Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer. However, it remains uncertain whether PGT-A improves the ...cumulative live-birth rate as compared with conventional in vitro fertilization (IVF).
In this multicenter, randomized, controlled trial, we randomly assigned subfertile women with three or more good-quality blastocysts to undergo either PGT-A or conventional IVF; all the women were between 20 and 37 years of age. Three blastocysts were screened by next-generation sequencing in the PGT-A group or were chosen by morphologic criteria in the conventional-IVF group and then were successively transferred one by one. The primary outcome was the cumulative live-birth rate after up to three embryo-transfer procedures within 1 year after randomization. We hypothesized that the use of PGT-A would result in a cumulative live-birth rate that was no more than 7 percentage points higher than the rate after conventional IVF, which would constitute the noninferiority margin for conventional IVF as compared with PGT-A.
A total of 1212 patients underwent randomization, and 606 were assigned to each trial group. Live births occurred in 468 women (77.2%) in the PGT-A group and in 496 (81.8%) in the conventional-IVF group (absolute difference, -4.6 percentage points; 95% confidence interval CI, -9.2 to -0.0; P<0.001). The cumulative frequency of clinical pregnancy loss was 8.7% and 12.6%, respectively (absolute difference, -3.9 percentage points; 95% CI, -7.5 to -0.2). The incidences of obstetrical or neonatal complications and other adverse events were similar in the two groups.
Among women with three or more good-quality blastocysts, conventional IVF resulted in a cumulative live-birth rate that was noninferior to the rate with PGT-A. (Funded by the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03118141.).
Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of ...multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer.
This multicentre, non-blinded, randomised controlled trial was undertaken in 21 academic fertility centres in China. 1650 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilisation were enrolled from Aug 1, 2016, to June 3, 2017. Eligible women were randomly assigned to either fresh or frozen single blastocyst transfer. The randomisation sequence was computer generated, with block sizes of two, four, or six, stratified by study site. For those assigned to frozen blastocyst transfer, all blastocysts were cryopreserved and a delayed frozen-thawed single blastocyst transfer was done. The primary outcome was singleton livebirth rate. Analysis was by intention to treat. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR-IOR-14005405.
825 women were assigned to each group and included in analyses. Frozen single blastocyst transfer resulted in higher rates of singleton livebirth than did fresh single blastocyst transfer (416 50% vs 329 40%; relative risk RR 1·26, 95% CI 1·14–1·41, p<0·0001). The risks of moderate or severe ovarian hyperstimulation syndrome (four of 825 0·5% in frozen single blastocyst transfer vs nine of 825 1·1% in fresh single blastocyst transfer; p=0·16), pregnancy loss (134 of 583 23·0% vs 124 of 481 25·8%; p=0·29), other obstetric complications, and neonatal morbidity were similar between the two groups. Frozen single blastocyst transfer was associated with a higher risk of pre-eclampsia (16 of 512 3·1% vs four of 401 1·0%; RR 3·13, 95% CI 1·06–9·30, p=0·029).
Frozen single blastocyst transfer resulted in a higher singleton livebirth rate than did fresh single blastocyst transfer in ovulatory women with good prognosis. The increased risk of pre-eclampsia after frozen blastocyst transfer warrants further studies.
The National Key Research and Development Program of China.
The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the ...live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome.
In this multicenter trial, we randomly assigned 1508 infertile women with the polycystic ovary syndrome who were undergoing their first IVF cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. After 3 days of embryo development, women underwent the transfer of up to two fresh or frozen embryos. The primary outcome was a live birth after the first embryo transfer.
Frozen-embryo transfer resulted in a higher frequency of live birth after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a rate ratio of 1.17 (95% confidence interval CI, 1.05 to 1.31; P=0.004). Women who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss (22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P<0.001), and of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of 0.19 (95% CI, 0.10 to 0.37; P<0.001), but a higher frequency of preeclampsia (4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There were no significant between-group differences in rates of other pregnancy and neonatal complications. There were five neonatal deaths in the frozen-embryo group and none in the fresh-embryo group (P=0.06).
Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.).
The endometrial preparation during frozen embryo transfer (FET) can be performed by natural cycle (NC), hormone replacement therapy (HRT) cycle and cycle with ovulation induction (OI). Whether ...different FET preparation protocols can affect maternal and neonatal outcomes is still inconclusive.
This was a retrospective cohort study that included 6886 women who delivered singleton live birth babies after 28 weeks of pregnancy underwent FET from January, 2015 to July, 2018. Women were divided into three groups according to the protocols used for endometrial preparation during FET: NC group (N = 4727), HRT group (N = 1642) and OI group (N = 517).
After adjusting for the effect of age, body mass index (BMI), irregular menstruation, antral follicle count (AFC), endometrial thickness, the levels of testosterone, anti-Müllerian hormone (AMH), preconceptional fasting glucose (PFG), systolic and diastolic pressure et al., the HRT group had higher risk of hypertensive disorders of pregnancy (HDP) compared with the NC group (adjusted odds ratio (aOR) 2.00, 95% confidence interval (CI) 1.54-2.60). Singletons born after HRT FET were at increased risk of low birth weight (LBW) compared to NC group (aOR 1.49, 95%CI 1.09-2.06). The risks of preterm birth (PTB) in the HRT and OI group were elevated compared with the NC group (aOR 1.78, 95%CI 1.39-2.28 and aOR 1.51, 95%CI 1.02-2.23, respectively).
The HRT protocol for endometrial preparation during frozen embryo transfer of blastocysts was associated with increased risk of maternal and neonatal complications, compared to the NC and OI protocol.
Randomized controlled trials and intent-to-treat analyses are important for infertility clinical studies. Dropouts or crossovers during the study process will disrupt the randomization design and ...affect the intent-to-treat analysis. In this review, we have briefly introduced the occurrence of dropout and crossover from our previous Reproductive Medicine Network and other related studies and provided some experience obtained from these studies on how to minimize and reduce the occurrence of dropout and crossover for infertility randomized clinical studies.
With a high incidence of insulin resistance, central obesity and dyslipidemia, women with polycystic ovary syndrome are susceptible to metabolic syndrome (MetS). Our objective was to explore whether ...metabolic syndrome had an effect on overall female fertility and in vitro fertilization outcomes in infertile women with polycystic ovary syndrome.
This was a secondary analysis of a multicenter randomized trial in 1508 women with polycystic ovary syndrome, which was originally designed to compare the live birth rate after fresh-embryo transfer vs frozen embryo transfer (Frefro-PCOS). At baseline, metabolic parameters, including body mass index, waist and hip circumference, blood pressure, lipid profile, fasting, and 2 hour glucose and insulin levels after a 75 g oral glucose tolerance test were measured. All subjects were divided into a metabolic syndrome group (metabolic syndrome) and absence of metabolic syndrome group (nonmetabolic syndrome) according to diagnostic criteria. Descriptive statistics and logistic regression models tested the association between metabolic syndrome and overall fertility and in vitro fertilization cycle stimulation characteristics and clinical outcomes.
Metabolic syndrome was identified in 410 of 1508 infertile women with polycystic ovary syndrome (27.2%). Patients with metabolic syndrome had longer infertility duration (4.0 ± 2.2 vs 3.7 ± 2.2, P = .004) compared with those without metabolic syndrome. During ovarian stimulation, those with metabolic syndrome required significantly higher and longer doses of gonadotropin and had lower peak estradiol level, fewer retrieved oocytes, available embryos, a lower oocyte utilization rate, and ovarian hyperstimulation syndrome than those with nonmetabolic syndrome. The cumulative live birth rate did not show a significant between-group difference (57.8% vs 62.2%, P = .119). Multivariate logistic regression analysis adjusted for age, duration of infertility, body mass index, thyroid-stimulating hormone, metabolic syndrome group, homeostatic model assessment of insulin resistance, metformin utilization, number of available embryos, and embryos transferred showed that the number of embryos transferred and the number of available embryos were positively but metabolic syndrome negatively associated with the cumulative live birth rate (odds ratio, 2.18, 1.10, and 0.70, respectively, P < .05).
Women with polycystic ovary syndrome with metabolic syndrome have a negative impact from female fecundity, and this suggests an adverse effect on in vitro fertilization cycle stimulation characteristics and clinical outcomes.
Introduction
Accumulating studies have suggested singletons born after frozen embryo transfer (FET) were higher than those born after fresh embryo transfer (Fre‐ET). However, fewer studies had ...investigated the gestational age‐specific between‐group difference in birthweight. This study aimed to investigate the gestational week‐specific difference in singleton birthweight after FET vs Fre‐ET and explore potential factors that impact the difference.
Material and methods
In this retrospective cohort study, a total of 25 863 singletons were included. Multivariable linear regression and logistic regression were used to evaluate the between‐group differences in mean birthweight and the incidences of large for gestational age (LGA) and small for gestational age (SGA), respectively.
Results
Multivariable regression analyses showed a statistically significant interaction between types of embryo transfer (ie FET vs Fre‐ET) and the gestational week on mean birthweight (P < 0.001) and on the risks of large for gestational age (P = 0.001) and small for gestational age (P < 0.001). When stratified by gestational week, the differences in mean birthweight and the risks of LGA and SGA were only observed in singletons born at 37 gestational weeks or later. After adjusting for confounders, full‐term but not preterm singletons born after FET had a higher birthweight (3497.58 ± 439.73 g vs 3445.67 ± 450.24 g; adjusted mean difference 58.35 g; 95% confidence interval CI 38.72–77.98 g), a higher risk of LGA (24.3% vs 21.1%; adjusted odds ratio OR 1.28, 95% CI 1.15–1.42) and a lower risk of SGA (3.1% vs 4.8%; adjusted OR 0.61, 95% CI 0.53–0.70) compared with those born after Fre‐ET.
Conclusions
The differences in birthweight between FET and Fre‐ET were observed in full‐term singletons but not preterm singletons.
Statistically significant differences in birthweight between frozen embryo transfer and fresh embryo transfer were found at 37 gestational weeks at birth or later. The between‐group differences seemed to occur earlier in women with a higher estradiol level on the day of hCG trigger.
Purpose
Mosaicism is a prevalent characteristic of human preimplantation embryos. This retrospective cohort study aimed to investigate pregnancy outcomes after transfer of mosaic or euploid embryos.
...Methods
The embryos, which had been transferred as “euploidy,” were processed using array-based comparative genomic hybridization (aCGH). The original aCGH charts of the transferred embryos were reanalyzed. Mosaic and control euploid embryos were defined according to log2 ratio calls.
Results
Overall, 102 embryos were determined to be mosaic, of which 101 were estimated to harbor no more than 50% aneuploid mosaicism. Additionally, 268 euploid embryos were matched as controls. The rates of live birth (46.6% vs. 59.1%, odds ratio (OR) 0.60, 95% confidence interval (CI) 0.38–0.95), and biochemical pregnancy (65.7% vs. 76.1%, OR 0.60, 95% CI 0.37–0.99) per transfer cycle were significantly lower after mosaic embryo transfer than after euploid embryo transfer. The rates of clinical pregnancy and pregnancy loss and the risks of obstetric outcomes did not differ significantly between the two groups.
Conclusions
Compared with euploid embryo transfer, mosaic embryo transfer is associated with a lower rate of live birth, which is mainly attributed to a decreased rate of conception. However, as mosaic embryo transfer yielded a live birth rate of 46.6%, patients without euploid embryos could be counseled regarding this alternative option.
Supraphysiological estradiol exposure after ovarian stimulation may disrupt embryo implantation after fresh embryo transfer. Women with polycystic ovary syndrome (PCOS), who usually overrespond to ...ovarian stimulation, have a better live birth rate after frozen embryo transfer (FET) than after fresh embryo transfer; however, ovulatory women do not.
To evaluate whether the discrepancy in live birth rate after fresh embryo transfer vs FET between these two populations is due to the variation in ovarian response (i.e., peak estradiol level or oocyte number).
This was a secondary analysis of data from two multicenter randomized trials with similar study designs. A total of 1508 women with PCOS and 2157 ovulatory women were randomly assigned to undergo fresh or FET. The primary outcome was live birth.
Compared with fresh embryo transfer, FET resulted in a higher live birth rate (51.9% vs 40.7%; OR, 1.57; 95% CI, 1.22 to 2.03) in PCOS women with peak estradiol level >3000pg/mL but not in those with estradiol level ≤3000 pg/mL. In women with PCOS who have ≥16 oocytes, FET yielded a higher live birth rate (54.8% vs 42.1%; OR, 1.67; 95% CI, 1.20 to 2.31), but this was not seen in those with <16 oocytes. In ovulatory women, pregnancy outcomes were similar after fresh embryo transfer and FET in all subgroups.
Supraphysiological estradiol after ovarian stimulation may adversely affect pregnancy outcomes in women with PCOS but not in ovulatory women.
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