Use Of Preimplantation Genetic Testing Research Articles

Fertility preservation practices for female oncofertility differ significantly across the USA: results of a survey of SREI members.

The field of oncofertility has maintained an important focus on improving access, yet standardized practices are lacking. To assess how female cancer patients are provided oncofertility care, we sought to determine provider-level differences and whether there are physician or practice characteristics that predict these variations. A cross-sectional survey was sent to SREI members. The survey included fifteen questions about physician practice characteristics and oncofertility cryopreservation protocols. Topics included ovarian stimulation protocols, fertilization techniques, stage of embryo cryopreservation, routine use of pre-implantation genetic testing for aneuploidy (PGT-A), and ovarian tissue cryopreservation (OTC). Statistical analyses assessed whether practice setting, geographic region, time in practice, and mandatory state insurance coverage had effects on cryopreservation protocols. A total of 141 (17%) from diverse REI practice backgrounds completed the survey. The median number of new female oncofertility consults per year was 30 (range 1 to 300). Providers in academic settings treated more patients (median 40 vs. 15, p < 0.001). Providers in academic settings more often use gonadotropin-releasing hormone agonists (85% vs. 52%, p < 0.001) and perform OTC (41% vs. 4%, p < 0.001). Providers in academic practices were less likely to perform intracytoplasmic sperm injection in every cycle (37% vs. 55%, p = 0.032) and less likely to usually advise PGT-A (21% vs. 36%, p = 0.001). Mandated state insurance coverage had no effect on oncofertility practices. Oncofertility practices vary among providers. Factors such as practice setting and region may affect the services provided. We do not yet know the best practices in oncofertility patients, and future research is needed.

The death of Roe and the future of ex vivo embryos

This article examines the possible effects of the end of a federal constitutional right to abortion on clinical practice and research involving ex vivo human embryos. It first analyzes the likely outcomes of Dobbs v. Mississippi, concluding the Supreme Court will either overrule the federal constitutional abortion right or restrict it in a way that leads to its rapid disappearance. Next, the article discusses a possible increase in use of preimplantation genetic testing as one result. It then forecasts the likely ramifications of such a court decision on state legislation affecting ex vivo human embryos in two ways. It examines the possibility that victory over Roe will inspire embryo support groups to push for limitations on in vitro fertilization, perhaps on its destruction of embryos and more likely on permissible grounds for prospective parents to use in choosing embryos for transfer. It ends by discussing the prospects of new laws in some states banning or limiting research with human embryos.

Use of preimplantation genetic testing for monogenic disorders and subsequent prenatal care and diagnostic testing.

The goal of preimplantation genetic testing for monogenic or single gene defects (PGT-M) is to identify inherited pathogenic variants in the embryo prior to embryo transfer, increasing the likelihood of an unaffected child. Prenatal diagnostic testing is recommended to confirm the results of PGT-M. The purpose of this study was to characterize the population undergoing PGT-M over time. This retrospective study examined patients who had a positive pregnancy test after PGT-M from 2012 to 2019. A query of the internal assisted reproductive technology database and chart review were used. One hundred and 42 patients completed IVF cycles for PGT-M during this time period and progressed past 10weeks gestation. There were more PGT-M cycles over time with 46 cycles between 2012 and 2015 and 96 cycles between 2016 and 2019. Patients varied on the decision to pursue prenatal diagnostic testing after PGT-M. For those with known follow-up (130/142), 16 patients underwent diagnostic testing (12%) and 114 did not. As PGT-M is increasingly utilized prior to pregnancy, it is important for genetic counselors and OB/GYNs to understand the characteristics and outcomes of the population of patients undergoing PGT-M, including how to counsel about the residual risk of an affected pregnancy after PGT-M.

Преимплантационное генетическое тестирование: православно-христианская рефлексия этических проблем метода

Background: Preimplantation genetic testing is used in In Vitro Fertilization to identify genetic abnormalities in embryos. Genetically defective embryos are not transferred to the uterus, resulting in a higher percentage of healthy babies born. Aim: to study the ethical problems of using preimplantation genetic testing in Orthodox Christian discourse. Materials and methods: An analysis of the provisions of Orthodox ethics, expressed in the church resolutions of the Russian Orthodox Church and the general church teaching on morality, was carried out in the context of their application for the biotic analysis of preimplantation genetic testing (PGT). Results: Despite the fact that PGT can have positive implications for the choice of the mode of delivery later on and for the earliest possible initiation of intrauterine treatment, this practice meets with certain ethical objections in Orthodox Christian discourse. Identified genetic abnormalities of embryos in PGT encourage women to refuse to transfer the "diseased" embryo, leading ultimately to its death. The absence of intrauterine interaction between a mother and an embryo makes such a choice easily feasible. Given that Orthodox Christianity affirms the beginning of human life from the moment of conception, refusing to become pregnant with a "sick embryo" would be tantamount to its murder. In addition, among the ethical problems of PGT is the possibility of the use thereof for the embryo selection according to sex or other chosen characteristics, which also belongs to immoral actions in Orthodox Christianity. Conclusion: Thus, the possibility for Orthodox couples to participate in assisted reproductive technology must exclude the use of pre-implantation genetic testing, which is ethically unacceptable within Orthodox Christianity. The couple starting IVF should be ready to give birth and bring up such a child, who will be the result of the fertilization in vitro.

State-Mandated Insurance Coverage and Preimplantation Genetic Testing in the United States.

To examine the association between state-mandated insurance coverage for infertility treatment in the United States and the utilization of and indication for preimplantation genetic testing. This was a retrospective cohort study of 301,465 in vitro fertilization (IVF) cycles reported to the Society for Assisted Reproductive Technology between 2014 and 2016. Binomial logistic regression was performed to examine associations between state-mandated insurance coverage and preimplantation genetic testing use. The neonate's sex from each patient's first successful cycle was used to calculate sex ratios. Sex ratios then were compared by state mandates and preimplantation genetic testing indication for elective sex selection. The proportion of IVF cycles using preimplantation genetic testing increased from 17% in 2014 to 34% in 2016. This increase was driven largely by preimplantation genetic testing for aneuploidy testing. Preimplantation genetic testing was less likely to be performed in states with mandates for insurance coverage than in those without mandates (risk ratio [RR] 0.69, 95% CI 0.67-0.71, P<.001). Preimplantation genetic testing use for elective sex selection was also less likely to be performed in states with mandates (RR 0.44, 95% CI 0.36-0.53, P<.001). Among liveborn neonates, the male/female sex ratio was higher for IVF cycles with preimplantation genetic testing for any indication (115) than for those without preimplantation genetic testing (105) (P<.001), and the use of preimplantation genetic testing specifically for elective sex selection had a substantially higher (164) male/female sex ratio than preimplantation genetic testing for other indications (112) (P<.001). The proportion of IVF cycles using preimplantation genetic testing in the United States is increasing and is highest in states where IVF is largely self-funded. Preimplantation genetic testing for nonmedical sex selection is also more common in states where IVF is self-funded and is more likely to result in male offspring. Continued surveillance of these trends is important, because these practices are controversial and could have implications for future population demographics.

Comparison of live birth rates after IVF–embryo transfer with and without preimplantation genetic testing for aneuploidies

Research questionDoes the use of preimplantation genetic testing for aneuploidies (PGT-A) result in higher live birth rates when compared with both fresh and frozen embryo transfers (FET) not utilizing PGT-A? DesignRetrospective cohort study at a single tertiary centre using inverse probability of treatment weighting (IPTW) to adjust for differences in baseline characteristics between groups. ResultsA total of 107 FET using PGT-A from 74 patients, along with 321 fresh and 286 FET not using PGT-A from 381 patients met the inclusion criteria for this study. In the IPTW-adjusted analysis of transfer-level data, PGT-A transfers resulted in a significantly higher live birth rate when compared with both non-PGT-A fresh (49.5% versus 38.6%, P = 0.036) and FET (50.6% versus 35.8%, P = 0.016). When data were analysed per retrieval level, the live birth rate was similar and acceptably high with or without PGT-A (63.7% versus 52.3%, P = 0.09). ConclusionWhen comparing PGT-A to non-PGT-A fresh and FET, PGT-A embryo transfers have a significantly higher live birth rate. However, this difference did not persist at a per-retrieval level. Further investigation is needed to understand in what scenarios PGT-A has clinical significance and whether differences in the number of available embryos for transfer negates the benefit of PGT-A.

Prevalence and performance of private equity-affiliated fertility practices in the United States

To quantify the proportion of annual assisted reproductive technology (ART) cycles performed at private equity-affiliated fertility practices and to test for differences in services and success rates between private equity-affiliated and nonaffiliated practices. Cross-sectional analysis of national data set. Not applicable. None. Not applicable. The primary outcome measures were the volume of ART cycles performed, the percentage of retrievals resulting in live births, and the percentage of transfers resulting in live births. The secondary outcomes included the median income of the practice location, the use of preimplantation genetic testing, the clinical service availability, and the patient reasons for seeking treatment. Of the practices listed on the Centers for Disease Control's 2018 Fertility Clinic Success Rates Report, 14.7% had a private equity affiliation. Of the 305,883 ART cycles performed in 2018, 29.3% (89,535) occurred at private equity-affiliated practices. Patients at private equity-affiliated practices were 6.75% (95% confidence interval [CI], -10.15%, -3.36%) less likely to initiate a cycle due to male factor infertility, and 10.60% (95% CI, 3.49, 17.76) more likely to use preimplantation genetic testing before embryo transfer. No statistically significant differences were found in success rates among women aged <35 years. The average median household income (standard error) in zip codes with private equity-affiliated practices compared with nonaffiliated practices was $83,610 ($35,990) and $72,161 ($32,314), respectively. A major portion of fertility practices in the United States are private equity-affiliated, and these practices perform an even greater portion of ART cycles in the United States each year. Fertility appears to be the medical specialty with the greatest market share owned by private equity. Our findings corroborate preliminary research, which forecasts the increasing involvement and consolidation by private equity in fertility. Future research should continue monitoring for differences in outcomes, financing, case mix, service use, and accessibility.

DOES EMBRYO BIOPSY INCREASE THE RISK OF ECTOPIC PREGNANCY?

With the increasing use of preimplantation genetic testing (PGT), there is an increasing need to understand the potential impact trophectoderm biopsy may have on embryo viability and implantation. As ectopic pregnancies are a result of abnormal implantation, it is possible that disruption to embryo integrity may alter this process. The objective of our study was to determine whether PGT tested embryos had an increased risk of ectopic pregnancy compared to non-PGT tested embryos.

COMPARISON OF SEX OUTCOMES AFTER FROZEN, SINGLE EMBRYO TRANSFER OF PREIMPLANTATION GENETICALLY TESTED AND UNTESTED EMBRYOS

The use of preimplantation genetic testing (PGT) has dramatically increased over the last decade. With the technology to detect aneuploidy comes the ability to determine embryo sex and the ethical dilemma of whether sex should be selected. The objective of this study is to describe sex outcomes after single embryo transfers in untested and PGT embryos in a practice with a specific sex selection policy. A retrospective cohort study was performed to evaluate outcomes of singleton pregnancies achieved via single blastocyst frozen embryo transfer at an urban university hospital between 2018-2020. The sex selection policy during this time was to allow patients to select the sex only if both sexes were available and each embryo had reasonably equal predicted success based on embryo grading. PGT for the sole indication of sex selection was not allowed. All patients had a diagnosis of infertility or were undergoing PGT for single gene mutation disease prevention. Chi square analysis was performed. Of the 541 pregnancies meeting inclusion criteria, 64.7% (N=350) underwent biopsy. The mean maternal age was higher in the biopsy cohort compared to the untested embryos (36.1 vs. 34.0, P<0.001). The mean BMI, gestational age and weight at delivery did not differ significantly between the two groups. Among the untested embryos, 55% (105/191) were female compared to 59.4% (208/350) in the PGT embryos (OR 0.83, 95% CI 0.58-1.2). Singletons born from a frozen single embryo transfer have a higher rate of female sex than male. Allowing sex selection using the policy described above did not statistically increase this ratio.

SEVERE MALE FACTOR DOES NOT AFFECT THE EUPLOID BLASTOCYST RATE. A FUNCTION OF SOURCE OR CONCENTRATION?

There is an increase in the use of preimplantation genetic testing (PGT) in the case of moderate to severe male factor populations. However, high rates of aneuploidy have been reported using low sperm concentration in severe male infertility (Kahraman et al., 2020). Therefore the objective of this study was to evaluate the euploid blastocyst rate of severe male factor sperm concentrations.

Utilization of preimplantation genetic testing in the USA

PurposeTo 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.MethodsThis 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.ResultsIn 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).ConclusionsA growing number of US clinics are offering PGT to their patients. These findings support re-evaluation of the application for PGT.

Preimplantaciono genetičko testiranje

The application of preimplantation genetic testing (PGT) began in the late 1980s. Pre-implantation genetic testing, as the earliest possible method of prenatal diagnosis, enables the selection of embryos with a normal karyotype for embryo transfer. The use of preimplantation genetic testing has proven to be a useful method in the following three groups of inherited diseases: monogenic disorders (single gene defects), trinucleotide repeat disorders, and chromosomal abnormalities. The success rate of in vitro fertilization (IVF) has increased significantly since the introduction of PGT into clinical practice. This paper presents a literature review with the aim of clearly determining the role of PGT in embryo selection before embryo transfer, as well as the role of this type of testing in increasing the success rate of IVF. One of the goals of the paper is also to review the development of molecular genetic methods that are currently, or have once been, in routine use when performing PGT. The current literature is an indicator of the development and progress of molecular genetics techniques applied in PGT. At the same time, it provides an opportunity and an incentive for further extensive research that will lead to the improvement of preimplantation genetic testing and thus increase the success rate of in vitro fertilization.

Child health after preimplantation genetic testing

Research questionDespite the increasing use of preimplantation genetic testing (PGT) for aneuploidy and monogenic diseases, for children conceived using PGT there is limited follow-up beyond 2 years of age. This study examined the health, well-being and development of school-aged children (5–8 years old) conceived following PGT. DesignRetrospective cohort study of children conceived after IVF with PGT (exposed cohort) and children conceived after IVF without PGT (unexposed cohort) at two IVF clinics in Melbourne, born between 2000 and 2008, recruited with a 1:2 ratio. Mothers of the children completed a questionnaire asking child-specific questions regarding health and well-being, mental health, development, educational achievement and family-specific questions regarding family functioning and parent–child attachment. ResultsA total of 155 participants were recruited to the PGT cohort and 303 participants to the IVF-only cohort. There were no differences between the two cohorts with regards to maternal characteristics, birth defect frequency and pregnancy characteristics, apart from delivery by Caesarean section, which was more frequent in PGT singletons (55%) compared with IVF-only singletons (36%). While no significant differences between the PGT and IVF-only cohorts were found for the majority of general health and psychological scales, there were differences when compared with population data. Children in the exposed cohort appeared to have more positive outcomes in many of the measures. ConclusionThe data from this study suggest that PGT does not cause adverse outcomes in children. However, the nature (self-report) and small sample size of the study must be taken into consideration when interpreting the data.

PREIMPLANTATION GENETIC TESTING FOR ANEUPLOIDY IN DONOR OOCYTE IVF CYCLES: A MATCHED, SIBLING OOCYTE COHORT STUDY

The use of preimplantation genetic testing for aneuploidy (PGT-A) has been shown to improve live birth rate per embryo transfer (ET) and reduce pregnancy loss.1 Whether PGT-A is beneficial in donor oocyte recipient cycles, with lower expected rates of aneuploidy, is less clear.2-4 A major concern is the possible lower positive predictive value of PGT-A when the technology is used to screen young donor-oocyte derived embryos, which may reduce the number of healthy embryos available for transfer and/or cryopreservation.

Preimplantation genetic testing as a component of root cause analysis of errors and reassignment of embryos in IVF

The risks of embryo/gamete mix-up are a threat to the integrity of the IVF process, with significant implications for affected families. The use of preimplantation genetic testing through single-nucleotide polymorphism array or next-generation sequencing technology can help to identify, characterize and ultimately help, in some cases, to find the root cause, and to mitigate the extent of these errors for a given patient or laboratory.

Non-invasive prenatal testing in the context of IVF and PGT-A.

The high incidence of chromosome aneuploidy in human gametes and embryos is a major cause of invitro fertilization (IVF) failure and miscarriage. In order to improve live birth rates with single embryo transfer, the use of preimplantation genetic testing for aneuploidy (PGT-A) has significantly increased. PGT encompasses methods that allow embryos to be tested for inherited conditions or screened for chromosomal abnormalities. However, PGT-A is a screening method and results can never be used to definitively predict the chromosomal status of the embryo and fetus. The objective of this manuscript is to review prenatal screening and diagnostic methods available in pregnancies conceived by IVF-PGT-A.

Preimplantation genetic testing for aneuploidy in severe male factor infertility

Research questionDoes the use of preimplantation genetic testing for aneuploidies (PGT-A) improve outcomes in couples with severe male factor infertility (SMFI)? DesignThis retrospective cohort study included SMFI cases that underwent blastocyst transfer with/without PGT-A. Inclusion criteria were SMFI (azoospermia and sperm count <1 million/ml), women aged 25–39 years, single vitrified–warmed blastocyst transfer, and no intracavitary pathologies. Patients were divided into PGT-A and non-PGT-A groups. The primary outcome was live birth rate (live birth of an infant after 24 weeks of gestation); secondary outcomes were implantation and clinical pregnancy rates. ResultsThe study included 266 SMFI cases (90 and 176 in the PGT-A and non-PGT-A groups, respectively). Men and women in the PGT-A group were significantly older than those in the non-PGT-A group. The groups did not differ in terms of male factor categories, sperm collection methods or additional female factors. Live birth rates in the PGT-A and non-PGT-A groups were 55.6% and 51.1%, respectively (odds ratio [OR] 1.19, 95% confidence interval [CI] 0.71–1.98, P = 0.495). The implantation rates were 65.6% and 64.2%, respectively (OR 1.06, 95% CI 0.62–1.80, P = 0.827). The clinical pregnancy rates were 62.2% and 58.0%, respectively (OR 1.19, 95% CI 0.71–2.01, P = 0.502). The use of PGT-A was not an independent factor for live birth (aOR 1.33, 95% CI 0.66–2.70, P = 0.421). Advanced age in women was the only independent factor associated with live birth (aOR 0.46, 95% CI 0.22–0.96, P = 0.041). ConclusionsThe use of PGT-A does not seem to be an independent factor associated with live birth per transfer in couples with SMFI.

Maternal and perinatal outcomes in programmed versus natural vitrified-warmed blastocyst transfer cycles.

Do maternal and perinatal outcomes differ between natural and programmed frozen embryo transfer (FET) cycles? Retrospective cohort study at a university-affiliated fertility centre including 775 patients who underwent programmed or natural FET cycles resulting in a singleton live birth using blastocysts vitrified between 2013 and 2018. A total of 384 natural and 391 programmed FET singleton pregnancies were analysed. Programmed FET resulted in higher overall maternal complications (32.2% [126/391] versus 18.8% [72/384]; P < 0.01), including higher probability of hypertensive disorders of pregnancy (HDP) (15.3% [60/391] versus 6.3% [24/384]; P < 0.01), preterm premature rupture of membranes (2.6% [10/391] versus 0.3% [1/384]; P = 0.02) and caesarean delivery (53.2% [206/387] versus 42.8% [163/381]; P = 0.03) compared with natural FET. After controlling for potential confounders, including age, body mass index, parity, smoking status, history of diabetes or chronic hypertension, infertility diagnosis, number of embryos transferred and use of preimplantation genetic testing, the adjusted odds ratio for HDP was 2.39 (95% CI 1.37 to 4.17) and for overall maternal complications was 2.21 (95% CI 1.51 to 3.22) comparing programmed with natural FET groups. The groups did not significantly differ for any perinatal outcomes analysed, including birth weight (3357.9 ± 671.6 g versus 3318.4 ± 616.2 g; P = 0.40) or rate of birth defects (1.5% [6/391] versus 2.1% [8/384]; P = 0.57), respectively. Vitrified-warmed blastocyst transfer in a programmed cycle resulted in a twofold higher probability of HDP compared with transfer in a natural cycle. Natural FET cycle should, therefore, be recommended as first line for all eligible patients undergoing FET to reduce the risk of HDP.

Prognostic role of preimplantation genetic testing for aneuploidy in medically indicated fertility preservation

To investigate the use of preimplantation genetic testing for aneuploidy (PGT-A) among patients pursuing embryo banking (EB) for medically indicated fertility preservation (FP). Retrospective cohort. University-affiliated fertility center. All patients who underwent invitro fertilization with or without PGT-A for medically indicated FP between January 2014 and April2018. None MAIN OUTCOME MEASURES: EB cycle characteristics, subsequent cycle pursuit/outcomes, and frozen embryo transfer (FET) outcomes. A total of 58 medical EB cycles were compared; 34 cycles used PGT-A. Of the EB patients with breast cancer, 67% used PGT-A; other indications were evenly divided between PGT-A (FP/PGT-A) and no PGT-A (FP). PGT-A use increased over the study period. Groups were similar in age, days of stimulation, and days from initial FP consultation to treatment initiation. Number of oocytes (14.5 [2-63] FP vs. 17.5 [1-64] FP/PGT-A), 2PN zygotes (7 [1-38] FP vs. 9 [0-36] FP/PGT-A), and blastocysts (5.5 [0-22] FP vs. 5 [0-18] FP/PGT-A) cryopreserved were similar between groups. Equal numbers cryopreserved both oocytes and embryos (5 vs. 3). Five FP/PGT-A patients underwent a second EB cycle. Among FP/PGT-A patients, an average of 6.7 ± 5 blastocysts underwent PGT-A, with 3.5 ± 3 (48.2%) euploid embryos cryopreserved for future FET compared to an average of 7.2 ± 7 untested embryos in the FP group. PGT-A in medical EB cycles increased over time and did not limit the use of other FP methods such as oocyte cryopreservation. In some cases, poor PGT-A results informed patients to pursue a second EB cycle. When counseling patients, the prognostic benefits of PGT-A must be weighed against the financial costs and potential for "terminal" fertility diagnosis.

Genetics in human reproduction.

Approximately 50% of the causes of infertility are of genetic origin. The objective of this study was to analyze the role of genetics in human reproduction by reviewing the main genetic causes of infertility and the use of preimplantation genetic testing in Brazil. This literature review comprised articles in English and Portuguese published on databases PubMed, Scielo, and Bireme from 1990 to 2019. Randomized clinical trials and specialized guidelines were given preference whenever possible. Genetic cause can be traced back to up to 20% of the cases of severe azoospermia or oligozoospermia. Subjects with these conditions are good candidates for genetic screening. In women, genetic causes of infertility (fragile X syndrome, X-trisomy, and Turner's syndrome, some of which diagnosed with karyotyping) culminate with premature ovarian failure. Genetic screening helps advise couples of the risk of experiencing early reproductive capacity loss and of the chances of their offspring carrying genetic disorders. In addition to enhancing the prevention of serious diseases in the offspring of couples at increased risk of genetic diseases, preimplantation genetic screening improves the success rates of assisted reproduction procedures by allowing the selection of euploid embryos for transfer. The interface between genetics and human reproduction has gained significant relevance, but discussions are still needed on which procedures are clinically and ethically acceptable and how they should be regulated.