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PubMed1987

Reproductive technologies: the two sides of the glass jar.

From our knowledge of fertilization and implantation, new methods of reproduction have been developed. These new reproductive technologies make possible new parenting arrangements, resetting the biological clock for women, selecting the timing of birth, sex and number of children, pre-implantation diagnosis and gene replacement. The new ways of making babies present us with a myriad of ethical, legal, social and psychological concerns.

Animals↗
PubMed2001

New reproductive technologies, ethics and legislation in Brazil: a delayed debate.

This paper focuses on the debate about the utilization of new reproductive technologies in Brazil, and the paths taken in the Brazilian National Congress in an attempt to draw up legislation to regulate the clinical practice of human assisted reproduction. British documents, such as the Warnock Report and Human Fertilization and Embriology [sic] Authority (HFEA) are used for thorough reference. The analysis of the Law Projects in the National Congress, the Resolution by the Federal Medicine Council, Resolution 196/96 and documents by the the Ministerio Publico (Public Prosecution Office), supplied the bases for the discussion. The principal question involved is the observation of different technical and moral prientations [sic] that influence the conduct of the issue in the legislative process. It is possible to observe that the main focus of the projects relates to the rights and interests of the children, to those possibly benefited by the technique and to embryo reduction. Very little attention has been directed to the issues of sexual and reproductive rights and to the health of the women submitted to the new reproductive techologies [sic].

Bioethics↗
PubMed2004

Autoimmunity, infertility and assisted reproductive technologies.

Despite strongly held opinions, a trustworthy scientific basis for most statements about autoimmunity, autoimmune diseases and assisted reproductive technologies (ART) does not exist. It is not likely that autoimmunity causes infertility, nor that patients with autoimmune diseases are unusually infertile. When carefully monitored in selected patients, ART does not appear to harm patients who have pre-existing autoimmune diseases, but the ovarian hyperstimulation syndrome and multiple gestation pregnancies impart independent risks. Stable autoimmune diseases without major organ damage probably do not affect the outcomes of ART pregnancies. Children born of ART pregnancies are apparently normal at birth, whether or not the genetic or birth mother has autoimmune disease, but long-term follow-up is not available. Male fertility is probably not altered by autoimmune disease. Fiscal, ethical and moral issues related to ART in patients with autoimmune diseases are beyond the scope of this discussion but remain important.

Autoimmune Diseases↗
PubMed2005

Thyroid function after assisted reproductive technology in women free of thyroid disease.

OBJECTIVE: To evaluate thyroid function in women undergoing a first assisted reproductive technology (ART) procedure and to compare women with ongoing pregnancy or miscarriage. DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENT(S): Seventy-seven women free of thyroid disease. INTERVENTION(S): Serum TSH and FT4 were determined before and 2, 4, and 6 weeks after ET. All women received the same ART protocol. MAIN OUTCOME MEASURE(S): Thyroid function. RESULT(S): Forty-five women had ongoing pregnancies, and 32 suffered a miscarriage after 6.7 weeks (range 5-11). Mean age and number of ET were similar in both groups. Compared with baseline values, TSH and FT4 increased significantly 2 weeks after ET (ongoing pregnancies group: TSH 2.5 +/- 1.3 vs. 1.6 +/- 0.8 mU/L and FT4 13.8 +/- 1.4 vs. 12.4 +/- 1.8 ng/L; miscarriage group: TSH 2.1 +/- 1.0 vs. 1.5 +/- 0.7 mU/L and FT4 14.2 +/- 2.0 vs. 12.4 +/- 1.9 ng/L). Pregnancy outcome did not affect thyroid function and its evolution over time. CONCLUSION(S): In women free of thyroid diseases, thyroid function changed significantly after ART, but these changes were not different between women with ongoing pregnancy and miscarriage.

Abortion, Spontaneous↗
PubMed2001

Electroejaculation and assisted reproductive technologies in the treatment of anejaculatory infertility.

OBJECTIVE: To determine the efficacy of electroejaculation in combination with assisted reproductive technology (ART). DESIGN: Case series. SETTING: University fertility program. PATIENT(S): One hundred twenty-one consecutive couples seeking treatment of anejaculatory infertility. INTERVENTION(S): Electroejaculation with IUI, or gamete intrafallopian transfer or IVF. MAIN OUTCOME MEASURE(S): Pregnancy and pregnancy outcome. RESULT(S): Fifty-two couples became pregnant (43%), 39 by IUI alone (32.2%). Cycle fecundity for IUI was 8.7%. No difference in cycle fecundity was seen among ovarian stimulation protocols (clomiphene citrate, 7.6%, hMG, 13.2%, and natural cycle, 11.2%). Pregnancy was unlikely when the inseminated motile sperm count was <4 million. Female management protocol and etiology of anejaculation did not affect results. Patients undergoing IVF had higher cycle fecundity (37.2%) than did those undergoing IUI. The rates of spontaneous abortion and multiple gestations were 23% and 12%, respectively. CONCLUSION(S): Electroejaculation with stepwise application of ART is effective in treating anejaculatory infertility. Intrauterine insemination with the least expensive monitoring protocol should be used for most couples, because use of more expensive monitoring did not improve results. It is cost-effective to bypass IUI and proceed directly to IVF in men who require anesthesia for electroejaculation and in those with a total inseminated motile sperm count < 4 million.

Ejaculation↗
PubMed2004

Can assisted reproduction technology compensate for the natural decline in fertility with age? A model assessment.

BACKGROUND: Maternal age is an important factor in reproduction. Can assisted reproduction technologies (ART) fully compensate for the decline in fertility with age? METHODS: We used a computer simulation (Monte Carlo) model of reproduction, combining the monthly probabilities of conceiving, the risk of miscarriage and the probability of becoming age-dependently permanently sterile. RESULTS: Under natural conditions, 75% of women starting to try to conceive at age 30 years will have a conception ending in a live birth within 1 year, 66% at age 35 years and 44% at age 40 years. Within 4 years the success rates will be respectively 91, 84 and 64%. If women turn to ART after 4, 3 or 2 years respectively without conception, and if the rate of success is as observed after two cycles of insemination in IVF, ART makes up for only half of the births lost by postponing a first attempt of pregnancy from age 30 to 35 years, and <30% after postponing from 35 to 40 years. CONCLUSIONS: Even if we relax some of the assumptions, ART in its present form cannot make up for all births lost by the natural decline of fertility after age 35 years.

Computer Simulation↗
PubMed2005

Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology.

PURPOSE: DNA-damaging factors have been reported in patients that failed to achieve pregnancy after assisted reproductive technologies (ART). The hypothesis was that increased circulating cell-free DNA released by damaged cells could predict unfavorable conditions leading to failed ART treatment. The objective was to compare the relative concentrations of cell-free DNA in the luteal phase sera of nonpregnant versus pregnant patients. METHODS: Frozen-thawed sera (30 IVF cases) were obtained 1 week after embryo transfer. There were 16 pregnant and 14 nonpregnant cases and controls consisting of male sera (n = 8 cases). Modified isocratic capillary electrophoresis was performed and the images analyzed for cell-free DNA. RESULTS: Circulating cell-free DNA were identified in the sera of all patients. The serum concentrations of high (12 kb) and low (1 kb) molecular weight cell-free DNA were similar for both nonpregnant and pregnant patients. Male control sera had higher cell-free DNA concentrations compared with females. Evaluation of sera from a control case showed no fluctuations in cell-free DNA concentrations throughout specific days of the menstrual cycle. CONCLUSIONS: The results do not support the use of the luteal phase cell-free DNA concentration as a marker for failed pregnancies. The equal concentrations of high and low molecular weight cell-free DNA and ladder band-like gel patterns suggested cell apoptosis as the source of DNA.

Adult↗
PubMed1998

Effect of intramural, subserosal, and submucosal uterine fibroids on the outcome of assisted reproductive technology treatment.

OBJECTIVE: To investigate the effect of subserosal, intramural, and submucosal fibroids on the outcome of assisted reproductive technology (ART) treatment. DESIGN: A retrospective comparative study. SETTING: A tertiary referral center for infertility. PATIENT(S): Treatment outcome of 106 ART cycles in 88 patients with uterine fibroids (33 subserosal, 46 intramural without cavity distortion, and 9 submucosal) was compared with that of 318 ART cycles in age-matched patients without fibroids. INTERVENTION(S): Controlled ovarian hyperstimulation and ART. MAIN OUTCOME MEASURE(S): Findings on transvaginal uterine ultrasonography performed before the initiation of treatment and pregnancy and implantation rates. RESULT(S): The pregnancy rates per transfer were 34.1%, 16.4%, 10%, and 30.1% in the patients with subserosal fibroids, intramural fibroids, submucosal fibroids and no fibroids, respectively. The implantation rates were 15.1%, 6.4%, 4.3%, and 15.7%, respectively. Both rates were significantly lower in patients with intramural fibroids than in those with subserosal fibroids or no fibroids. CONCLUSION(S): Pregnancy and implantation rates were significantly lower in the groups of patients with intramural and submucosal fibroids, even when there was no deformation of the uterine cavity. Pregnancy and implantation rates were not influenced by the presence of subserosal fibroids. Surgical or medical treatment should be considered in infertile patients who have intramural and/or submucosal fibroids before resorting to ART treatment.

Adult↗
PubMed2006

A formal comparison of the practice of assisted reproductive technologies between Europe and the USA.

In this study, we compared pregnancy and delivery outcomes after the utilization of assisted reproductive technologies (ART) in Europe and the United States (US). ART outcomes were compared between Europe and the US for the year 2001, based on formal reports published by the European Society for Human Reproduction and Embryology (ESHRE) and the Center for Disease Control and Prevention (CDC) in collaboration with the American Society for Reproductive Medicine (ASRM) and Society for ART (SART). Europe utilizes ART at approximately twice the rate of the US (P < 0.001). United States patients showed a significantly decreased likelihood of reaching oocyte retrieval (P < 0.001) and embryo transfer (P < 0.001). Despite this lower chance of reaching oocyte retrievals and embryo transfers, US patients experienced significantly higher clinical pregnancy rates (P < 0.001) and delivery rates per started cycle (P < 0.001) than European patients. Amongst patients reaching oocyte retrieval, the difference in clinical pregnancy rates and live birth rates was even more pronounced in favour of the US. However, US patients received significantly more embryos per embryo transfer (P < 0.001) and experienced a significantly higher multiple pregnancy rate (P < 0.001). Significant differences in favour of US patients in pregnancy rates and live birth rates were also observed for frozen embryo cycles and oocyte donation cycles, where the difference was most pronounced. The better pregnancy and live birth outcomes in the US are not explainable by the transfer of larger embryo numbers alone.

Adult↗
PubMed1993

The relevance and use of mouse embryo bioassays for quality control in an assisted reproductive technology program.

OBJECTIVE: To define both the limits of a mouse embryo bioassay for quality control in an assisted reproductive technology (ART) program and the areas where it can be effectively used. DESIGN: Embryos at the pronuclear and two-cell stage from three different strains of mice were used to assess the effectiveness of this assay for media quality control using five different media routinely used in ART. Pronuclear and two-cell embryos from CD-1 mice were used to test the ability of a mouse embryo bioassay to control for water quality, contaminants in the culture system, and fluctuations in the environmental conditions using a medium, culture system, and scoring technique that were optimized for this strain. RESULTS: The mouse embryo bioassay is not effective in differentiating media appropriate for supporting human embryo development since the development of mouse embryos in vitro is strain, stage, and media related. However, CD-1 embryos were shown to be sensitive to variations in water quality, pH, temperature, incubator conditions, and contaminants in the system when grown in a protein-free medium optimized for their development. Both total blastocyst number and the cell count in the blastocysts were affected. Pronuclear embryos were more sensitive to perturbations in the culture system than two-cell embryos. CONCLUSIONS: A mouse embryo bioassay can be effectively used as a means of quality control of water, chemicals, and contact materials and for technique standardization and training in an assisted reproduction program. All the conditions of the test should be defined, pronuclear embryos should be used, and the end point should be fully expanded blastocysts and/or cell numbers in these blastocysts where appropriate.

Animals↗
PubMed2005

Factors affecting assisted reproductive technology (ART) pregnancy rates: a multivariate analysis.

PURPOSE: To determine factors instrumental in achieving a clinical pregnancy in assisted reproductive technology (ART) patients. METHODS: This study included 205 women undergoing their first ART cycle. Univariate and multivariate analyses were performed for patient demographics, in vitro production data, and factors associated with embryo transfer. Odds ratios (OR) were performed where appropriate. RESULTS: Our analyses indicated that age (OR: 0.879), specific year in which the cycle was performed (OR: 2.959), and use of intracytoplasmic sperm injection (OR: 2.867) altered potential pregnancy rate. In addition, percent fertilization (OR: 1.028), number of embryos transferred (OR: 1.842), type of catheter used to transfer the embryos (OR: 0.377), presence of blood on the catheter (OR .414), and embryologist (OR: 2.338) also altered pregnancy rate. CONCLUSIONS: Our data indicate patients' age, use of the Cook catheter, and presence of blood on the catheter reduce pregnancy rates. Performing ART in 1999, using ICSI, increasing fertilization rate, increasing number of embryos transferred (albeit less desirable when the chance of multiple gestation may occur), and transferring embryos via a particular embryologist, improve pregnancy rates.

Adult↗
PubMed2005

Assisted reproductive technologies (ART) in Canada: 2001 results from the Canadian ART Register.

OBJECTIVE: To present the success rates of assisted reproductive technologies (ART) cycles performed in 2001 in Canada. DESIGN: Retrospective cohort study. SETTING: Nineteen of 22 ART centers in Canada. PARTICIPANTS: Couples undergoing ART treatment in Canada during 2001. METHODS: Data on each ART cycle performed during 2001 were submitted electronically to the Canadian ART Register (CARTR) by participating centers. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth rate per cycle started, multiple birth rate. RESULT(S): A total of 7,884 ART cycles was reported to CARTR. There were 5,393 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles using the woman's own oocytes. Per cycle started, the pregnancy rate was 28.3%, and the live birth rate was 23.1%; the multiple birth rate per delivery was 32.8%. Of cycles with oocytes retrieved, IVF was performed in 44% and ICSI in 56%; the outcomes were similar with the two procedures. There were 301 IVF/ICSI cycles using donor oocytes. The pregnancy rate was 29.2%, and the live birth rate was 22.4%; the multiple birth rate was 43.5%. There were 1,936 frozen embryo transfer cycles using the woman's own oocytes. The pregnancy rate was 18.9%, and the live birth rate was 15.4%; the multiple birth rate was 24.9%. CONCLUSION(S): For 2001, CARTR achieved 86% voluntary participation from Canadian ART centers. Pregnancy and live birth rates comparable to those of other countries were achieved.

Adult↗
PubMed1996

A randomized clinical trial to evaluate the clinical effects of split- versus single-dose human menopausal gonadotropins in an assisted reproductive technology program.

OBJECTIVE: To compare the effect of twice (split) versus once (single) daily administration of hMG on assisted reproductive technology (ART) cycle parameters. DESIGN: A randomized clinical trial. SETTING: Hospital-based academic ART program. PATIENTS: A total of 171 patients undergoing their initial ART cycle were enrolled. All patients received one of two hMG regimens and were excluded from the study if they were receiving medications other than leuprolide acetate (LA) and hMG for ovulation induction. INTERVENTIONS: Subjects were randomized to receive an initial dose of 300 IU/d of hMG in either split-dose (i.e., 150 IU twice daily) or single-dose fashion for four successive days after down-regulation with LA. Thereafter, their daily dose was individualized, maintaining a split-or single-dose schedule. All cycles were managed in accordance with our standard ART protocols. MAIN OUTCOME MEASURES: Cancellation rate, total hMG requirements, number of days treated with hMG, E2 and P responses, oocyte yield and maturity, fertilization rate, total number of embryos, embryo quality, number of embryos transferred, implantation rate, clinical and ongoing-delivered pregnancy rates. RESULTS: Split-dose hMG administration resulted in a significantly higher implantation rate, but significantly lower normal and polyspermic fertilization rates than single-dose hMG administration. No significant differences were noted between the two dosage protocols with respect to the other outcome measures. CONCLUSIONS: Split-dose hMG administration may be associated with significantly higher implantation rates; single-dose hMG with significantly higher fertilization rates. Although our data also demonstrate a trend toward higher clinical and ongoing-delivered pregnancy rates with split-dose therapy, demonstration of a significant difference would require a multicenter trial. Based on our data, clinicians may want to consider split-dose therapy for patients with repeated implantation failures.

Adult↗
PubMed2004

Half-dose depot triptorelin in pituitary suppression for multiple ovarian stimulation in assisted reproduction technology: a randomized study.

BACKGROUND: Pituitary suppression by depot GnRH agonist may be excessive for ovarian stimulation in assisted reproduction technology. This study compares the efficacy of standard and half-dose depot triptorelin in a long protocol. METHODS: A total of 180 patients were randomized into two groups using sealed envelopes. Pituitary desensitization was obtained in group 1 (90 patients) with half-dose (1.87 mg) triptorelin depot in the mid-luteal phase of their menstrual cycle, and in group 2 (90 patients) with full-dose (3.75 mg) triptorelin. RESULTS: There was no premature LH surge, with LH levels being lower in the full-dose group (1.04+/-0.05 versus 0.7+/-0.06 IU/l on the day of hCG). The number of FSH ampoules used was lower in group 1 (42+/-2 versus 59+/-3). The numbers of mature oocytes (10.1+/-0.54 versus 7.4+/-0.55), of fertilized oocytes (8.24+/-0.35 versus 6.34+/-0.37) and of embryos (7.8+/-0.36 versus 5.9+/-0.37) were significantly higher in group 1. No significant differences were found in pregnancy (38.8 versus 25.3%), implantation (22.6 versus 13.8%) or abortion (6.1 versus 5.0%) rates. Cumulative pregnancy (fresh plus frozen embryo transfers: 56.8 versus 35.4%) rate was significantly higher in group 1. CONCLUSION: A half-dose of depot triptorelin can be successfully used in ovarian stimulation for IVF and produce a higher number of good quality embryos with a good chance of implantation.

Adult↗
PubMed1991

Severe ovarian hyperstimulation syndrome in assisted reproductive technology: definition of high risk groups.

In a retrospective analysis of 637 cycles of ovarian stimulation and transvaginal follicular aspiration for various assisted reproductive technologies, severe ovarian hyperstimulation syndrome (SOH) occurred in six (0.94%) cycles. The patients at a high risk of developing SOH in cycles of assisted reproduction were those who had excessive serum oestradiol levels on the day of human chorionic gonadotrophin (HCG) administration (oestradiol greater than 6000 pg/ml; 38% SOH) and a high number of oocytes obtained (greater than 30 oocytes; 23% SOH). In those patients with both oestradiol greater than 6000 pg/ml on the day of HCG administration and greater than 30 eggs retrieved, the chance of developing SOH was 80%. The higher the serum oestradiol levels and the more eggs retrieved, the higher the pregnancy rates observed. High oestradiol level did not appear to have a detrimental effect on pregnancy rates and outcome. Furthermore, our results are not consistent with suggestions that the addition of gonadotrophin-releasing hormone agonist to ovarian stimulation protocols, follicular aspiration and/or luteal support with progesterone may reduce the incidence of ovarian hyperstimulation syndrome.

Cell Count↗
PubMed2005

The 2004 Italian legislation regulating assisted reproduction technology: a multicentre survey on the results of IVF cycles.

BACKGROUND: The new Italian law, passed in 2004, regulating assisted reproduction technology imposes that no more than three oocytes can be fertilized at one time and that all embryos obtained must be transferred simultaneously. Oocyte cryopreservation is allowed while embryo cryostorage is banned. The aim of this study was to evaluate the clinical impact of these limitations. METHODS: Seven Italian infertility centres were invited to collect data on IVF cycles performed over the first 4 months of application of the new legislation. As a control, all centres provided data on cycles performed in the same solar period, 1 year before. RESULTS: Data from 1861 cycles were obtained, 961 in the pre-law period and 900 in the post-law period. Pregnancy rate per oocyte retrieval and rate of multiple pregnancies in the pre- and post-law periods were 27.0 and 24.2% (P=0.18) and 25.8 and 20.9% (P=0.11) respectively. However, the prohibition to freeze embryos does appear to have markedly reduced the cumulative rate of success. CONCLUSIONS: The rate of success of IVF-ICSI cycles using fresh embryos is not significantly influenced by the new legislation while the prohibition to freeze embryos seems to result in a more relevant impact.

Adult↗
PubMed2003

Spontaneous abortion among pregnancies conceived using assisted reproductive technology in the United States.

OBJECTIVE: To examine rates and risk factors for spontaneous abortion among pregnancies conceived using assisted reproductive technology (ART). METHODS: Subjects were 62,228 clinical pregnancies resulting from ART procedures initiated in 1996-1998 in US clinics. Spontaneous abortion was based on ART clinic report and was defined as loss of the entire pregnancy. Spontaneous abortion rates for ART pregnancies were compared with spontaneous abortion rates from the National Survey of Family Growth, a population-based survey of US women 15-44 years. RESULTS: The spontaneous abortion rate among ART pregnancies was 14.7%. This was similar to rates among pregnancies reported in the National Survey of Family Growth. Among pregnancies conceived with the patient's oocytes and freshly fertilized embryos, the spontaneous abortion risk ranged from 10.1% among women 20-29 years to 39.3% among women older than 43. Spontaneous abortion risk among pregnancies conceived with donor eggs was 13.1% with little variation by patient age. Spontaneous abortion risk was increased for pregnancies conceived with frozen and thawed embryos and decreased among multiple-gestation pregnancies. Spontaneous abortion risk was increased among women reporting previous spontaneous abortions and ART attempts, and among women who used clomiphene or zygote intrafallopian transfer. Pregnancies conceived by young women, but gestated by a surrogate, were at increased risk for spontaneous abortion in comparison with young women who gestated their own pregnancies. CONCLUSION: These findings suggest that ART does not pose a risk for spontaneous abortion. Factors related to oocyte or embryo quality are of primary importance in assessing spontaneous abortion risk.

Abortion, Spontaneous↗
PubMed1993

Stimulation regimens in Assisted Reproductive Technology (ART) programme: experience in the University Hospital, Singapore.

Ovarian stimulation is critical to the success of patients in Assisted Reproductive Technology (ART) programmes. We compared two stimulation regimes retrospectively for ART in the NUH programme. These were the 2:1 and the GnRHa-FSH/hMG regimes. The former was our first-line regime while the latter was used for cycles where there was a prior endogenous LH surge, previous poor response, or an elevated LH level between days three to five of the cycle. All cycles in our ART programme in 1991 were studied, except those for special research procedures, e.g. micro-insemination sperm transfer (MIST) cycles, a total of 241 cycles. Cancellation rates were 14.4% (21 of 146 cycles) and 37.3% (19 of 51 cycles) for the 2:1 and GnRHa-FSH/hMG regimes respectively (p > 0.001). For the 2:1 regime, the majority of cancellations were due to ovulation prior to the oocyte recovery (42.9%; nine of 21 cycles). However, for the GnRHa-FSH/hMG regime, almost all the cancellations were due to poor response (84.2%; 16 of 19 cycles). Fertilisation rates were lower for the 2:1 regime (for both IVF-ER and IVF-TET, where sperm quality was poorer) compared to the GnRHa-FSH/hMG (55.0 and 66.6% respectively; p < 0.001). Pregnancy rates were higher for the 2:1 regime when IVF-ER and IVF-TET were used (16.4% and 23.3% respectively per oocyte recovery, versus 9.8% and 18.8% respectively for the GnRHa-FSH/hMG regime).

Drug Evaluation↗