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A review of the epidemiologic aspects of embryo transfer from Brucella abortus -infected cows.

Available information on the epidemiologic aspects of embryo transfer from Brucella -infected cattle is reviewed to provide a knowledgeable perspective upon which the risk of transmission of this agent by the embryo can be assessed. Accumulated evidence indicates that exposure of preimplantation embryos to Brucella abortus in the uteri of superovulated, infected cows is unlikely. Further, it has been shown that embryo-washing procedures insure freedom from B. abortus even without antibiotics. The use of antibiotics with the proper cryoprotectant provides additional insurance that Brucella will not be transferred with frozen-thawed embryos. Four hundred fifteen (415) ova collected in 74 nonsurgical recoveries from Brucella -infected cows were culture-negative when examined for the presence of Brucella . After reviewing studies conducted on embryo transfer from Brucella abortus -infected cows, the authors conclude that B. abortus will not be transmitted when emphasis is placed on proper handling of embryos between collection from donors and transfer to recipients.

Journal Article↗

Evidence that specific cellular immunity cannot account for death of Mus caroli embryos transferred to Mus musculus with severe combined immune deficiency disease.

Mus caroli blastocysts transferred to pseudopregnant Mus musculus implant but die about midgestation. Death of the M caroli embryos is associated with infiltration of the fetoplacental units by M musculus lymphocytes, including functional cytotoxic T lymphocytes (CTL). To determine if specific maternal antifetal immune responses are responsible for the initiation of M caroli failure, survival of M caroli embryos transferred to M musculus with severe combined immune deficiency disease (SCID) was studied. C.B.-17 scid mice, homozygous for the scid gene, are reported to be unresponsive to T cell or B cell mitogens and to alloantigens. We have evaluated responses of C.B.-17 scid mice to M caroli xenoantigens in vivo and in vitro. C.B.-17 scid fail to reject M caroli skin grafts, and their spleen cells do not proliferate when mixed with M caroli splenocytes in a 1-way mixed leukocyte culture. Further, neither primary nor secondary challenge of C.B.-17 scid footpads with M caroli splenocytes elicits a delayed-type hypersensitivity (DTH) response. These results suggest that C.B.-17 scid mice are unable to recognize or respond specifically to M caroli xenoantigens. M caroli embryos transferred to C.B.-17 scid mice implant but fail to survive while cotransferred M musculus embryos are normal. Histologic examination of resorbing embryos revealed granulocytes, macrophages, large granular lymphocytes, but very few small lymphocytes at the implantation sites. Thus, it appears that specific maternal antifetal immune responses are not responsible for initiation of M caroli embryo failure in the M musculus uterus. These studies also indicate that efficient resorption of embryos does not require the function of T cells or B cells.

Animals↗

What is the most relevant standard of success in assisted reproduction? Redefining success in the context of elective single embryo transfer: evidence, intuition and financial reality.

Treatment-related multiple pregnancy poses the biggest threat to the safety of IVF. Despite a double embryo transfer (DET) policy in most European centres, twin rates continue to be unacceptably high, at 20-35%. Elective single embryo transfer (SET) is an effective way to minimize twin pregnancies, but the debate surrounding its routine clinical use continues. A review of the literature was undertaken in order to seek evidence about the effectiveness of SET, and identify barriers to its acceptance in clinical practice. Data from randomized controlled trials (RCTs) indicate that SET results in lower live birth rates per fresh IVF cycle (odds ratio 0.53; 95% confidence interval 0.31-0.89; P = 0.02) in comparison with DET. Data on cumulative live birth rates are unavailable from RCTs, although the expectation is that these are comparable in the two groups. SET is unlikely to be suitable for all women undergoing IVF and outcomes may be sensitive to different laboratory protocols. The perceived effectiveness of SET is influenced by the way existing evidence is interpreted. Other factors affecting the routine use of SET include laboratory techniques, individual preferences and funding issues.

Embryo Transfer↗

Subendometrial-myometrial contractility in conception and non-conception embryo transfer cycles.

This study describes the characteristics of subendometrial-myometrial contractions seen on transvaginal sonography on the day of embryo transfer in assisted conception cycles and their significance for pregnancy outcome.A total of 112 cycles were studied where three embryos with minimal or no fragmentation were transferred. Transvaginal sonography was performed just prior to embryo transfer. A sagittal view of the uterine cavity was obtained and the ultrasound probe was held steady for 2 min. The video recorded image was analyzed at normal, three and five times normal speed. The frequency (contractions/min), direction (fundally or cervically directed) and length (entire cavity or localized) of contractions were noted. Conception and non-conception cycles were compared by determining the standard error of difference between means and proportions and the confidence intervals. The mean frequencies of contractions in the conception and non-conception cycles were 2.09 (SD = 0.8) and 1.92 (SD = 0.85), respectively. A total of 57.6% of cycles in the conception group and 46% in the non-conception group had contractions directed towards the cervix. There was no statistically significant difference between the two groups in any of the parameters studied. However, when frozen embryo replacement cycles (n = 40) were studied separately, the incidences of fundally directed contractions were 28.6% and 66.7% in conception and non-conception cycles, respectively. This was statistically significant. Comparison of cycles resulting in miscarriage with those leading to pregnancies beyond 16 weeks revealed no statistical difference in the characteristics of the contractions. We concluded that subendometrial-myometrial contractions studied on the day of embryo transfer (luteal day 2) do not predict the outcome in in vitro fertilization cycles.

Journal Article↗

The influence of the number of embryos transferred in 1060 in-vitro fertilization pregnancies on miscarriage rates and pregnancy outcome.

To assess the incidence of miscarriage, multiple pregnancy and outcome of pregnancy in relation to the number of embryos transferred during in-vitro fertilization (IVF), an analysis was performed of 1060 pregnancies conceived in a tertiary-referral IVF clinic. There was no difference in the miscarriage rate after transfer of one or two embryos (37.7% and 34.6%), or after three or four embryos (22.5% and 25.2%). The miscarriage rate was, however, higher when one or two embryos were transferred compared with three (P < 0.01) or four embryos (P < 0.02). Of the 724 ongoing pregnancies, 524 (72.3%) were singleton, 164 (22.7%) twin, 33 (4.6%) triplet and three (0.4%) quadruplet. The mean (+/- SD) ages of women with singleton, twin, triplet and quadruplet pregnancies were 32.5 (+/- 3.8), 32.0 (+/- 3.5), 29.76 (+/- 4.3) and 29.67 (+/- 2.5) years respectively. The mean age of women with singleton and twin pregnancies was similar and both were greater than that of triplet pregnancies (P < 0.007). The overall perinatal mortality rate (PNMR) was 39.7/1000. The PNMR for singletons was 17.2/1000, for twins 80.0/1000 and for triplets 30.6/1000. All of the babies from the three quadruplet pregnancies survived. There were more babies lost in the twin pregnancies than any other group, although this only reached significance for singletons versus twins (P < 0.00005). We conclude that the incidence of miscarriage is increased in women in whom one or two embryos are transferred. Multiple pregnancies are more likely to occur in younger women and are associated with a significantly higher rate of perinatal mortality.

Abortion, Spontaneous↗

Determinants of multiple pregnancies in in vitro fertilization other than number of transferred embryos.

The aim of this study is to assess the many different parameters involved in the incidence of multiple pregnancies, such as maternal age, stimulation, endometrium, receptivity and the quality of the transferred embryos. During a 3.5 year period, 86 pregnancies were recorded in our IVF unit. A single gestational sac was identified by early ultrasonography in 67 patients, while in 19 others, multiple sacs were noted. Patient characteristics, treatment cycles and embryology results were similar in the two groups. When the number of transferred embryos was kept similar in both groups, EIR was found to be a valuable prognostic determinant for multiple pregnancies in IVF.

Abortion, Spontaneous↗

The relationship of tubal blockage, infertility of unknown cause, suspected male infertility, and endometriosis to success of in vitro fertilization and embryo transfer.

The success of in vitro fertilization (IVF) and embryo transfer has been examined with regard to five categories of infertility over a 2-year period. Fertilization rates in vitro were highest in women with bilateral tubal blockage and women treated for endometriosis. There was a significant reduction of approximately 13% in the fertilization rate of couples with idiopathic infertility and women who had failed to conceive after 12 cycles of artificial insemination by donor. A further substantial reduction in the fertilization rate occurred when the husband had low quality semen, particularly when no abnormality was detected in the wife. Repeated IVF in couples with idiopathic infertility eventually resulted in fertilization. It is recommended that donor spermatozoa not be used for cases of idiopathic infertility, but it may be needed in cases of poor semen quality. There were no differences in the pregnancy rates following embryo replacement in any of the groups studied, nor was there any detectable effect of age on fertilization or pregnancy rates up to the age of 44 years.

Adult↗

Sonographic diagnosis of triplet tubal pregnancy after in vitro fertilization and embryo transfer.

Ectopic pregnancy (EP) after in vitro fertilization and embryo transfer (IVF/ET) is not rare, but triplet tubal pregnancy after IVF/ET is very rare. We describe a patient with hydrosalpinx in whom a triplet tubal pregnancy occurred on the same side as the hydrosalpinx. Close hormonal and sonographic monitoring of pregnancies achieved through IVF is recommended to ensure the early diagnosis of EP and to avert complications. A triplet tubal EP was considered highly probable after 3 gestational sacs were observed outside the uterus during sonography performed at 6 weeks' gestation. Therapeutic laparoscopy was then performed because methotrexate treatment failed. Appropriate management strategies are discussed.

Adult↗

Successful pregnancy rates achieved with day 4 embryo transfers.

OBJECTIVE: To assess the success of day 4 embryo transfers (ETs) following IVF at one institution. DESIGN: Retrospective analysis. SETTING: A university hospital IVF program. PATIENT(S): Two hundred nondonor, fresh IVF cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE: Outcomes of IVF. Outcome assessments after day 4 ETs included rates of implantation, clinical pregnancy, and singleton and multiple live births. RESULT(S): The overall live-birth rate was 54.4%. Implantation rates were highest in younger age groups, and similar in patients 35-40 years of age. Pregnancy and live-birth rates were similar across all age groups up to age 40 years. Multiple gestations were highest in women < or =40 years of age. CONCLUSION: Acceptable pregnancy rates can be achieved with day 4 ETs.

Adult↗

Embryo transfer technique as a cause of ectopic pregnancies in in vitro fertilization.

Against an overall risk of around 2% ectopic pregnancies in in vitro fertilization programs around the world, we report an incidence more than three times greater (5 tubal ectopic pregnancies in 80 clinical in vitro fertilization pregnancies). Of two techniques used for embryo transfers, one produced a significantly higher risk for ectopic pregnancy (P less than 0.05). Four of the ectopic pregnancies occurred in a small group of 24 patients in whom the embryo transfer technique attempted to deliver the embryos at the uterine fundus (mean distance of catheter insertion 62.9 +/- 7.9 mm from the external cervical os). Only one ectopic pregnancy occurred in 56 patients whose embryos were transferred to a standard, generally midcavity position. It is concluded that the delivery catheter need be inserted only 55 mm as a routine and less in patients with a shortened cervix or with the hypoplastic uterus usually encountered in women with primary ovarian failure who have ovum or embryo donation. In such cases an ultrasonic measurement of length may indicate that a shorter transfer distance is required.

Animals↗

Salpingitis or oophoritis: what causes fever following oocyte aspiration and embryo transfer?

BACKGROUND: Febrile morbidity following in vitro fertilization and embryo transfer (IVF-ET) is a rare but possibly serious complication. This report describes a case of salpingitis after IVF-ET and discusses the possible reasons for febrile morbidity following this common procedure. CASE: A 37-year-old woman undergoing IVF-ET for tubal factor infertility developed sudden, severe pelvic pain, fever, and leukocytosis 24 hours after ET. Laparoscopy revealed bilateral suppurative pyosalpinges with cystic, hemorrhagic ovaries. Pain, fever, and leukocytosis resolved with conservative surgery and intravenous antibiotic therapy. CONCLUSIONS: This case presents laparoscopic documentation of a rare complication of oocyte aspiration and/or ET, namely, salpingitis. Possibilities for the development of salpingitis following IVF-ET include activation of quiescent bacteria within the fallopian tubes from a previous pelvic infection, puncture of the bowel during oocyte aspiration, inoculation of the pelvis with cervicovaginal flora during oocyte aspiration, and introduction of bacteria-laden secretions or air into the fallopian tubes during ET. Although rare, the possibility of severe pelvic infection following IVF-ET warrants consideration of prophylactic antibiotic coverage.

Adult↗

Treatment-independent, treatment-associated, and pregnancies after additional therapy in a program of in vitro fertilization and embryo transfer.

Although the technique of in vitro fertilization and embryo transfer (IVF-ET) was developed for couples with untreatable tubal factor infertility, IVF-ET is now being applied to women with other causes of infertility and normal pelvic anatomy. In an effort to determine the treatment-independent pregnancy rate, we retrospectively reviewed the first 245 couples enrolled in the IVF-ET program at Duke University Medical Center. There were 19 treatment-independent pregnancies in 18 women and 3 treatment-associated pregnancies in cycles in which the oocyte retrieval was canceled (in 2 women washed intrauterine insemination was substituted for oocyte retrieval). Six pregnancies were established after an unsuccessful attempt at IVF-ET with additional non-IVF-ET therapy, including washed intrauterine insemination in three couples, and donor insemination in two couples. These observations suggest that a significant number of treatment-independent pregnancies will occur in couples clinically deemed appropriate for IVF-ET, pregnancies can be established in cycles of controlled hyperstimulation without oocyte retrieval, and additional non-IVF-ET therapy can result in pregnancy despite failure of IVF-ET in selected couples.

Adult↗

Single embryo transfer and IVF/ICSI outcome: a balanced appraisal.

This review considers the value of single embryo transfer (SET) to prevent multiple pregnancies (MP) after IVF/ICSI. The incidence of MP (twins and higher order pregnancies) after IVF/ICSI is much higher (approximately 30%) than after natural conception (approximately 1%). Approximately half of all the neonates are multiples. The obstetric, neonatal and long-term consequences for the health of these children are enormous and costs incurred extremely high. Judicious SET is the only method to decrease this epidemic of iatrogenic multiple gestations. Clinical trials have shown that programmes with >50% of SET maintain high overall ongoing pregnancy rates ( approximately 30% per started cycle) while reducing the MP rate to <10%. Experience with SET remains largely European although the need to reduce MP is accepted worldwide. An important issue is how to select patients suitable for SET and embryos with a high putative implantation potential. The typical patient suitable for SET is young (aged <36 years) and in her first or second IVF/ICSI trial. Embryo selection is performed using one or a combination of embryo characteristics. Available evidence suggests that, for the overall population, day 3 and day 5 selection yield similar results but better than zygote selection results. Prospective studies correlating embryo characteristics with documented implantation potential, utilizing databases of individual embryos, are needed. The application of SET should be supported by other measures: reimbursement of IVF/ICSI (earned back by reducing costs), optimized cryopreservation to augment cumulative pregnancy rates per oocyte harvest and a standardized format for reporting results. To make SET the standard of care in the appropriate target group, there is a need for more clinical studies, for intensive counselling of patients, and for an increased sense of responsibility in patients, health care providers and health insurers.

Adult↗

Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer.

The objective of this study was to compare the implantation rate, pregnancy rate and endometrial thickness of frozen-thawed embryo transfers using endometrial preparation with either an artificial cycle or stimulated cycle. This was a prospective randomized trial at a single academic IVF centre. Seventy-seven patients undergoing artificial cycles received oral oestradiol; patients with endometrium < 7 mm on day 9-10 were switched to vaginal oestradiol. Eighty-six patients undergoing stimulated cycles received recombinant FSH followed by human gonadotrophin hormone injection. Vaginal progesterone was begun 2 or 3 days prior to embryo transfer. There was no difference in implantation rate (8.5% versus 7.3%), pregnancy rate (16% versus 13%), cancellation rate (both 23%) or endometrium thickness (8.7 +/- 1.1 mm versus 8.7 +/- 1.0 mm) between artificial and stimulated cycles. Stimulated cycles had a higher incidence of thin endometrium (27% versus 5%, P < 0.01). In artificial cycles, patients switched to vaginal oestradiol had improved pregnancy rate (31%) versus patients who received oral oestradiol alone (13%) (P = 0.05). It is concluded that artificial and stimulated cycles produce comparable pregnancy rates, implantation rates, cancellation rates and endometrial thickness, although stimulated cycles have a higher incidence of thin endometrium. Vaginal oestradiol supplementation improved implantation rates.

Adult↗

The merits of blastocyst versus cleavage stage embryo transfer: a Cochrane review.

UNLABELLED: This paper is based on a Cochrane review published in The Cochrane Library, issue 2, 2002 (see www.CochraneLibrary.net for information) with permission from The Cochrane Collaboration and John Wiley and Sons. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review. BACKGROUND: The aim of this study was to determine the relative merits of blastocyst versus cleavage stage embryo transfer, concerning the chance of pregnancy, live birth, multiple pregnancy and the factors contributing to these primary outcomes, from the best available evidence. METHODS: A systematic review employing the principles of the Cochrane Menstrual Disorders and Subfertility Group was undertaken. Fourteen randomized controlled trials, all comparing day 2/3 with day 5/6 embryo transfer, were included in a meta-analysis. RESULTS: For day 2/3 versus day 5/6 transfer, there was no significant difference in the odds of pregnancy [odds ratio (OR) = 0.91, 95% confidence interval (CI) 0.71-1.17] nor of live birth (OR = 0.83, 95% CI 0.48-1.42) per treated couple. These results were similar whether all trials, only trials with transfer of equal numbers of day 2/3 versus day 5/6, or only trials with transfer of fewer day 5/6 than day 2/3 embryos, were pooled. There was no significant difference in the odds of multiple pregnancy for day 2/3 versus day 5/6 transfer overall (OR 0.77, 95% CI 0.52-1.13) nor when fewer day 5/6 than day 2/3 embryos were transferred (day 2/3 versus day 5/6 OR 0.69, 95% CI 0.42-1.12). CONCLUSION: The current evidence fails to support a widespread change of practice from cleavage stage to blastocyst stage embryo transfer in couples undergoing IVF.

Blastocyst↗

Translaparoscopic tubal embryo transfer: preliminary experience at National Taiwan University Hospital.

Forty-six couples with various causes of infertility were treated by tubal embryo transfer. Oocyte retrievals were carried out under ultrasound guidance transvaginally and embryos were transferred 48 hours later by laparoscopy into fallopian tubes. Totally 52 cycles were stimulated and 45 retrievals were performed with an average of 8.1 oocytes per retrieval. The average fertilization rate was 54.8%. The implantation rate was 23.8% and the pregnancy rate was 53.5% per transfer. The pregnancy rate per transfer was comparable whether 3 or 4 embryos were transferred. Nine (39.1%) of the 23 pregnancies had multiple pregnancies. Six cases (26.1%) aborted in the first trimester and the remaining 17 were ongoing or term delivery.

Adult↗

Removal of lysed blastomeres from frozen-thawed embryos improves implantation and pregnancy rates in frozen embryo transfer cycles.

OBJECTIVE: To evaluate the effect of degenerated (lysed) blastomere removal on implantation and pregnancy rates in cleavage-stage cryo-embryo transfer (ET) cycles. DESIGN: Randomized clinical trial. SETTING: Private reproductive medical center. PATIENT(S): A total of 88 patients who received frozen-thawed ET, divided into two groups. INTERVENTION(S): Embryo freezing and thawing; opening of the zona pellucida and removal of cryodamaged blastomeres (in the study group), followed by same-day ET. MAIN OUTCOME MEASURE(S): Extent of survival of cleavage-stage embryos after the freeze-thaw procedure; embryo implantation and clinical pregnancies. RESULT(S): Oocyte number per patient, fertilization rate, embryo development rate (and quality), and freezing rates were similar in the two groups in the fresh cycle. In the control group, a total of 55 embryos (25%) of the 217 thawed remained fully intact, and 53 (26%) of the 207 in the study group remained intact. The average number of embryos transferred per group was similar (control, 3.4 +/- 0.9; study, 3.3 +/- 0.9). Implantation rates were 12% and 26% in the control and study groups, respectively. The clinical pregnancy rate was 23% in the control group and 64% in the study group when lysed cell removal was performed. CONCLUSION(S): The results show that pregnancy and implantation rates are higher in the study group; therefore, the removal of degenerated blastomeres may be beneficial to all patients who undergo cleavage-stage, frozen-thawed ET.

Adult↗

The role of tubal pathology and other parameters in ectopic pregnancies occurring in in vitro fertilization and embryo transfer.

Contradictory findings were reported concerning the role of tubal disease in the genesis of ectopic pregnancy in in vitro fertilization and embryo transfer (IVF-ET). We report on six ectopics that occurred in 141 IVF-ET pregnancies (4.3%). All of the six cases were among 84 patients with tubal disease, and none occurred in the remaining 57 patients with other etiological factors. No correlation was found in other parameters including: ovulation induction, number of embryos transferred, and luteal support. A comparison between the ectopics and six matched controls demonstrated similar estradiol levels, but beta-hCG levels on day 15 to 17 after ET were lower. Homolateral salpingectomy was performed in all six cases, but a contralateral resection was carried out in three of them. More comprehensive studies are needed to clarify whether tubal pathology really increases the risk for ectopic gestation in IVF-ET.

Adult↗