Continuous administration of gonadotrophin-releasing hormone analogues (GnRHa) in patients stimulated for the purpose of IVF might have a direct effect on the ovary. We have evaluated the IVF outcome of patients treated with Buserelin and subsequently with a combination of follicle-stimulating hormone (FSH) and human menopausal gonadotrophin (HMG). Patients were divided into three groups according to the number of oocytes obtained by transvaginal ultrasound-guided follicular aspiration: group 1 (n = 35), in which 1-5 oocytes were retrieved; group 2 (n = 30), in whom 6-10 oocytes were obtained; group 3 (n = 32), in whom greater than or equal to 11 oocytes were collected. Only couples with normal semen samples at oocyte retrieval were included in this study. The dose of Buserelin employed was not different between groups. However, the amount of FSH/HMG necessary to reach an optimal response significantly (P less than 0.01) decreased as follicular development increased. The quality of the oocytes obtained was evaluated based on the appearance of the oocyte-corona-cumulus complex, fertilization rate, morphological appearance of the embryos, and implantation rate. The fertilization rate was significantly (P less than 0.01) decreased in group 3 (57.2%) in comparison with groups 1 (77.1%) and 2 (74.2%). There was no significant difference between the groups in the quality of the embryos obtained or the quality of those replaced into the uterus. The implantation rate per embryo transferred was significantly (P less than 0.05) higher in group 1 (16.5%) in comparison with groups 2 (6.6%) and 3 (8.2%).(ABSTRACT TRUNCATED AT 250 WORDS)
Gonadotrophin-releasing hormone analogues (GnRH-a) are currently used in combination with gonadotrophins in ovarian stimulation for in-vitro fertilization (IVF). The present study evaluates follicular recruitment and outcome of IVF in patients treated with GnRH-a, starting in different phases of the menstrual cycle. Ovarian quiescence was achieved by s.c. injection of a GnRH-a (600 micrograms/day). Three groups of patients were randomly established. Patients in group 1 (n = 14) started GnRH-a treatment 4-7 days after ovulation. Women in group 2 (n = 15) started GnRH-a 8-10 days after ovulation. Patients in group 3 (n = 15) began the analogue 1-3 days after the onset of menses. Multiple follicular development was achieved by a combination of pure follicle-stimulating hormone and human menopausal gonadotrophin. Oocyte collection was performed 35 h after administration of human chorionic gonadotrophin. Luteolysis was successfully induced in 15% of cases in group 1 and 40% in group 2. Ovarian arrest was achieved in a significantly (P less than 0.01) shorter period of time in group 3 in comparison to groups 1 and 2. There was no difference between groups in the dose of gonadotrophins necessary to reach an optimal response. Patients in group 1 showed a significant decrease (P less than 0.05) in the number and size of follicles developed in comparison to groups 2 and 3. Fertilization and cleavage rates were similar in all three groups. The pregnancy rate was 40% in group 3, while it decreased to 14.3 and 13.3% in groups 1 and 2, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
The incidence of ovarian cyst formation during stimulation with additional pituitary suppression was retrospectively studied in 359 patients included in our in-vitro fertilization (IVF) programme. Women were classified according to the type of pituitary desensitization with subcutaneous buserelin used in group A (long protocol; n = 285) and group B (short protocol; n = 74). The rate of appearance of single follicular ovarian cysts for group A was 9.82% and for group B 22.97% (P less than 0.005). Ovarian cystic formations were usually asymptomatic and nonfunctional. The presence of these cysts did not seem to interfere with the ovarian response to stimulation treatment. Oocyte retrieval and pregnancy rate were similar between patients who developed ovarian cysts during gonadotrophin-releasing hormone analogue (GnRHa) therapy and those without cyst formation. These results suggest that ovarian cysts developing during GnRHa treatment are probably the consequence of the initial gonadotrophin rise and that the presence of ovarian cysts in these conditions should not be considered a necessary cause of cancellation for IVF patients.
Regression analysis of the proportion of unfertilized oocytes on the number of oocytes retrieved per patient was applied to three different ovarian stimulation protocols in order to establish the relativity of the concept 'high responder to gonadotrophins' for in-vitro fertilization (IVF) patients. After fitting the data to the model: probit(proportion of unfertilized oocytes) + 5 = intercept + B Log10(oocytes retrieved per patient), women with a number of oocytes retrieved greater than or equal to the value necessary to obtain 50% fertilization were defined as high responders. Exogenous gonadotrophin stimulation which was commenced after complete suppression of ovarian activity by a gonadotrophin-releasing hormone analogue (GnRHa) (long protocol) resulted in a significantly higher number of oocytes retrieved (10.15) to obtain 50% fertilization compared to a short protocol (6.84) (exogenous stimulation began 2 days after the GnRHa administration). Women stimulated without use of a GnRHa showed an intermediate response. Implantation, pregnancy and miscarriage rates showed no difference between low-moderate and high responders. These results demonstrate the relativity of the concept 'high responder to gonadotrophins' and indicate that the drawback of low fertilization in high responders could be balanced by the high number of oocytes retrieved per patient (and available embryos for transfer) and the selection of the best embryos for transfer.
Several reports in the literature suggest delayed implantation of in vitro-fertilized human embryos compared to in vivo-fertilized eggs. The use of high-frequency transvaginal transducers for early detection of pregnancy has allowed the identification of the gestational sac with very low serum human chorionic gonadotropin (beta-hCG) levels. Thus, the present study evaluated whether retarded implantation can be identified using this novel technology. We studied 13 single pregnancies after in vitro fertilization (IVF) and 14 pregnancies after artificial insemination either by husband (n = 6) or donor (n = 8). In the IVF patients, oocytes were retrieved 35 hours after hCG administration. Embryo transfer occurred approximately 48 hours after retrieval. Artificial insemination was performed 24 and 48 hours after hCG administration. Transvaginal ultrasound scans and serum beta-hCG levels were evaluated every 3 days starting day 12 post-hCG administration. Serum beta-hCG levels rose in parallel when in vitro- and in vivo-fertilized embryos were compared. Similarly, there was no difference between groups in the mean time needed to detect early embryonic structures, such as the embryonic sac, yolk sac, and heartbeats, or the growth rate of the gestational sac. In conclusion, there was no difference in detecting implantation and early embryonic development of human embryos fertilized in vivo versus in vitro as ascertained by ultrasound scans and serum beta-hCG levels. An embryonic sac is detected 23-24 days after hCG administration in pregnancies achieved by assisted reproductive techniques.
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