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A prediction model for selecting patients undergoing in vitro fertilization for elective single embryo transfer.

OBJECTIVE: Construction of a prediction model to enable the selection of patients for elective single ET. DESIGN: Retrospective cohort study. SETTING: Fertility center in a tertiary referral university hospital. PATIENT(S): Six hundred forty-two women undergoing their first IVF treatment cycle in which no more than two embryos were transferred. INTERVENTION(S): Database analysis. MAIN OUTCOME MEASURE(S): Ongoing pregnancy and multiple pregnancy. RESULT(S): In multivariate analysis, the best predictors for ongoing pregnancy were female age, the number of retrieved oocytes, the developmental stage score and the morphology score of the two best embryos available for transfer, and the day of transfer. Younger age and high quality of transferred embryos were the best predictors for increased risk of multiple pregnancy. The resulting model enables the calculation of probabilities of pregnancy and twin pregnancy. Depending on embryo quality, there is a threshold age under which the chance of singleton pregnancy is higher if one embryo is transferred compared with two embryos. CONCLUSION(S): Application of this model may enable a reduction in the chance of twin pregnancy without compromising singleton pregnancy rates in a subgroup of patients undergoing IVF.

Adult↗

Effect of mitochondrial DNA (mtDNA) type on pregnancy rate after embryo transfer in rats.

Because the mtDNA is maternally inherited, embryos resulting from matings or artificial inseminations have the same type of mtDNA as that of the mother. However, when embryos are transferred the mtDNA of the embryos may be different to that of the recipient and this may interfere with maternal recognition and the establishment of pregnancy. This study was done to determine whether differences in the mtDNA between embryos and recipients would influence the survival to term of transferred embryos.A total of 1,220 rat embryos were recovered from non-superovulated donors of known mtDNA type. The number and distribution of developmental stages of embryos collected from 51 rats of mtDNA type A (n = 595) were not different (P>0.05) from those collected from 50 rats of mtDNA type B (n = 625). The overall pregnancy rate after transfer of embryos to pseudopregnant rats was 54% (26 48 ). The pregnancy rate was not affected (P>0.05) by the type of mtDNA of the recipient or of the embryo, and the interaction between mtDNA type of embryos and recipients was also not significant (P>0.05). Embryonic survival to birth was low (78 622 , 12.5%) but was not affected (P>0.05) by the type of mtDNA of the recipient (A = 28 250 ; B = 50 372 ) or of the embryo (A = 41 306 ; B = 37 316 ). Survival of pups to weaning was affected by the type of mtDNA of the embryo (P < 0.01) but not by the type of mtDNA of the recipient (P>0.05) and the interaction between mtDNA type of embryos and recipients was also not significant (P>0.05). More pups (P < 0.005) derived from donor rats of mtDNA type A (34 41 ) survived to weaning age than pups from donor rats of mtDNA type B (18 37 ). These results indicate that differences in the type of mtDNA between embryos and recipients do not interfere with establishment of pregnancy in pseudopregnant recipients.

Journal Article↗

Freemartinism among singleton bovine females born from multiple embryo transfer.

Heterosexual chimerism among singleton females produced by multiple nonsexed embryo transfer (MNET singleton females) was investigated using chromosome typing and PCR (polymerase chain reaction)-amplification of male-specific DNA (msDNA). Of the 22 animals tested, 21 were classified as normal by both methods (i.e., showing no male cells among 100 metaphase spreads in chromosome typing and being msDNA negative in PCR). No morphological abnormalities of the genital organs were observed among 19 MNET single females. One MNET singleton female was, however, classified as a freemartin by PCR (male-specific DNA positive), but it was classified as normal cytogenetically. This individual probably had a low degree of heterosexual chimerism, and it seems that the chimerism derived from MNET was difficult to diagnose by chromosome typing, although it was detectable by PCR. The genital organs of this individual (15-mo-old Aberdeen Angus) were normal in form (both external and internal) and size. However, a very small structure, resembling seminiferous tubule, was found in the left ovary. It may be concluded that most MNET singleton females are expected to have normal reproductive function.

Journal Article↗

The management of hydrosalpinges before in-vitro fertilization and embryo transfer.

Several recent studies have shown that the presence of hydrosalpinges adversely affects clinical pregnancy rates achieved with in-vitro fertilization and embryo transfer. Hydrosalpinx fluid may be toxic to the endometrium or embryo, or may mechanically interfere with implantation. Some authors recommend surgical correction of hydrosalpinges before in-vitro fertilization and have shown promising results with this approach. Proper patient selection for this therapy still needs to be defined.

Embryo Transfer↗

Rabbit oocyte cytoplasm supports development of nuclear transfer embryos derived from the somatic cells of the camel and Tibetan antelope.

This study was designed to examine the ability of rabbit metaphase II oocyte cytoplasm to support the development of interspecies nuclear transfer embryos reconstructed using donor nuclei from different species. Skin fibroblast cells from a camel and Tibetan antelope were used as donor nuclei. As a first step, we investigated the efficiency of different activation protocols by comparing the parthenogenetic development of rabbit oocytes. The protocol that yielded the highest blastocyst rate was used to activate the reconstructed embryos in nuclear transfer experiments. In addition, the effect of donor cell serum starvation on the development of the reconstructed embryo was also examined. More than half of the karyoplast-cytoplast couplets could be fused, and about one third of the reconstructed embryos were capable of completing first cleavage, regardless of the species of donor nuclei. Some of the cleaving reconstructed embryos were even capable of progressing further and developing to the blastocyst stage (1.4-8.7% for the Tibetan antelope and 0-7.5% for the camel, respectively). Our results suggest that the mechanisms regulating early embryo development may be conserved among mammalian species and some factors existing in rabbit oocyte cytoplasm for somatic nucleus reprogramming and dedifferentiation may not be species-specific. Rabbit oocyte cytoplasm can reprogram donor nuclei regardless of the origin of the nucleus and support in vitro development to an advanced stage.

Animals↗

Ovariectomized steroid-treated mares as embryo transfer recipients and as a model to study the role of progestins in pregnancy maintenance.

Embryo transfer into ovariectomized steroid-treated mares was used as a model to evaluate various progestin/estradiol treatments and to determine the level of progesterone necessary for the maintenance of pregnancy in mares. Once a donor mare was in estrus and had a >/=35 mm follicle, an ovariectomized recipient was selected and assigned to one of three groups: 1) 1 mg estradiol (E(2)) was injected subcutaneously daily until the donor mare ovulated; on the day of the donor mare's ovulation, daily intramuscular injections of 300 mg progesterone (P4) were commenced and continued until the end of the experiment (Day 35); 2) E(2) and P4 treatments were identical except E(2) was continued daily until Day 20; and 3) The same E(2) treatment as Group 1, 0.044 mg altrenogest per kilogram body weight were administered daily until Day 35. Embryos were recovered 7 d after the donor mare's ovulation and were transferred via surgical flank incision. Twenty additional embryos (controls) were transferred into intact recipients that ovulated 1 d before to 3 d after the donor. Pregnancy rates did not differ (P>0.05) among groups at Days 14 or 35. Pregnancy rates at Day 35 for mares administered injectable P4 (70%) were identical to those given altrenogest. Overall, pregnancy rates for ovariectomized-progestin treated recipients (28 of 40, 70%) were similar (>0.05) to that of intact mares (16 of 20, 80%). Dose of P4 was decreased in Groups 1 and 2 to 200 mg (Days 35 to 39), 100 mg (Days 40 to 44), 50 mg (Days 45 to 49) and 0 mg (>/=Day 50). Blood samples were collected once on Days 34, 35, 39, 40, 44, 45, 49 and 50 and assayed for P4. Dose of altrenogest was decreased to 0.022, 0.011, 0.0055 and 0 mg per kilogram body weight at Days 35 to 39, 40 to 44, 45 to 49 and >/=50. Number of mares in Groups 1 and 2 that lost their pregnancy while given 200, 100, 50 or 0 mg P4 was 0, 2, 8 and 4, respectively. Doses of 0.022, 0.011, 0.0055 and 0 mg altrenogest per kilogram body weight resulted in 0, 6, 4 and 3 mares aborting. Fetal death did not occur until concentrations of P4 decreased below 2.56 ng/ml 24 h after injection.

Journal Article↗

Barriers to treatment of infertility by in-vitro fertilization and embryo transfer.

A survey was made of 121 patients who withdrew from an in-vitro fertilization and embryo transfer programme, and the reasons leading to withdrawal were solicited by a questionnaire. The most common reasons stated by the 91 patients who returned the survey questionnaires were the heavy financial burden and psychosocial stresses that accompanied treatment. Seventy per cent of these patients expressed a desire to re-enter the programme at a later date.

Adult↗

Performance of different embryo transfer catheters in a human in vitro fertilization program.

In a prospective and randomized study on 400 consecutive embryo transfers (ETs), the performance of three different transfer catheters was evaluated. In cases of difficult ET, the TDT catheter (Prodimed, Neuilly-en-Thelle, France) performed the best. However, the pregnancy rate with this catheter was the lowest (9.2%/ET). A better pregnancy rate (19.4%/ET) can be achieved when TDT catheter was used under ultrasound guidance. The Frydman catheter (Prodimed, Neuilly-en-Thelle, France) yielded the highest pregnancy rate (32.3%/ET) but also the highest frequency of difficult transfer procedures. The Wallace catheter (H.G. Wallace Limited, Colchester, England) showed similar performance, but the pregnancy rate was lower (19.2%/ET) compared with the Frydman catheter. Therefore, the Frydman catheter is used as the first choice, and for difficult transfers the TDT catheter under ultrasound guidance can be recommended.

Animals↗

Very early pregnancy wastage in in vitro fertilization and embryo transfer (IVF-ET).

The occurrence and incidence of early pregnancy wastage in an in vitro fertilization and embryo transfer (IVF-ET) program have been studied in 750 patients. In 297 (39.6%) a pregnancy was diagnosed; of these, 14.8% were biochemical and 24.8% clinical pregnancies. In the latter group 23.6% aborted, while 75.8% had clinical ongoing pregnancies. The mean embryo quality score of the biochemical pregnancy group was similar to that of the clinical ongoing pregnancy group but statistically different from that of the clinical abortion group (P less than 0.005). Furthermore, the clinical ongoing pregnancy rate in women with previous biochemical pregnancy was 24.7%, a significantly higher percentage compared to clinical ongoing pregnancies achieved in IVF-ET cycles (P less than 0.05). It is possible that biochemical pregnancy does not represent an index for infertility but rather an intact stage of reproduction leading toward implantation. The high clinical pregnancy rate in subsequent cycles may probably serve as an encouraging sign or a marker for future clinical pregnancy.

Abortion, Incomplete↗

Transabdominal ultrasound-guided embryo transfer does not increase pregnancy rates in oocyte recipients.

OBJECTIVE: To determine whether transabdominal ultrasound guidance during embryo transfer (ET) is a useful tool for increasing pregnancy rates in patients undergoing oocyte donation. DESIGN: Prospective, randomized, controlled trial. SETTING: In vitro fertilization academic center. PATIENT(S): Three hundred seventy-four infertile patients undergoing oocyte donation. INTERVENTION(S): Transabdominal ultrasound-guided ET. MAIN OUTCOME MEASURE(S): We measured the pregnancy rate and implantation rate after transabdominal ultrasound-guided ET versus the rates in a control group who did not receive transabdominal ultrasound-guided ET. RESULT(S): Clear visualization at ultrasound during ET was achieved in 90.8% of the patients who had ultrasound-guided ET. A similar number of easy transfers were performed in both the ultrasound-guided and the control groups (84.5% vs. 86.6%). The pregnancy rate was comparable between the groups (59.9% ultrasound vs. 55.1% control), as was the implantation rate (30.6% ultrasound vs. 26.3% control). No differences were found in the miscarriage rate (10.7% ultrasound vs. 9.1% control) or in the multiple pregnancy rate (21.4% ultrasound vs. 22.5% control). Although all ectopic pregnancies occurred in the group that did not receive ultrasound guidance, the differences were not statistically significant (0 vs. 2.7%). CONCLUSION(S): We could not show any benefit in terms of pregnancy rate in oocyte recipients for whom ET was performed under direct transabdominal ultrasound visualization of the endometrial cavity. There was a lower ectopic pregnancy rate when ultrasound guidance was used, but this rate was not statistically significant in comparison with the pregnancy rate without ultrasound guidance.

Abdomen↗

Advantages of day 4 embryo transfer in patients undergoing preimplantation genetic diagnosis of aneuploidy.

PURPOSE: Following preimplantation genetic diagnosis of aneuploidy, embryo transfer was executed on day 4, with the aim of providing more time for expanding from six to nine the number of diagnosed chromosomes per single cell (Group 2; 45 cycles). The results obtained were compared to those derived from conventional day 3 transfer (Group 1; 71 cycles). METHODS: For multicolor fluorescence in situ hybridization analysis, two panels of probes were used: the first, specific for chromosomes XY, 13, 16, 18, and 21, was tested in all patients (Groups 1 and 2); the second was implemented only in Group 2 patients for the detection of chromosomes 14, 15, and 22. RESULTS: A total of 406 embryos underwent fluorescence in situ hybridization analysis in Group 1, and 236 in Group 2. Comparable percentages of both chromosomal abnormalities (61% and 62%) and pregnancy and implantation rates (36% and 24.5% in Group 1, 41% and 23.6% in Group 2) resulted, regardless of the higher mean age in Group 2. CONCLUSIONS: The diagnosis of the nine chromosomes which are most frequently associated with aneuploidy in humans could have an immediate impact on the rate of spontaneous abortions. Additional advantages are represented by the more accurate morphological evaluation of euploid embryos; the advanced compaction, which means that embryos are less exposed to damage during the transfer procedure; and the possibility of performing a reanalysis in cases where a fluorescence in situ hybridization diagnosis is not obtained.

Adult↗

Epidural anesthesia in an in vitro fertilization and embryo transfer program.

OBJECTIVES: To investigate the potential advantages of epidural anesthesia in an in vitro fertilization and embryo transfer program. STUDY DESIGN: Between January 1991 and December 1992, 148 infertile patients underwent transvaginal ultrasound guided oocyte retrieval. A total of 44 patients (group A) had 50 retrievals under epidural anesthesia, and 104 patients (group B, control group) 112 retrievals under intravenous sedation (propofol) with mask-assisted ventilation (nitrous oxide). RESULTS: In group A satisfactory anesthesia was achieved in 49 of the 50 cases (98%); one patient required additional intravenous administration of propofol owing to extreme anxiety. No complications were observed. Adversely, in group B nausea was observed in 16 cases (14%) and nausea and vomiting in 7 cases (6%). In group A the fertilization, cleavage and pregnancy rates were 67.2%, 92% and 20% respectively, while in group B the rates were 69.3%, 93% and 19.6% respectively; the differences are not statistically significant. CONCLUSIONS: Epidural anesthesia is an effective method for transvaginal oocyte retrieval but does not improve the treatment outcome as compared to an intravenous sedation with mask-assisted ventilation using propofol and nitrous oxide.

Administration, Inhalation↗

The prognostic value and significance of preclinical abortions in in vitro fertilization-embryo transfer programs.

UNLABELLED: Preclinical abortions occur in natural conceptions as well as in in vitro fertilization-embryo transfer (IVF-ET) cycles. Nevertheless, although known, this entity is ill defined. OBJECTIVE: The purpose of this study was to propose a classification of these pregnancies on the basis of pathophysiological evidence and to evaluate their future clinical impact. DESIGN: Of 970 IVF-ET cycles, 114 cycles (11.7%) terminated in preclinical abortions. Abortions were divided according to peak beta human chorionic gonadotropin (beta-hCG) values into chemical abortions (52%) occurring 2 weeks after ET with beta-hCG values not higher than 21 mIU/mL and peri-implantation abortions (47%) terminating spontaneously 4 weeks after ET; the latter had higher beta-hCG values for a longer period of time but without any sonographic evidence of gestational sac. No woman in the two groups needed curettage. RESULTS: After a chemical abortion, the pregnancy outcome had better ongoing pregnancy rates (24.7%) in comparison with the 17% achieved in the total IVF-ET cycles. CONCLUSIONS: It is concluded that these two groups most probably have different pathophysiological backgrounds and concomitantly different future clinical impacts.

Abortion, Spontaneous↗

Relationship of antisperm antibodies to oocyte fertilization in in vitro fertilization-embryo transfer.

Antisperm antibodies (ASA) appear to impair reproduction; however, their clinical significance in in vitro fertilization-embryo transfer (IVF-ET) is unestablished. For examination of this question, the immunobead binding technique was used to identify IgA, IgG, and IgM ASA in the serum, semen, and follicular fluid (FF) of 40 couples undergoing IVF-ET. ASA binding to sperm tail tip did not predict the fertilization rate of uniformly inseminated mature oocytes. Similarly, ASA binding to sperm head in semen and male serum did not predict fertilization. However, the fertilization rate in couples with ASA to sperm head (ASA-H) of at least one isotype in female serum (n = 6) was significantly less than in those without ASA-H (n = 34; 34% versus 74%, P less than 0.01). Among these women, oocyte fertilization rates were 33% versus 71% (P less than 0.001). Sixty percent of women whose ova did not fertilize (n = 5) had ASA-H in their serum versus 6% of those whose ova did (n = 35; P less than 0.05). The presence of ASA-H in FF also correlated with fertilization. ASA-H in female serum reduced the zygote cleavage rate from 91% to 67% (P = 0.51). We conclude that the presence of ASA-H in female serum and FF is associated with reduced fertilization in IVF-ET.

Antibodies↗

[In vitro fertilization and embryo transfer. 1. The first 100 pregnancies].

The results of treatment of infertility by in vitro fertilization and embryo transfer (IVF-ET) in Rigshospitalet, Copenhagen, are reviewed for 143 patients in whom treatment was completed during the period 1.9.1985-21.2.1988 and for 100 pregnancies during the period 1.9.1985-15.11.1988. Among the 143 patients in whom treatment was completed, 48 became pregnant on one or more occasions as pregnancy occurred in 53 cycles. A total of 44 women delivered 55 infants. There were 35 singleton deliveries, seven twin deliveries and two triplet deliveries. One woman became biochemically pregnant, four aborted before the 12th week of pregnancy an one woman aborted on two occasions in the second trimester. Three women were treated operatively for extrauterine pregnancies. A total of 33.6% of the patients became pregnant, the baby-take-home rate per patient was 30.8%, the pregnancy rate per ET was 23.5% and the delivery rate per transplantation was 19.6%. Non-completed pregnancies per pregnant woman were 20.8%. Only preliminary account of the 100 pregnancies can be given as treatment has not been completed in all of these patients. Among the 100 pregnancies, there were 59 singleton pregnancies, ten twin pregnancies and three triplet pregnancies and 29 pregnancies which were not completed. The age distribution of the pregnant and non-pregnant women (23% over 34 years became pregnant and 53% under 29 years became pregnant) emphasizes the importance of commencing treatment as early as possible.

Denmark↗

[The effect of different anesthetic procedures on hormone levels in women. Studies during an in vitro fertilization-embryo transfer (IVF-ET) program].

Different anaesthetic procedures that were used during an in vitro fertilisation and embryo transfer (IVF-ET) program have been analysed in order to determine their influence on plasma levels of estradiol, progesterone, prolactin, and beta-endorphin and results of IVF-ET. METHODS. Fifty-four patients awaiting transvaginal oocyte aspiration were randomised into three groups: (1) anaesthesia with ketamine as an induction agent and analgesic (n = 20); (2) general intubation anaesthesia using thiopentone for induction and enflurane for maintenance (n = 18); and (3) no anaesthesia (n = 16). Estradiol, progesterone, prolactin, and beta-endorphin were measured from day 3 to 14 referring to follicle aspiration. Differences between preoperative hormone levels and their intra- and postoperative peaks were analysed using the Kruskal-Wallis test (P < 0.03). The results were corrected using the Holms method (alpha = 0.05). RESULTS. No differences were observed in estradiol and progesterone levels (Figs. 1, 2). Prolactin levels were 1.4 times higher (P < 0.001) when ketamine was used and 2.2 times higher (P < 0.001) after short general anaesthesia than in the control group (Fig.3). Similar results were observed with respect to beta-endorphin: in comparison with the control group we found significant elevation by a factor of 2.1 when ketamine was used (P < 0.001). The discrepancy became even more marked with general anaesthesia: beta-endorphin was 3.9 times higher compared to the controls (P < 0.001) (Fig.4). Comparing the two groups who were given anaesthetics, prolactin and beta-endorphin levels were also significantly different (P < 0.001). The IVF procedure itself did not appear to be affected by different anaesthetic procedures during oocyte aspiration (Table 2). CONCLUSIONS. The increased prolactin and beta-endorphin plasma levels associated with ketamine and general anaesthesia reflect a significant alteration of the observed hormone levels. When anaesthesia is indicated, we try to avoid general intubation anaesthesia in favor of ketamine.

Adult↗

Implantation sites after embryo transfer into the central area of the uterine cavity.

A total of 63 pregnancies (47 singleton, 15 twin, 1 triplet) from intracytoplasmic sperm injection cycles were analysed. In all embryo transfers, the catheter was introduced into the endometrial cavity guided by abdominal ultrasound, with the catheter tip placed at the middle point of the endometrial cavity. Gestational sacs (GS) were located 21-24 days after transfer (gestational age=5 weeks) by two-dimensional and three-dimensional transvaginal ultrasound. The uterine cavity was divided into three parts: upper, middle and lower. Furthermore, the upper region was subdivided into right, middle and left areas, and the middle region was subdivided into right and left areas. The frequency of gestational sacs in each area was evaluated. In singleton pregnancies 66.0% (31/47) of the GS were detected in the upper region, 29.8% (14/47) in the middle region and 4.2% (2/47) in the lower region. In multiple pregnancies (twins and triplet) 45.5% (15/33) of the GS were detected in the upper region, 51.5% (17/33) in the middle region and 3.0% (1/33) in the lower region. In conclusion, the results demonstrate that when embryos are transferred to the central area of the uterine cavity there is an increase in implantation rate in the middle region compared with the rate expected in naturally conceived pregnancies (9-15%).

Abortion, Spontaneous↗