). Hospital stay was significantly shorter in the CATSA group than in the albumin group (10.0 +/- 5.7 versus 13.9 +/- 6.2 days, P < 0.01). Haematocrit value reached <40% significantly earlier in the CATSA group (on hospital days 3.9 +/- 3.2 versus 5.9 +/- 2.5, P < 0.01). Using a single procedure, haemoconcentration, urinary output and pulse pressure were markedly improved in the CATSA group compared with the albumin group. Discomfort due to massive ascites diminished promptly and did not recur in nine of 18 CATSA group patients, whereas it persisted in all 36 patients in the albumin group. The serum concentration of protein was maintained in the CATSA group, whereas it did not increase in the albumin group despite daily supplementation with 37. 5 g of albumin. Apparent adverse effects of each procedure were not observed in either group. The mean values of several parameters in the serum pertinent to the coagulation-fibrinolysis system did not change significantly in either group after the procedure. It was concluded that the CATSA procedure expanded circulating plasma volume without exogenous albumin and appeared to lead to a prompt recovery from severe conditions of OHSS. (+info)
Synchronization of ovulation in crossbred dairy heifers using gonadotrophin-releasing hormone agonist, prostaglandin F2alpha and human chorionic gonadotrophin or estradiol benzoate.
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Girolando (Gir x Holstein) is a very common dairy breed in Brazil because it combines the rusticity of Gir (Bos indicus) with the high milk yield of Holstein (Bos taurus). The ovarian follicular dynamics and hormonal treatments for synchronization of ovulation and timed artificial insemination were studied in Girolando heifers. The injection of a gonadotrophin-releasing hormone (GnRH) agonist was followed 6 or 7 days (d) later by prostaglandin F2alpha (PGF2alpha). Twenty-four hours after PGF2alpha injection either human chorionic gonadotropin (hCG, GPh-d6 and GPh-d7 groups) or estradiol benzoate (EB, GPE-d6 and GPE-d7 groups) was administered to synchronize ovulation and consequently allow timed artificial insemination (AI) 24 and 30 h after hCG and EB injection, respectively. Follicular dynamics in Girolando heifers was characterized by the predominance of three follicular waves (71.4%) with sizes of dominant follicles (10-13 mm) and corpus luteum (approximately 20 mm) similar to those for Bos indicus cattle. In the GnRH-PGF-hCG protocol, hCG administration induced earlier ovulation (67.4 h, P<0.01) compared to the control group (GnRH-PGF) and a better synchronization of ovulation, since most of it occurred within a period of 12 to 17 h. Pregnancy rate after timed AI was 42.8 (3/7, GPh-d6) to 50% (7/14, GPh-d7). In contrast, estradiol benzoate (GnRH-PGF-EB protocol) synchronized ovulation of only 5 of 11 heifers from the GPE-d7 group and of none (0/7) from the GPE-d6 group, which led to low pregnancy rates after timed AI (27.3 and 0%, respectively). However, since a small number of Girolando heifers was used to determine pregnancy rates in the present study, pregnancy rates should be confirmed with a larger number of animals. (+info)
Reduction of the developmental competence of sheep oocytes by inhibition of LH pulses during the follicular phase with a GnRH antagonist.
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A GnRH antagonist (Antarelix) treatment was used during the breeding season of Romanov ewes, to investigate whether LH pulses are required the day before the preovulatory surge for normal early embryo development in vivo (Expt 1) and in vitro (Expt 2). In Expt 1, at the onset of oestrus after removal of a fluorogestone acetate sponge, group A0.5 (n = 22) received a subcutaneous injection of 0.5 mg Antarelix, and ovulation was induced with an intravenous injection of 3 mg pig LH 24 h later. The control group (group C, n = 20) were untreated. All ewes were mated naturally at 36 and 48 h after oestrus and embryos were recovered 8 days after sponge removal. There were significant differences in the decrease in LH and in the increase in FSH concentration after Antarelix treatment between treated and control groups. The ovulation rate and embryo recovery rate were not significantly different between the two groups but the blastocyst rate was lower (P < 0.0001) in group A0.5 than in group C, with more unfertilized or degenerated oocytes in group A0.5 (69.2%). In Expt 2, 24 h after sponge removal, group A (n = 10) and group B (n = 10) received one subcutaneous injection of 0.5 mg Antarelix. The control group (group C, n = 10) was left untreated. LH pulsatility was re-established in group B with hourly intravenous injections of 5 micrograms ovine LH for 24 h. Oocytes were collected by flushing the oviducts 28 h after the LH surge, and were fertilized and cultured in vitro for 7 days. Ovulation and cleavage rates were not significantly different among the three groups but a higher rate of blastocysts (P < 0.01) was obtained after Antarelix treatment when LH pulsatility was re-established (group B). Oestradiol concentration was strongly depressed (P < 0.0003) after Antarelix treatment in group A, but was maintained after injection of LH pulses in group B, although at a lower value than before the preovulatory surge in the control group. In conclusion, inhibition of endogenous LH pulses 1 day before the preovulatory surge was not essential for ovulation and in vitro fertilization but was associated with a decrease in plasma oestradiol concentrations and inferior embryo development both in vivo and in vitro. When LH pulsatility was re-established, oestradiol concentrations increased and embryo development was restored. (+info)
Characterization of cellular and vascular changes in equine follicles during hCG-induced ovulation.
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In contrast to other species, the histology of the equine follicle during ovulation has not been described. Preovulatory follicles were isolated during oestrus at 0, 12, 24, 30, 33, 36 and 39 h (n = 5-6 follicles per time point) after an ovulatory dose of hCG to characterize the cellular and vascular changes associated with ovulation in mares. Pieces of follicle wall were formalin-fixed and processed for light microscopy to evaluate the general follicular morphology and quantify selected parameters. Marked changes were observed in the histology of equine follicles in the hours before ovulation. The thickness of the granulosa cell layer doubled between 0 and 39 h after hCG (77.8 +/- 4.8 versus 158.8 +/- 4.8 microns, respectively; P < 0.01). This expansion was caused primarily by a pronounced accumulation of acid mucosubstances between granulosa cells, which was first detected at 12 h after hCG and peaked at 36-39 h. In contrast, a significant thinning of the theca interna was observed after hCG treatment. Fewer cell layers were present; theca interna cells appeared smaller than before hCG; and the presence of occasional pyknotic cells was noted at 36 and 39 h after hCG. In addition, the theca layers were invaded by numerous eosinophils. No eosinophils were observed in preovulatory follicles isolated between 0 and 24 h after hCG, but the number increased to 14.0 +/- 0.8 and 5.6 +/- 0.3 eosinophils per field (x 400) in theca interna and theca externa, respectively, 39 h after hCG treatment (P < 0.01). Severe oedema, hyperaemia and haemorrhages, and significant increases in the number of blood vessels in theca interna and externa were observed at 33, 36 and 39 h after hCG. This study provides the first in-depth characterization of the sequential cellular and vascular changes that occur in equine follicles before ovulation. (+info)