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Frozen embryo transfer outcome according to reason for freezing the embryos.

PURPOSE: To determine if cryopreservation influences pregnancy outcome following transfer. METHODS: Retrospective cohort analyses of frozen embryo transfer (ET) cycles divided into five different categories according to reason for freezing. RESULTS: Frozen embryos remaining as a result of failing to conceive with the previous fresh transfer or those remaining because of cancellation of fresh ET related to inadequate endometrial thickness, result in lower pregnancy rates (PRs). CONCLUSIONS: The fact that embryos never deselected in a group whose fresh ET was canceled because of risk of ovarian hyperstimulation did not have the best results suggests that these oocytes may not be of equal quality to those attained with a more modest response.

Abortion, Spontaneous↗

[Effect of early cleavage of embryos after intracytoplasmic sperm injection (ICSI) into oocytes on results of fertilization in vitro (IVF) and embryo transfer (ET)].

OBJECTIVE: To evaluate the influence of early cleavage in embryos obtained using ICSI on the success rate of IVF-ET. DESIGN: A prospective study. SETTING: Centre of Assisted Reproduction, Department of Obstetrics and Gynecology, Medical Faculty, Palacký University, Olomouc. METHODS: The rate of the first cleavage of embryos was checked between 23 to 26 hours after ICSI in 115 cycles IVF-ET. "Early Cleavage" (EC) embryos which were already cleaved were cultivated separately from the "slow" (No Early Cleavage, NEC) embryos. After 3 days cultivation, no more than three 6- to 8-cell embryos were transferred. Only EC embryos were transferred in 43 cycles and only NEC embryos were transferred also in 43 cycles. The remaining 29 cycles, where both EC and NEC embryos had to be transferred, were not evaluated. In both groups the following entry parameters were compared: age of the patient, number of fertilized oocytes, fertilization rate (FR), number of frozen and evaluated embryos, number of EC embryos recorded and number of transferred embryos. The outcome parameters compared were: pregnancy rate (PR), number of gestational sacs with heart beats per number of transferred embryos (implantation rate, IR), abortions (AB) and the frequency of multiple pregnancy. Statistical evaluation was performed by t-test, chi 2 test and by Sheffe analysis. RESULTS: EC embryos were found in 57% of cycles (n = 66) after ICSI. Early cleavage was observed in 198 of 563 embryos (35%). Among entry parameters the only statistically significant differences (P < 0.05) were found in the number of retrieved oocytes as well as in the ratio of frozen embryos which were higher in the cycles with the transfer of only EC embryos. FR was the same (74%) in both types of transfer. Outcome parameters in the transfer of only EC versus NEC embryos were higher in PR (40% vs. 33%), about equal in IR (27% vs. 25%) and lower in AB (2% vs. 5%). Moreover, multiple pregnancies were less frequent in the transfer of only EC embryos: 65% of singleton pregnancy, 35% of twins and no triplet versus 36%, 57% and 7%, resp., in the transfer of only NEC embryos. The differences in outcome parameters are not statistically significant (P > 0.05) because of small numbers. CONCLUSION: The speed of the first cell cleavage is a useful additional criterion for better evaluation of quality and viability of embryos.

Adult↗

Embryo transfer procedure and its use as a research technique.

The technique of superovulation and embryo transfer not only has the potential to increase the reproductive rate of the female but because the number, genotype, age of embryo, site of transfer and other factors can be controlled, also has the potential in a broad research context. The current efficiency of the total procedure involved, including superovulation, embryo recovery, embryo storage and embryo transfer is reviewed. Some of the main experimental uses that embryo transfer has already or may, in the future, be put to, are also reviewed.

Animals↗

Combination clomiphene citrate/human menopausal gonadotropin stimulation protocols for in vitro fertilization-embryo transfer.

Various protocols have been utilized for stimulation of multiple ovarian follicles in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Previous studies have suggested that the combination of clomiphene citrate (CC) and human menopausal gonadotropins (hMG) is superior to either CC or hMG alone in terms of follicular development, oocyte recovery, and embryo transfer. However, no significant increase in viable pregnancy rates has been reported with any of the protocols. This report examines five different CC/hMG protocols. While differences were seen in terms of serum estradiol response and fertilization rates of mature oocytes among the various protocols, no significant differences were found in terms of follicular development, oocyte recovery, embryo transfer, or pregnancy. The pregnancy rate in IVF-ET appears unaffected by variations in the dose and timing of CC and hMG in a combination protocol.

Adult↗

High incidence of embryo transfer cancellations in patients with polycystic ovarian syndrome.

This study was aimed at assessing the outcome of in-vitro fertilization (IVF) and embryo transfer in patients with polycystic ovarian syndrome (PCOS). The results of IVF and embryo transfer in PCOS patients (PCOS group, 78 cycles of 26 patients) were compared with those of a control group (423 cycles in 202 patients without male factor; age and ovarian stimulation protocol were matched). Although the pregnancy rate per transfer was not different in the two groups of patients (25 versus 34%, PCOS versus control group), the PCOS group had a significantly lower pregnancy rate per follicle aspiration (19 versus 31%, P < 0.05). A notable result was a significantly higher incidence of embryo transfer cancellations in the PCOS group (22 versus 8%, P < 0.01), which resulted from unpredictable failure of either oocyte recovery or fertilization. The incidence of unexplained complete failure of fertilization was significantly higher in the PCOS group (18 versus 5%, P < 0.01). These results may reflect a reduced quality of the oocytes in the PCOS group, and there was a subgroup of PCOS patients who repeatedly produced poor results of treatment. Although the ovarian stimulation regimen best suited to PCOS patients remains to be determined, special care should be taken during ovarian stimulation, especially when the PCOS patients had experienced unexplained failure of oocyte recovery or fertilization in the previous treatment cycle(s).

Adult↗

Psychological study of in vitro fertilization-embryo transfer participants' attitudes toward the destiny of their supernumerary embryos.

OBJECTIVE: To study the motivations underlying IVF-ET participants' choice to donate or destroy their supernumerary embryos. DESIGN: Couples' opinions are studied through a questionnaire and a psychological interview. PARTICIPANTS: Two hundred couples about to undergo IVF-ET. SETTING: The fertility unit of an academic hospital. MAIN OUTCOME MEASURES: Couples' choice for supernumerary embryos' destiny; opinions on embryo status, on importance of genetic lineage in the filial bonding, on gamete donation, and on multiple pregnancy risk. RESULTS: Donation is the most frequent choice but destruction is tolerated by almost all the couples (92%). Couples considering the embryo as a child choose destruction as frequently as donation but refuse experimentation on the embryo. Donation is highest among couples who stress education more than genetic lineage in parental bonding. This is confirmed by the choice of the couples requiring donor gametes. Couples express differing attitudes toward risks of twins and risks of triplets: twins are much more desired than triplets, which are frequently refused. CONCLUSIONS: Couples' opinions on the respective importance of genetic lineage and education in defining parental bonding are more determinant in their decision to destroy or to donate their supernumerary embryos than their opinions on the in vitro embryo status, which only determines their attitude toward experimentation.

Attitude↗

Does preoperative administration of metamizol (Novalgin) affect postoperative body weight and duration of recovery from ketamine-xylazine anaesthesia in mice undergoing embryo transfer: a preliminary report.

Thirty-two female mice used for embryo transfer or as controls received either metamizol or equal volumes of normal saline administered subcutaneously following induction of anaesthesia with ketamine-xylazine. Body weight was measured immediately before surgery, after 24 and after 48 h. The duration of the surgical anaesthesia was recorded and postoperative behavioural responses were measured. Comparison of the treatment groups revealed no significant differences in body weight and recovery times, nor were other signs of discomfort detected in either treatment group. It was concluded that administration of metamizol did not provide additional analgesia following embryo transfer in mice anaesthetized with ketamine-xylazine.

Anesthesia↗

Dummy embryo transfer using methylene blue dye.

The aim of this prospective work was to evaluate different catheters and techniques used for embryo transfer. Studies were performed on 105 IVF patients before the start of treatment cycles. Each patient was used as her own control to study the expulsion of methylene blue (MB) dye after dummy embryo transfer. Group A (n = 35) underwent the test twice, before and after aspiration of the cervical mucus. Group B (n = 30) underwent the test twice with and without the presence of two air bubbles in the embryo transfer catheter. Group C (n = 40) underwent the test twice using two different catheters, the Wallace and the Craft catheters. The results showed that the dye was extruded at the external os in 57% of the cases when the cervical mucus was not aspirated compared to 23% when the mucus was aspirated (P = 0.01). The dye was extruded in 33% of the cases with air bubbles in the catheter as compared to 27% when no air was present (P > 0.05). When the Wallace catheter was used expulsion occurred in 25.5% compared to 77.5% when the Craft catheter was used. We concluded that using soft catheters and complete aspiration of cervical mucus significantly reduced the expulsion of the dye. The presence of air bubbles did not affect rate of expulsion of the dye.

Air↗

Synchronization of estrus in embryo transfer recipients after using a combination of PRID or CIDR-B plus PGF2alpha.

The use of CIDR-B or PRID in combination with prostaglandin F2alpha (PGF2alpha) for synchronizing estrus in embryo transfer recipients was evaluated in 2 experiments. In Experiment 1, virgin heifers (n=263) were synchronized using either a PRID (including estradiol benzoate capsule) or a CIDR-B in a combined program in which devices were inserted on Day 1, an injection of prostaglandin was given on Day 6, and devices were withdrawn on Day 7. The interval from device removal to the onset of estrus was significantly shorter for CIDR-B than for PRID-treated animals (50.44 vs 55.50 hours; P<0.003). The CIDR-B treatment resulted in a similar degree of synchrony to the PRID treatment (74.0 vs 70.4%; P=0.68). InExperiment 2, cows (n=95) and heifers (n=93) were allocated at random to be synchronized using a PRID (excluding estradiol benzoate capsule) plus PGF2alpha or a CIDR-B device plus PGF2alpha. The devices were inserted on Day 1, an injection of prostaglandin was given on Day 10 and the devices were removed on Day 12. Estrus was observed earlier following the CIDR-B treatment (43.50 vs 47.04 hours; P=0.01), but the degree of synchrony was similar (76.2 vs 76.3%; P>0.10) for the CIDR-B and PRID-treated animals. In both experiments, there were no significant differences in the proportions of animals observed in estrus, selected as embryo transfer recipients, or which achieved pregnancy consequent on embryo transfer between those synchronized using CIDR-B or PRID regimens. We conclude that the CIDR-B is a suitable device for synchronizing estrus in embryo transfer recipients.

Journal Article↗

Early hormonal markers of pregnancy outcome after in vitro fertilization and embryo transfer.

PURPOSE: To investigate the relative power of HCG, estradiol, and progesterone determinations in the prediction of pregnancy outcome after IVF. These prognostic hormonal factors were studied as single and combined predictors. METHODS: Serum concentrations of beta-HCG, progesterone, and estradiol were measured 12-13 days after embryo transfer (study point 1) and 7 days later (study point 2) in a series of 20 consecutive infertile patients having a first-trimester spontaneous clinical abortion after an IVF-embryo transfer cycle. As a control group (n = 60), the next three IVF-embryo transfer cycles resulting in an ongoing pregnancy after each miscarried IVF cycle in our assisted reproduction program was used. The discrimination attained between the two study groups (ongoing pregnancies and miscarriages) was evaluated by logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: Mean hormone concentrations at study points 1 and 2 were higher in the ongoing pregnancy than in the abortion group. Regarding pregnancy outcome the percentage increment of HCG serum levels (> or = 1321%), with an accuracy (predictive value of pregnancy outcome) of 81.2% (sensitivity 98%, specificity 50%), had the best prognostic reliability but no significant differences were found when this parameter was compared with the predictive value of HCG concentration (> or = 72 IU/l) at study point 1 (diagnostic accuracy 80.5%; sensitivity 70%; specificity 80%). When ROC analysis was used, the best predictor of ongoing pregnancy according to the AUC(ROC) was HCG concentration at study point 2 but again no significant differences were found when this parameter was compared with the predictive value of HCG serum levels at study point 1. A multiple marker strategy did not help distinguish viable from nonviable pregnancies. CONCLUSION: A single, early (days 12-13 after embryo transfer) HCG quantitative serum measurement in IVF cycles not only is diagnostic but also has good predictive value for pregnancy outcome.

Adult↗

Does laparoscopic ovarian diathermy affect the outcome of IVF-embryo transfer in women with polycystic ovarian syndrome? A retrospective comparative study.

Controlled ovarian stimulation for IVF and embryo transfer and outcome parameters were compared retrospectively in 31 women with clomiphene-resistant polycystic ovarian syndrome (PCOS). Of these women, 15 had previously undergone laparoscopic ovarian diathermy before IVF (group A, total 22 cycles) and 16 had not had surgical treatment (group B, total 24 cycles). No statistically significant differences were observed in the number of oocytes retrieved, although the number of embryos available for transfer was significantly higher in group B (7.1 +/- 3.8 versus 4.6 +/- 2.7, P < 0.01). The clinical pregnancy rate per embryo transfer appeared to be higher in group B (63.2 versus 41.2%), as did the miscarriage rate (66.7 versus 28.6%), giving an apparent improved ongoing pregnancy rate per embryo transfer in group A (29.4 versus 10.5%), but this was not statistically significantly different. The incidence of severe ovarian hyperstimulation syndrome (OHSS) was apparently higher in group B (4.2 versus 0%), but this difference was not statistically significant. No cases of severe OHSS were seen in group A. Ovarian diathermy does not appear to have a deleterious effect on controlled ovarian stimulation, and the outcome of IVF-embryo transfer may be beneficial in decreasing the risk of severe OHSS and improving the ongoing clinical pregnancy rate.

Adult↗

Pelvic abscess complicating transcervical embryo transfer.

A severe pelvic infection resulting in a tuboovarian abscess after transcervical embryo transfer is reported. The case is unique in that the recipient was an agonadal woman who had not undergone prior transvaginal aspiration. Although rare, pelvic infection after embryo transfer may occur in spite of normal precautions.

Abscess↗

Serum progesterone concentrations in cows receiving embryo transfers.

Progesterone concentrations in systemic blood were determined by radioimmunoassay in crossbred cattle used as recipients in an embryo transfer programme. An embryo was transferred surgically to the uterine horn of 528 females which were in oestrus within one half-day of the donor. Jugular blood was obtained at the time embryos were transferred (3-7 days after oestrus) and again from most females between Days 9 and 14. Pregnancy was determined by rectal palpation 45-65 days after oestrus. There were no significant differences between serum progesterone levels of females which remained pregnant and those which did not. Out of 177 pregnant recipients, none had serum progesterone levels less than 0.5 ng/ml on Days 10, 11, or 12 but in 8, values were less than 1.0 ng/ml. Blood samples were also taken on Days 20, 21, or 22 from 113 of these recipients. The mean +/- s.e.m. concentration of progesterone in the pregnant females (5.14 +/- 0.34 ng/ml) was significantly higher (P less than 0.001) than in the non-pregnant females (1.17 +/- 0.25 ng/ml). The correlation coefficients between progesterone levels on Days 3, 4, 5 or 6 and 10-12 ranged from 0.18 to 0.37 (all P less than 0.02). Progesterone levels were not related to length of the previous cycle, the time of day an animal was first noticed in oestrus or the side of the corpus luteum. However, cows with a short oestrus had higher progesterone levels on Days 3-7 (P less than 0.01) than those in oestrus for a longer time.

Animals↗

Serum HCG 12 days after embryo transfer in predicting pregnancy outcome.

BACKGROUND: Assisted reproduction treatment (ART) entails a risk of ectopic pregnancy and early pregnancy loss. Serum HCG has been found to be predictive of pregnancy outcome. Our aim was to assess the clinical value of a single early HCG assay in ART pregnancies taking into account the aetiology and treatment of infertility. METHODS: During 1994-1999, we studied 774 embryo transfer cycles resulting in pregnancy defined as a serum HCG concentration of > or =5 IU/l on day 12 following embryo transfer. The treatment included IVF in 518, ICSI in 119, and frozen embryo transfer in 137 cycles. Serum HCG concentrations were measured by fluoroimmunometric assay. Pregnancies were classified as viable (live fetus at > or =22 weeks gestation) or non-viable (biochemical pregnancy, miscarriage, ectopic pregnancy and molar pregnancy). Data on the outcomes were retrospectively retrieved from the records. RESULTS: The median HCG concentration was 126 IU/l in viable pregnancies and 31 IU/l in non-viable pregnancies (P < 0.0001). The median HCG concentration was 115 IU/l in singleton pregnancies and 201 IU/l in multiple pregnancies (P < 0.0001). Male factor infertility was associated with viable pregnancies (P = 0.004) and tubal factor with non-viable pregnancies (P = 0.003); the lowest HCG level (88 IU/l) was observed in subjects with both male factor infertility and ICSI treatment (P = 0.001). An HCG value of 76 IU/l emerged as the most suitable cut-off point to predict viable pregnancy. Probabilities of each type of outcome related to the HCG level are given. CONCLUSIONS: A single HCG reading on day 12 after embryo transfer helps to plan the subsequent follow-up. Male factor infertility and ICSI are associated with relatively low HCG values in viable pregnancies.

Chorionic Gonadotropin↗

Incidence of multiple pregnancy after in-vitro fertilisation and embryo transfer.

7 multiple pregnancies occurred in a series of 20 pregnancies after oocyte recovery for in-vitro fertilisation and embryo transfer. After ovarian stimulation with clomiphene alone or with human menopausal gonadotropin, 102 laparoscopies were carried out in 62 women and the ongoing pregnancy rate beyond the first trimester was 17/102 laparoscopies (17%), including 5 sets of twins. 1 triplet and 1 twin pregnancy showed evidence of regression of two sacs and one sac, and both are progressing as singleton pregnancies at 16 and 34 weeks, respectively. 3 abortions occurred at 7, 8, and 9 weeks--a spontaneous abortion rate of 15%. The pregnancy and multiple pregnancy rates after stimulation with clomiphene alone or with human menopausal gonadotropin were comparable, but oocyte pickup based on a knowledge of the duration of the endogenous rise in luteinising hormone, rather than 36 h after administration of human chorionic gonadotropin, increased the pregnancy rate. As the quality and number of embryos transferred to the uterus increased, the risk of multiple pregnancy also rose. Consideration should therefore be given to restricting the number of embryos transferred to limit multiple pregnancies to twins.

Adult↗

Population pharmacokinetic modelling of Emfilermin (recombinant human leukaemia inhibitory factor, r-hLIF) in healthy postmenopausal women and in infertile patients undergoing in vitro fertilization and embryo transfer.

AIMS: The aim of this analysis was to develop a population pharmacokinetic model for Emfilermin (recombinant human leukaemia inhibitory factor, r-hLIF) following subcutaneous administration to healthy postmenopausal women and to infertile patients undergoing in vitro fertilization and embryo transfer (IVF-ET). METHODS: Data from three studies, a single and a repeat dose Phase I study in postmenopausal women as well as a proof of concept study in patients undergoing in vitro fertilization and embryo transfer were combined and analyzed. The structural pharmacokinetic model was developed using the rich data from the Phase I studies and the full pharmacostatistical model was then derived using all the data. RESULTS: The pharmacokinetics of r-hLIF after repeated subcutaneous administration were described by a one-compartment disposition model with a zero order input. The duration of the absorption phase was short (0.8 h) and invariant. The apparent clearance in postmenopausal women was 57 l h(-1) (CV = 17%). In in vitro fertilization and embryo transfer patients, the apparent clearance was decreased by 35% compared with postmenopausal women. The apparent volume of distribution was 235 l (interindividual CV = 28%) and exhibited an interoccasion variability of 23%. It increased (for weight above 62 kg) or decreased (for weight below 62 kg) by 29% for every 10 kg body weight. The median posthoc estimates of apparent clearance and volume of distribution and their variability were consistent with the population estimates. In postmenopausal women, the results were consistent with those obtained by noncompartmental analysis. The residual variability on r-hLIF serum concentrations was 20%. CONCLUSIONS: The pharmacokinetics of r-hLIF after repeated SC administration were described by a one compartment disposition model, with zero order input, in postmenopausal women and those undergoing IVF or intracytoplasmic sperm injection and embryo transfer. Absorption of r-hLIF was rapid as was its subsequent clearance. The apparent volume of distribution of r-hLIF was moderate to high, depended on body weight and showed interoccasion variability.

Administration, Cutaneous↗

The effect of general anaesthesia on the success of embryo transfer following human in-vitro fertilization.

In this study the effect of general anaesthesia on the success of embryo transfer was investigated. Between January and August 1986, in a preliminary trial using general anaesthesia for embryo replacement (sodium thiopentone and alfentanyl), the overall pregnancy rate was 36% (n = 86), compared to 21% in a group of matched controls without anaesthesia (n = 131). Following the preliminary study in a larger series of patients between August 1986 and December 1987, all embryo transfers were performed using general anaesthesia. In a total of 795 embryo replacements the pregnancy rate was 19%. This was neither significantly different from the overall pregnancy rate of the non-anaesthetic controls of the preliminary study (21%), nor from a group of 603 patients who received embryo replacement without anaesthesia between June 1984 and December 1985. The results of this study indicate no obviously adverse effect of the anaesthesia on the induction of pregnancy. The results of the preliminary study even indicate a beneficial effect of anaesthesia on the pregnancy rate. However, to assess accurately the effect of general anaesthesia, a large prospective randomized study is needed. The type of anaesthesia used in this study, however, may be useful in cases of difficult transfer procedures, due to psychological stress to the patient, or technical/mechanical problems during the embryo transfer procedure.

Anesthesia, General↗

Dependence of DNA synthesis and in vitro development of bovine nuclear transfer embryos on the stage of the cell cycle of donor cells and recipient cytoplasts.

The effect of the stage of the cell cycle of donor cells and recipient cytoplasts on the timing of DNA replication and the developmental ability in vitro of bovine nuclear transfer embryos was examined. Embryos were reconstructed by fusing somatic cells with unactivated recipient cytoplasts or with recipient cytoplasts that were activated 2 h before fusion. Regardless of whether recipient cytoplasts were unactivated or activated, the embryos that were reconstructed from donor cells at the G0 phase initiated DNA synthesis at 6-9 h postfusion (hpf). The timing of DNA synthesis was similar to that of parthenogenetic embryos, and was earlier than that of the G0 cells in cell culture condition. Most embryos that were reconstructed from donor cells at the G1/S phase initiated DNA synthesis within 6 hpf. The developmental rate of embryos reconstructed by a combination of G1/S cells and activated cytoplasts was higher than the rates of embryos in the other combination of donor cells and recipient cytoplasts. The results suggest that the initial DNA synthesis of nuclear transfer embryos is affected by the state of the recipient oocytes, and that the timing of initiation of the DNA synthesis depends on the donor cell cycle. Our results also suggest that the cell cycles of somatic cells synchronized in the G1/S phase and activated cytoplasts of recipient oocytes are well coordinated after nuclear transfer, resulting in high developmental rates of nuclear transfer embryos to the blastocyst stage in vitro.

Animals↗