scholarly journals Utilization of preimplantation genetic testing in the USA

Author(s):  
Kaitlyn Roche ◽  
Catherine Racowsky ◽  
Joyce Harper

Abstract Purpose To evaluate the use of preimplantation genetic testing (PGT) and live birth rates (LBR) in the USA from 2014 to 2017 and to understand how PGT is being used at a clinic and state level. Methods This study accessed SART data for 2014 to 2017 to determine LBR and the CDC for years 2016 and 2017 to identify PGT usage. Primary cycles included only the first embryo transfer within 1 year of an oocyte retrieval; subsequent cycles included transfers occurring after the first transfer or beyond 1 year of oocyte retrieval. Results In the SART data, the number of primary PGT cycles showed a significant monotonic annual increase from 18,805 in 2014 to 54,442 in 2017 (P = 0.042) and subsequent PGT cycles in these years increased from 2946 to 14,361 (P = 0.01). There was a significant difference in primary PGT cycle use by age, where younger women had a greater percentage of PGT treatment cycles than older women. In both PGT and non-PGT cycles, the LBR per oocyte retrieval decreased significantly from 2014 to 2017 (P<0001) and younger women had a significantly higher LBR per oocyte retrieval compared to older women (P < 0.001). The CDC data revealed that in 2016, just 53 (11.4%) clinics used PGT for more than 50% of their cycles, which increased to 99 (21.4%) clinics in 2017 (P< 0.001). Conclusions A growing number of US clinics are offering PGT to their patients. These findings support re-evaluation of the application for PGT.

Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
Linjun Chen ◽  
Zhenyu Diao ◽  
Jie Wang ◽  
Zhipeng Xu ◽  
Ningyuan Zhang ◽  
...  

Summary This study analyzed the effects of the day of trophectoderm (TE) biopsy and blastocyst grade on clinical and neonatal outcomes. The results showed that the implantation and live birth rates of day 5 (D5) TE biopsy were significantly higher compared with those of D6 TE biopsy. The miscarriage rate of the former was lower than that of the latter, but there was no statistically significant difference. Higher quality blastocysts can achieve better implantation and live birth rates. Among good quality blastocysts, the implantation and live birth rates of D5 and D6 TE biopsy were not significantly different. Among fair quality and poor quality blastocysts, the implantation and live birth rates of D5 TE biopsy were significantly higher compared with those of D6 TE biopsy. Neither blastocyst grade nor the day of TE biopsy significantly affected the miscarriage rate. Neonatal outcomes, including newborn sex, gestational age, preterm birth, birth weight and low birth weight in the D5 and D6 TE biopsies were not significantly different. Both blastocyst grade and the day of TE biopsy must be considered at the same time when performing preimplantation genetic testing–frozen embryo transfer.


2019 ◽  
Vol 2019 (3) ◽  
Author(s):  
N Gleicher ◽  
V A Kushnir ◽  
D H Barad

Abstract With steadily improving pregnancy and live birth rates, IVF over approximately the first two and a half decades evolved into a highly successful treatment for female and male infertility, reaching peak live birth rates by 2001–2002. Plateauing rates, thereafter, actually started declining in most regions of the world. We here report worldwide IVF live birth rates between 2004 and 2016, defined as live births per fresh IVF/ICSI cycle started, and how the introduction of certain practice add-ons in timing was associated with changes in these live birth rates. We also attempted to define how rapid worldwide ‘industrialization’ (transition from a private practice model to an investor-driven industry) and ‘commoditization’ in IVF practice (primary competitive emphasis on revenue rather than IVF outcomes) affected IVF outcomes. The data presented here are based on published regional registry data from governments and/or specialty societies, covering the USA, Canada, the UK, Australia/New Zealand (combined), Latin America (as a block) and Japan. Changes in live birth rates were associated with introduction of new IVF practices, including mild stimulation, elective single embryo transfer (eSET), PGS (now renamed preimplantation genetic testing for aneuploidy), all-freeze cycles and embryo banking. Profound negative associations were observed with mild stimulation, extended embryo culture to blastocyst and eSET in Japan, Australia/New Zealand and Canada but to milder degrees also elsewhere. Effects of ‘industrialization’ suggested rising utilization of add-ons (‘commoditization’), increased IVF costs, reduced live birth rates and poorer patient satisfaction. Over the past decade and a half, IVF, therefore, has increasingly disappointed outcome expectations. Remarkably, neither the profession nor the public have paid attention to this development which, therefore, also has gone unexplained. It now urgently calls for evidence-based explanations.


2020 ◽  
Vol 35 (11) ◽  
pp. 2408-2412
Author(s):  
James M Kemper ◽  
Rui Wang ◽  
Daniel L Rolnik ◽  
Ben W Mol

ABSTRACT Questions continue to be raised regarding the benefit of genetic assessment of embryos prior to transfer in IVF, specifically with regards to preimplantation genetic testing for aneuploidy (PGT-A). To evaluate and quantify these concerns, we appraised the most recent (2012–2019) randomized controlled trials on the topic. Only two of these six studies listed cumulative live birth rates per started cycle, with both eliciting a statistically non-significant result. This article describes the concern that a focus on results from the first embryo transfer compared to cumulative outcomes falsely construes PGT-A as having superior outcomes, whilst its true benefit is not confirmed, and it cannot actually improve the true pregnancy outcome of an embryo pool.


2019 ◽  
Vol 112 (3) ◽  
pp. e401 ◽  
Author(s):  
Julia G. Kim ◽  
Gayathree Murugappan ◽  
Ruth B. Lathi ◽  
Jonathan D. Kort ◽  
Brent M. Hanson ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
L Trevisan ◽  
F Forzano ◽  
Y Khalaf ◽  
C Tomlinson ◽  
P Renwick ◽  
...  

Abstract Study question Does conception by Preimplantation Genetic Testing (PGT-M, PGT-SR) adversely affect health outcomes in children born through this assisted reproductive technique? Summary answer No significant difference was noted in the rate of congenital malformations in children born after PGT-M and PGT-SR compared with IVF-ICSI children. What is known already It is already known that the risk of congenital anomalies in IVF-ICSI pregnancies is higher when compared with pregnancies conceived naturally. Study design, size, duration This is a prospective study on 747 children born between December 1999 and July 2016 after a cycle of PGT-M or PGT-SR (IVF +/- ICSI + embryo biopsy) performed at a single London reproductive centre. PGT-A is not performed in the Centre, so pregnancy outcomes in this group are not relevant. The children were examined at birth, at 12 and 24 months of age and the data collected in three questionnaires. Participants/materials, setting, methods 747 PGT-M and PGT-SR children were enrolled in the study. 742/747 were examined at birth, 444/747 at 12 months and 168/747 at 24 months. The assessment consisted of three separate questionnaires completed at birth, 12 months and two years of age. The first questionnaire focused on the detection of congenital anomalies in newborn babies. The questionnaire at follow up recorded growth data and examination of the baby’s health and development. Main results and the role of chance We found no evidence that PGT-M and PGT-SR increased the risk of an adverse perinatal outcome when compared with children born after IVF-ICSI. The overall malformation rate in our group of live born after PGT-M and PGT-SR was 3.9% and of major malformations was 2%. These values are comparable with literature data on malformation risk in children born after IVF-ICSI. In terms of misdiagnosis, we had one misdiagnosis of SMA type 1 in 658 pregnancies obtained. This was very early on in the centre’s experience of offering PGT-M. Follow-up visits in our cohort allowed us to evaluate their development. Unfortunately, the low participation rate at 24 months (23%) significantly reduced the size of our cohort. We observed a cumulative value of 10% at 24 months of babies with developmental delay which is comparable with the value of 10% given by the WHO, but is twice the incidence Global Research on Developmental Disabilities Collaborators described in the UK in 2016 (4.6%). To our knowledge, no large studies have assessed the risk of developmental delay in children born after PGT. We cannot draw conclusions on this from our small cohort at 24 months and recommend further studies. Limitations, reasons for caution Although our sample is one of the largest reported, it is too small to generalise results due to the heterogeneity of the conditions for which PGT was being offered and the rarity of these conditions. There were multiple confounding factors including couple’s fertility background, varying fertility treatments and embryological techniques. Wider implications of the findings: Our results support published literature highlighting the safety of PGT-M and PGT-SR techniques. We followed up at birth, 12 months and 24 months a large cohort of children, in one of the largest datasets published so far. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Takahashi ◽  
N Hisa ◽  
R Kotake ◽  
Y Suzuki ◽  
S Akimoto ◽  
...  

Abstract Study question Are one live birth rates (LBRs) similar in minimal stimulation cycle IVF with letrozole only and natural cycle IVF for the first ART cycle? Summary answer LBRs after first ART cycle in minimal stimulation cycle IVF with letrozole only are superior to natural cycle IVF. What is known already The addition of letrozole to gonadotropins in ovarian stimulation (OS) may reduce the risk of OHSS, but there is no significant difference were reported in ongoing pregnancy rate or number of oocytes retrieved in the letrozole + FSH group compared to the FSH only. No differences were also reported in clinical pregnancy rates or number of mature oocytes in the additional of letrozole in an GnRH antagonist protocol group compared to the GnRH antagonist group. There are no previous study comparing LBRs after first ART cycle in minimal stimulation cycle IVF with letrozole and natural cycle IVF. Study design, size, duration Data for this retrospective cohort study were obtained 643 women, 30–39 years of age started their first ART cycle at one private fertility clinic between January 2016- December 2019. Participants/materials, setting, methods A total of 643 women were scheduled their first oocyte retrieval cycle. 118 women started with letrozole (LE) and 525 women started natural cycle (NC). The main strategy for OS in our center is minimal stimulation and natural cycle IVF. Patients consulted with gynecologists to determine their treatment plan based on patients’ preference or their menstrual cycle. All pregnancies generated from oocyte retrieval during the first IVF cycle including fresh and frozen-thaw cycles were registered. Main results and the role of chance The number of retrieved oocytes and the normal fertilization rates were significantly higher in the LE than NC (4.4 vs 3.4, 77.6% vs 71.1%), p &lt; 0.05 respectively). There was no significant difference in the clinical pregnancy rates (CPRs) per embryo transfer (ET) (fresh cleavage stage ET: 32.9% vs 28.0%, frozen-thaw blastocyst ET: 39.4% vs 44.9% ns). However, the CPRs and LBRs per oocyte retrieval (OR) were significantly higher in the LE group (39.0% vs 28.6, 33.9% vs 21.9%, p &lt; 0.05 respectively). In a subsequent regression analyses, LBRs per OR of LE was significantly higher than NC as well. (adjusted OR = 1.63 (95% CI: 1.02–2.58, p = 0.041). Limitations, reasons for caution The strength of the present study was the use of a large cohort of women who underwent minimal stimulation IVF with letrozole only. Although our results are promising, limited by retrospective cohort study. These interpretations prompted the need for a perspective cohort study to evaluate the efficacy of letrozole. Wider implications of the findings: When comparing minimal stimulation IVF with letrozole only and natural cycle IVF, we found significantly higher LBRs per OR in minimal stimulation IVF with letrozole only, despite similar CPRs per ET. Trial registration number none


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Spinella ◽  
A Victor ◽  
F Barnes ◽  
C Zouves ◽  
A Besser ◽  
...  

Abstract Study question To explore the effect of chromosomal mosaicism detected in preimplantation genetic testing (PGT-A) on prenatal and postnatal outcome of mosaic embryo pregnancies Summary answer No significant difference between euploid and mosaic embryos was observed in terms of weeks of gestation, average weight, and developmental defect of the babies born What is known already Mosaic embryos have the potential to implant and develop into healthy babies. Transfer of these embryos is now offered as an option for women who undergo IVF resulting in no euploid embryos. While, prenatal diagnosis has shown the depletion of chromosomal mosaicism in mosaic embryos, several concerns remain. For instance, the direct effects of different kind of mosaicism on prenatal/postnatal outcome and the possibility that intra-biopsy mosaicism in the TE is a poor predictor of the ploidy status of the ICM. Thus, there is certainly a need for comprehensive analyses of obstetrical and neonatal outcome data of transferred mosaic embryos. Study design, size, duration Compiled analysis from multicenter data on transfers of mosaic embryos (n = 1,000) and their outcome, with comparison to a euploid control group (n = 5,561). To explore the effect of embryonic mosaicism on newborns, we matched mosaic embryos resulting in a birth with a euploid embryo by a series of parameters (maternal age, embryo morphology, and indication for PGT-A). Prenatal tests and birth characteristics of &gt; 200 neonates from mosaic embryo transfers were compared to &gt; 200 euploid embryos. Participants/materials, setting, methods PGT-A was performed on blastocyst-stage embryos with 24-Chromosome whole genome amplification (WGA)-based Next Generation Sequencing (NGS). In accordance with established guidelines, embryos were categorized as mosaic when PGT-A results indicated 20-80% aneuploid content. Prenatal testing where performed in 30% of pregnancies with amniocentesis, 4% did an extra analysis for potential UPD for the suspected mosaic chromosome, and an additional 16% performed chorionic villus sampling (CVS) and 9.5% performed noninvasive prenatal testing (NIPT). Main results and the role of chance Of the 465 mosaic embryos that implanted, about 20% miscarried, and out of those, 75% were early spontaneous abortions. Of the pregnancies, 3 out of 368 were stillborn (2 out of them were twins that were extremely premature at 23 weeks, and the other died during pregnancy from a heart defect). The remaining 99% of those have been born or are late ongoing pregnancies at the time of analysis. Prenatal tests were performed in &gt; 200 pregnancies and the vast majority tested normal. All 5 abnormal cases were amniocentesis tests showing microdeletions or insertions of sizes smaller than the resolution used during PGT-A, so they were unrelated to the mosaicism detected with PGT-A. In fact, in none of the cases did the prenatal test reflect the mosaicism detected at the embryonic stage. Matching each of the 162 mosaic embryos resulting in a birth with a euploid embryo, we found that the length of gestation was similar on average, and so was the average weight of the babies at birth. We also gathered information on the routine physical examination performed on babies at birth, and of those 162 babies from mosaic embryo transfers, none had obvious developmental defects or gross abnormalities. Limitations, reasons for caution Even though newborns resulting from mosaic embryo transfers in this study invariably appeared healthy by routine examination, concerns for long-term health cannot yet be entirely dispelled. The question must therefore be carefully considered by each clinic and patient situation. Wider implications of the findings Prenatal testing of &gt; 200 pregnancies from mosaic embryo transfers showed no incidence of mosaicism that matched the PGT-A findings, indicating the involvement of self-corrective mechanisms. Pregnancy and obstetric data indicates that mosaic embryos prevailing through gestation and birth have similar chromosomal and physiological health compared to euploid embryos. Trial registration number none


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Esiso ◽  
F Lai ◽  
D Cunningham ◽  
D Garcia ◽  
B Barrett ◽  
...  

Abstract Study question Does rapid or delayed insemination after egg retrieval affect fertilization, blastocyst development and live birth rates in CI and ICSI cycles? Summary answer When performing CI or ICSI &lt;1.5h and &gt;6.5h after retrieval, detrimental effects are moderate on fertilization but do not impact blastocyst usage and birth rates. What is known already Several studies have shown that CIor ICSI performed between 3 to 5 h after oocyte retrieval has improved laboratory outcomes. However, some studies indicate that insemination of oocytes, by either CI or ICSI, within 2 hours or more than 8 hours after oocyte retrieval has a detrimental effect on the reproductive outcome. With some ART centres experiencing an increase in workload, respecting these exact time intervals is frequently challenging. Study design, size, duration A single-center retrospective cohort analysis was performed on 6559 patients (9575 retrievals and insemination cycles) between January 1st2017 to July 31st2019. The main outcome measures were live-birth rates. Secondary outcomes included analysis of fertilization per all oocytes retrieved, blastocyst utilization, clinical pregnancy, and miscarriage rates. All analyses used time of insemination categorized in both CI and ICSI cycles. Fertilization rates across categories was analyzed by ANOVA and pregnancy outcomes compared using Chi-square tests. Participants/materials, setting, methods As part of laboratory protocol, oocyte retrieval was performed 36 h post-trigger. Cycles involving injection with testicular/epidydimal sperm, donor or frozen oocytes were excluded. The time interval between oocyte retrieval and insemination was analyzed in eight categories: 0 (0- &lt;0.5h), 1 (0.5-&lt;1.5h), 2 (1.5-&lt;2.5h), 3 (2.5-&lt;3.5h), 4 (3.5-&lt;4.5), 5 (4.5-&lt;5.5), 6 (5.5-&lt;6.5) and 7 (6.5-&lt;8h). The number of retrievals in each group (0–7) was 586, 1594, 1644, 1796, 1836, 1351, 641 and 127 respectively. Main results and the role of chance This study had a mean patient age of 36.0 years and mean of 12.2 oocytes per retrieval in each category. There were 4,955 CI and 4,620 ICSI retrievals. The smallest groups were time category 7 and 0 for CI and ICSI respectively. The results showed that the mean fertilization rate per egg retrieved for CI ranged from 54.1 to 64.9% with a significant difference between time category 0 and 5 (p &lt; 0.001) and category 1 and 5 (p &lt; 0.0.001). Mean fertilization rate for ICSI per egg retrieved ranged from 52.8 to 67.3% with no significant difference between time categories compared to category 5. Blastocyst utilization rate for CI and ICSI were not significantly different for all time categories. In the CI and ICSI groups there were 6,540 and 6,178 total fresh and frozen transfers. The miscarriage and clinical pregnancy rate in CI and ICSI were not significantly different across time categories. The overall mean live birth rate for CI was 32.4% (range: 23.1 to 35.5%). Live-birth rates differed significantly (p = 0.04) in CI with time categories 0 and 7 the lowest. In the ICSI group, the overall mean live birth rate was 30.8% (range: 29.1 to 35.7%),with no significant differences between time categories. Limitations, reasons for caution As this is a retrospective study, the influence of uncontrolled variables cannot be excluded. The group spread was uneven with the early and late time categories having the lowest number of representative retrievals and this could have affected the results obtained. Wider implications of the findings: Our results indicate that both CI and ICSI are optimal when performed between 1.5–6.5 hours after oocyte retrieval. Further prospective studies on reproductive outcomes related to time of insemination are warranted. This data indicates a minimal detrimental effect when it is untenable to follow strict insemination time intervals. Trial registration number 2015P000122


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Elkhatib ◽  
N D Munck ◽  
A Abdala ◽  
A Arnanz ◽  
A Eldamen ◽  
...  

Abstract Study question Do delayed mature oocytes result in similar euploid blastocyst rates as their immediate mature sibling oocytes? Summary answer Once a blastocyst is obtained, delayed mature oocytes have similar euploid rates compared to immediate mature oocytes. What is known already Intracytoplasmic sperm injection (ICSI) of metaphase II oocytes few hours post oocyte retrieval is standard practice in IVF laboratories. Immature metaphase I (MI) and prophase I (GV) oocytes are usually discarded. Immature oocytes may mature overnight, after which ICSI can be performed. Studies demonstrated lower fertilization and blastulation rates for these delayed mature oocytes. However, live births have been reported from blastocysts transferred. The evidence available is not compelling, since most of the studies had either low sample size, no preimplantation genetic testing for aneuploidies (PGT-A), or the outcome was not compared to sibling MII oocytes at time of denudation. Study design, size, duration A single-center retrospective sibling oocyte study was performed between January 2019 and December 2020 at ART Fertility clinics Abu Dhabi, UAE. A total of 345 PGT-A cycles, with at least one delayed mature oocyte inseminated by ICSI, were included: 2506 immediate mature oocytes and 669 delayed mature oocytes. Participants/materials, setting, methods Following controlled ovarian stimulation, MII oocytes at the time of denudation were inseminated by ICSI/IVF (immediate mature). Immature oocytes (MI/GV) were cultured for 16–24 hours in fertilization medium and injected the next day if matured (delayed mature). Trophectoderm biopsy was performed on day 5/6/7 and samples were subjected to Next Generation Sequencing to screen the ploidy state of the blastocyst. Main results and the role of chance The 345 controlled ovarian stimulation cycles resulted in the insemination of 2506 MII oocytes on the day of oocyte retrieval (Day0) and 669 delayed mature oocytes on day 1. Normal fertilization rate was significantly higher in the immediate mature oocytes compared to delayed mature oocytes (68% vs 56%, p &lt; 0.0001). Similarly, the usable blastocyst rate was significantly higher in immediate mature oocytes (59% vs 19%, p &lt; 0.0001). On day 5 of development, a significantly higher-good quality blastocyst formation rate was obtained from immediate mature oocytes (65% vs 27%, p &lt; 0.0001). The rate of good quality blastocyst on the day of biopsy was significantly higher in the immediate mature oocytes group (76% vs 62%, p &lt; 0.015). Fisher’s Exact Test was performed to compare the euploid rate of blastocysts biopsied on day 5/6/7 originating from immediate mature oocytes or sibling delayed mature oocytes. The euploid potential of blastocyst biopsied showed no significant difference between the two groups (p = 0.388). Limitations, reasons for caution The timing of MI/GV oocytes transition to MII stage was not recorded since the incubation was done in a benchtop incubator. Furthermore, the same sperm sample was used to inseminate immediate and delayed mature oocytes, which might contribute to the compromised embryo development due to increased sperm DNA fragmentation. Wider implications of the findings: Insemination of delayed mature oocytes by ICSI, should be considered as a tool to increase patients’ chances of obtaining a euploid embryo. Especially in cases where low yield of euploid embryos is expected. Trial registration number Not applicable


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