New reproductive technologies: a report from Argentina.
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The increasing incidence of male subfertility as an indication for ART is first discussed. The tendency to use assisted reproduction techniques in such cases is attributed to the disappointing results of classical treatments. The Authors deal with two problems: the choice of the best treatment methods of the sperm and the choice of the best technique of ART for treating male infertility. The analysis of 138 couples treated for male subfertility showed that the centrifugation on discontinuous Percoll gradients (CDPG) and especially on the mini-Percoll (mini CDPG) offers the best results if compared with pellet swim up and other techniques. With reference to the technique of choice, an accurate analysis of tubal (TET and ZIFT) and uterine (IVF/ET) transfers shows that no advantage seems to be obtained with the more sophisticated and exacting tubal transfer. This final conclusion is presently evaluated on the basis of a retrospective study.
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Due to the research on assisted human reproduction and the application of its results we face new type ethical dilemma which had never existed before. The traditional system of ethical values does not provide a safe basis for judgement of our actions. One of the challenging questions is who has the right to authorize or prohibit performing different procedures. There might be necessary and justifiable taking into account the opinions of various bodies (professional committees, national and institutional ethical committees, religious bodies, parliamentary representatives and private organizations or persons). The authors introduce the activities of the role and importance of these bodies and investigate the position of the research and clinical professionals in obtaining permission for the application of ethically sound or less criticizable procedures. The importance of the provision of continuous and many-sided information for wide range of the society is underlined.
The clinical results including all in vitro fertilization (IVF) cycles with oocyte pick-up in 1990 are presented. Different types of treatment including classical IVF and embryo transfer, laparoscopic replacement of zygotes in the fallopian tube (ZIFT), IVF with donor sperm (IVF-D), cross fertilization test, embryo freezing, oocyte donation and IVF with epididymal sperm were performed. The total pregnancy rate obtained reaches 38% per oocyte pick-up, 30% of clinical pregnancies (including 4 pregnancies obtained with frozen and thawed embryos). The anticipated "Take Home Baby Rate" will be around 25% per oocyte pick-up, 26 of these 40 pregnancies being today over 20 weeks of gestation. Particular ethical aspects of the program are presented: a study on couple's attitudes regarding embryo freezing as well as the final destination of possibly remaining supernumerary embryos will stress the importance of a precise clear decision on that matter before entering IVF treatment. Indeed the couple's idea on embryo destiny were very precise but also very different. The oocyte donation program has the originality of preserving the donor's anonymity by exchanging the donors recruited by the patients. It will be stressed that this kind of approach combines higher pregnancy chances for the patients, respect of ethical principles linked to gamete donation and gives satisfaction to the patients. The global normalized pregnancy cumulative curve shows that 60% of the couples entering IVF treatment will obtain a child within the first three pick-up cycles.
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BACKGROUND: hMG and recombinant FSH, have both been used successfully for controlled ovarian hyperstimulation in in vitro fertilization and embryo transfer (IVF-ET). OBJECTIVES: To compare the effectiveness of hMG with rFSH in ovarian stimulation protocols in IVF or ICSI treatment cycles. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 3rd Jan 2002), PubMed, MEDLINE, Web of Science (all searched 1985 to May 15 2002), and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Randomised trials comparing hMG with rFSH for ovarian stimulation in IVF or ICSI treatment for treatment of infertility in normogonadotrophic women. DATA COLLECTION AND ANALYSIS: The main outcome measure was ongoing pregnancy/live birth per woman. Secondary outcomes included total gonadotrophin dose used, cancellation, number of oocytes retrieved, implantation, clinical pregnancy per woman, multiple pregnancy, spontaneous abortion and ovarian hyperstimulation syndrome. Peto odds ratios (OR) for hMG relative to rFSH were calculated after testing for homogeneity of treatment effect across all trials. Analyses were performed separately for the three different GnRHa protocols used: (1) without GnRHa down-regulation, (2) with GnRHa down-regulation using a short protocol and (3) with GnRHa down-regulation using a long protocol. MAIN RESULTS: Eight trials that met the inclusion criteria could be identified. One trial did not use down-regulation, one trial used a short protocol and six trials used a long down-regulation protocol. In the one trial with non-down-regulated women and in the one trial that used a short down-regulation protocol there was no evidence of a difference between hMG and rFSH in any clinical outcome. Data of four truly randomised trials in women down-regulated using a long protocol could be pooled. There was no evidence of a difference between hMG and rFSH in ongoing pregnancy/live birth per woman (OR 1.27; 95% CI 0.98 to 1.64). Furthermore there was no clear difference on any of the secondary outcomes, although the clinical pregnancy rate per woman was of borderline significance in favour of hMG (summary OR 1.28; 95% CI 1.00 to 1.64). The other secondary outcomes were comparable for both gonadotrophins. REVIEWER'S CONCLUSIONS: For all three GnRHa protocols analysed there is insufficient evidence of a difference between hMG and rFSH on ongoing pregnancy or live birth. More large randomised trials are needed to estimate the difference between hMG and rFSH more precisely. Such trials should preferably (1) use a consistent long GnRHa protocol and (2) use a fixed dose of gonadotrophin such to prevent potentially subjective decisions of the clinician in dosing and (3) take live birth as primary endpoint. At this moment in time however, in prescribing gonadotrophins for ovarian hyperstimulation in IVF one should use the least expensive medication.
OBJECTIVE: Analyse outcome of FSH therapy alone after pituitary desensitization for assisted conception to compare with published results of conventional hMG. DESIGN: Descriptive study of complete series of patients undergoing IVF-ET or GIFT treatment using the chosen drug protocol without exception. SETTING: University private IVF-ET clinic within a comprehensive fertility service. PATIENTS: All couples (n = 773), including 10% > or = 40 years old, treated by IVF-ET or GIFT (1,097 cycles started and 1,012 attempted egg recoveries) for mainly tubal pelvic infective damage (36% of cycles), endometriosis (16%), sperm disorders (14%) and prolonged unexplained infertility (34%) during 3 calendar years, 1990 to 1992. INTERVENTIONS: Ovarian stimulation using FSH alone (urofollitropin, Metrodin; Serono Laboratories Limited, Welwyn Garden City, United Kingdom) after pituitary desensitization using buserelin acetate nasal spray (Suprefact; Hoechst, Hounslow, United Kingdom) from the previous midluteal phase, monitored by ultrasonography and serum E2 measurements, followed by standard IVF-ET or GIFT treatment methods limited to the transfer of no more than three embryos or eggs. OUTCOME MEASURES: Rates per cycle started of cancellation of egg recovery, failure of egg recovery, clinical pregnancy (ultrasound detection of sac), livebirths, and cumulative pregnancy rates (PR) and birth rates. RESULTS: In women < 40 years old and men with favorable sperm (77% of couples and 84% of cycles) the cycle cancellation rate of egg recovery was 7%; attempted egg recovery was successful in every case. For IVF-ET the clinical PR per started cycle and the livebirth rate were 27% and 23%, respectively, and for GIFT 39% and 33%, respectively. The four-cycle cumulative PR by either treatment was 77% and livebirth rate 68%. In women > 40 years old, the cycle PR and birth rate were 14% and 8%, respectively. In cases of sperm disorder the rates in women < 40 years old were 17% and 14%, respectively, and > 40 years old were 18% and 0, respectively. CONCLUSIONS: By comparison with the best worldwide results of assisted conception employing pituitary desensitization, the findings demonstrate that FSH alone to stimulate the ovaries is fully effective and highly successful, and supplementation with LH is not needed.
OBJECTIVE: To investigate if the presence of an abnormally large follicle during controlled ovarian hyperstimulation (COH) under pituitary suppression has any effect on the outcome of the cycle. DESIGN: Prospective, observational. SETTING: The reproductive endocrinology unit of a university hospital. PATIENTS: One hundred fifty patients undergoing COH for assisted reproductive techniques during a 6-month period (August 1990 to January 1991). INTERVENTIONS: Transvaginal follicular aspiration and IVF-uterine ET. RESULTS: A total of 19 cycles had abnormally large follicles identified on day 8 of the stimulation cycle after normal baseline ultrasound. Gonadotropins were continued and hCG injection was indicated when two or more follicles of the main cohort achieved a diameter of 20 to 22 mm. Twenty preovulatory oocytes were retrieved from 22 large follicles. Two were transferred for GIFT and 18 were inseminated in vitro, resulting in a 72.0% fertilization rate. The mean number of oocytes retrieved per patient was 10.9, 71.4% of which were mature with a fertilization rate of 67.7%. All these figures were comparable with the results obtained in the 131 patients of the control group undergoing IVF. No evidence of premature luteinization was observed in the study group, based on plasma P levels (x 0.83 ng/mL [conversion factor to SI unit, 3.180], range 0.31 to 1.40 ng/mL). The clinical pregnancy rate for the group with abnormally large follicles did not differ from the control group (27.8% versus 28.2%, respectively). CONCLUSIONS: The presence of an abnormally large follicle during COH under pituitary suppression does not affect the outcome of the cycle. Moreover, under these conditions, continuous gonadotropin stimulation of a follicle to diameters considerably larger than the standard ones does not have a detrimental effect on the oocyte contained in it, suggesting that oocyte aging is an independent process from follicular growth once LH surge is prevented.
BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) appears to be caused by increased capillary permeability in the vascular endothelial cells. Such cells secrete excess amounts of von Willebrand factor (vWF), a large adhesive glycoprotein. METHODS: We retrospectively evaluated the circulating levels of vWF and of vascular endothelial growth factor (VEGF) twice, on the days of oocyte retrieval and embryo transfer, in 46 women who developed early-onset OHSS. RESULTS: Nineteen, 14, and 13 women developed mild, moderate, and severe OHSS, respectively. Inconsistent changes were observed in the VEGF during oocyte retrieval and embryo transfer. However, the net increase in serum vWF during that period showed an increase in absolute value at the time of embryo transfer that paralleled an increase in the severity of OHSS. That is, in mild OHSS, the serum vWF increased from 140 +/- 44 to 164 +/- 28%; in moderate OHSS, it increased from 113 +/- 47 to 186 +/- 22%; and in severe OHSS, it increased from 120 +/- 35 to 274 +/- 63%. All 9 women with a vWF level > 230% at embryo transfer developed severe OHSS, while 9 of 13 women with severe OHSS exhibited a vWF > 230% at embryo transfer. CONCLUSION: The results suggest that a rise of the serum level of vWF occurs prior to clinical manifestation of OHSS in patients with severe OHSS but not in patients with mild OHSS.