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Day three versus day two embryo transfer following in vitro fertilization or intracytoplasmic sperm injection.

BACKGROUND: Embryo transfer (ET) was traditionally performed two days after oocyte retrieval; however, developments in culture media have allowed embryos to be maintained in culture for longer periods. Delaying transfer from day two to day three would allow for further development of the embryo and might have a positive effect on pregnancy outcomes. OBJECTIVES: To determine if there is any difference in live birth and pregnancy rates when ET is performed on day three, compared with day two, in infertile couples undergoing treatment with in vitro fertilization (IVF), including intracytoplasmic sperm injection (ICSI). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (17th December 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003) and Biological Abstracts Databases (1980 to 2003), the National Research Register (NRR), the Medical Research Council's Clinical Trials Register, the NHS Centre for Reviews and Dissemination, citation lists of relevant publications, review articles and included studies, as well as abstracts of appropriate scientific meetings. SELECTION CRITERIA: Randomized controlled trials that compared day three versus day two embryo transfer after oocyte retrieval during an IVF or ICSI treatment cycle in subfertile couples. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. The primary outcome measures were live birth rate and ongoing pregnancy rate. MAIN RESULTS: Ten studies involving 2027 women were included, but only three studies reported live birth and four reported ongoing pregnancy rates. The pooled odds ratios (day three compared to day two) were 1.07, 95% CI 0.84 to 1.37 for live birth and 1.05, 95% CI 0.83 to 1.32 for ongoing pregnancy. From ten studies, the pooled odds ratio for clinical pregnancy was 1.26, 95% CI 1.06 to 1.51. Sub-group analysis revealed that this advantage occurred in those undergoing ICSI cycles. A higher miscarriage rate with day 3 ET in ICSI cycles works to negate the increased clinical pregnancy rate, in agreement with the finding of no significant difference between treatments in live birth rate. REVIEWERS' CONCLUSIONS: Although an increase in clinical pregnancy rate with day three embryo transfer was demonstrated, at present there is not sufficient good quality evidence to suggest an improvement in live birth when embryo transfer is delayed from day two to day three.

Embryo Transfer↗

Uterine fluid human decidua-associated protein 200 and implantation after embryo transfer.

Uterine fluid samples from 109 patients undergoing in-vitro fertilization and embryo transfer were obtained so as to examine the relationship between the uterine fluid concentration of human decidua-associated protein (hDP) 200 and the implantation rate. The sampling was performed on the day of embryo transfer with a Wallace catheter, used for the testing of cervical patency before embryo replacement. The implantation rate, as well as the pregnancy rate, demonstrated a significantly positive correlation with the concentration of hDP 200 in the uterine fluid, measured just before embryo transfer. These results indicate that hDP 200, identified as a rheumatoid factor secreted by the endometrium, may be involved in the implantation process.

Decidua↗

Immediate ambulation after embryo transfer: a prospective study.

OBJECTIVE: To assess whether bed rest following the embryo transfer (ET) procedure contributes to the implantation process and pregnancy rate. DESIGN: A prospective (patient-influenced) study. SETTING: An in vitro fertilization (IVF) unit of an academic medical center. PATIENT(S): Four hundred six patients undergoing controlled ovarian hyperstimulation and IVF. INTERVENTION(S): All women undergoing in vitro fertilization-embryo transfer (IVF-ET) cycles in our unit were given a special individual counseling session before the ET procedure in which they were informed that our previous experience showed no advantage for bed rest over immediate ambulation after ET. The women were allowed to select the practice of their choice, and they were assured that their decision would have no influence on their further treatment. MAIN OUTCOME MEASURE(S): The stimulation pattern and cycle outcome were compared between the two groups (bed rest and immediate ambulation). RESULT(S): Of the 406 patients counseled during the study period, 167 preferred immediate ambulation and 239 opted to stay in the unit for 1 hour's bed rest. There were no significant differences between the groups in mean patient age, number of embryos transferred, and other variables of the assisted reproductive technique cycles. Pregnancy rates did not differ between the groups: 41 out of 167 (24.55%) in the immediate-ambulation group and 51 out of 239 (21.34%) in the bed-rest group. CONCLUSION(S): Immediate ambulation following the ET procedure has no adverse influence on the ability to conceive.

Adult↗

[Embryo transfer in horses--current status and future perspectives].

Although foals born after embryo transfer are eligible for registration in the majority of horse breeds, application of embryo transfer is still rare. This is mainly due to the lack of a possibility for superovulation. Uterine stage embryos can be recovered by a non-surgical flushing technique. Transfer can be accomplished by non-surgical as well as surgical methods. In contrast to the situation in cattle, most related technologies are scarcely available. Methods of cryopreservation as well as bisection of embryos are hampered by the fact that suitable embryos (morula) can be collected from the uterus only during a very short period. In vitro production of embryos by in vitro maturation, fertilization and embryo culture is currently under investigation. Progress has been made to establish ultrasound-guided transvaginal oocyte aspiration. These techniques will provide an important stimulus for application of embryo transfer in equine species and enhance our knowledge about reproductive biology in the mare.

Animals↗

Enhanced oestradiol secretion briefly after embryo transfer in conception cycles from IVF.

The hypothesis was tested that conception cycles (CC) resulting from IVF can be distinguished from non-conception cycles (NC) by differences in corpora lutea function that are detectable at the earliest stage of embryo implantation. Luteal oestradiol secretion was analysed retrospectively in 409 ovarian stimulation cycles of 296 patients from the day of embryo transfer until 14 days after embryo transfer (ET+14) in IVF/intracytoplasmic sperm injection (ICSI) cycles. Human chorionic gonadotrophin (HCG) was administered in 330 of 409 cycles in addition to vaginal progesterone in all cycles. Differences in serum oestradiol concentrations between CC and NC increased from day ET+1 onward and became statistically significant on days ET+4 through ET+14, with higher oestradiol concentrations in CC compared with NC. Even though exogenous HCG administration prevented the fall in luteal oestradiol concentrations after ET+4 both in CC and NC, increasing differences in oestradiol concentrations between CC and NC after embryo transfer were observed in both groups of HCG-supplemented and non-supplemented cycles. It is concluded that luteal oestradiol secretion is affected at the earliest stage of embryo implantation. The putative early signal to the corpus luteum associated with embryo attachment and early implantation appears to be superimposed onto the effect of exogenous luteal HCG administration and is clearly distinguishable as early as 4 days after embryo transfer in conception cycles.

Chorionic Gonadotropin↗

Effects of prepartum lipid supplementation on FSH superstimulation and transferable embryo recovery in multiparous beef cows.

The objective of this experiment was to determine the effect of prepartum lipid supplementation on the number and quality of embryos recovered following ovarian super-ovulation in postpartum suckled beef cows. Mature cows (n = 40) were assigned to one of two treatments (lipid versus. no lipid) and supplemented for approximately 40 days prior to calving. Supplements provided to cows were isocaloric and isonitrogenous. The treatment group was fed 1.6 kg hd(-1) per day of whole soybeans (WSB; 19.8% ether extract, and 41.8% crude protein) and the control group received a supplement consisting of 1.8 kg hd(-1) day of a soybean meal and soy-hull combination (SBS; 2.15% EE and 36.81% CP). Cows were synchronized using a GnRH [Cystorelin((R)) 100 microg im]-GnRH-PGF(2alpha) [Lutalyse 25 mg im] protocol. Cows were administered two injections of GnRH seven days apart and PG seven days after the second GnRH injection. Twenty-eight cows (WSB, n = 15; SBS, n = 13) responded to estrus synchronization and were superstimulated. Super-ovulation was initiated on day 8-10 of the synchronized cycle by twice-daily injections of pFSH (Pluset) over four days in decreasing doses using a total of 608.4 IU per cow. Prostaglandin F(2alpha) was administered 96 and 108 h after super-stimulation was initiated with FSH. Days postpartum (WSB = 59 days; SBS = 57 days) at initiation of FSH treatments were similar (P > 0.10) for both treatments. Cows were monitored for estrus activity by the HeatWatch Estrus Detection System. Twenty-seven cows (WSB, n = 15; SBS, n = 12) exhibited estrus after FSH and inseminated at 0, 12, and 24 h after the onset of estrus with 1, 2, and 1 units of semen, respectively. Embryos were recovered and evaluated 7-8 days later. Only cows that responded to FSH and that were inseminated were used for statistical analysis. Data were analyzed using the General Linear Models Procedure of SAS. Body condition scores did not differ (P > 0.10) between treatments when cows were evaluated at the initiation of the experiment, two weeks prior to calving, and at initiation of superovulation with FSH. Estrous cyclicity prior to the initiation of estrus synchronization did not differ (P > 0.10) between treatments. There was no difference (P > 0.10) between treatments in recovery of total embryos (WSB, 14.7 +/- 3.5; SBS, 17.5 +/- 3.0), transferable embryos (WSB, 10.3 +/- 2.5; SBS, 13.6 +/- 2.6), degenerate embryos (WSB, 3.3 +/- 1.1; SBS, 1.6 +/- 1.7) or unfertilized ova (WSB, 1.1 +/- 0.5; SBS, 2.3 +/- 1.2). Cows that were supplemented with whole soybeans prior to parturition failed to produce an increased total number of ova or transferable embryos following super-ovulation.

Animals↗

In vitro fertilisation when normal sperm morphology is less than fifteen per cent. Results of in vitro fertilisation and embryo transfer at H.F. Verwoerd Hospital, Pretoria.

The outcome of in vitro fertilisation and embryo transfer in 90 couples where the husband's normal sperm morphology was less than 15% were analysed. Based on the percentage of morphologically normal spermatozoa the patients were divided into three groups: group A--normal morphological features 0-5%; group B--6-10%; and group C--11-14%. A control group had normal morphological features greater than or equal to 15%. The fertilisation rate and number of embryos transferred was not significantly different in these groups. However, the pregnancy rate per embryo transfer was significantly different for groups A and B compared with group C and the control group (0% and 5.9% for groups A and B v. 13.9% and 18.3% for group C and the control group, respectively). It is concluded that when the normal sperm morphology is less than 11% the prospect of a pregnancy is poor.

Embryo Transfer↗

In vitro fertilization-embryo transfer in the United States: 1988 results from the IVF-ET Registry. Medical Research International. Society for Assisted Reproductive Technology. American Fertility Society.

This is the third annual report of the U.S. Registry of in vitro fertilization-embryo transfer (IVF-ET) and related practices. The present report describes the 1988 experiences of 135 U.S. member clinics with respect to treatments and outcomes. During 1988 the clinics reported performing 22,649 ovarian stimulation cycles, with 3,508 (15%) resulting in a clinical pregnancy and 2,627 (12%) in a live delivery. Ninety-three percent of the clinics had at least one delivery, and overall a total of 3,427 babies were born. The overall live delivery rates were 12% for IVF (based on 13,647 retrievals), 21% for gamete intrafallopian transfer (GIFT) (based on 3,080 retrievals), and 20% for IVF and GIFT in combination (based on 671 retrievals). In addition to these treatments, detailed results are presented for zygote intrafallopian transfer, frozen embryo transfers, and IVF of donated oocytes.

Embryo Transfer↗

Embryo implantation in in vitro fertilization and intracytoplasmic sperm injection: impact of cleavage status, morphology grade, and number of embryos transferred.

OBJECTIVE: The aims of this study were to compare preimplantation embryo quality in intracytoplasmic sperm injection (ICSI) with standard IVF and to examine the impact of age and number and quality of embryos transferred on implantation and pregnancy. DESIGN: Retrospective, controlled clinical study. SETTING: Academic tertiary center. PATIENT(S): We examined 211 consecutive couples undergoing ICSI who were matched with 211 couples undergoing IVF therapy during the same time frame. INTERVENTION(S): In vitro embryo culture. MAIN OUTCOME MEASURE(S): Day 3 embryo quality as judged by the number of blastomeres and morphology scoring. RESULT(S): Patients undergoing ICSI had a significantly reduced number of embryos with good morphology and cleavage compared with IVF cases. Nevertheless, pregnancy and abortion rates were similar when adjusted by age and number of embryos transferred. Average cleavage status and age were significant predictors of implantation. Women of advanced age had significantly lower embryo cleavage and implantation rates. CONCLUSION(S): [1] The cleaving status of day 3 embryos is a valuable, although limited, indicator of implantation outcome. [2] In vitro fertilization-derived embryos had better cleavage rates and morphology scores than ICSI-derived embryos; however, the implantation potential was similar for both groups. [3] The age-related decline in implantation rate was associated with impaired embryo growth rates.

Adult↗

[Intra-tubal embryo transfer (IVF/IT-ET) in the treatment of non-tubal-induced sterility. Initial studies of the value of a new and expensive therapy procedure].

Intratubar embryo transfer is a form of sterility treatment, in which the in-vitro-fertilized pre-implantation embryos are transferred into the intact fallopian tube(s). This enables the benefits of in-vitro fertilization (information of the gamete fertilization behavior, specific incubation of dysmature oocytes, reduction of the polyploidy rate, risk of multiple pregnancies) to be combined with those of gamete intrafallopian transfer (GIFT; tubar environment for the further development of the pre-implantation embryos). Intratubar embryo transfer is indicated in cases of sterility that are not due to the fallopian tubes; in addition to idiopathic sterility, particular emphasis is put on a certain form of immunological sterility (antibodies against sperm antigens), which seems to be a special indication for this method. Intratubar embryo transfer demands a two sided approach. It is advisable to collect the oocytes transvaginally, guided by ultrasound, since general anaesthesia maybe dispensed with - if so desired. The embryo transfer itself still requires a pelviscopy, which is only performed once fertilization of the oocyte has been confirmed; which is in contrast to GIFT, in which pelviscopy is an inherent part of each treatment cycle. In spite of this advantage, intratubar embryo transfer is a method, which is associated with a high expenditure. The aim of the study was, to evaluate the success rate when all the alternative, less costly options have been exhausted. Our first results are demonstrating, that intratubar embryo transfer is successful, even as a second line therapy. Therefore the method has a significance in the treatment of sterility, not caused by the tubes and the expenditure, with which it is associated, can be justified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A simple technique for nonsurgical embryo transfer in mice.

A simple method was developed for nonsurgical transfer of mouse embryos which enabled transfer to both uterine horns. Embryos were picked up in a modified capillary tube and transferred through the cervix into each uterine horn of an unanesthetized mouse. A glass speculum was used to facilitate location of the cervix. The technique was found to be as successful (up to 60% of embryos transferred developed to term) as surgical methods yet was simpler and eliminated surgical trauma to the recipient mouse.

Animals↗

Evolution of a highly successful in vitro fertilization-embryo transfer program.

During the first 2 1/2 years of operation of the University of California at Los Angeles in vitro fertilization-embryo transfer program, 47 clinical pregnancies were achieved in 154 laparoscopies for oocyte aspiration (31%). Two of these pregnancies were achieved through transfer of cryopreserved embryos when ongoing pregnancy did not result from embryo transfer in the stimulated cycle. An increase in clinical implantation was noted with a reduction of transfer volume and proportion of air, with 34% of laparoscopies being followed by clinical pregnancy over the last 18 months. No difference in the rate of clinical pregnancy was noted relative to uterine depth or position. The high rate of multiple implantation (47%) suggested a high level of embryo quality. The success rate was attributed to a strong ovarian, human menopausal gonadotropin stimulation, accurate timing of human chorionic gonadotropin, a high oocyte retrieval rate, meticulous laboratory technique, atraumatic, high-fundal transfer of embryos, and initiation of embryo cryopreservation.

Embryo Transfer↗

Factors influencing the success of embryo transfer in the pig.

Progress in reproductive biotechnologies has led to an increased use of embryo transfer in both swine research and swine production. This review article describes the history and subsequent development of porcine embryo transfer. Special attention is given to aspects of the overall process of embryo transfer which are unique to pigs.

Age Factors↗

Current status and potential of embryo transfer and reproductive technology in dairy cattle.

Significant use of embryo transfer in dairy cattle commenced with the introduction of nonsurgical embryo recovery in the mid-1970s and developed with the use of nonsurgical transfers in the late 1970s. Numbers of registered Holstein calves from embryo transfer doubled yearly through 1980, after which the rate of increase slowed; the total reached nearly 19,000 calves in 1990. However, the efficacy of superovulation procedures and commercial success rates of transferred fresh embryos have not improved the past 10 to 15 yr. Fertilization rates in superovulated donors remain low. Although embryo-splitting techniques were perfected in the early 1980s, they are not used widely. A practical, commercial embryo-sexing procedure remains unavailable. Recent significant improvement is apparent in the technology of ultrasound-guided oocyte collection and in vitro oocyte maturation, fertilization, and embryo culture. In the future, this technology may be used in conjunction with sperm separated by sex with a flow cytometer. Modest numbers of embryo clones have been produced in several commercial programs via nuclear transfer techniques. However, the efficiency of gene transfer experiments involving ova of cattle and other domestic species has been low. Recently, DNA probe technology has begun to provide genotype information for cattle and will ultimately be applied to embryos.

Animals↗

In vitro fertilization and embryo transfer in Pretoria.

Details of the in vitro fertilization and embryo transfer programme at the Department of Obstetrics and Gynaecology of the H. F. Verwoerd Hospital and the University of Pretoria are presented. From 1 March 1982 to 30 November 1983, 67 cycles in 47 patients were induced using clomiphene citrate and human chorionic gonadotrophin (hCG) (46 patients) and human postmenopausal gonadotrophin/hCG (1 patient). In 5 patients ovum recovery was unsuccessful owing to severe adhesions. In the remaining 42 patients 59 oocyte recoveries out of a total of 62 attempts were successful, a 95% recovery rate. One hundred and seventy-nine ova were recovered (2,9 per laparoscopy), of which 143 (80%) were viable. Forty-six per cent of fertilized ova cleaved actively. Forty-one transfers of 66 embryos (average 1,6 embryos per transfer) resulted in 5 pregnancies (12% pregnancy rate per transfer). Three preclinical pregnancies aborted spontaneously. Two pregnancies are ongoing at 30 and 32 weeks' gestation. Thus, the programme has so far led to 2 third-trimester pregnancies. Consolidation and refinement of techniques should lead to a steady increase in success at this centre.

Culture Media↗

Different perspectives of patients and health care professionals on the potential benefits and risks of blastocyst culture and multiple embryo transfer.

BACKGROUND: A trade-off exists between the risk of multiple pregnancy and prospects of pregnancy itself in assisted reproduction. Blastocyst culture and embryo transfer after approximately 5 days may be one method of reconciling this dilemma, although a controversial one. METHODS AND RESULTS: We presented a questionnaire to groups of patients, embryologists and clinicians to solicit views on the potential benefits and risks of blastocyst culture and multiple pregnancy. The results indicate that patients are more accepting of multiple pregnancy as a prospective outcome of treatment than those involved in their treatment, despite awareness of the risks. Our data tend to support a genuine difference in values on this point. We also sought views on the patient selection criteria and treatment protocols which should apply in a planned randomized controlled trial comparing blastocyst culture with cleaving embryo transfer (e.g. numbers of embryos to transfer, acceptable levels of risk of twin and triplet pregnancy, the proportion of patients who would be put off from entering the trial by the risk of no embryo transfer). These are presented and discussed with reference to their likely impact on trial recruitment, highlighting differences in perspective between patients and professionals. CONCLUSIONS: We conclude that there are differences among patients, embryologists and clinicians in their perceptions of the desirability of multiple pregnancy, their preferences in certain practical aspects of treatment such as embryo transfer numbers, and their ideas on blastocyst culture and its prospective outcomes and risks.

Attitude of Health Personnel↗

Comparison of pulsatility indices on the day of oocyte retrieval and embryo transfer.

Transvaginal ultrasonography with colour blood flow imaging and analysis of impedance to uterine arterial blood flow has been used to provide an index of uterine receptivity for implantation after IVF/embryo transfer. A mean uterine arterial pulsatility index (PI) > 3.0 at the time of embryo transfer predicted 35% of failures to become pregnant. Cryopreserving embryos in non-receptive cycles and transferring them in receptive cycles would be expected to improve pregnancy rates. Earlier decisions regarding embryo cryopreservation can be made if receptive cycles can be predicted at the time of oocyte retrieval rather than at embryo transfer. To assess differences in uterine artery impedance, PI were measured serially in 107 women on both the day of oocyte retrieval and the day of embryo transfer. Mean PI on the day of oocyte retrieval was 2.52 +/- 0.59, and on the day of embryo transfer was 2.78 +/- 0.45. No significant difference was observed when PI determined on the day of oocyte retrieval were compared with PI on the day of embryo transfer. These data suggest that the PI measurement done on the day of oocyte retrieval could substitute for the measurement done on the day of embryo transfer. This would allow prediction of non-receptive endometria earlier in the cycle. Further studies are needed to evaluate whether cryopreservation of embryos and transfer when the uterus is more receptive will increase the implantation rates.

Adult↗

[Heterotopic pregnancy with intrauterine dizygotic twins following embryo transfer in the blastocyst phase].

Ectopic pregnancy is a common complication of in vitro fertilization and embryo transfer (IVF-ET). On other hand, heterotopic pregnancy complicates 1-2% of all IVF-ET pregnancies. Tubal damage as reason for treatment and multiple embryo transfer might predispose patients to this complication. We present a successful treated case of an infertile patient that developed simultaneous twin intra- and single extra- uterine pregnancy after blastocyst-stage embryo transfer. In IVF-ET patients presence of an intrauterine gestation not exclude the possibility of a concomitant extrauterine pregnancy. Awareness of the possibility of heterotopic pregnancy after IVF-ET plays an important role in the successful treatment of this reproductive complication. Transfer of good quality embryos can be a risk factor to develop heterotopic pregnancy.

Adult↗