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Prevention of scrapie transmission in sheep, using embryo transfer.

Reciprocal embryo transfers were made between scrapie-inoculated and scrapie-free sheep (Cheviot and Suffolk breeds) to measure scrapie transmission via the embryo (using offspring from embryos of scrapie-inoculated donors and scrapie-free recipients) and via the uterus (using offspring from embryos of scrapie-free donors and scrapie-inoculated recipients taken by cesarean section). Two control groups of offspring, 1 from scrapie-free parents (negative) and 1 from scrapie-inoculated parents (positive), also were included. All sheep were observed for clinical signs of scrapie until death or for a minimum of 60 months. Final diagnosis was made on the basis of histopathologic findings or results of mouse inoculation and/or proteinase-K-resistant protein analysis. Thirty to 61% of the scrapie-inoculated donor/recipient sheep within groups developed scrapie within 8 to 44 months after inoculation. None of the scrapie-free donor/recipients, including those gestating embryos from scrapie-inoculated donors, developed scrapie. Also, none of the offspring observed to > or = 24 months of age from reciprocal cross, via embryo (0/67), or via the uterus (0/25), or from the negative-control group (0/33) developed scrapie. Fifty-six of the offspring via embryo, 19 of these via the uterus, and 31 negative controls survived to > or = 60 months of age. Of the 21 sheep in the positive-control group, 2 (9.5%) developed scrapie, 1 at 31 months of age and 1 at 42 months of age. In the Cheviot offspring, the percentage of sheep carrying the short incubation allele ranged from 24 to 44% and the percentage in the Suffolk offspring ranged from 61 to 83%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The presence of blood in the transfer catheter negatively influences outcome at embryo transfer.

BACKGROUND: Embryo transfer (ET) influences pregnancy rates in patients undergoing assisted reproduction. Data are conflicting as to which variables affect ET success. This study examines variables that may affect outcome after ET in assisted reproductive technology patients who had high-quality embryos transferred. METHODS: Over a 23 month period, 669 consecutive cycles were examined. Only patients having grade I and grade II embryos, or blastocyst transfers, were included in this retrospective analysis. A total of 584 consecutive cycles met study criteria. At the time of ET, the following variables were recorded: aborted first attempt at ET; presence of blood and/or mucus in or on the transfer catheter after ET; ease of ET as judged by provider; need for mock embryo transfer immediately before the actual transfer and retention of embryos in the transfer catheter. These variables were retrospectively analysed for their impact on implantation rate (IR) and clinical pregnancy rate (CPR). RESULTS: There were 290 gestations (49.7% CPR). Multiple attempts at ET, subjective difficulty of ET, performance of a sham pass immediately prior to embryo transfer, and presence of mucus on or in the catheter did not affect the CPR or IR. No difference was noted in the mean age of patients having or lacking any of these factors. There was a significant association between the presence of blood on or in the catheter and decreased IR (P = 0.015) and CPR (P = 0.004). Retained embryos also decreased IR (P = 0.03). Multivariable analysis confirmed that the presence of blood on the transfer catheter was the most important of these transfer characteristics in predicting IR (P = 0.042) and CPR (P = 0.018). CONCLUSIONS: These results suggest that when only high-grade embryos or blastocysts are transferred, the presence of blood on the catheter is associated with decreased IR and CPR in assisted reproduction.

Adult↗

Ovarian stimulation in women undergoing in-vitro fertilization and embryo transfer using recombinant human follicle stimulating hormone (Gonal-F) in non-down-regulated cycles.

In order to assess the efficacy and safety of recombinant human follicle stimulating hormone (FSH) in routine clinical use, ovarian stimulation with recombinant human FSH was performed in 71 patients prior to in-vitro fertilization (IVF) without gonadotrophin-releasing hormone (GnRH) analogues in a multicentre, non-comparative study. Human chorionic gonadotrophin (HCG) was administered to 58 patients (81.7%), 15 of whom underwent 19 cycles with an initial dosage of three ampoules daily of recombinant FSH and 43 of whom underwent 152 cycles with four ampoules daily from day 3 onwards. No significant differences were detected between these two groups in all test parameters. The mean duration of treatment was 9.06 and 8.86 days respectively with a mean number of 24.06 and 23.25 vials of recombinant human FSH administered. A mean number of 6.26 and 5.88 oocytes respectively was collected. The number of transferred embryos was 2.4 and 2.2. A clinical pregnancy rate of 23.8% (10 out of 42) per transfer was achieved (30.9 and 20.6% respectively). Local tolerance of s.c. administration was excellent. Mild pain at the injection site was the dominant finding in < 20% of patients. Two cases of ovarian hyperstimulation syndrome were noted. Recombinant human FSH is very attractive to patients because it can be self-administered s.c. and the preparation does not come from a human source. In conclusion, these data support the safety and efficacy of recombinant human FSH in routine use for IVF.

Adolescent↗

Successful nonsurgical deep uterine embryo transfer in pigs.

At present, it is possible to transfer pig embryos directly into the uterine body of sows by nonsurgical procedures. The aim of this study was to develop a procedure for nonsurgical embryo transfer (ET) into the upper part of one uterine horn in gilts and sows. In experiment 1, 29 gilts and 43 sows were used. Intrauterine insertions took place for each female at days 4-6 of the estrous cycle (D0 = onset of estrus). An artificial insemination (AI) spirette was inserted into the cervix to assist with the guidance of a modified flexible catheter originally developed for deep intrauterine insemination in pigs. The flexible catheter length inserted anterior to the inserted AI spirette was 43.0 +/- 1.7 cm. The time required to complete the procedure was affected by the type of female (P < 0.001) and by the difficulties encountered for inserting the catheter (P < 0.001). However, when no or minor difficulties were encountered during the insertion of the catheter (in approximately 70 and 80% of gilts and sows, respectively), the time required to complete the procedure did not differ between gilts (2.5 +/- 0.1 min) and sows (2.3 +/- 0.1 min). In experiment 2, 24 to 31 fresh morulae and/or blastocysts were transferred to each of 24 recipients. Seventeen animals (70.8%) farrowed an average of 6.9 +/- 0.7 piglets, of which 0.6 +/- 0.3 piglets were born dead. In conclusion, the procedure described in this study offers new possibilities to transfer embryos nonsurgically to the uterine horn of pigs.

Animals↗

Intravenous immunoglobulin preceding in vitro fertilization-embryo transfer for patients with repeated failure of embryo transfer.

OBJECTIVE: To determine the effectiveness of immunotherapy with high-dose IV immunoglobulin preceding IVF-ET for patients with repeated failure of ET. DESIGN: Prospective, observational. SETTING: Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona, a tertiary care setting. PATIENTS: Twelve consecutive tubal infertility patients experiencing repeated unexplained IVF-ET failure including at least three ETs replacing three to four fresh embryos each. Two women shared three or more human leukocyte antigens (HLA) with the husband. INTERVENTION: During the subsequent new IVF-ET cycle, each patient received 400 mg/kg IV immunoglobulin daily for 5 days during ovarian stimulation, that is, 5 to 7 days before ET. MAIN OUTCOME MEASURES: Clinical pregnancies. RESULTS: No implantation occurred. There were no side effects. CONCLUSIONS: High-dose IV immunoglobulin is not a useful tool for IVF-ET failure.

Adult↗

Treatment with piroxicam before embryo transfer increases the pregnancy rate after in vitro fertilization and embryo transfer.

OBJECTIVE: To examine the effect of beta-cyclodextrin piroxicam treatment for priming of the uterus on the pregnancy outcome of IVF-embryo transfer (ET) programs. DESIGN: Prospective, randomized, double-blinded placebo-controlled clinical study. SETTING: Large urban medical center. PATIENT(S): One hundred eighty-eight consecutive cycles of fresh IVF-ET and 78 cycles of frozen-thawed ET. The patients underwent IVF because of tubal, male infertility, unexplained, or endometriosis factors. They were randomly divided into treatment and control groups. INTERVENTION(S): In the treatment group, 94 cycles in fresh ET and 39 cycles in frozen-thawed ET the patients received an oral dose of 10 mg of piroxicam. In the control group, the same number cycles corresponding to the treatment group were treated with placebo. Both groups started piroxicam or placebo treatment 1-2 hours before ET. Patients and staff were blinded to the treatment. MAIN OUTCOME MEASURE(S): Implantation rate (IR) and pregnancy rate (PR). RESULT(S): Piroxicam increased significantly IR (18.7%) and PR (46.8%) compared to the control group (8.6% and 27.6%, respectively) in fresh cycles. With the exception of an unexplained factor, patients with the tubal, male infertility, or endometriosis factor had significantly higher PR in the treatment group compared to the control group. The beneficial effect of piroxicam was found in patients less than 40 years old, but was not found in patients more than 40 years. In frozen-thawed cycles, there were statistically significant differences between the treatment group and the control group in IR (9.4% vs. 2.3%) and PR (25.6% vs. 7.7%), respectively. CONCLUSION(S): Our study showed that piroxicam increases IR and PR after IVF-ET in both fresh and frozen-thawed ET cycles. The beneficial effect seems to be more remarkable in patients less than 40 years old with tubal, male infertility, or endometriosis factors. These results suggest that piroxicam treatment before ET is very effective in the priming of a uterus suitable for embryo implantation. This is the first study to investigate the possible consequence of piroxicam for improving the PR after IVF-ET.

Adult↗

Genetic aspects of embryo transfer.

Use of embryo transfer can lead to increases in rates of genetic improvement from selection programs from as little as 5% to a maximum of near 100%, depending on species, trait, and extent of use of other tools such as A.I. In general, embryo transfer will have much less impact on rates of genetic improvement than A.I., and in a dairy cattle program where A.I. is used effectively, embryo transfer is likely to add less than 10% to rate of genetic improvement. The potential for increasing rate of genetic improvement appears to be greater in beef cattle. In any species with low reproductive rate, embryo transfer offers a potential means of rapidly increasing numbers of animals of a breed, strain, mutant genotype or group exceeding a stringent threshold; such use may be of considerable value to a specific genetic research or multiplication program. Maximizing selection intensity through combined use of A.I. and embryo transfer can lead to a rapid increase in inbreeding, and steps should be taken to avoid this in any population which it is desired to maintain in the long term. Embryo transfer offers an effective tool for research on maternal-fetal and fetal-fetal interactions, and in this way can make important indirect contributions to more efficient breeding programs. With improved embryo storage capability, embryo transfer has the potential for useful contributions in the areas of transfer of germ plasm between countries, preservation of rare breeds, and provision of genetically stable control populations.

Journal Article↗

Technical note: porcine non-surgical embryo transfer.

The cervix is a barrier for transferring porcine embryos non-surgically. A non-surgical embryo transfer instrument composed of four parts has been developed that allows the delivery of embryos into the lumen of one uterine horn. Part 1, a modified artificial insemination spirette, is used to produce a cervical lock and to assist in manipulating Part 2 through the cervix. Part 2 is made of stainless steel tubing with a unique curved tip that can be manipulated through the folds of the cervix. Part 3 is a testing bar to ensure that the tip of Part 2 reaches the bifurcation of the uterus. Part 4, a disposable tubing complex for embryo delivery, is composed of a soft plastic leader tubing, a double opened connector for embryo loading and unloading, a semi-hard plastic tubing, and a hard tubing with a water-sealable plunger. Embryos (4-cell to blastocyst stages) were surgically collected and maintained in vitro up to 5 h before the non-surgical embryo transfer. Five of 16 recipients became pregnant (31%) and farrowed an average of 6.2 +/- 3.1 pigs per litter. This easily learned non-surgical embryo transfer technique will simplify embryo transfer in the swine industry and may lead to improvements in swine breeding and scientific research.

Animals↗

Blood on the embryo transfer catheter is associated with decreased rates of embryo implantation and clinical pregnancy with the use of in vitro fertilization-embryo transfer.

OBJECTIVE: To examine the relation between blood found on the transfer catheter after ET and the rates of embryo implantation and clinical pregnancy with the use of IVF-ET. DESIGN: Retrospective cohort study. SETTING: A tertiary care center for assisted reproductive technology. PATIENT(S): Three hundred seven couples who underwent 354 ETs between January 1, 1994, and June 30, 1996. INTERVENTION(S): A semiquantitative system for recording the amount of blood found inside and outside the transfer catheter after ET. MAIN OUTCOME MEASURE(S): Embryo implantation rate and clinical pregnancy rate (PR). RESULT(S): Blood found outside the transfer catheter after ET was associated with decreased rates of embryo implantation and clinical pregnancy. In contrast, blood located inside the transfer catheter after ET, the type of catheter used for ET, the number of transfer attempts, and the time required for ET did not significantly affect either the embryo implantation rate or the clinical PR. CONCLUSION(S): Blood found outside, but not inside, the transfer catheter after ET is associated with lower rates of embryo implantation and clinical pregnancy with the use of IVF-ET. An emphasis on atraumatic transfer techniques, with prevention of bleeding at the time of ET, should contribute to improved pregnancy outcome with the use of IVF-ET.

Catheterization↗

Treatment of patients with unexplained infertility: gamete intrafallopian transfer (GIFT) versus tubal embryo transfer (TET).

This study compares the results of 65 cycles of gamete intrafallopian transfer (GIFT), and 19 cycles of tubal embryo transfer (TET) in couples with unexplained infertility (UI). Oocyte retrievals were carried out by laparoscopy in GIFT and transvaginally in TET, in which the embryos were transferred by laparoscopy into the fallopian tubes 48 hours later. The mean age, duration of infertility, serum estradiol levels on the day of human chorionic gonadotropin administration, number of large follicles (mean diameter greater than 10 mm) and the number of oocytes recovered were similar between these two groups. From the 65 GIFT cycles, 20 clinical pregnancies resulted (30.8%). From the 19 cycles of TET, 10 conceptions occurred (52.6%). The implantation and pregnancy rates after TET were higher than that after GIFT, but the differences were not statistically significant. The data suggest that GIFT has a similar success rate to TET in couples with UI.

Adult↗

Mock embryo transfer in early luteal phase, the cycle before in vitro fertilization and embryo transfer: a descriptive study.

OBJECTIVE: To investigate visually the uterine retention or sequestration of boluses of radiopaque dye, mimicking embryo transfer (ET). DESIGN: During the cycle before in vitro fertilization (IVF) and ET, patients underwent a mock ET of 40 microL of radiopaque dye into the uterine cavity. The patient was positioned supine for retroverted or axial and knee chest for anteverted uteri. The position of the dye at injection, during and after catheter removal, and during patient roll over and standing was monitored. SETTING: Treatment of infertility in a private practice. PATIENTS: Thirty-four IVF patients. INTERVENTIONS: During the cycle before IVF/ET, patients underwent a mock ET using a bolus of 40 microL of radiopaque dye. MAIN OUTCOME MEASURES: Planned before visual observation began. RESULTS: The dye remained primarily in the uterine cavity in only 68% (optimum ET position is knee chest for anteverted and supine for retroverted or axial uterus) and 48% (nonoptimum position is supine for anteverted uterus) at mock ET; in those groups, a 33% clinical pregnancy rate (PR) per retrieval resulted. Dye motility into the fallopian tube(s), cervix, and/or vagina is 38.2%, 8.8%, and 11.8%, respectively. CONCLUSIONS: If the mock ET had been the actual ET, 32% (optimum ET position) and 52% (nonoptimum ET position) of all patients would have lost their opportunity for pregnancy as a result of the ET procedure. Our 33% PR per retrieval among those patients who retained the dye in utero is more consistent with our expectations, given the advanced technologies of IVF/ET today.

Embryo Transfer↗

The role of gamete intrafallopian transfer (GIFT) and tubal embryo transfer (TET) in the treatment of patients with patent tubes associated with male infertility factor.

PURPOSE: The relative effectiveness of gamete intrafallopian transfer (GIFT) and tubal embryo transfer (TET) combined with superovulation in the treatment of infertile patients with patent tubes were compared. Four hundred fifty consecutive cycles were divided into two periods. During the first period (216 cycles), the only technique employed was GIFT, couples being divided into two groups: group A, couples with normospermic partners (118 cycles); and group B, couples with male infertility factor (98 cycles). During the second period (234 cycles), 140 cycles of GIFT were performed in couples with normospermic partners (group C). TET was utilized in 94 cycles (group D), in the case of couples with male infertility factor. RESULTS: Results demonstrate that the pregnancy rate with GIFT in the case of oligoasthenospermic partners (group B) is significantly lower than that of normospermic partners (groups A and C) (P = 0.0001) and than that with TET in the case of oligoasthenospermic partners (group D) (P = 0.0001). CONCLUSION: The implantation rate is also significantly different between these groups (B vs A, P = 0.0001; B vs C, P = 0.0001; B vs D, P = 0.01).

Embryo Transfer↗

Blastocyst-stage embryo transfer in patients who failed to conceive in three or more day 2-3 embryo transfer cycles: a prospective, randomized study.

OBJECTIVE: To compare blastocyst-stage embryo transfers (ETs) with day 2-3 ETs in patients who failed to conceive in three or more day 2-3 IVF/ET cycles. DESIGN: Prospective, randomized. SETTING: Fertility unit in a university medical center. PATIENT(S): Fifty-four patients with an adequate ovarian response underwent oocyte retrievals. The patients were prospectively and randomly divided into blastocyst-stage and day 2-3 ET groups. INTERVENTION(S): Ovarian down-regulation was obtained using GnRH agonist, and controlled ovarian hyperstimulation was achieved using daily administration of gonadotropins. MAIN OUTCOME MEASURE(S): The rate of blastocyst formation, ET cancellations, pregnancies, implantation, multiple gestation, and live births. RESULT(S): The clinical pregnancy rates per oocyte retrieval were 21.7% and 12.9% per blastocyst and day 2-3 ETs, respectively. Although there was a significantly higher implantation rate for blastocyst embryos (21.2%) as compared with 48- to 72-hour embryos (6%), the multiple-pregnancy rate was not significantly different between both groups. An ET cancellation rate of 26% and 6.4% for blastocyst and day 2-3 ETs, respectively, was observed. The presence of two or more 8-cell embryos on day 3 in culture carried a high probability of obtaining blastocysts for transfer. CONCLUSION(S): This prospective randomized study suggests that in patients with an adequate ovarian response who failed to conceive in at least three IVF/ET cycles [1]. transfer of blastocyst-stage embryos carries a significantly higher implantation rate; [2]. the pregnancy rate per oocyte retrieval and ET are higher in the blastocyst-stage group, even if it did not reach statistical significance; [3]. a higher ET cancellation rate was observed in the whole blastocyst-stage group; [4]. the ET cancellation rate was reduced significantly if the decision to proceed to blastocyst transfer was made on day 3 after oocyte retrieval, which is a post hoc conclusion.

Birth Rate↗

Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial.

BACKGROUND: Twin pregnancies after IVF are still frequent and are considered high-risk pregnancies leading to high costs. Transferring one embryo can reduce the twin pregnancy rate. We compared cost-effectiveness of one fresh cycle elective single embryo transfer (eSET) versus one fresh cycle double embryo transfer (DET) in an unselected patient population. METHODS: Patients starting their first IVF cycle were randomized between eSET and DET. Societal costs per couple were determined empirically, from hormonal stimulation up to 42 weeks after embryo transfer. An incremental cost-effectiveness ratio (ICER) was calculated, representing additional costs per successful pregnancy. RESULTS: Successful pregnancy rates were 20.8% for eSET and 39.6% for DET. Societal costs per couple were significantly lower after eSET (7334 euro) compared with DET (10,924 euro). The ICER of DET compared with eSET was 19,096 euro, meaning that each additional successful pregnancy in the DET group will cost 19,096 euro extra. CONCLUSIONS: One cycle eSET was less expensive, but also less effective compared to one cycle DET. It depends on the society's willingness to pay for one extra successful pregnancy, whether one cycle DET is preferred from a cost-effectiveness point of view.

Adult↗