Comparison of pregnancy outcomes between 4th day morula and 5th day blastocyst after embryo transfer: a retrospective cohort study.

BACKGROUND: This study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5). METHODS: From September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes. RESULTS: In single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P < 0.05). The preterm delivery rate, twin delivery rate, cesarean delivery rate, and percentage of low birthweight infants were lower in the D5A group than in the D5B group (P < 0.05). Analysis of factors influencing live birth outcomes further confirmed the absence of a significant difference between D4 and D5 transplantation in achieving live birth (P > 0.05). CONCLUSION: When factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.

Ongoing pregnancy rates in single euploid frozen embryo transfers remain unaffected by female age: a retrospective study.

RESEARCH QUESTION: Is female age a significant factor in the likelihood of an ongoing pregnancy in single euploid frozen embryo transfers (FET)? DESIGN: Retrospective study of 1923 single euploid FET cycles in 1464 women, either in a natural cycle or a hormone replacement therapy cycle. The primary outcome was the ongoing pregnancy rate (OPR). RESULTS: There were 990 (51.48%) ongoing pregnancies among 1923 included transfers. The OPR were 51.4%, 49.1%, 53.3% and 52.3% for women aged ≤35, >35-≤37, >37-≤40 and >40 years at oocyte retrieval (OCR), without a significant trend for decreasing OPR (P = 0.679). No significant differences in female age at embryo transfer (P = 0.609) and female age at OCR (P = 0.816) were found between the groups (ongoing pregnancy versus no pregnancy or miscarriage). Women who received good-quality embryos (P < 0.001), had a lower body mass index (BMI) (P < 0.001), had achieved at least one pregnancy previously (P < 0.001), and underwent natural cycle endometrial preparation (P < 0.001) were more likely to achieve an ongoing pregnancy. Multivariable regression analysis (adjusted for BMI, embryo quality and endometrial preparation) did not show a significant effect of female age at OCR on achieving an ongoing pregnancy. Compared with women aged ≤35 years, none of the age groups had significantly higher or lower OPR. A multinomial regression analysis showed that BMI, embryo quality and endometrial preparation were associated with miscarriage/no pregnancy versus ongoing pregnancy (P = 0.001, 0.001 and 0.001, respectively). Female age had no significant association with either outcome. CONCLUSIONS: Female age in itself does not have a substantial impact on the OPR in single euploid FET cycles, but the OPR is impacted significantly by embryo quality, BMI, previous parity, and a natural cycle endometrial preparation protocol.

Comparisons of benefits and risks of single embryo transfer versus double embryo transfer: a systematic review and meta-analysis.

BACKGROUND: Evidence referring to the trade-offs between the benefits and risks of single embryo transfer (SET) versus double embryo transfer (DET) following assisted reproduction technology are insufficient, especially for those women with a defined embryo quality or advanced age. METHODS: A systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were searched based on established search strategy from inception through February 2021. Pre-specified primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR). Odds ratio (OR) with 95% confidence interval (CI) were pooled by a random-effects model using R version 4.1.0. RESULTS: Eighty-five studies (14 randomized controlled trials and 71 observational studies) were eligible. Compared with DET, SET decreased the probability of a live birth (OR = 0.78, 95% CI: 0.71-0.85, P < 0.001, n = 62), and lowered the rate of multiple pregnancy (0.05, 0.04-0.06, P < 0.001, n = 45). In the sub-analyses of age stratification, both the differences of LBR (0.87, 0.54-1.40, P = 0.565, n = 4) and MPR (0.34, 0.06-2.03, P = 0.236, n = 3) between SET and DET groups became insignificant in patients aged ≥40 years. No significant difference in LBR for single GQE versus two embryos of mixed quality [GQE + PQE (non-good quality embryo)] (0.99, 0.77-1.27, P = 0.915, n = 8), nor any difference of MPR in single PQE versus two PQEs (0.23, 0.04-1.49, P = 0.123, n = 6). Moreover, women who conceived through SET were associated with lower risks of poor outcomes, including cesarean section (0.64, 0.43-0.94), antepartum haemorrhage (0.35, 0.15-0.82), preterm birth (0.25, 0.21-0.30), low birth weight (0.20, 0.16-0.25), Apgar1 < 7 rate (0.12, 0.02-0.93) or neonatal intensive care unit admission (0.30, 0.14-0.66) than those following DET. CONCLUSIONS: In women aged < 40 years or if any GQE is available, SET should be incorporated into clinical practice. While in the absence of GQEs, DET may be preferable. However, for elderly women aged ≥40 years, current evidence is not enough to recommend an appropriate number of embryo transfer. The findings need to be further confirmed.

Monochorionic twins after single blastocyst transfer: retrospective cohort and blinded time lapse annotation analysis.

RESEARCH QUESTION: Is it possible to identify monochorionic twin pregnancies before blastocyst transfer based on maternal or embryo characteristics registered by time lapse? DESIGN: A retrospective cohort study including women who received fertility treatment (n = 6501) between 2010 and 2019 at two fertility clinics in central Denmark. The treatment resulted in 2239 pregnancies after single embryo transfer (SET) and, of those, 43 (1.92%) were monochorionic twins. Baseline characteristics, information on assisted reproductive technology and ultrasonic findings at gestational week 8 were collected on all women. Furthermore, a blinded time lapse annotation analysis was conducted by two independent laboratory technicians on a total of 85 embryos. A total of 22 embryos leading to monochorionic pregnancies were matched with 63 embryos leading to singleton pregnancies. RESULTS: A monochorionic twin rate of 1.92% was found. No significant difference was found in maternal age, the use of intracytoplasmic sperm injection compared with IVF, indication for treatment or other maternal characteristics. In the blinded annotation analysis, inner cell mass grade A was associated with an increased risk of twinning (P = 0.04) in fresh embryos. The s3 division timing was found to be significantly shorter in fresh twin compared with singleton embryos (P = 0.006). No other time lapse parameters were found to be characteristic of twin embryos. CONCLUSION: To the best of our knowledge, this is the first blinded annotation study to identify aspects in time lapse resulting in monochorionic twins after SET. Whether inner cell mass grade A and s3 reflect a biological background for monochorionic twinning merits further investigation.

Deep learning neural network analysis of human blastocyst expansion from time-lapse image files.

RESEARCH QUESTION: Can artificial intelligence (AI) discriminate a blastocyst's cellular area from unedited time-lapse image files using semantic segmentation and a deep learning optimized U-Net architecture for use in selecting single blastocysts for transfer? DESIGN: This platform was retrospectively applied to time-lapse files from 101 sequentially transferred single blastocysts that were prospectively selected for transfer by their highest expansion ranking within cohorts using a 10 h expansion assay rather than standard grading. RESULTS: The AI platform provides expansion curves and raw data files to classify and compare blastocyst phenotypes within both cohorts and populations. Of 35 sequential unbiopsied single blastocyst transfers, 23 (65.7%) resulted in a live birth. Of 66 sequential single euploid blastocyst transfers, also selected for their most robust expansion, 49 (74.2%) resulted in live birth. The AI platform revealed that the averaged expansion rate was significantly (P = 0.007) greater in euploid blastocysts that resulted in live births compared with those resulting in failure to give a live birth. The platform further provides a framework to analyse fragmentation phenotypes that can test new hypotheses for developmental regulation during the preimplantation period. CONCLUSIONS: AI can be used to quantitatively describe blastocyst expansion from unedited time-lapse image files and can be used to quantitatively rank-order blastocysts for transfer. Early clinical results from such single blastocyst selection suggests that live birth rates without biopsy may be comparable to those found using single euploid blastocysts in younger, good responder patients.

The biochemical pregnancy loss rate remains stable up irrespective of age and differs in pattern from clinical miscarriages.

INTRODUCTION: As women age, the increasing rate of aneuploidy lead to an augmentation in the incidence of clinical miscarriages. It was anticipated that biochemical pregnancy rates would also rise with maternal age. However, no study has previously evaluated the effect of maternal age on biochemical pregnancy rates. MATERIAL AND METHODS: A retrospective cohort study of 2177 subjects who underwent single embryo transfer (SET) as part of a fresh or thawed IVF cycle were recruited from 2008 through 2012, resulting in 952 pregnancies. Data was stratified for age and compared using analysis of variance (continuous data) and chi-squared tests (categorical data). RESULTS: The likelihood of a clinical miscarriage increased with age (p < .001). Surprisingly, advancing age had no effect on the biochemical pregnancy loss rate (p = .72) (Age 21-30 y: 10.7%, Age 31-35 y:9.8%, Age 36-40y:11.5%, Age 41-42 y:13.6%). CONCLUSIONS: Biochemical pregnancy loss rate did not increase as a function of age in women 21 to 42 years of age.

Rate of true recurrent implantation failure is low: results of three successive frozen euploid single embryo transfers.

OBJECTIVE: To study the true prevalence of recurrent implantation failure. DESIGN: Retrospective cohort study. SETTING: A private assisted reproductive technology center. PATIENT(S): Women (n = 4,429) with anatomically normal uterus who underwent up to three consecutive frozen euploid single embryo transfers (FE-SETs) were included in the study. Cycles with donor eggs or gestational carriers were excluded. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cumulative outcomes from these cycles were analyzed. A logistic regression model was used to assess the differences of outcomes between first, second, and third FE-SET and a Kaplan-Meier curve as used to analyze cumulative implantation rate. RESULT(S): The mean age of the patients included in the study was of 35.4 years. The sustained implantation rates of the first, second, and third FE-SET were 69.9%, 59.8%, and 60.3% per transfer, respectively. The cumulative sustained implantation rate after up to three consecutive FE-SET was 95.2%. The live birth rates after the first, second, and third FE-SET were 64.8%, 54.4%, and 54.1% per transfer, respectively. The cumulative live birth rate after up to three consecutive FE-SET was 92.6%. The miscarriage rate after observing a positive heartbeat was not different between the first (7.2%), second (8.8%), and third (12.7%) FE-SET. CONCLUSION(S): Our findings suggest that true recurrent implantation failure is rare. For those patients with the ability to make euploid blastocysts, <5% would fail to achieve a clinical pregnancy with three embryos transferred. It remains to be further investigated whether this threshold identifies a truly recalcitrant group or simply a statistical certainty based on random variation.

Does the transfer of a poor quality embryo with a good quality embryo benefit poor prognosis patients?

BACKGROUND: While single embryo transfer (SET) is widely advocated, double embryo transfer (DET) remains preferable in clinical practice to improve IVF success rate, especially in poor prognosis patients with only poor quality embryos (PQEs) available in addition to one or no good quality embryos (GQEs). Furthermore, previous studies suggest PQE might adversely affect the implantation of a GQE when transferred together. This study aims to evaluate the effect of transferring an additional PQE with a GQE on the outcomes in poor prognosis patients. METHODS: A total of 5037 frozen-thawed blastocyst transfer (FBT) cycles between January 2012 and May 2019 were included. Propensity score matching was applied to control for potential confounders, and we used generalized estimating equations (GEE) models to identify the association between the effect of an additional PQE and the outcomes. RESULTS: Overall, transferring a PQE with GQE (Group GP) achieved significantly higher pregnancy rate (PR), live birth rate (LBR) and multiple pregnancy rate (MPR) than GQE only (group G). The addition of a PQE increased LBR in patients aged 35 and over and in patients who received over 3 cycles of embryo transfer (ET) (48.1% vs 27.2%, OR:2.56, 95% CI: 1.3-5.03 and 46.6% vs 35.4%, OR:1.6, 95% CI: 1.09-2.35), but not in women under 35 and in women who received less than 3 cycles of ET (48.7% vs 43.9%, OR:1.22, 95% CI: 0.93-1.59 and 48.3% vs 41.4%, OR:1.33, 95% CI: 0.96-1.85). Group GP resulted in significantly higher MPR than group G irrespective of age and the number of previous IVF cycles. CONCLUSIONS: An additional PQE does not negatively affect the implantation potential of the co-transferred GQE. Nevertheless, the addition of a PQE contributes to both live birth and multiple birth in poor prognosis patients. Physicians should still balance the benefits and risks of DET.

Outcome of two sequential singleton pregnancies and twin pregnancies among primiparous women at advanced age undergoing IVF.

PURPOSE: To compare the obstetrical and detailed neonatal outcomes of primipara of advanced maternal age conceiving two sequential singleton pregnancies by IVF with those of primipara conceiving twins by IVF. METHODS: A retrospective study of all primiparous women aged ≤ 38 years and conceived by IVF who delivered sequential singletons or delivered twins at a single tertiary university affiliated medical center between 2011 and 2019. We performed two main comparisons: 1. First vs. second singleton pregnancies. 2. Two singleton pregnancies vs. twin pregnancies. RESULTS: Overall, there were 63 women with consecutive singleton IVF pregnancies. The median age was 40.0 at first pregnancy and 42.0 in the second pregnancy. Pregnancy and delivery complications rates did not differ significantly between the first and the second singleton pregnancies, including gestational hypertensive disorders (7 (11.1%) vs. 4 (6.3%), p = 0.530), gestational diabetes mellitus (13 (20.6%) vs 18 (28.5%), p = 0.410), intrauterine growth restriction (6 (9.5%) vs. 4 (6.3%), p = 0.744), or cesarean delivery (25 (39.7%) vs. 29 (46%), p = 0.589). Rates of delivery before 32 weeks gestation were similar for both first and second singleton pregnancies (1.6%, p > 0.999). The proportion of neonatal adverse outcome in both first and second singleton pregnancies groups was low and did not differ between the groups. Compared with women who delivered sequential singletons, women with twin pregnancies had significantly higher cesarean delivery rates (113 (83.7%) vs. 29 (46%), p < 0.001) and lower gestational ages at delivery (36.2 vs. 38.4, p < 0.001) than women with two singleton deliveries. Adverse neonatal outcomes were significantly higher for twin pregnancies, including birthweight < 1500 g (17 (12.6%) vs. 2 (3.2%), p = 0.036), neonatal intensive care unit admission (57 (42.2%) vs. 4 (6.3%), p < 0.001), neonatal hypoglycemia (23 (17%) vs. 3 (4.8%), p = 0.017), and respiratory distress syndrome (14 (10.4%) vs. 1 (1.6%), p = 0.040). Length of neonatal hospitalization was significantly longer for twins (9 vs. 5 days, p < 0.001). The rate of gestational hypertensive disorders (preeclampsia and gestational hypertension) was similar between the groups, but the rates of severe preeclampsia trended higher among women who carried twins (8 (5.9%) vs. 0, p = 0.057). CONCLUSIONS: Sequential singleton pregnancies at primipara women of advanced maternal age have an overall very good outcome, with no clinically significant difference between the pregnancies. In addition, their outcome is much better compared with twins.

Does the sex ratio of singleton births after frozen single blastocyst transfer differ in relation to blastocyst development?

PURPOSE: To investigate the associations between blastocyst development and the sex ratio (male:female) among singleton live births resulting from single-blastocyst frozen embryo transfer (FET) cycles. METHODS: Patients with singleton live births following the first autologous single FET of non- preimplantation genetic testing (PGT) blastocysts in a single reproductive medicine department between January 2015 and February 2019 were included in this retrospective study. The primary outcome measure was the singleton sex ratio. Multivariable logistic regression models were used to estimate the associations between blastocyst quality and singleton sex ratio after adjustment for some potential confounders. RESULTS: There were 638 high-quality and 572 poor-quality single blastocyst FETs, and the blastocysts were conceived via 855 IVF and 355 ICSI treatments. A total of 1210 singleton live births were assessed. High-quality single blastocyst FET resulted in a significantly higher sex ratio than did poor-quality single blastocyst FET (60% vs. 49.7%, P < 0.001). The infertility cause was not associated with sex ratio among singleton live births (P = 0.537). The results of a multivariate analysis revealed that a high-quality blastocyst has a 150% higher probability of being male than a poor-quality blastocyst (adjusted odds ratio (aOR) 1.57; 95% CI 1.24-2, P < 0.001). Among the three blastocyst morphological parameters, Grade B trophectoderm was significantly associated with a higher sex ratio than Grade C (aOR 1.71; 95% CI 1.33-2.21. P < 0.001). Neither expansion degree nor inner cell mass degree were significantly associated with the singleton sex ratio. CONCLUSIONS: A single high-quality blastocyst FET has a higher chance of resulting in a male infant than a female infant. The results demonstrate that grade B trophectoderm confers benefits in improving the implantation potential of male blastocysts.

Association between infertility treatment and intrauterine growth: a multilevel analysis in a retrospective cohort study.

OBJECTIVES: This study aimed to identify intrauterine growth differences according to infertility treatment compared with spontaneous conception and to describe intrauterine growth trajectories. DESIGN: Retrospective cohort study. SETTING: A single primary and tertiary medical centre in Japan. PARTICIPANTS: This study included singleton pregnant women with prenatal check-ups and delivery at the University of Yamanashi Hospital between 1 July 2012 and 30 September 2017. Patients were divided into four groups: spontaneous conception, infertility treatment without assisted reproductive technology (ART), fresh-embryo transfer and frozen embryo transfer (FET). INTERVENTIONS: Differences in intrauterine growth according to the infertility treatment, including ART, and birth weight were evaluated. Multilevel analysis was employed to evaluate intrauterine growth trajectories stratified by the sex of the offspring. PRIMARY OUTCOME MEASURE: Estimated fetal weight (EFW) assessed by ultrasound examination. RESULTS: We assessed data from 37 239 prenatal examination results from 2377 pregnant women (spontaneous conception, n=1764; infertility treatment without ART, n=171; fresh-embryo transfer, n=112; and FET, n=330) in the final analysis. Multilevel analysis was adjusted for gestation duration, gestation period, parity, hypertensive disorders of pregnancy, type of infertility treatment, maternal age, smoking status, placenta previa, thyroid disease, gestational diabetes mellitus and the interaction between each potential confounding factor and gestation duration. In male fetuses, the interaction between FET and gestational duration (estimate: 0.36; 95% CI: 0.06 to 0.67) significantly affected the EFW. Similarly, in female fetuses, FET (estimate: -69.85; 95% CI: -112.09 to -27.61) and the interaction between FET and gestation duration (estimate: 0.57; 95% CI: 0.28 to 0.87) significantly affected the EFW. CONCLUSIONS: This study shows that FET affects intrauterine growth trajectory from the second trimester to term, particularly in female fetuses. Our findings require further prospective research to examine the effect of infertility treatment on fetal growth.

Assisted reproductive technology outcome in United States of America and Australia with New Zealand: comparison of annual reports 2005-2016.

In vitro fertilization can be considered as causative factor of increasing rate of multiple pregnancies. Analysis of factors contributing to reduction in the percentage of multiple pregnancies may contribute to overall improvement of ART results. We compared annual reports from The Australian and New Zealand Assisted Reproduction Database and US National Summary Reports presented by The Centers for Disease Control and Prevention. The aim of this study was to analyze results of ART outcomes in two countries presenting opposite approach to ART, particularly to number of transferred embryos and number of eSETs (elective single embryo transfers). We found significant increase in total number of initiated cycles and transfers with significant shift toward frozen cycles and transfers in both countries. Percentage of eSET increased while average number of embryos transferred per one transfer decreased significantly in both countries without significant difference between countries. We also noticed significant decrease in the rate of multiple pregnancies and percentage of pregnancies resulting in triplets in Australia with New Zealand. Decreasing number of multiple pregnancies and higher percentage of transfers and pregnancies resulting in singleton live birth are the changes in ART politics found in our analysis. United States of America have more significant changes toward eSET, although Australia and New Zealand have significantly higher percentage of eSET from the beginning of analysis.

Single and double embryo transfer provide similar live birth rates in frozen cycles.

Research question: Do live birth rates (LBRs) differ in frozen cycles of women who received single versus double embryo transfer?Design: Retrospective cohort study including women who underwent their first frozen embryo transfer (FET) in a tertiary referral University Hospital between 2009-2014.Results: 3601 patients were included in the analysis with 1936 (53.8%) having a single embryo transfer (SET) and 1665 (46.2%) having a double embryo transfer (DET). Overall, 657/3601 (18.24%) had a live birth. LBR were similar between SET and DET either for cleavage [100/757 (13.1%) versus 153/1032 (14.8%), p = .33] or blastocyst stage FET [256/1179 (21.7%) versus 148/633 (23.4%), p = .4). Ongoing pregnancy rates were comparable between DET and SET [316/1665 (18.9%) versus 359/1936 (18.5%)]. Multiple delivery rates were significantly higher in women with DET compared to SET [53/316 (16.7%) versus 7/359 (1.9%), p < .001]. Multivariate logistic regression analysis allowing adjustment for relevant confounders showed that the number of embryos transferred in the frozen cycle was not related to LBR.Conclusions: This is the largest study providing evidence that both SET and DET may result in similar LBR, albeit multiple pregnancy rates are significantly lower in case of SET. Therefore, SET should be the main strategy in women undergoing FET.

Analysis of 122 triplet and one quadruplet pregnancies after single embryo transfer in Japan.

RESEARCH QUESTION: What is the prevalence of triplet and quadruplet pregnancies after single embryo transfer (SET) in Japan. DESIGN: A retrospective observational study was conducted on 274,605 pregnancies after 937,848 SET cycles in registered assisted reproductive technology (ART) data from the Japanese ART national registry database between 2007 and 2014. A questionnaire survey of ART centres was also conducted. Data on pregnancies with embryo division into three or more after SET were analysed. RESULTS: According to the Japanese ART national registry database, SET resulted in 109 triplet pregnancies (0.04% of pregnancies), and the questionnaire reports from 31 centres revealed 33 triplet and one quadruplet pregnancies. After exclusion of 20 duplicated cases, 122 triplet and one quadruplet pregnancies included 46 monochorionic (one gestational sac [37.4%]), 18 dichorionic (two gestational sacs [14.6%]) and 59 trichorionic pregnancies (three gestational sacs [48.0%]). Compared with singleton pregnancies, patients with monozygotic triplet or quadruplet pregnancies were less frequently diagnosed with unexplained infertility (P = 0.004), more often received gonadotrophin injections for ovarian stimulation in 39 cases with information available (P = 0.021) and underwent more blastocyst transfers and assisted hatching (P = 0.002 and P < 0.001, respectively). The proportion of live birth, defined as at least one baby born, excluding induced abortion, was 64.6% (73/116 pregnancies) of monozygotic triplet or quadruplet pregnancies. CONCLUSIONS: Combined Japanese ART national registry and survey data revealed 122 triplet and one quadruplet pregnancies, the majority after cryopreserved embryo transfer. Most were conceived after blastocyst transfer and often after assisted hatching, which are potential risk factors for zygotic splitting.

Is Embryo Cryopreservation Causing Macrosomia-and What Else?

The number of embryos transferred during an IVF cycle is directly related to the high incidence of multiple births, which is the culprit of perinatal morbidity. Therefore, single fresh embryo transfer (ET) strategy, or freeze-all, followed by a single frozen-thawed embryo transfer (FET) cycle, may dramatically reduce the rate of multiple births, without compromising the cumulative live birth rates (LBRs). A literature review was conducted for all available evidences assessing obstetrics and perinatal outcomes associated with FET compared to fresh ET and natural conception. While studies comparing fresh and FET cycles in normal responders have yielded conflicting results for pregnancy rate, FET was associated with lower risk of prematurity and low birth weight and increased risk of large for gestational age (LGA) and/or macrosomic in singletons, when compared with fresh ET. Macrosomic/LGA births have a higher risk of fetal hypoxia, stillbirth, shoulder dystocia, perineal lacerations, cesarean section, postpartum hemorrhage and neonatal metabolic disturbances at birth. Nonetheless, it seems that other than higher risk of fetal macrosomia, there are additional obstetric complications associated with FET. The relative risk of hypertensive disorders in pregnancy, as well as perinatal mortality were also demonstrated to be increased in FET compared with singletons from fresh ET and natural conception. Therefore, when considering elective freeze-all policy, in addition to LBR and the risk of ovarian hyperstimulation syndrome, physicians should consider the aforementioned increased FET cycles' pregnancy complications, including LGA/ macrosomia, hypertensive disorders of pregnancy, as well as perinatal mortality.

High implantation and clinical pregnancy rates with single vitrified-warmed blastocyst transfer and optional aneuploidy testing for all patients.

This study reports the results of a 2-year long IVF programme ('One by One') in which all patients (median age 40 years; range 27-45 years) were offered preimplantation genetic testing for aneuploidy (PGT-A) and had all blastocysts vitrified (freeze-only), followed later by single vitrified-warmed blastocyst transfer (vSET) in managed cycles. Between January 2016 and December 2017, a total of 155 patients started 222 treatment cycles and 99 (45%) cycles resulted in one or more vitrified blastocysts (untested or with normal copy number for all chromosomes) available for transfer. Seventeen patients (11%) aged ≤35 years opted out of PGT-A. Over this period, 85 vSETs in 74 patients resulted in an implantation rate of 80% (68/85) and a singleton clinical pregnancy rate of 66% (56/85). Cumulative live birth rates will not be known for 1-2 years. Nevertheless, these high success rates with vSET confirm larger studies using selected patients and are likely to deliver similar, if not higher, live birth rates per cycle started than rates typically reported in national registries with conventional IVF and transfer of one or more fresh and/or frozen embryos.

Single or double embryo transfer? Decision-making process in patients participating in an oocyte donation program.

In IVF/ICSI programs, after receiving the information about the success results of single embryo transfer (SET) vs double embryo transfer (DET) and the risks of multiple pregnancy, a significant number of patients opt for SET. Up to date, no comparable studies have been published in oocyte recipients. The aim of this study was to evaluate if the counseling provided to oocyte recipients influence their decision on the number of embryos to be transferred. Fifty-five recipients expressed their preference and the relevance for the decision-making process that they attribute to certain factors through an anonymous questionnaire completed pre and post-counseling. Before counseling, 32 out of 55 recipients preferred DET, 13 preferred SET and 10 were undecided. From the 32 recipients who preferred DET, 16 (50%) maintained their preference after counseling, 13 (40.6%) changed their decision to SET and 3 (9.4%) changed to undecided (McNemar's test: p < .05). After counseling, the patients attached less importance to the probability of pregnancy and more importance to maternal and perinatal risks (p < .05). We conclude that after counseling, a significant number of recipients changed their preferences from DET to SET.

Experience of using time lapse microscopy in the IVF program in patients with good ovarian reserve.

The aim of this study is to evaluate the outcomes of single embryo transfer in patients with good ovarian reserve in the IVF program using time-lapse microscopy. This is a retrospective cohort study in a private IVF center in Russia. Comparison was done between 90 IVF cycles using time-lapse (study group) and 113 IVF cycles using standard culture (control group). Within each group, subgroups were selected with selective transfer of one embryo for 5 days (5SET) and elective transfer of one embryo for 5 days (5eSET). The primary outcome of the study was pregnancy rate. Secondary outcomes were miscarriage rates, live birth. Pregnancy rate did not significantly differ between the groups - 64.2% in the study group and control group. In the study group, the delivery rate was 54% in the subgroup 5eSET and 51.1% in the subgroup 5SET (p = .940). In the control group, the type of the embryo transfer significantly influenced on the delivery rate: in the 5eSET subgroup the birth rate was 54.4%, and in the 5SET subgroup it was 34.3% (p = .055; by Fisher's exact method p = .052). There were no adverse effects of the intervention. Selection of a single blastocyst based on information derived from time-lapse monitoring can help embryo selection for transfer.

Fine-tuning blastocyst selection based on morphology: a multicentre analysis of 2461 single blastocyst transfers.

RESEARCH QUESTION: Which blastocyst morphology parameter is associated with live birth after controlling for female age and endometrial receptivity? DESIGN: Retrospective study including fresh single blastocyst transfers (n = 2461) where the value of serum progesterone on day of human chorionic gonadotrophin trigger (PdHCG) was available. Generalized estimating equation regression models evaluated the independent effects of developmental stage (DevSt), inner cell mass (ICM) and trophectoderm grade on live birth rates while controlling for the confounding effects of female age and PdHCG. RESULTS: DevSt was strongly associated with the probability of live birth (P < 0.0001) independently of female age (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.87-0.91) and PdHCG (OR 0.80, 95% CI 0.74-0.87). For full blastocysts, expanded blastocysts and hatching blastocysts, addition of ICM and trophectoderm grading in the multivariable analysis suggested that besides female age (OR 0.92, 95% CI 0.90-0.94) and PdHCG (OR 0.80, 95% CI 0.73-0.87), only DevSt (P = 0.001) and trophectoderm quality (P = 0.004) were independent predictors of live birth, while the predictive capacity of ICM was no longer significant. The mean probability of live birth was highest for AA blastocysts (35.0%), followed by BA blastocysts (31.2%) and AB blastocysts (27.7%). CONCLUSION: This large study analyses for the first time the independent role of blastocyst morphology in predicting live birth while controlling for female age and PdHCG. Its findings suggest that DevSt and then trophectoderm grade are stronger predictors of live birth over ICM grade when selecting a single blastocyst for transfer.

A propensity-matched study of the association between pre-pregnancy maternal underweight and perinatal outcomes of singletons conceived through assisted reproductive technology.

RESEARCH QUESTION: Is pre-pregnancy maternal underweight associated with perinatal outcomes of singletons who were conceived through assisted reproductive technology (ART)? DESIGN: A 10-year (2006-2015) Chinese sample of 6538 women and their singleton infants who were conceived through ART was used to examine the association between pre-pregnancy maternal underweight and perinatal outcomes. Propensity scores for underweight were calculated for each participant using multivariable logistic regression, which was used to match 740 (91.36% of 810) underweight women with 740 normal weight women; the effects of underweight on birth weight and gestational age were then assessed by generalized estimating equation model. RESULTS: After propensity score matching, the birth weight was lower (difference -136.83 g, 95% CI -184.11 to -89.55 g) in the underweight group than in the normal weight group. The risks of low birth weight (LBW) and small for gestational age (SGA) were increased in the underweight group compared with those in the normal weight group (LBW: RR 1.64, 95% CI 1.01 to 2.67; SGA: RR 1.46, 95% CI 1.06 to 2.02). The risks of fetal macrosomia and being large for gestational age (LGA) were decreased in the underweight group compared with those in the normal weight group (macrosomia: RR 0.39, 95% CI 0.26 to 0.61; LGA: RR 0.36, 95% CI 0.24 to 0.53). The associations between underweight, gestational age and preterm birth were not statistically significant. CONCLUSIONS: Among women undergoing ART, pre-pregnancy maternal underweight was associated with lower birth weight, increased LBW and SGA risks, and decreased fetal macrosomia and LGA risks in singleton infants.