Effect of developmental stage of embryo at freezing on pregnancy outcome of frozen-thawed embryo transfer

BACKGROUND: The study aim was to investigate the impact of the developmental stage of embryos on pregnancy outcome of frozen embryo transfer (FET). METHODS: The survival rates of embryos after thawing and pregnancy outcome following FET were compared retrospectively between three cryopreservation strategies utilizing either zygote, day 2 or day 3 embryo freezing. RESULTS: A total of 4006 embryos was analysed in 1657 thaw cycles. The highest (P < 0.0001) survival rate (all cells survived) was observed for zygotes (86.5%), followed by day 2 (61.7%) and day 3 (43.1%) embryos. FET was performed in 1586 (95.7%) of all thaw cycles, resulting in overall clinical pregnancy and implantation rates of 20.7 and 14.2% respectively. The delivery rate per transfer was 16.5%, and live birth rate per transferred embryo 11%. There were no significant differences in clinical pregnancy, implantation, delivery and birth rates between frozen zygote, day 2 and 3 embryo transfers. However, an elevated miscarriage rate was observed in the day 3 group (45%) compared with zygotes (21.3%; P = 0.049) and day 2 embryos (18.3%; P = 0.004). The overall efficacy of FET (birth rate per thawed embryo) was 7.3%. The efficacy was lower in day 3 group (4.2%) than in the zygote (7.1%; P = 0.082) and day 2 (7.6%; P = 0.027) groups. CONCLUSIONS: The developmental stage of embryos at freezing has a profound effect on their post-thaw survival, but seems to have little effect on rates of clinical pregnancy, implantation, delivery and birth after FET. The elevated miscarriage rate for day 3 frozen embryo transfers may be caused by damage during freeze-thaw procedures. The low survival rate and elevated miscarriage rate were both responsible for a reduced overall efficacy for day 3 FET when compared with zygotes and day 2 embryos.     

Ultrasound-guided soft catheter embryo transfers will improve pregnancy rates in in-vitro fertilization

Attempts to improve clinical pregnancy rates after in-vitro fertilization (IVF) and embryo transfer are constantly being made. Two changes in technique of embryo transfer of potential clinical importance were evaluated over two contiguous time periods in order to observe any corresponding change in clinical pregnancy (CP) rate per transfer: (i) embryo transfer catheter; (ii) ultrasound guidance. Catheter choices were hard: Tefcat, Tom Cat, or Norfolk; or soft: Frydman or Wallace. Ultrasound visualization was considered to be excellent/good when the catheter could be followed from the cervix to the fundus by transabdominal ultrasound with retention of the embryo-containing fluid droplet; fair/poor if visualization could not document the sequence of events. Embryo transfers were performed in 518 cycles. CP rates per transfer using soft and hard catheters was 36 and 17% (P < 0.000) respectively. CP rates per transfer for transfers performed with and without ultrasound guidance were 38 and 25% (P < 0.002) respectively. A statistically significant difference was also noted when visualization ranks were compared. CP rates per transfer in all excellent/good ultrasound-guided transfers was 41.5 versus 16.7% for fair/poor transfers (P < 0.038). In conclusion, performance of embryo transfer with a soft catheter under ultrasound guidance with good visualization resulted in a significant increase in clinical pregnancy rates.     

Ultrasound-guided embryo transfer improves pregnancy rates and increases the frequency of easy transfers

BACKGROUND: Recent reports have suggested that ultrasound (US) guidance during embryo transfer might improve pregnancy rates. METHODS: A prospective randomized (computer-generated random table) trial was performed to compare embryo transfer under abdominal US guidance (n = 255 women) with clinical touch embryo transfer (n = 260). RESULTS: The clinical pregnancy rate was 26.3% (67/255) in the US-guided transfer group compared with 18.1% (47/260) in the clinical touch transfer group (P < 0.05). The implantation rate was 11.1% (100/903) in the US group compared with 7.5% (66/884) in the clinical touch group (P < 0.05). US-guided transfer was associated with a decrease in the difficulty of the transfers: 97% of transfers were easy in the US-guided group compared with 81% in the clinical touch group (P < 0.05). CONCLUSIONS: US-guided embryo transfer increased pregnancy and implantation rates in IVF cycles, as well as the frequency of easy transfers. It is suggested that the decrease in cervical and uterine trauma can play a role in the increase in pregnancy rates associated with US-guided transfer. It is recommended that embryo transfer should be performed under US guidance.     

Cervical dilatation has a positive impact on the outcome of IVF in randomly assigned cases having two previous difficult embryo transfers

BACKGROUND: The difficulty of embryo transfer has been reported to affect success rates in some centres, but not in others. Cervical dilatation has been proposed as a means to overcome difficult embryo transfer, but consistent criteria for patient selection are lacking. In a prospective randomized study, we examined the influence of cervical dilatation 1-3 months before embryo transfer on the outcome of IVF in cases having difficult embryo transfer in two previously failed IVF cycles. METHODS: Two alternative methods of embryo transfer preparation were evaluated in 283 randomly assigned women having difficult embryo transfers in two previously failed IVF attempts. Randomization was made using a computer-generated random number table. Cervical dilatation before starting any IVF treatment was used in 145 cases, and no dilatation was performed in 138 cases. RESULTS: The cervical dilatation group yielded a significantly higher pregnancy rate than the non-dilated group (40% versus 24%; P < 0.01). Likewise, the implantation rate (24.1% versus 14.9%; P < 0.01) and the live birth rate (34.48% versus 19.56%; P < 0.01) were significantly higher in the dilatation group than in the non-dilated group. CONCLUSIONS: In patients with prior difficult embryo transfer, cervical dilatation 1-3 months before embryo transfer lead to an improved pregnancy rate.     

Frozen-thawed embryo transfer: influence of clinical factors on implantation rate and risk of multiple conception.

BACKGROUND: Frozen embryo transfer is an important supplementary procedure in the treatment of infertility. While general information concerning the outcome of frozen embryo transfer has been documented, few studies have addressed the potential of embryo implantation in particular clinical situations. Importantly, the risk of multiple conception following frozen embryo transfer has been poorly documented compared with the information available for fresh embryo transfer. METHODS: This is a retrospective study analysing 3570 frozen embryo transfer cycles (1438 couples) with a view to increasing our understanding of the clinical circumstances that influence the potential for embryo implantation. RESULTS: The overall implantation rate was 9.1%. The characteristics associated with a more favourable implantation rate were the success of the previous fresh embryo transfer cycle, age < 40 years and non-tubal factor aetiology of infertility. Such women had an increased risk of multiple conception. CONCLUSION: Female age, the aetiology of infertility and the outcome of fresh embryo transfer are the most important factors influencing the implantation rate following frozen embryo transfer. A prognostic table has been constructed that may assist with the determination of the optimal number of embryos to be replaced in frozen embryo transfer to provide better individualized counselling and to secure an optimal chance of pregnancy while reducing the risk of multiple conception.     

Implantation: Two instead of three embryo transfer in in-vitro fertilization

The rational of transferring two instead of three embryos wasstudied through 468 in-vitro fertilization (IVF) treatment cyclesin 287 couples. The quality of 1224 embryos was determined accordingto the fragmentation rate and the morphology as good (A) andpoor (B). The influence of the number of embryos transferred(two or three) on the pregnancy rate when the same quality orcombinations of good and poor quality embryos transferred wasexamined. When only good quality embryos were transferred thepregnancy rates in double (AA) and triple (AAA) embryo transferwere 40.5 (17/42) and 42.9% (30/70) respectively (not significant).When only poor quality embryos were transferred, the pregnancyrates in double (BB) and triple (BBB) embryo transfers were11.0% (11/ 100) and 22.9% (16/70) respectively (P < 0.001).On the other hand, when good and poor quality embryos were transferredtogether as AB in double and as AAB and ABB in triple embryotransfer, the pregnancy rates were 36.8 (14/38) and 39.9% (59/148)respectively (not significant). There was no difference in themiscarriage rate between double and triple embryo transfers;16.7 and 18.1% respectively. The multiple pregnancy rate was14.3% for double embryo transfers and 32.4% for triple embryotransfers (P < 0.001). This study demonstrates that if thereis at least one good quality embryo available for transfer,then double instead of triple embryo transfer will not yielda significantly lower pregnancy rate. The influence of the numberof embryos transferred on the pregnancy rate became significantwhen only poor quality embryos were transferred. In conclusion,as long as at least one good quality embryo is available fortransfer, we may consider the transfer of double instead oftriple embryos.     

Ultrasound-guided embryo transfer does not offer any benefit in clinical outcome: a randomized controlled trial

BACKGROUND: Ultrasound-guided embryo transfer (ET) is widely suggested as a standard clinical practice that improves overall embryo implantation and pregnancy rates. Various studies of this issue suffer from methodological pitfalls, so that a randomized controlled trial, which overcomes these problems, might be valuable. METHODS: Three hundred women aged <40, who underwent fresh ET, were included in this randomized, double-blind controlled trial. The K-J-SPPE echo tip soft catheter was used for the ultrasound-guided ET and the traditional K-Soft catheter for ETs not using ultrasound. One experienced operator performed all ETs. The primary study outcome was overall pregnancy rate (defined as the number of positive hCG results per transfer). RESULTS: No significant differences between groups were found regarding baseline patient and embryological characteristics, except for male factor and unexplained infertility (higher in the blind and ultrasound-guided ET group, respectively, P < 0.05). Overall pregnancy rates were 53.3 and 51.3% in the ultrasound-guided and blind ET group, respectively. Two ectopic pregnancies were reported in each group. Difficulty in cervical negotiation did not differ between the two groups. CONCLUSIONS: In patients undergoing ET by an experienced operator, ultrasound guidance did not provide any benefit in terms of overall clinical pregnancy and embryo implantation rates.     

Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial.

A prospective randomized study comparing single embryo transfer with double embryo transfer after in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) was carried out. First, top quality embryo characteristics were delineated by retrospectively analysing embryos resulting in ongoing twins after double embryo transfer. A top quality embryo was characterized by the presence of 4 or 5 blastomeres at day 2 and at least 7 blastomeres on day 3 after insemination, the absence of multinucleated blastomeres and <20% cellular fragments on day 2 and day 3 after fertilization. Using these criteria, a prospective study was conducted in women <34 years of age, who started their first IVF/ICSI cycle. Of 194 eligible patients, 110 agreed to participate of whom 53 produced at least two top quality embryos and were prospectively randomized. In all, 26 single embryo transfers resulted in 17 conceptions, 14 clinical and 10 ongoing pregnancies [implantation rate (IR) = 42.3%; ongoing pregnancy rate (OPR) = 38.5%] with one monozygotic twin; 27 double embryo transfers resulted in 20 ongoing conceptions with six (30%) twins (IR = 48.1%; OPR = 74%). We conclude that by using single embryo transfer and strict embryo criteria, an OPR similar to that in normal fertile couples can be achieved after IVF/ICSI, while limiting the dizygotic twin pregnancy rate to its natural incidence of <1% of all ongoing pregnancies.     

The impact of the embryo transfer catheter on the pregnancy rate in IVF

BACKGROUND: The aim was to assess whether the type of embryo transfer set used for embryo transfer affects the ongoing pregnancy rate in IVF. METHODS: The TDT set was compared with the K-soft 5000 in a large, prospective, randomized study. Patients were randomized moments before transfer by drawing a consecutively numbered, sealed, opaque envelope indicating the catheter to be used. RESULTS: 2059 embryo transfers in 1296 patients were analysed. The ongoing pregnancy rate was significantly higher in the K-soft group. If the first transfer of a patient (n = 1296) within this study period was analysed, the ongoing pregnancy rates were 27.1 versus 20.5% (P = 0.006). If the analysis is limited to patients that underwent their very first transfer ever (n = 607), the ongoing pregnancy rates were 30.3 versus 20.0% (P = 0.003) in favour of the K-soft. CONCLUSION: We conclude from these data that the type of embryo transfer set used for embryo transfer does affect the ongoing pregnancy rate and that the impact of the variable transfer catheter on the ongoing pregnancy rate increases when the a priori chance of pregnancy increases.     

High serum oestradiol concentrations in fresh IVF cycles do not impair implantation and pregnancy rates in subsequent frozen-thawed embryo transfer cycles

High oestradiol concentrations may be detrimental to the success of in-vitro fertilization (IVF) treatment. A total of 1122 women aged <40 years who were undergoing their first IVF cycle were evaluated retrospectively. Serum oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration were categorized into three groups: group A <10 000 pmol/l; group B 10 000-20 000 pmol/l and group C >20 000 pmol/l. In fresh cycles, group A had significantly lower pregnancy rates per transfer (16.2 versus 23.7% respectively, P = 0.005, chi(2)) and implantation rates (8.7 versus 11.7% respectively, P = 0.037, chi(2)), when compared with group B. The pregnancy rate per transfer in group C was significantly lower than that in group B (12.1 versus 23.7%, P = 0.049, chi(2)) and group C had the lowest implantation rate (6.4%). In frozen-thawed embryo transfer cycles, implantation rates in groups A, B and C were similar (7.5, 8.1 and 9.6% respectively) and the pregnancy rates were also comparable in all groups. In conclusion, high serum oestradiol concentrations in fresh IVF cycles may adversely affect implantation and pregnancy rates. Embryo quality seemed unaffected as excess embryos from different groups had similar implantation and pregnancy rates in frozen-thawed embryo transfer cycles. The reduced implantation was probably due to an adverse endometrial environment resulting from high serum oestradiol concentrations.     

IVF-ET新鲜周期移植不孕而冷冻周期妊娠的相关因素分析

目的探讨IVF-ET助孕治疗中新鲜周期移植不孕而后续的冷冻周期成功妊娠的原因以指导治疗。方法回顾性分析体外受精或单精子卵母细胞浆内注射-胚胎移植术（IVF/ICSI-ET）治疗患者950个周期,其中新鲜周期妊娠组780个周期和新鲜周期未孕冷冻周期妊娠组170个周期,比较两组患者年龄、不孕年限、病因及基础FSH水平、Gn使用情况、hCG日内膜、激素水平、卵泡数、获卵及胚胎情况的差异。采用单因素分析筛选出差异有统计学意义的因素进行多因素分析。结果经Logistic回归分析得出hCG日P4、hCG日E2/1000是妊娠的独立影响因素。hCG日P4（OR=1.653,P=0.015,95%CI：1.101～2.482）,hCG日E2/1000（OR=1.219,P=0.001,95%CI：1.085～1.369）。hCG日酮孕每增加1ng/ml,新鲜周期不孕而冷冻周期妊娠的风险将增加1.653倍。hCG日E2每增加1000pg/ml,新鲜周期不孕而冷冻周期妊娠的风险将增加1.219倍。结论 hCG日的P4和E2是导致新鲜移植不孕而冷冻周期妊娠的重要原因。P4和E2过高,可考虑放弃新鲜移植,采用冷冻移植。     

Day 2 elective single embryo transfer in clinical practice: better outcome in ICSI cycles

BACKGROUND: Single embryo transfer (SET) after IVF/ICSI has been shown to result in an acceptable pregnancy rate in selected subjects. In our unit, SET is routinely carried out among women under the age of 36 in the first or second treatment cycle when a top-quality embryo is available. In order to define further the selection criteria for SET, we have analysed the outcome of elective SET (eSET), including the cumulative pregnancy rate after frozen embryo transfers, performed in the years 2000-2002 in the Oulu Fertility Center. METHODS: During the study period, a total of 1271 transfers were performed, and in 468 cycles SET (39% of all transfers) was carried out. Of the SET cycles, in 308 cases a top-quality embryo was transferred on day 2 and extra embryos were frozen. Of these eSET cycles, ICSI was carried out in 87 cycles (28%). RESULTS: The overall clinical pregnancy rate per transfer was 34.7% in the eSET cycles. In the eSET ICSI cycles, the clinical pregnancy rate was significantly higher than in the corresponding IVF cycles (50.6 versus 28.5%, P < 0.001). The cumulative pregnancy rate per patient after fresh and frozen embryo transfers was also significantly higher after ICSI (71.2 versus 53.4%, P < 0.01). CONCLUSIONS: A high cumulative pregnancy rate per oocyte retrieval can be achieved after eSET in daily clinical practice. The implantation rate of fresh top-quality embryos in the ICSI cycles was significantly higher than in the IVF cycles, possibly due to more successful selection of the embryo for embryo transfer on day 2 after ICSI. In addition, our data suggest that embryo quality is a more important determinant of outcome than the age of the woman.     

冷冻前和复苏后胚胎质量对临床结局的影响

目的将复苏后胚胎按冷冻前是否含有优胚和/或是否同冻存时分组,比较他们的妊娠结局,探讨是冷冻前的胚胎质量还是复苏后胚胎是否同冻存时,对妊娠结局的影响更大。方法本中心2008.01-2010.12期间促排获得胚胎并冻存,患者年龄<35岁,复苏并移植2枚胚胎的683周期,共分四组:A组同冻存时,≥1枚优胚;B组同冻存时,0枚优胚;C组≥1枚有球溶解可用胚,≥1枚冻前优胚;D组≥1枚有球溶解可用胚,0枚冻前优胚。分析各组妊娠率、多胎率的差异。结果总复苏率94.08%,冻前优胚复苏率98.01%(395/403),高于冻前非优胚复苏率92.56%(971/1049),P<0.01。A组比B组、A比D组、A+C组比B+D组妊娠率高(P<0.01),C组比B组妊娠率高(P<0.05),多胎率没有统计学差异;A组比C组、B组比D组、A+B组比C+D组的妊娠率、多胎率都没有统计学差异。结论冷冻前胚胎质量比复苏后胚胎是否同冻存时对妊娠结局有更大影响。     

The usefulness of ultrasound guidance in frozen-thawed embryo transfer: a prospective randomized clinical trial

BACKGROUND: Recent randomized controlled trials have shown that implantation and pregnancy rates were improved with ultrasound-guided embryo transfer compared with clinical touch in fresh IVF cycles associated with supraphysiological ovarian steroid levels. However, the usefulness of ultrasound guidance in frozen-thawed embryo transfer where potential hormonal influences are lacking has not been appropriately investigated. METHODS: A total of 184 consecutive patients undergoing thawed embryo transfer cycles with hormone replacement under pituitary suppression were randomized by computer-generated randomization table to two study groups: 93 had ultrasound-guided (group 1) and 91 had clinical touch (group 2) embryo transfer. RESULTS: There was equal distribution between the two study groups with respect to the main demographic and baseline characteristics of the patients as well as the characteristics of both prior IVF cycles from which embryos were generated and cryopreserved-thawed embryo transfer cycles. However, both pregnancy and implantation rates in group 1 (34.4 and 19.8% respectively) were significantly higher than the corresponding values (19.7 and 11.9%) in group 2. CONCLUSIONS: Ultrasound guidance in frozen-thawed embryo transfer significantly increases pregnancy and implantation rates.     

Obstetric and neonatal outcome after single embryo transfer

BACKGROUND: Single embryo transfer (SET) pregnancies practically lack vanishing twins and may be associated with improved neonatal outcome. Our objective was to compare the obstetric and neonatal outcome of SET singletons with the outcome of singletons following double embryo transfer (DET) and spontaneous conception. METHODS: A 7-year (1997-2003) cohort of fresh SET (n = 269) and DET (n = 230, including 25 vanishing twins) cycles resulting in singleton birth at Helsinki University Central Hospital, Finland, was linked to the Finnish Medical Birth Register and the obstetric and neonatal outcome data compared with that from 15 037 spontaneously conceived singleton pregnancies. RESULTS: The obstetric and neonatal outcome of the SET group was comparable to that in the DET group. Compared with the comparison cohort, gestational hypertension (P = 0.005), placenta praevia (P < 0.001), preterm contractions (P = 0.01) and maternal hospitalization (P < 0.001) was more typical of women in the SET group. After adjusting for age, parity and socio-economic status the SET pregnancies showed increased risks of Caesarean section [odds ratio (OR) 1.54 with 95% confidence interval (CI) 1.18-2.00], preterm birth (OR 2.85; 95% CI 1.96-4.16) and low birthweight (OR 2.01; 95% CI 1.19-3.99) compared with the comparison cohort. CONCLUSIONS: Our results indicate that subject- and infertility-related mechanisms other than the number of transferred embryos influence the neonatal outcome of singleton IVF pregnancies.     

Ultrasound-guided embryo transfer and the accuracy of trial embryo transfer

BACKGROUND: Studies have suggested that ultrasound-guided embryo transfer (UG-ET) may improve the outcome in IVF; however, several factors may account for the improvement in pregnancy rate. This study examines the use of ultrasound to determine the accuracy of trial transfer (TT) in preparation for ET. METHODS: Sixty-seven consecutive patients prospectively underwent UG-ET over a 2 month period. Total cavity length by US was compared with the length noted by TT. A difference of > or = 1 cm was considered significant. All embryos were placed within 1-2 cm of the fundus by US. RESULTS: Twenty patients (29.9%) had a difference of > or = 1 cm and 13 patients (19.4%) had a difference of < or = 1.5 cm. Patients with a difference of > or = 1 or > or = 1.5 cm had a significantly greater depth at transfer (P < 0.001) and uterine cavity length (P < 0.001) when compared with patients without a difference. Clinical pregnancy, implantation, delivery and overall miscarriage rates did not differ between patients with a difference of > or = 1 or > or = 1.5 cm versus no difference. There were no ectopic pregnancies. CONCLUSIONS: Nineteen percent of patients had a discrepancy of > or = 1.5 cm and approximately 30% had a difference of > or = 1 cm from TT at UG-ET, suggesting a benefit to UG-ET. A large prospective randomized trial comparing UG-ET with blind transfer is required to assess further if UG-ET should be used in all cases of ET.     

Single top quality embryo transfer as a model for prediction of early pregnancy outcome

BACKGROUND: Single embryo transfer (particularly of a top quality embryo) is an excellent model to correlate embryo quality in terms of morphological criteria to early pregnancy. We investigated whether this model could provide us with more information on what happens after implantation in the first trimester of pregnancy. METHODS: The outcome of 370 consecutive single top quality embryo transfers in patients younger than 38 years was analysed for pregnancy and first-trimester pregnancy loss (FTPL) before 13 weeks of gestation. Analysis was done on each cohort of embryos from which the transferred top quality embryo was selected. Serum HCG levels were measured on day 8 and day 12 after day 3 embryo transfer. The HCG index was calculated as the level of HCG on day 12/HCG on day 8. RESULTS: The pregnancy rate after single top quality embryo transfer was 51.9%. This was independent of the patients' age. FTPL, however, appeared to be age dependent: 15.4% for the whole group, 9% in patients younger than 30 years and 19% in patients above 30 years. The pregnancy rate was 50% in IVF cycles and 52% in ICSI cycles; FTPL was 19% in IVF cycles and 10% in ICSI cycles. Multiple regression analysis showed that these differences originated from age differences between both populations rather than from technique-related factors. An HCG level >or=45 IU/l on day 12 was predictive for ongoing pregnancy with 75.6% sensitivity and 100% specificity; an HCG index >or=3.5 similarly predicted ongoing pregnancy with 72.3% sensitivity and 100% specificity. CONCLUSIONS: These data show that embryo selection for transfer on day 3 can be used as an excellent tool for prediction of pregnancy but not for prediction of FTPL. The pregnancy rate of a single top quality embryo is not related to age, whereas FTPL is age dependent.     

A randomized controlled clinical trial of 2295 ultrasound-guided embryo transfers

BACKGROUND: We wanted to test the hypothesis that using abdominal ultrasoundat the time of embryo transfer to guide replacement, improvedpregnancy rates by at least 5%. METHODS: An RCT in a large assisted conception unit. A pilot study andpower calculation suggested that at least 2000 embryo transferswere required to demonstrate a difference of 5%, for a testwith 80% power and Type 1 error 0.05. Randomization, data entryand analysis were arranged independently. Randomization wasstratified for age and fresh/frozen embryo transfer. Analysiswas by intention to treat. RESULTS: There was no difference in clinical pregnancy or live birthrates between the two groups. The clinical pregnancy rate forultrasound-guided embryo transfer was 22% and for non-ultrasound-guidedembryo transfer was 23% (odds ratio: 0.96; 95% confidence interval:0.79–1.18). CONCLUSIONS: We set out to determine whether ultrasound-guided embryo transferimproved clinical pregnancy rates and live birth rates in assistedconception. We used an appropriately powered RCT design. Wedid not demonstrate a difference. This outcome is at odds withthe UKs National Institute of Clinical Excellence recommendationsfor fertility treatment (Fertility Assessment and Treatmentfor People with Fertility Problems. London, UK: RCOG Press,2004, 112.) which used a meta-analysis of four smaller trials(range 362–800 patients, totalling 2051 embryo transfers)to conclude that ultrasound should be offered. We suggest thatthe current Cochrane review should be updated with data fromour trial and recommend that consideration is given to accountingfor heterogeneity between the included trials.     

The use of fibrin sealant for embryo transfer: development and clinical studies.

Many embryo transfers after in-vitro fertilization may fail because of expulsion of the embryos from the uterus. Approximately 5-8% of pregnancies resulting from embryo transfer are ectopic. The aim of our study was to find a technique to avoid ectopic pregnancies and to improve the pregnancy rate. We used a two-component fibrin sealant which also contains a fibrinolysis inhibitor (aprotinin) at various concentrations. After gaining experience with mouse embryos, the sealant was used in human embryo transfer with great success. The results of a pilot study encouraged us to perform a prospective randomized study on 546 patients (270 with fibrin sealant, 276 conventional embryo transfers). There were 47 (17.0%) orthotopic pregnancies and 6 (2.2%) ectopic pregnancies in the control group, whereas there were 51 (18.9%) intrauterine and no ectopic pregnancies in the treatment group. The difference in ectopic pregnancies was statistically significant (P less than 0.05). With regard to the aprotinin concentration, there was a trend towards better results with 100-150 kIU (28.5% clinical pregnancies) in comparison to 250-300 kIU (19.2%) or no aprotinin (20.4%) (not significant). Further improvements of the technique may raise the pregnancy rate when fibrin sealant is used. As shown in our prospective randomized study, ectopic pregnancies may be completely avoided.     

High outcome predictability after IVF using a combined score for zygote and embryo morphology and growth rate

BACKGROUND: A scoring system has been developed to determine preimplantation embryo quality, and used to select embryos for transfer into the uterus of patients. METHODS AND RESULTS: The system was used to study early embryo development and to test whether these scores alone can accurately predict IVF outcome. Following zygote and embryo scores through early development, the data showed that a top quality zygote does not necessarily indicate that the resulting embryo will be top quality after in-vitro culture. The embryo quality score can change dramatically when embryos are cultured to day 2 or 3 post-fertilization. Pregnancy rates and implantation rates were compared with the cumulative and separated zygote and embryo scores. Analysis of the predictability of scoring systems suggested that morphological scores alone are relatively unpredictive of IVF outcome. When weighted for in-vitro growth rate, scores were highly predictive, more so than the rate of development alone. CONCLUSIONS: These data suggested that a combination of in-vitro growth rate and morphological analysis both of zygotes and embryos was highly indicative of outcome after IVF. The results can be adopted to the single embryo transfer approach to IVF.