Non-homogeneous hyperechogenic pattern 3 days after embryo transfer is associated with lower pregnancy rates

The purpose of this study was to investigate the relationship between mid-luteal phase echo patterns and IVF-embryo transfer outcome in women who have demonstrated adequate endometrial development by the late proliferative phase. A prospective study was carried out of 86 patients undergoing IVF-embryo transfer and 86 patients undergoing frozen embryo transfer who all underwent sonographic monitoring of the endometrium 3 days after embryo transfer. The cycles were classified into two groups: those with the homogeneous hyperechogenic (HH) pattern and those without it. The women who had an HH pattern had higher clinical pregnancy (32.8 versus 10.7%, P < 0.05) and implantation rates in stimulated cycles (14.3 versus 4.1%, P < 0.05 respectively) than those that did not. There was no significant difference in the clinical pregnancy or implantation rates by echo pattern (18.2 and 8.1% for non-HH and 18. 7 and 8.0% for HH respectively) in frozen embryo transfer cycles. These data demonstrate that in embryo transfer cycles where ovarian stimulation was used, there were decreased pregnancy and implantation rates in cycles where the HH pattern was not observed 3 days after transfer. The failure of the endometrium to display this pattern may indicate some endometrial abnormality resulting in implantation defects.     

The embryo versus endometrium controversy revisited as it relates to predicting pregnancy outcome in in-vitro fertilization-embryo transfer cycles

To evaluate embryonic and endometrial factors for their value in predicting pregnancy outcome in in-vitro fertilization (IVF) and embryo transfer, a retrospective data collection and prospective uterine artery colour Doppler imaging study was performed in a university-based IVF-embryo transfer programme setting. A total of 210 patients were included and grouped as follows: (I) IVF with controlled ovarian stimulation (214 cycles); (II) frozen-thaw cycle of autologous embryos (30 cycles); (III) oocyte donation, no cryopreservation (12 cycles); (IV) frozen-thaw cycle with embryos from donated oocytes (10 cycles). Embryo quality was significantly better in pregnant than non-pregnant cycles (group I, P = 0.0104; groups II-IV, P = 0.0418). The endometrial echo was significantly thicker in pregnant versus non-pregnant patients in group I (P = 0.0059), but not in groups II-IV (P = 0.741). Past uterine surgery or abnormalities had no effect on pregnancy outcome. There were no significant differences in mean uterine artery resistance index or peak systolic velocity in pregnant versus non-pregnant patients in groups II-IV. Thus, embryo quality is the most reliable predictor of pregnancy outcome. Endometrial measurements were significantly thicker in subsequently pregnant patients only in group I, where the endometrium reflects the hormonal environment. Doppler parameters were not useful in predicting pregnancy outcome.      

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。     

1169例冻融胚胎移植周期的临床妊娠结局分析

目的探讨影响冻融胚胎移植(FET)妊娠结局的相关因素。方法回顾分析2017年1月至2019年12月在深圳市妇幼保健院行FET的1169对夫妇的临床数据,采用单因素分析和Logistic多因素回归分析探讨FET妊娠结局的相关因素。结果1169个FET周期的临床妊娠率为50.13%;单因素分析表明,年龄>35岁、不孕年限>6年显著降低胚胎种植率和临床妊娠率(P<0.01),但囊胚或多个优胚数目移植可提高胚胎种植率和临床妊娠率(P<0.01);移植多个胚胎提高胚胎种植率(P<0.05),但子宫内膜厚度>12 mm提高临床妊娠率(P<0.05)。多因素Logistic回归分析显示年龄增加和优胚移植数目减少是临床妊娠率的危险因素(P<0.01)。结论患者年龄和移植优胚数目是影响FET的主要因素;年龄增加是临床妊娠结局的危险因素。     

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.     

Antiphospholipid antibodies and the outcome of pregnancy after the first in-vitro fertilization and embryo transfer cycle

Increased antiphospholipid antibody prevalence has been demonstrated by a number of recent studies in in-vitro fertilization (IVF) patients but the potential effects of antiphospholipid antibodies on the different components of the reproductive process and the consideration of whether to test IVF patients for antiphospholipid antibodies are controversial. The present study was undertaken to investigate the possible association between the presence of circulating antiphospholipid antibodies (namely the lupus anticoagulant and anticardiolipin antibodies), among a series of 21 consecutive IVF patients having a clinical spontaneous abortion after their first embryo transfer. As a control group (n=42), the nearest IVF cycle resulting in an ongoing pregnancy before and after each miscarried IVF cycle (i.e. the closest cycles in temporal relationship to the index cycle) was used. One patient (4.8%) in the study group and two women (4.8%) among controls were seropositive for antiphospholipid antibodies. These low and similar seropositivity rates found in the two groups studied lead us to conclude that antiphospholipid antibodies testing in IVF patients should be considered only in those women having repeated failures of implantation/clinical abortion after embryo transfer but not in an infertile general population reaching an IVF programme.      

Maternal serum inhibin A concentrations in early pregnancy after IVF and embryo transfer reflect the corpus luteum contribution and pregnancy outcome

To compare maternal serum inhibin A concentrations in early pregnancy with pregnancy outcomes and treatment protocols, serum samples were collected from 237 women undergoing in-vitro fertilization (IVF) and embryo transfer cycles. Samples were collected on day 16 after oocyte retrieval for beta human chorionic gonadotrophin (HCG) pregnancy testing and inhibin A measurement. The samples were divided into non-pregnant (n = 128) and pregnant (n = 109) groups, the pregnancies were followed and outcomes determined. Inhibin A concentrations were significantly lower in non-pregnant women than in women with ongoing pregnancies (P: < 0.001) and those resulting in spontaneous abortions (P: < 0.001). In ongoing pregnancies, inhibin A concentrations were significantly lower in the absence of functioning ovaries (donor oocyte/embryo) (P: < 0.01) and in natural cycles (frozen-thawed embryo transfer) (P: < 0.01) compared with concentrations after ovarian stimulation. Further, since inhibin A concentrations were not significantly different between singleton and multiple pregnancies in the ovarian stimulation protocol, the size of the early trophoblast does not appear to influence the secretion of inhibin A. These data strongly support the concept that the corpus luteum is a major source of circulating inhibin A in early pregnancy. Additionally, low concentrations of serum inhibin A may be useful in predicting betaHCG-positive preclinical 'biochemical' pregnancies.     

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.     

胚胎移植后不同早孕结局的早期预测

目的建立IVF-ET/ICSI治疗妊娠后早期妊娠结局的预测模型。方法回顾分析114例经IVF-ET/ICSI治疗妊娠的病例,比较孕妇年龄、阴道出血情况、孕酮和β-HCG的动态变化,B超结果和妊娠结局,筛查出有差别的选项建立Fisher判别模型预测妊娠结局。结果利用年龄、ET 14天的激素值、ET 25d前HCG倍增至10 000对妊娠结局的判断准确率为88.6%和71.1%,结合ET 35d的B超表现判断准确率分别为93.0%和96.5%。结论利用以上模型判断妊娠结局具有临床价值,特别当孕5w左右各项情况欠佳时,应加强孕妇管理及早发现异位妊娠。     

Pregnancy outcome after blastocyst transfer as compared to early cleavage stage embryo transfer

BACKGROUND: Retrospective cohort study to evaluate differences in outcome when embryo transfer was performed either on day 2-3 (cleavage stage, CS-group) or on day 4-5 (blastocyst stage, BS-group). METHODS: A total of 1259 consecutive cycles yielding 500 live born babies performed at a single centre in Bregenz, Austria, were included. Main outcome measures were implantation and (multiple) pregnancy rates and neonatal outcome including birth defects. RESULTS: Total Pregnancy rate was 44% vs 28% (P < 0.001) and the total 'take home baby rate' was 37% vs 22% in the BS-group and the CS-group, respectively. Rate of multiple gestations (34% vs 17%, P = 0.001) was significantly higher among the BS-group, resulting in a higher rate of preterm deliveries < 36 weeks (26% vs 17%, P = 0.045). Female factor causing infertility (40% vs 21%, P < 0.001) was significantly higher among the BS-group. For the CS-group, rate of singleton pregnancies (83% vs 66%, P = 0.001) and idiopathic cause of infertility (34% vs 22%, P = 0.012) were significantly higher. No statistically significant differences were found in sex, Caesarean section rate, Apgar score and umbilical artery pH-values, total mean birth weight, admission rate to intensive care unit, days of hospitalization and number of minor and major birth defects. CONCLUSIONS: Our data suggest that blastocyst transfer may lead to a higher pregnancy rate with an overall better take-home baby rate (THBR) at the cost of higher rates of multiples and preterm deliveries.     

The degree of difficulty of embryo transfer is an independent factor for predicting pregnancy

BACKGROUND: The role of embryo transfer as regards the success of IVF/ICSI treatments is recognized but has not been comprehensively evaluated. In order to determine its importance, the degree of difficulty of 4807 embryo transfers after IVF/ICSI was analysed retrospectively. METHODS: Logistic regression analysis identified the age of the subject, type of treatment (IVF versus ICSI), number of embryos transferred and degree of difficulty of embryo transfer as independent factors predicting pregnancy. The main focus of the study was to evaluate the importance of the difficulty of embryo transfer after taking into account the other confounding variables. RESULTS: Embryo transfer was classified as easy (2821), intermediate (1644) or difficult (342). The transfer was considered difficult if it was time consuming, the catheter met great resistance, there was a need to change the catheter, if sounding or cervical dilatation was needed or if blood was found in any part of the catheter. Easy or intermediate transfers resulted in a 1.7-fold higher pregnancy rate than difficult transfers (P < 0.0001; 95% confidence interval: 1.3-2.2). CONCLUSIONS: This study demonstrates that the degree of difficulty of embryo transfer is an independent factor as regards achieving pregnancy after IVF/ICSI. All efforts should be made to avoid difficult embryo transfers. Physicians should be alert to the factors associated with embryo transfer and should be instructed to use a stepwise approach in difficult transfers.     

Relationship between antithyroid antibody and pregnancy outcome following in vitro fertilization and embryo transfer

Objective: To investigate the impact of antithyroid antibody on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET).Methods: A total of 90 patients (156 cycles) positive for antithyroid antibody (ATA+ group) and 676 infertile women (1062 cycles) negative for antithyroid antibody (ATA- group) undergoing IVF/ICSI from August 2009 to August 2010 were retrospectively analyzed.Results: There was no significant difference in the days of ovarian stimulation, total gonadotropin dose, serum E2 level of HCG day and number of oocytes retrieved between the two groups. The fertilization rate, implantation rate and pregnancy rate following IVF-ET were significantly lower in women with antithyroid antibody than in control group (64.3% vs 74.6%, 17.8% vs 27.1% and 33.3% vs 46.7%, respectively), but the abortion rate was significantly higher in patients with antithyroid antibody (26.9% vs 11.8%).Conclusion: Patients with antithyroid antibody showed significantly lower fertilization rate, implantation rate and pregnancy rate and higher risk for abortion following IVF-ET when compared with those without antithyroid antibody. Thus, the presence of antithyroid antibody is detrimental for the pregnancy outcome following IVF-ET.     

女性乙肝病毒携带者体外受精-胚胎移植妊娠结局分析

目的探讨女性乙肝病毒（HBV）携带者行体外受精-胚胎移植（IVF-ET）助孕治疗后的妊娠结局。方法回顾性总结分析2010年3月至2012年12月在我中心因女性不孕进行IVF-ET助孕治疗的患者病历资料共422周期,以女方HBsAg阳性而男方HBsAg阴性为A组：HBV携带组共81个周期;双方均HBsAg阴性为B组：正常对照组共341个周期。比较两组的IVFET治疗结局。结果两组患者在年龄、不孕年限、Gn使用天数及总使用量、获卵数、移植胚胎数无差异的情况下,其受精率、卵裂率、D3优质胚胎率、胚胎种植率、临床妊娠率、早期流产率及总流产率亦无显著性差异（P〉0.05）。结论女性HBV携带者行IVF-ET助孕治疗对妊娠结局没有影响。     

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.     

Ongoing normal pregnancy after transfer of zona-free blastocysts: implications for embryo transfer in the human

Recent reports suggest that transfer of day 5 blastocysts improves implantation rates in in-vitro fertilization programmes. This paper reports a successful ongoing pregnancy after the transfer of zona-free day 6 expanded and hatching blastocysts. The patient was 37 years old and had undergone six stimulated and two thaw cycles previously, all of which had failed. Stimulation was by down-regulation and oocytes recovered transvaginally by ultrasound guidance. Two pronuclear embryos were co-cultured on Vero cells to day 6. The zonae of two hatching and two fully expanded blastocysts were removed using 0.5% pronase, and the zona-free blastocysts were then transferred. Pregnancy was confirmed on day 18 with a positive human chorionic gonadotrophin (HCG) and ultrasound at 6 weeks showed a single healthy fetal heart inside a clear sac. At 14 weeks a triple test (oestriol, J-HCG and alpha- fetoprotein) was normal and at 22 weeks a detailed ultrasound scan showed no congenital anomalies. This is the first report in the human of a normal ongoing pregnancy after the transfer of zona-free day 6 embryos.      

Influence of antiphospholipid antibodies on pregnancy outcome in women undergoing in vitro fertilization and embryo transfer

PROBLEM: Antiphospholipid antibodies (APA) are thought to be involved in recurrent pregnancy loss. Therefore, we investigated the impact of APA on pregnancy outcome in women undergoing in vitro fertilization and embryo transfer (IVF-ET). METHOD OF STUDY: Blood samples taken from 54 Korean women referred for IVF were tested for the presence of APA, anticardiolipin antibody IgG and IgM and lupus anticoagulant. The standard gonadotropin-releasing hormone agonist long protocol was used for ovarian stimulation. RESULTS: Nine patients (16.7%) were positive and 45 (83.3%) were negative for APA. There were no significant differences between the two groups in clinical characteristics such as age, infertility duration, and response to controlled ovarian hyperstimulation. However, pregnancy outcome significantly differed between the two groups (p < 0.05). The APA positive group and APA negative group had abortion rates of 62.5% and 20.0%, respectively and delivery rates of 37.5% and 80.0%, respectively. CONCLUSION: The presence of APA in women undergoing IVF-ET was associated with a poor pregnancy outcome.     

Reply: Pregnancy outcome after blastocyst transfer as compared to early cleavage stage embryo transfer

Sir, We appreciate the interest of van der Ven and Montag in ourstudy and their useful comments. The primary aim of our retrospective cohort study was neonataloutcome. Hence, the purpose     

Transvaginal ultrasound-guided embryo transfer improves pregnancy and implantation rates after IVF.

BACKGROUND: Attempts are constantly being made to improve clinical pregnancy rates after IVF and embryo transfer. Since November 1998, we have gradually been adopting transvaginal ultrasound guidance during embryo transfer. We retrospectively examined the efficacy of this method on pregnancy and implantation rates. METHODS: The results of 846 cycles from our IVF-embryo transfer programme were analysed and comparisons were made between those carried out using ultrasound guidance and those by the clinical touch method. RESULTS: Higher pregnancy and implantation rates (28.9 and 15.2% respectively) were found in the group using the transvaginal ultrasound guidance during embryo transfer compared with those in the group using the clinical touch method (13.1 and 7.0% respectively). The differences were statistically significant (P < 0.01). There was no significant difference in ectopic pregnancy rates between the two groups. CONCLUSION: The use of transvaginal ultrasound-guided embryo transfer significantly improved both pregnancy and implantation rates. Although technically difficult, we suggest its use may maximize the chances of achieving a successful pregnancy outcome.