Clinical outcomes of elective single morula embryo transfer versus elective single blastocyst embryo transfer in IVF-ET

Purpose

To compare the clinical outcomes of elective single morula embryo transfer (eSMET) versus elective single blastocyst embryo transfer (eSBET) in selected patients.

Methods

This study was a retrospective study which analyzed for 271 cycles in women under 37 years of age who are undergoing their first or second trial of in vitro fertilization-embryo transfer (IVF-ET) from January 2008 to December 2009. The eSMET was performed on day 4 (n = 130) and the eSBET was conducted on day 5 (n = 141).

Results

The clinical pregnancy rate (51.5% vs. 51.8%, p = 0.97), implantation rate (52.3% vs. 52.5%, p = 0.98), and live birth rate (39.2% vs. 44.7%, p = 0.36) were similar in the eSMET and eSBET groups, respectively. The miscarriage rate of the eSMET group (23.9%) was slightly higher than that of the eSBET group (13.7%) (p = 0.12), without reaching statistical significance. There was only one case of monozygotic twin pregnancy in each group.

Conclusions

The clinical outcomes of day 4 eSMET were comparable to those of day 5 eSBET. Therefore, day 4 eSMET is a viable option or an alternative to day 5 eSBET, with no difference in success rates.     

Contribution of embryo cryopreservation to elective single embryo transfer in IVF-ICSI

Single embryo transfer is the best way to reduce the risk of multiple pregnancy in IVF-intracytoplasmic sperm injection (ICSI). Between June 2002 and December 2004, all patients (first cycle, female age <38 years) were offered the choice between having one (SET) or two (DET) embryos transferred. Among 493 couples, 428 had at least two good quality embryos, and among them, 32% opted for SET. The SET and DET populations were not comparable (patients in the SET group were younger and had more oocytes retrieved), and therefore a paired, case-control analysis was performed involving 130 SET couples and 130 DET couples, matched according to the female partners' ages and the numbers of embryos available. All of the SET patients, and 82% of the DET group, had at least one embryo cryopreserved, (3.9 versus 2.8 embryos). The option of SET was continued for the frozen-thawed embryo transfers. The pregnancy rate following embryo transfer was significantly lower after SET compared with DET for both fresh (27.6 versus 36.9%; P < 0.05) and frozen-thawed (14.4 versus 23.5%) embryos. However, the cumulative live birth rates following the transfer of fresh and frozen embryos were identical between the two groups (43 versus 45%), with a high prevalence of twins following DET (34 versus 0%).     

Evaluation of possible criteria for elective single embryo transfer

Purpose  

A major problem of assisted reproductive technology (ART) is multiple gestation, which impacts neonatal and perinatal medicine. The literature contains a number of reports that elective single embryo transfer (eSET) is effective for the control of multiple pregnancies; however, to date, uniform criteria have not been established.     

Factors predicting double embryo implantation following double embryo transfer in assisted reproductive technology: implications for elective single embryo transfer

Purpose

The aim of this study was to identify factors associated with double embryo implantation following double embryo transfer (DET) during assisted reproductive technology (ART) procedures and to evaluate the implications of findings in selecting candidates for elective single embryo transfer (eSET).

Methods

Factors predicting double embryo implantation, defined as embryo transfers with two or more heartbeats on 6-week ultrasound following DET, were assessed using the US National ART Surveillance System data from 2000 to 2012 (n?=?1,793,067 fresh, autologous transfers). Adjusted risk ratios (aRRs) were estimated after stratifying by prognosis. Favorable prognosis was defined as first-time ART with supernumerary embryo(s) cryopreserved. Average prognosis was defined as first-time ART without supernumerary embryo(s) cryopreserved, prior unsuccessful ART with supernumerary embryo(s) cryopreserved, or prior ART with previous birth(s) conceived with ART or naturally. Rates and factors associated with double embryo implantation were compared with single embryo implantation following DET among both prognosis groups.

Results

Double embryo implantation was positively associated with blastocyst (versus cleavage) transfer in favorable (aRR?=?1.58 (1.51–1.65)) and average (aRR?=?1.67 (1.60–1.75)) prognosis groups and negatively associated with age >35 years in both prognosis groups. For average prognosis patients, double embryo implantation was associated with retrieving >10 oocytes (aRR?=?1.22 (1.18–1.24)).

Conclusions

Regardless of prognosis, patients aged <35 years with blastocyst-stage embryos and average prognosis patients from whom >10 oocytes were retrieved may be good candidates for eSET. Physicians may consider using these data to counsel patients on eSET, which would reduce multiple gestations and associated complications.

     

Belgian legislation and the effect of elective single embryo transfer on IVF outcome

In order to reduce the number of multiple pregnancies following IVF, the Belgian government agreed to reimburse laboratory expenses for six IVF cycles up to the age of 42 years, in exchange for restriction of the number of embryos replaced. Data on assisted reproduction outcome before and after the introduction of this new legislation were analysed retrospectively in terms of implantation, pregnancy and multiple pregnancy rates. After the introduction of the new law, the percentage of single embryo transfer increased from 14 to 49%. Implantation rates were 25.9 and 23% respectively. There was no difference in the overall pregnancy rate before and after the introduction (36 versus 37%). Twin pregnancies, however, decreased from 19 to 3%. These findings indicate that elective single embryo transfer significantly decreases the twin pregnancy rate without a reduction in the overall pregnancy rate.     

Early cleavage: an additional predictor of high implantation rate following elective single embryo transfer

The value of early cleavage (EC) assessment is still being debated. The aim of this prospective study was to examine the predictive value of EC assessment performed exactly 26 h after insemination by IVF or intracytoplasmic sperm injection (ICSI) in a programme of elective single embryo transfer (SET) performed at day 2. If day 2 scoring demonstrated several embryos with high implantation potential, an EC embryo was transferred preferentially. EC was assessed only during normal laboratory hours so that there were two groups: EC assessed, and EC not assessed, the latter being the control. A total of 277 elective SET were performed in women under 37 years undergoing their first IVF or ICSI cycle (mean age 30.5 years, range 21-37). The overall clinical and ongoing pregnancy rates were 40.1% (111/277) and 32.9% (91/277) respectively. Significantly higher overall clinical and ongoing pregnancy rates were obtained after transfer of an EC embryo than a non-EC embryo: 49.4 versus 33.3% (P < 0.05) and 42.4 versus 25.9% (P < 0.02) respectively. However there was no significant difference between the EC assessed and control groups: 40.4 versus 39.3% and 33.2 versus 32.1 respectively. These findings confirm the value of EC assessment for selection of embryos with high implantation potential.     

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.     

Preimplantation genetic testing and frozen embryo transfer synergistically decrease very pre-term birth in patients undergoing in vitro fertilization with elective single embryo transfer

Purpose

To study the effects of frozen embryo transfer (FET) and FET post-PGT on pre-term and very pre-term births in patients undergoing in vitro fertilization (IVF).

Materials and methods

A study was conducted using the SART National Summary Report from 2014 to 2017. Cycle inclusion criteria were eSET, fresh embryo transfers (ET), frozen embryo transfers without PGT (FET), and frozen embryo transfers with PGT (FET/PGT). Exclusion criteria were use of gestational carriers and donor eggs. Pregnancy outcomes included live births and gestational age at birth.

Results

A total of 161,550 eSETs were analyzed for the effect of FET and FET/PGT on IVF outcome and pre-term births including 43,618 ET, 58,812 FET, and 59,120 FET/PGT cycles. Live birth rates in patients with FET/PGT were significantly higher than those in ET (52.9% vs 46.4%, P < 0.0001) and FET (52.9% vs 43.1%, P < 0.0001). Patients with FET had a significantly lower live birth rate compared with that of ET (43.1% vs 46.4%, P < 0.0001). Both FET and FET/PGT significantly decreased total pre-term births compared with ET (10.8% and 10.5% vs 11.5%, P < 0.05 and < 0.001). FET/PGT significantly reduced very pre-term births when compared with ET and FET (1.5% vs 2.0%, P < 0.0001 and 1.5% vs 1.9%, P = 0.0002).

Conclusion

This study demonstrates that PGT significantly improves IVF outcome. Moreover, patients undergoing FET/PGT had significantly decreased total pre-term births. More importantly, patients with FET/PGT had significantly lower very pre-term births.

     

Towards a single embryo transfer

The delivery of a single, healthy child is the desired outcome of human assisted reproduction techniques. To attain this goal, there is an increasing movement toward single embryo transfer. The question is, therefore, at what stage to transfer the human embryo back to the uterus? Maximal implantation rates reported to date have come from the transfer of blastocysts (70% fetal heart rate). In any given cycle of treatment the probability of conceiving a child will be further increased by the ability to cryopreserve those embryos not transferred. It is therefore proposed that the transfer of a single blastocyst is the best treatment for most patients, given the high implantation rates of fresh transfers, and that it is now possible to cryopreserve supernumerary blastocysts effectively. The next decision is how to culture the human embryo to the blastocyst stage. The use of sequential culture media, designed not only to allow for changes in nutrient requirements and metabolism as development proceeds, but also to minimize intracellular trauma, can facilitate the development of highly viable blastocysts. Sequential culture media have been evaluated against a single-step culture system. It has been shown that sequential media (G1/G2) produce more viable blastocysts than those embryos cultured in a single medium formulation (simplex optimized medium with elevated potassium and with amino acids, KSOM(AA)) throughout the preimplantation period. Furthermore, even if KSOM(AA) is used for embryo culture, it is essential that the medium be renewed after 48 h to alleviate the toxicity associated with ammonium build-up. Of great significance, embryos cultured in sequential media G1 and G2 have the same rate of development as embryos developed in vivo.     

Elective single embryo transfer versus double embryo transfer in assisted reproduction

High numbers of embryos transferred during assisted reproduction have become implicated as the cause of higher than normal twinning and multiple gestation rates following this form of therapy. However, reducing the number to a single embryo transferred has been shown to carry unfavourable results in the first cycle, but with similar cumulative live birth rates. This study tested the theory by performing a randomized controlled trial of elective single embryo transfer (SET) versus double embryo transfer (DET) in young women, and follow them up for 1 year to determine the result of cryo-embryo transfer cycles in the two cohorts. The results showed that the probability of a live birth was not significantly different between the two groups, but with a higher rate of twins in the DET group. In addition, during the 1-year follow-up period, the live birth, clinical pregnancy and multiple pregnancy rates were also similar, and in line with the results of the randomized trial. In conclusion, the results of this prospective randomized trial and 1-year follow-up show that in young women, elective SET should be the first line of choice. Even so, these results should be confirmed by larger randomized studies.     

Impact of elective single embryo transfer criteria on the twin pregnancy rate in a French population

To reduce the twin pregnancy rate and their morbidity, several recommendations have been proposed to practice the "elective single embryo transfer" in a selected population. We decided to apply the criteria that were proposed in five articles from the literature to our population to evaluate the percentage of our population concerned and the impact on our twin pregnancy rate. The result is that these criteria only concern 2,4 to 10,8% of our population with a minor reduction of our twin pregnancy rate with a potential lake of chance concerning the pregnancy rate. We should study others possibilities than the population's criteria to reduce the number of embryo transferred.     

Elective single embryo transfer: Comparison of blastocyst and cleavage-stage embryo transfer

Objective:   Blastocysts are reportedly suitable for preventing multiple pregnancies as a result of the high implantation rate per embryo. The present study compared clinical results for elective single embryo transfer (ET) between blastocysts and cleavage-stage embryos in order to ascertain the usefulness of blastocyst culturing in single ET.
Methods:   Between January 2002 and December 2004, conventional in vitro fertilization ET and/or intracytoplasmic sperm injection was carried out for single ET in 86 cycles, to prevent multiple pregnancies (for medical reasons or because of patient wishes).
Results:   Among the 80 cycles in which a fresh embryo was transferred, pregnancy/implantation rates per ET were 35.3% for day 2/3 ET and 50.0% for day 5 ET, and pregnancy/implantation rates per oocyte retrieval were 35.3% for day 2/3 ET and 44.2% for day 5 ET. Ongoing pregnancy/delivery rates per oocyte retrieval were 32.4% for day 2/3 ET and 38.5% for day 5 ET. Monozygotic twinning occurred in one case of day 5 ET.
Conclusions:   Pregnancy rates per single ET tended to be higher for day 5 ET than for day 2/3 ET. However, no marked differences were identified in ongoing pregnancy/delivery rates per oocyte retrieval between groups. (Reprod Med Biol 2005; 4 : 197–201)     

Monochorionic triplets after single embryo transfer

A 40-year-old patient underwent intracytoplasmic sperm injection and assisted hatching, and a single embryo was transferred. Ultrasonography demonstrated a single gestational sac containing monochorionic tri-amniotic pregnancy. Several factors that have been implicated in the aetiology of monozygotic triple pregnancies after IVF appear to be present in this case. To avoid multiple pregnancies after IVF, it is time to have definite predictive factors for the occurrence of monozygotic multiple pregnancies as well as transferring only a single embryo.     

Safety versus success in elective single embryo transfer: women's preferences for outcomes of in vitro fertilisation

Objective  To assess whether women waiting to undergo in vitro fertilisation (IVF) view adverse outcomes associated with twin pregnancy as more desirable than having no pregnancy at all.
Design  Women's preference values for five adverse birth outcomes associated with twin pregnancy were compared with their preference value for treatment failure (TF), i.e. no pregnancy at all.
Setting  Aberdeen Fertility Centre, University of Aberdeen, UK.
Population  A total of 74 women waiting to undergo IVF.
Methods  The standard gamble method was used to elicit women's preference values for giving birth to a child with physical impairments (PI), cognitive impairments (CI), or visual impairments (VI), perinatal death (PD) without a subsequent pregnancy, premature delivery (PremD), and TF (no pregnancy).
Main outcome measures  Preference values were elicited on a scale where 1 represents giving birth to a healthy child and 0 represents immediate death.
Results  The median preference values for having a child with PI, CI, or VI were 0.940, 0.970, and 0.975, respectively. The median values for PremD, PD, and TF were 0.955, 0.725, and 0.815, respectively. Having no child at all was valued significantly lower than having a child with PI, CI, or VI ( P < 0.01) but significantly higher than PD ( P < 0.01).
Conclusions  Some women waiting for IVF treatment view severe child disability outcomes associated with double embryo transfer as being more desirable than having no child at all. Women embarking on IVF may be influenced more strongly by considerations of 'treatment success' rather than future risks to their offspring.     

Towards single embryo transfer in IVF

Assisted reproductive technologies have, during the last two decades, managed to overcome a majority of the reasons for infertility in both women and men. Also, infertility associated to a specific couple can generally be successfully treated. The techniques have been proven both safe and cost effective. There is, however, one major shortcoming: an adverse effect in terms of multiple pregnancy, sometimes in the high order. The present communication gives suggestions on how to avoid multiple pregnancy by correct application and improvement of techniques already utilized today. Controlled ovarian hyperstimulation, fertilization and culture procedures, preimplantation genetic diagnosis, freezing procedures and prolonged embryo culture are all techniques and applications which need improvement if the goal of a predominance for singletons with only occasional twins should be reached within a predictable future.