Preimplantation Genetic Screening Group Research Articles

The relationship between the percent of euploid embryo and the tolerance of embryo biopsy in preimplantation genetic screening: A systematic review and meta-analysis of randomized controlled trials.

The aim of this study was to analyze the relationship between the percent of euploid embryo and the tolerance of embryo biopsy in preimplantation genetic screening (PGS).PubMed and trial registers were searched for clinical studies that patients were randomized to the PGS group or the control group from 1995 to October 2017. The patients of advanced maternal age, repeated implantation failure, and good prognosis with or without PGS in randomized controlled trials (RCTs) were collected.Original data from 9 RCT studies comparing in-vitro fertilization with and without PGS including 1642 patients were obtained and they were divided into 3 subgroups according to the percent of euploid embryo. PGS significantly increased live birth babies per embryo transferred (risk ratio: 2.98, 95% confidence interval: 1.54–5.75) in ≤30% of euploid embryo subgroups and but in other 2 groups, PGS has no effect. Significant negative correlation was found between the percent of euploid embryo and the tolerance of embryo biopsy in PGS (r = 0.80, P = 0.010)The tolerance of embryo biopsy in PGS was associated negatively with the percent of euploid embryo. There was a beneficial effect when PGS was used in the patients with the lowest percent of euploid embryo.

Preimplantation genetic screening (PGS) in egg donor (ED) cycles: is it a valid option?

A recent study demonstrates a high variability among different centers in the euploidy rate of embryos generated from donated eggs (Munnè et al., 2017). Using SNP array analysis, most embryonic meiotic aneuploidies have been found to be from maternal origin. From these observations, it may be speculated that the ovarian stimulation may affect the embryo euploidy rate independently from the oocyte source. Despite this, PGS in ED cycles is often considered unnecessary. Very few studies examined the use of PGS in ED cycles thus far and the results were inconclusive. In order to investigate the utility of PGS in ED cycles, we compared the clinical outcomes of frozen embryo transfers (FET) cycles involving oocyte donation in which PGS was performed to controls in which PGS was not used. This is a retrospective, single-center cohort study. 622 FET cycles with embryo derived from donated eggs, conducted between 1 January 2015 and 31 December 2016, were included. In 570 cycles the embryos were tested by PGS and in 52 cycles the embryos were not tested. In order to have a group as homogenous as possible, only the first FET cycle from freeze-all cycles (Cryotech Vitrification and Warming®) was considered. Both NGS and aCGH were used for the genetic screening. Setting the α error at 0.05, our study had a power of 80% to observe a decrease of 20% in the ongoing pregnancy and implantation rate (G*power 3, post hoc analysis) between the PGS and no-PGS groups and of 12% among the PGS subgroups. The results are reported in Table I. The percentage of euploid blastocyst from egg donors was 54.6%; the aneuploid blastocysts 30.9% and the mosaic blastocysts 13.9%. No results were 0.6%.Table IClinical outcome of FET cycles involving oocyte donation with and without PGSNo-PGS totPGS totNo-PGS single ETPGS single ETNo PGS ≥ 2 ETPGS ≥ 2 ETP valueET Cycles525701532937241Egg donor age25.5±2.925.5±2.925.6±3.1Survival rate after thawing98.0%97.6%88.9%97.3%100%97.8%Average n of euploid embryos-4.9±3.7-4.7±3.8*-5.6±3.4**p=0.006Average n of emb transferred1.8± 0.6*1.4±0.5*1.0±0.01.0±0.02.1±0.42.0±0.2*p=0.0003Ongoing PR57.7%57.2%20.0%*50.5%* ** ***72.9%**64.7%**** p=0.032 **p=0.009 ***p=0.0008Ongoing IR40.9%47.2%20.0%*50.5%*44.9%42.4%*p=0.032AR10.0%9.5%0.0%11.4%11.1%7.1%Twin rate26.7%19.0%0%0%* **29.6%*34.0%***p=0.0001 **p=0.0001PR: Pregnancy Rate, IR: Implantation Rate; AR: Abortion Rate Open table in a new tab PR: Pregnancy Rate, IR: Implantation Rate; AR: Abortion Rate Considering only the first FET cycle with embryos derived from donated eggs, we found a significant increase in the ongoing pregnancy and implantation rate in cases of single embryo transfer in the PGS group compared with the non-tested group. Transferring ≥2 embryos statistically increased the ongoing pregnancy but also the twin rate in both PGS and no-PGS group compared to the single embryo transfer, and no differences between the PGS and the control group were found. In terms of chances of achieving a single pregnancy in the first FET attempt, the PGS seems to have a valid role also in ED cycles. Transferring ≥2 embryos may overcome the advantage of the PGS but twin rates is high.

Preimplantation genetic screening (PGS) with next generation sequencing (NGS) achieves ongoing pregnancy with fewer transfers and total miscarriages compared to non-PGS cycles

To determine the cumulative ongoing pregnancy/live birth rates (OP/LBR) of PGS cycles with NGS compared to non-PGS cycles using an intention to treat analysis. Cohort Study All patients undergoing an oocyte retrieval for IVF or IVF/PGS with NGS and their subsequent frozen embryo transfer (FET) cycles at a single university-based fertility center were collected from 1/2014 through 7/2016. Embryo banking cycles, donor oocyte cycles, cycles utilizing PGS with array comparative genomic hybridization, and IVF cycles with no blastocyst stage embryos were excluded. Cumulative OP/LBRs were calculated per retrieval including up to 4 transfers and analyzed by age-group. IVF/PGS cycles with no euploid embryos available for transfer were included. Secondary outcomes included the number of embryos transferred per cycle, cumulative OP/LBR after the first embryo transfer (ET), and cumulative spontaneous abortion rate (SABR) per clinical pregnancy. Statistical analysis was performed using Fisher’s exact test with P<0.05 considered significant. 2547 cycles meeting inclusion criteria were identified. 844 retrievals and 525 FET cycles were performed in the PGS with NGS group. In the no PGS group, there were 953 retrievals and 225 FET cycles. 242 retrieval cycles did not form blastocysts and were excluded. The number of embryos transferred per cycle was significantly higher in the no PGS group than the PGS with NGS group (1.58±0.69 vs 1.01±0.11, p<0.001). Primary and secondary outcomes are summarized in the table. Per retrieval, there was no statistical difference in cumulative OP/LBR between groups. Pregnancy was achieved more often after the first transfer in women 38-40 years old. The cumulative OP/LBR per retrieved patient with embryos available for transfer was significantly higher for the PGS group over age 35. The cumulative SABR was significantly higher for ages 38-42yo in the no PGS group.Tabled 1Cumulative OP/LBR Per Retrieval (%) by agePGS with NGSNo PGSP- value<3562.6% (97/155)70.1% (169/241)0.1535-3750.3% (86/171)53.8% (78/145)0.6138-4042.4% (109/257)38% (62/163)0.4341-4217.9% (29/162)21.1% (15/71)0.68>427.1% (7/98)10.3% (8/78)0.64OP/LBR after 1st ET per Retrieval (%) by agePGS with NGSNo PGSP- value<3554.2% (84/155)47.3% (114/241)0.2235-3745.6% (78/171)40.7% (59/145)0.4438-4039.3% (101/257)29.4% (48/163)0.04941-4216% (26/162)18.3% (13/71)0.8>426.1% (6/98)9% (7/78)0.66Cumulative OP/LBR per retrieved patient with embryos available for transfer (%) by agePGS with NGSNo PGSP-value<3574.6% (97/130)70.1% (169/241)0.4335-3771.1% (86/121)53.8% (78/145)0.00638-4070.8% (109/154)38% (62/163)<0.00141-4267.4% (29/43)21.1% (15/71)<0.001>4246.7% (7/15)10.3% (8/78)0.004Cumulative SABR per clinical pregnancy (%) by agePGS with NGSno PGSP- value<3510.2% (11/108)14.5% (28/193)0.3735-3714.9% (15/101)20.4% (20/98)0.3638-4011.7% (14/120)28.6% (24/84)0.00441-4214.7% (5/34)46.4% (13/28)0.013>4212.5% (1/8)55.6% (10/18)0.1 Open table in a new tab Overall, cumulative OP/LBRs are similar in women undergoing IVF with or without PGS, but IVF cycles without PGS have significantly more embryos transferred per cycle. Retrievals utilizing PGS with NGS result in OP/LB with fewer embryo transfers in women 38-40 years old and fewer miscarriages in women ages 38-42.

Differences in pregnancy outcomes in donor egg frozen embryo transfer (FET) cycles following preimplantation genetic screening (PGS): a single center retrospective study

PurposeThis study aims to test the hypothesis, in a single-center retrospective analysis, that live birth rates are significantly different when utilizing preimplantation genetic screening (PGS) compared to not utilizing PGS in frozen–thawed embryo transfers in our patients that use eggs from young, anonymous donors. The question therefore arises of whether PGS is an appropriate intervention for donor egg cycles.MethodsLive birth rates per cycle and live birth rates per embryo transferred after 398 frozen embryo transfer (FET) cycles were examined from patients who elected to have PGS compared to those who did not. Blastocysts derived from donor eggs underwent trophectoderm biopsy and were tested for aneuploidy using array comparative genomic hybridization (aCGH) or next-generation sequencing (NGS), then vitrified for future use (test) or were vitrified untested (control). Embryos were subsequently warmed and transferred into a recipient or gestational carrier uterus. Data was analyzed separately for single embryo transfer (SET), double embryo transfer (DET), and for own recipient uterus and gestational carrier (GC) uterus recipients.ResultsRates of implantation of embryos leading to a live birth were significantly higher in the PGS groups transferring two embryos (DET) compared to the no PGS group (GC, 72 vs. 56 %; own uterus, 60 vs. 36 %). The live birth implantation rate in the own uterus group for SET was higher in the PGS group compared to the control (58 vs. 36 %), and this almost reached significance but the live birth implantation rate for the SET GC group remained the same for both tested and untested embryos. Live births per cycle were nominally higher in the PGS GC DET and own uterus SET and DET groups compared to the non-PGS embryo transfers. These differences almost reached significance. The live birth rate per cycle in the SET GC group was almost identical.ConclusionsSignificant differences were noted only for DET; however, benefits need to be balanced against risks associated with multiple pregnancies. Results observed for SET need to be confirmed on larger series and with randomized cohorts.

Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with recurrent pregnancy loss.

In an intent to treat analysis, are clinical outcomes improved in recurrent pregnancy loss (RPL) patients undergoing IVF and preimplantation genetic screening (PGS) compared with patients who are expectantly managed (EM)? Among all attempts at PGS or EM among RPL patients, clinical outcomes including pregnancy rate, live birth (LB) rate and clinical miscarriage (CM) rate were similar. The standard of care for management of patients with RPL is EM. Due to the prevalence of aneuploidy in CM, PGS has been proposed as an alternate strategy for reducing CM rates and improving LB rates. Retrospective cohort study of 300 RPL patients treated between 2009 and 2014. Among two academic fertility centers, 112 RPL patients desired PGS and 188 patients chose EM. Main outcomes measured were pregnancy rate and LB per attempt and CM rate per pregnancy. One attempt was defined as an IVF cycle followed by a fresh embryo transfer or a frozen embryo transfer (PGS group) and 6 months trying to conceive (EM group). In the IVF group, 168 retrievals were performed and 38 cycles canceled their planned PGS. Cycles in which PGS was intended but cancelled had a significantly lower LB rate (15 versus 36%, P = 0.01) and higher CM rate (50 versus 14%, P < 0.01) compared with cycles that completed PGS despite similar maternal ages. Of the 130 completed PGS cycles, 74% (n = 96) yielded at least one euploid embryo. Clinical pregnancy rate per euploid embryo transfer was 72% and LB rate per euploid embryo transfer was 57%. Among all attempts at PGS or EM, clinical outcomes were similar. Median time to pregnancy was 6.5 months in the PGS group and 3.0 months in the EM group. The largest limitation is the retrospective study design, in which patients who elected for IVF/PGS may have had different clinical prognoses than patients who elected for expectant management. In addition, the definition of one attempt at conception for PGS and EM groups was different between the groups and can introduce potential confounders. For example, it was not confirmed that patients in the EM group were trying to conceive for each month of the 6-month period. Success rates with PGS are limited by the high incidence of cycles that intend but cancel PGS or cycles that do not reach transfer. Counseling RPL patients on their treatment options should include not only success rates with PGS per euploid embryo transferred, but also LB rate per initiated PGS cycle. Furthermore, patients who express an urgency to conceive should be counseled that PGS may not accelerate time to conception. None. N/A. N/A. N/A.

The Effect of Preimplantation Genetic Screening on Implantation Rate in Women over 35 Years of Age.

Advanced maternal age (AMA) is an important factor in decreasing success of assisted reproductive technology by having a negative effect on the success rate of intra-cytoplasmic sperm injection (ICSI), particularly by increasing the rate of embryo aneuploidy. It has been suggested that the transfer of euploid embryos increases the implantation and pregnancy rates, and decreases the abortion rate. Preimplantation genetic screening (PGS) is a method for selection of euploid embryos. Past studies, however, have reported different results on the success of pregnancy after PGS in AMA. Investigating the pregnancy rate of ICSI with and without PGS in female partners over 35 years of age referred to infertility centers in Tehran. In this randomized controlled trial, 150 couples with the female partner over age of 35 were included. Fifty couples underwent PGS and the remaining were used as the control group. PGS was carried out using fluorescent in situ hybridization (FISH) for chromosomes 13, 18, 21, X and Y. Results of embryo transfer following PGS were evaluated and compared with those in the control group. Implantation rates obtained in the PGS and control groups were 30 and 32% respectively and not significantly different (P>0.05). PGS for chromosomes 13, 18, 21, X and Y does not increase implantation rate in women over 35 years of age and therefore the regular use of PGS in AMA is not recommended.

Effectiveness of in vitro fertilization with preimplantation genetic screening: a reanalysis of United States assisted reproductive technology data 2011–2012

To assess effectiveness of preimplantation genetic screening (PGS) in fresh IVF cycles. Reanalysis of retrospective US national data. Not applicable. A total of 5,471 fresh autologous IVF cycles with PGS and 97,069 cycles without PGS, reported in 2011-2012 to the Centers for Disease Control and Prevention. Not applicable. Cycles that reached ET, miscarriage rates, live birth rates per cycle and per transfer. More PGS than non-PGS cycles reached ET (64.2% vs. 62.3%), suggesting favorable patient selection bias for patients using PGS. Nevertheless, live births rates per cycle start (25.2% vs. 28.8%) and per ET (39.3% vs. 46.2%) were significantly better in non-PGS cycles, whereas miscarriage rates were similar (13.7% vs. 13.9%). With a maternal age >37years significantly more cycles in the PGS group reached ET (53.1% vs. 41.9%), suggesting a significant selection bias for more favorable patients in the PGS population. This bias rather than the PGS procedure may partially explain the observed improved live birth rate per cycle (17.7% vs. 12.7%) and lower miscarriage rate (16.8% vs. 26.0%) in the older PGS group. Overall, PGS decreased chances of live birth in association with IVF. National improvements in live birth and miscarriage rates reported with PGS in older women are likely the consequence of favorable patient selection biases.

Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis.

CONTEXT:A majority of human embryos produced in vitro are aneuploid, especially in couples undergoing in vitro fertilization (IVF) with poor prognosis. Preimplantation genetic screening (PGS) for all 24 chromosomes has the potential to select the most euploid embryos for transfer in such cases.AIM:To study the efficacy of PGS for all 24 chromosomes by microarray comparative genomic hybridization (array CGH) in Indian couples undergoing IVF cycles with poor prognosis.SETTINGS AND DESIGN:A retrospective, case–control study was undertaken in an institution-based tertiary care IVF center to compare the clinical outcomes of twenty patients, who underwent 21 PGS cycles with poor prognosis, with 128 non-PGS patients in the control group, with the same inclusion criterion as for the PGS group.MATERIALS AND METHODS:Single cells were obtained by laser-assisted embryo biopsy from day 3 embryos and subsequently analyzed by array CGH for all 24 chromosomes. Once the array CGH results were available on the morning of day 5, only chromosomally normal embryos that had progressed to blastocyst stage were transferred.RESULTS:The implantation rate and clinical pregnancy rate (PR) per transfer were found to be significantly higher in the PGS group than in the control group (63.2% vs. 26.2%, P = 0.001 and 73.3% vs. 36.7%, P = 0.006, respectively), while the multiple PRs sharply declined from 31.9% to 9.1% in the PGS group.CONCLUSIONS:In this pilot study, we have shown that PGS by array CGH can improve the clinical outcome in patients undergoing IVF with poor prognosis.

Assessment of aneuploidy formation in human blastocysts resulting from donated eggs and the necessity of the embryos for aneuploidy screening.

To examine the prevalence of aneuploidy in human blastocysts resulting from donated eggs and embryo implantation after transfer of normal euploid embryos. Also, to assess the necessity of preimplantation genetic screening (PGS) for embryos produced with donor eggs. Blastocysts from donor-recipient cycles were biopsied for PGS (PGS group) and the samples were analyzed with DNA microarray. Euploid blastocysts were transferred to the recipients, and both clinical pregnancy and embryo implantation were examined and compared with embryos without PGS (control group). After PGS, 39.1% of blastocysts were abnormal, including aneuploidy and euploid with partial chromosome deletion and/or duplication. Transfer of normal euploid blastocysts brought about 72.4% of clinical pregnancy, 65.5% of ongoing/delivery and 54.9% of embryo implantation rates; these rates were slightly higher than those in the control group (66.7, 54.0 and 47.8%, respectively), but there was no statistical difference between the two groups. By contrast, the miscarriage rate was higher in the control group (19.2%) than in the PGS group (9.5%), but no statistical difference was observed. Transfer of two or more embryos did not significantly increase the ongoing/delivery rates in both groups, but significantly increased the twin pregnancy rates (50.0% in the PGS group and 43.8% in the control group). High proportions of human blastocysts derived from donor eggs are aneuploid. Although pregnancy and embryo implantation rates were increased, and miscarriage rates were reduced by transfer of embryos selected by PGS, the efficiency was not significantly different as compared to the control, suggesting that PGS may be necessary only in some specific situations, such as single embryo transfer.

Impact of blastocyst biopsy and comprehensive chromosome screening technology on preimplantation genetic screening: a systematic review of randomized controlled trials

Embryonic aneuploidy is highly prevalent in IVF cycles and contributes to decreased implantation rates, IVF cycle failure and early pregnancy loss. Preimplantation genetic screening (PGS) selects the most competent (euploid) embryos for transfer, and has been proposed to improve IVF outcomes. Use of PGS with fluorescence-in-situ hybridization technology after day 3 embryo biopsy (PGS-v1) significantly lowers live birth rates and is not recommended for use. Comprehensive chromosome screening technology, which assesses the whole chromosome complement, can be achieved using different genetic platforms. Whether PGS using comprehensive chromosome screening after blastocyst biopsy (PGS-v2) improves IVF outcomes remains to be determined. A systematic review of randomized controlled trials was conducted on PGS-v2. Three trials met full inclusion criteria, comparing PGS-v2 and routine IVF care. PGS-v2 is associated with higher clinical implantation rates, and higher ongoing pregnancy rates when the same number of embryos is transferred in both PGS and control groups. Additionally, PGS-v2 improves embryo selection in eSET practice, maintaining the same ongoing pregnancy rates between PGS and control groups, while sharply decreasing multiple pregnancy rates. These results stem from good-prognosis patients undergoing IVF. Whether these findings can be extrapolated to poor-prognosis patients with decreased ovarian reserve remains to be determined.

Blood pressure and anthropometrics of 4-y-old children born after preimplantation genetic screening: follow-up of a unique, moderately sized, randomized controlled trial

Recent studies suggest that in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are associated with suboptimal cardiometabolic outcome in offspring. It is unknown whether preimplantation genetic screening (PGS), which involves embryo biopsy, affects blood pressure (BP), anthropometrics, and the frequency of received medical care. In this prospective multicenter follow-up study, we assessed BP, anthropometrics, and received medical care of 4-y-old children born to women who were randomly assigned to IVF/ICSI with PGS (n = 49) or without PGS (controls; n = 64). We applied linear and generalized linear mixed-effects models to investigate possible effects of PGS. BP in the PGS and control groups was similar: 102/64 and 100/64 mm Hg, respectively. Main anthropometric outcomes in the PGS vs. control group were: BMI: 16.1 vs. 15.8; triceps skinfold: 108 vs. 98 mm; and subscapular skinfold: 54 vs. 53 mm (all P values > 0.05). More PGS children than controls had received paramedical care (speech, physical, or occupational therapy: 14 (29%) vs. 9 (14%); P = 0.03 in multivariable analysis). The frequency of medicial treatment was comparable. PGS does not seem to affect BP or anthropometrics in 4-y-old children. The higher frequency of received paramedical care after PGS may suggest an effect of PGS on subtle developmental parameters.

The effect of preimplantation genetic screening on neurological, cognitive and behavioural development in 4-year-old children: follow-up of a RCT

Does embryo biopsy inherent to preimplantation genetic screening (PGS) affect neurological, cognitive and behavioural development of 4-year-old children? PGS does not seem to affect neurological, cognitive and behavioural development of 4-year-old singletons; however, our data suggest that it may be associated with altered neurodevelopment in twins. Evidence concerning the safety of PGS on neurodevelopmental outcome in offspring is scarce. The present study provides information on neurodevelopmental, cognitive and behavioural outcome of 4-year-old PGS offspring. A prospective, assessor-blinded follow-up study of children born to women who participated in a multi-centre RCT on the effect of IVF with or without PGS. At 4 years, 49 children (31 singletons, 9 sets of twins) born following IVF with PGS and 64 children (42 singletons, 11 sets of twins) born following IVF without PGS (controls) were assessed (post-natal attrition 18%). Neurological development was evaluated with the standardized, age-specific and sensitive neurological examination according to Hempel, resulting in a neurological optimality score (NOS), a fluency score and the rate of adverse neurological outcome. Primary outcome was the fluency score, as fluency of movements is easily reduced by subtle dysfunction of the brain. Cognitive development was evaluated with the Kaufman Assessment Battery for Children; behavioural development was evaluated with the Child Behavior Checklist. The effect of PGS was analysed with a mixed effects model. Based on the intention to treat analysis, neurodevelopmental outcome of PGS children was similar to that of controls. However, additional analyses indicated that PGS affected neurodevelopmental outcome of twins in a different way than that of singletons. The fluency score of singletons born following PGS was similar to that of control singletons [mean values, 95% confidence intervals (CIs): 12.2 (11.5;12.8) and 12.2 (11.6;12.8)], respectively, P = 0.977) that was also true for the other neurodevelopmental parameters. The fluency score of PGS twins was significantly lower than that of control twins [mean values, 95% CIs: 10.6 (9.8;11.3) and 12.3 (11.5;13.1)], respectively, P = 0.001); the same was true for the NOS. In addition, PGS in twins was associated with a higher sequential intelligence quotient score. On the other hand, other neurodevelopmental parameters were similar for PGS twins and control twins. Post hoc sample size calculation for the primary outcome parameter, the fluency score, indicated that the study groups, including the subgroups of singletons and twins, were adequately powered. We assessed singletons and twins who contributed to the generalizability of the study. A limitation of our study is the relative small size of our study groups and the selective dropout in both groups (dropouts PGS group: higher gestational age; control group: less well-educated parents). These preclude the conclusion that PGS per se is not associated with neurodevelopmental, cognitive and behavioural problems in singletons and the conclusion that PGS is associated with altered neurodevelopmental outcome in twins. The need for careful long-term monitoring of children born following embryo biopsy remains, as it is still applied in the form of PGD and it is still unknown whether embryo biopsy affects long-term neurodevelopmental outcome.

Preimplantation genetic screening using fluorescence in situ hybridization in patients with repetitive implantation failure and advanced maternal age: two randomized trials

To evaluate the usefulness of preimplantation genetic screening (PGS) using fluorescence in situ hybridization (FISH) for two different indications: repetitive implantation failure (RIF) and advanced maternal age (AMA). Two prospective, randomized controlled trials with patients allocated in two arms: blastocyst transfer on day 5 (group A) or PGS with transfer on day 5 (group B). University-affiliated private clinics. The RIF study included women <40 years with three or more failed IVF cycles without other known causal factors (91 patients). The AMA study included intracytoplasmic sperm injection patients aged between 41 and 44 (183 patients). In the PGS group, single-cell day 3 biopsy was performed with aneuploidy screening for chromosomes 13, 15, 16, 17, 18, 21, 22, X, and Y. In both the blastocyst transfer group and the PGS group, ET was performed on day5. Live-birth rate per patient and per started cycle. A significant increase in live-birth rates per patient was found in the PGS group compared with the blastocyst group for the AMA study (30/93 patients [32.3%] vs. 14/90 patients [15.5%]; odds ratio, 2.585; confidence interval, [1.262-5.295]). In the RIF study no significant differences were observed (23/48 patients [47.9%] vs. 12/43 patients [27.9%]). PGS with FISH was shown to be beneficial for the AMA group.

The nature and origin of binucleate cells in human preimplantation embryos: relevance to placental mesenchymal dysplasia

Cleavage-stage embryos often have nuclear abnormalities, one of the most common being binucleate blastomeres, which may contain two diploid or two haploid nuclei. Biopsied cells from preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) cycles were studied to determine the relative frequency of binucleate cells with two haploid versus two diploid nuclei. The frequency of mononucleate haploid biopsied blastomeres was also recorded. In the chromosomal PGD cycles 45.2% of the biopsied binucleate cells were overall diploid and 38.7% were overall tetraploid, compared with 50.0% and 29.2% for the PGS group, respectively. Placental mesenchymal dysplasia is a rare condition associated with intrauterine growth restriction, prematurity and intrauterine death. Recent work suggests that androgenetic diploid/haploid mosaicism may be a causal mechanism. There are two possible origins of haploid nuclei, either the cell contained only one parental genome initially or they may be derived from the cytokinesis of binucleate cells with two haploid nuclei. Binucleate formation therefore may be a way of doubling up the haploid genome, to produce diploid cells of androgenetic origin as seen in placental mesenchymal dysplasia. Since the early studies in human embryos haploid cells were seen whose origin was unknown. Preimplantation embryos often have nuclear abnormalities, one of the most common being binucleate blastomeres, i.e. cells that contain two nuclei. These nuclei could be both diploid but many binucleate cells contain two haploid nuclei. Biopsied cells from preimplantation genetic diagnosis and preimplantation genetic screening cycles were studied to determine the relative frequency of binucleate cells with two haploid versus two diploid nuclei. The frequency of mononucleate haploid biopsied blastomeres was also recorded. There are two possible origins of haploid nuclei, either the cell contained only one parental genome initially or they may be derived from the cytokinesis of binucleate cells with two haploid nuclei. Binucleate formation therefore may be a way of doubling up the haploid genome, to produce diploid cells of androgenetic origin as seen in placental mesenchymal dysplasia, a rare condition associated with intrauterine growth restriction, prematurity and intrauterine death.

Redefining advanced maternal age as an indication for preimplantation genetic screening

In this retrospective study, the utility of preimplantation genetic screening (PGS) in patients with advanced maternal age is evaluated. The patient population consisted of women aged 38-44years and included in a regular IVF programme with or without PGS analysis. Transfer rate, ongoing implantation rate and ongoing pregnancy rate were the main outcome parameters measured. A trend of better ongoing pregnancy rate per oocyte retrieval was observed in patients aged 38 and 39years in the non-PGS group when compared with PGS groups, but better ongoing pregnancy rate per oocyte retrieval was observed in patients 41-44years old in the PGS group. When patients with a low ovarian response accumulated oocytes in several stimulation cycles, clinical outcomes were comparable to those of normal-responder patients. These results show that, although PGS does not benefit patients less than 40years of age, reproductive success increases more than two-fold in patients over 40years, especially in patients with more than six metaphase II oocytes, as a result of a good ovarian response or gamete accumulation, suggesting a redefinition of advanced maternal age as indication for PGS. In this retrospective study, the utility of preimplantation genetic screening (PGS) in patients with advanced maternal age is evaluated. Patient population consisted of women aged 38-44 years and included in a regular IVF programme with or without PGS analysis. Transfer rate, ongoing implantation rate and ongoing pregnancy rate were the main outcome parameters measured. A trend of better ongoing pregnancy rate per ovarian stimulation cycle was observed in patients aged 38-39 years in the non-PGS group when compared with PGS groups, but better ongoing implantation rate was observed in patients aged 41-44 years old in the PGS group. When patients with a low ovarian response (low number of oocytes available for the IVF cycle) accumulated oocytes in several stimulation cycles, their reproductive possibilities were comparable to those of normal-responder patients. These results show that, although PGS does not benefit patients less than 40 years of age, reproductive success increases more than 2-fold in patients over 40 years, especially in patients with more than six metaphase II oocytes, as a result of a good ovarian response or gamete accumulation, suggesting a redefinition of advanced maternal age as indication for PGS.

Neurological Condition of Infants Born After In Vitro Fertilization With Preimplantation Genetic Screening

Aim of this study was to evaluate the effect of preimplantation genetic screening (PGS) on neurodevelopmental outcome in children. We conducted a prospective follow-up study of children born to women randomly assigned to in vitro fertilization with or without PGS. Primary outcome was adverse neurologic outcome at 18 mo; secondary outcomes were types of minor neurologic dysfunction (MND), neurologic outcome before 18 mo, neonatal intensive care admission, and congenital malformations. Twenty women in the PGS group participated with 25 children and 26 women in the control group participated with 31 children. Five PGS pregnancies (25%) and four control pregnancies (15%) resulted in birth of at least one child with an adverse neurologic outcome (adjusted odds ratio: 2.3 [0.4-12.0]). Dysfunction in fine motor abilities and posture and muscle tone dysregulation tended to be present more frequently after PGS. Neurologic outcome before 18 mo, neonatal intensive care admission, and prevalence of congenital malformations were similar in study and control pregnancies. Nevertheless, at child level, rates of adverse outcome were higher after PGS. In conclusion, outcome in pregnancies after in vitro fertilization (IVF) with and without PGS was similar. The small sample size precludes the conclusion that PGS is not associated with less favorable neurologic outcome. Safety of new assisted reproductive techniques should be evaluated before large-scale implementation. :

Preimplantation genetic screening for aneuploidy of embryos after in vitro fertilization in women aged at least 35 years: a prospective randomized trial

To test the hypothesis that patients with advanced maternal age (AMA) have a higher implantation rate (IR) after embryo transfer of embryos with a normal chromosomal pattern for the chromosomes studied with preimplantation genetic screening (PGS) compared with patients who had an embryo transfer without PGS. Prospective randomized controlled trial (RCT). Academic tertiary setting. Patients with AMA (> or =35 years). In an RCT, the clinical IR per embryo transferred was compared after embryo transfer on day 5 or 6 between the PGS group (analysis of chromosomes 13, 16, 18, 21, 22, X, and Y) and the Control group without PGS. No differences were observed between the PGS group and the Control group for the clinical IR (15.1%; 14.9%; rate ratio 1.01; exact confidence interval [CI], 0.25-5.27), the ongoing IR (at 12 weeks) (9.4%; 14.9%), and the live born rate per embryo transferred (9.4%; 14.9%; rate ratio 0.63; exact CI, 0.08-3.37). Fewer embryos were transferred in the PGS group (1.6 +/- 0.6) than in the Control group (2.0 +/- 0.6). A normal diploid status was observed in 30.3% of the embryos screened by PGS. In this RCT, the results did not confirm the hypothesis that PGS results in improved reproductive outcome in patients with AMA.

A prospective randomized controlled trial of preimplantation genetic screening in the “good prognosis” patient

To determine whether the routine use of preimplantation genetic screening (PGS) in "good prognosis" women improves in vitro fertilization (IVF) cycle outcome. Randomized, controlled, prospective clinical study. Private infertility clinic. Infertile women predicted to have a good prognosis as defined by: age <39 years, normal ovarian reserve, body mass index <30 kg/m(2), presence of ejaculated sperm, normal uterus, <or=2 previous failed IVF cycles. Patients were randomized to the PGS group or the control group on day 3 after oocyte retrieval; 23 women underwent blastomere biopsy on day 3 after fertilization (PGS group), and 24 women underwent routine IVF (control group). All embryos were transferred on day 5 or 6 after fertilization. Pregnancy, implantation, multiple gestation, and live birth rates. No statistically significant differences were found between the PGS and control groups with respect to clinical pregnancy rate (52.4% versus 72.7%). However, the embryo implantation rate was statistically significantly lower for the PGS group (31.7% versus 62.3%) as were the live birth rate (28.6% versus 68.2%) and the multiple birth rate (9.1% versus 46.7%). In a "good prognosis" population of women, PGS does not appear to improve pregnancy, implantation, or live birth rates.

Preimplantation genetic screening in women of advanced maternal age caused a decrease in clinical pregnancy rate: a randomized controlled trial

Advanced maternal age (AMA) is an important parameter that negatively influences the clinical pregnancy rate in IVF, in particular owing to the increased embryo aneuploidy rate. It has thus been suggested that only transferring euploid embryos in this patient group would improve the pregnancy rate. The purpose of this study was to test whether employing preimplantation genetic screening (PGS) in AMA patients would increase the clinical pregnancy rate. We conducted a two-center, randomized controlled trial (RCT) to analyze the outcome of embryo transfers in AMA patients (>or=38 years of age) after PGS using FISH analysis for chromosomes X, Y, 13, 16, 18, 21 and 22. The PGS group was compared with a control group. The primary outcome measure was clinical pregnancy rate after 6-7 weeks of gestation per randomized patient. The study was terminated early as an interim analysis showed a very low conditional power of superiority for the primary outcome. Of the 320 patients calculated to be included in the study, 56 and 53 patients were randomized into the PGS and control groups, respectively. The clinical pregnancy rate in the PGS group was 8.9% (95% CI, 2.9-19.6%) compared with 24.5% (95% CI, 13.8-38.3%) in the control group, giving a difference of 15.6% (95% CI, 1.8-29.4%, P = 0.039). Although the study was terminated early, this RCT study provides evidence against the use of PGS for AMA patients when performing IVF. ISRCTN38014610.

Preimplantation genetic screening does not improve delivery rate in women under the age of 36 following single-embryo transfer

Single-embryo transfer is a well-accepted strategy to avoid multiple pregnancies in an assisted reproductive technology (ART) programme. Besides the morphological quality and embryo kinetics up to the blastocyst stage, preimplantation genetic screening (PGS) of aneuploidy has been advocated as an adjuvant approach to select the embryo. Couples with a female partner younger than 36 were randomly assigned to undergo transfer of a single blastocyst in a cycle with or without PGS using FISH for the chromosomes X, Y, 13, 16, 18, 21, 22. After the enrolment of 120 of the projected 447 patients in each group, study recruitment was terminated prematurely on the basis of futility. The observed live birth delivery rates after ART were 30.8 versus 30.8% per randomized patient, 34.6 versus 34.6% per cycle initiated, 37.8 versus 37.0% per aspirated cycle and 41.6 versus 43.5% per embryo transfer for the control versus the PGS group, respectively, with absolute between-group differences (95% CI; P value) of 0% (-11.7 to 11.7; P = 1.00), 0% (-12.7 to 12.7; P = 1.00), -0.8% (-14.2 to 12.7; P = 0.91) and 2.1% (-12.7 to 16.7; P = 0.79), respectively. Even in this younger age group, only 61% of the embryos had a normal diploid status. The absence of a beneficial treatment effect in this randomized clinical trial provides no arguments in favour of PGS to improve live birth delivery rate following single-embryo transfer in women under the age 36. Clinical Trials.gov: NCT00670059.