The impact of (very) young donor age on euploid rates: An analysis of 1831 trophectoderm biopsies evaluated with 24-chromosome NGS screening in oocyte donation cycles.

RESEARCH QUESTION: Conflicting data exists regarding whether a younger age of donors has a negative influence on the outcomes of oocyte donation cycles. Is there any correlation between a younger age of donors and the rate of embryonic aneuploidy in oocyte donation cycles? DESIGN: Retrospective study including 515 oocyte donation cycles carried out between February 2017 and November 2022. Comprehensive chromosomal screening was performed on 1831 blastocysts. 1793 had a result which were categorised into groups based on the age of the donor: 18-22 (n = 415), 23-25 (n = 600), 26-30 (n = 488), and 31-35 years (n = 290). The analysis aimed to determine the percentage of biopsy samples that were euploid and the number that were aneuploid, relative to the age group of the oocyte donor. Additionally, linear regression was employed to examine the relationship between age and the proportion of aneuploid embryos, while controlling for relevant variables. RESULTS: Aneuploidy increased predictably with donor age: 18-22 years: 27.5 %; 23-25 years: 31.2 %; 26-30 years: 31.8 %; and 31-35 years: 38.6 %. In the donor group aged 31-35 years, a higher percentage of aneuploid embryos was observed compared to younger donors in univariate analysis (OR: 1.66, 95 % CI: 1.21-2.29, p = 0.002) and multivariate logistic analysis (OR: 2.65, 95 % CI: 1.67-4.23, p < 0.001). The rates of embryonic mosaicism revealed no significant differences. CONCLUSION: The lowest risk of embryonic aneuploidy was found among donors aged <22 years. Conversely, an elevated prevalence was evident within the donor group aged 31-35 years, in contrast to the younger cohorts. The incidence of mosaic embryos remained consistent across all age groups.

The role of zygotic genome activation in genetic-related reproductive medicine: Technological perspective, religious and bioethical concerns, challenges and benefits.

Zygotic Genome Activation (ZGA) is a crucial developmental milestone in early embryogenesis, marking the transition from maternal to embryonic control of development. This process, which varies in timing across species, involves the activation of the embryonic genome, paving the way for subsequent cell differentiation and organismal development. Recent advances in genomics and reproductive medicine have highlighted the potential of ZGA in the realm of genetic screening, providing a window into the genetic integrity of the developing embryo at its earliest stages. The intersection of ZGA and genetic screening primarily emerges in the context of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). These techniques, often employed during assisted reproductive technologies, aim to detect potential genetic abnormalities or chromosomal imbalances before embryo implantation. Given that ZGA represents the onset of embryonic gene expression, understanding its intricacies can significantly enhance the accuracy and predictive power of these screening processes. With the advent of next-generation sequencing and other high-throughput genomic techniques, detailed mapping of the transcriptomic changes during ZGA has become feasible. Such advancements have deepened our insights into the dynamics of early embryonic development and the onset of genetic disorders. As our knowledge in this realm expands, it promises to revolutionize our capabilities in detecting, understanding, and potentially rectifying genetic anomalies at the earliest stages of human life, thereby optimizing reproductive outcomes.

Preimplantation genetic testing in the current era, a review.

BACKGROUND: Preimplantation genetic testing (PGT), also referred to as preimplantation genetic diagnosis (PGD), is an advanced reproductive technology used during in vitro fertilization (IVF) cycles to identify genetic abnormalities in embryos prior to their implantation. PGT is used to screen embryos for chromosomal abnormalities, monogenic disorders, and structural rearrangements. DEVELOPMENT OF PGT: Over the past few decades, PGT has undergone tremendous development, resulting in three primary forms: PGT-A, PGT-M, and PGT-SR. PGT-A is utilized for screening embryos for aneuploidies, PGT-M is used to detect disorders caused by a single gene, and PGT-SR is used to detect chromosomal abnormalities caused by structural rearrangements in the genome. PURPOSE OF REVIEW: In this review, we thoroughly summarized and reviewed PGT and discussed its pros and cons down to the minutest aspects. Additionally, recent studies that highlight the advancements of PGT in the current era, including their future perspectives, were reviewed. CONCLUSIONS: This comprehensive review aims to provide new insights into the understanding of techniques used in PGT, thereby contributing to the field of reproductive genetics.

Preferred strategy for euploid single embryo transfer in advanced maternal age: Fresh versus frozen.

OBJECTIVE: The purpose of this study was to compare fresh and frozen-thawed euploid blastocyst transfer protocols following preimplantation genetic screening (PGS) in cases of advanced maternal age. METHODS: A total of 330 patients were examined retrospectively. PGS was performed on the embryos of 146 patients for whom fresh transfers were chosen. In contrast, frozen-thawed euploid single embryo transfer (ET) was selected after PGS for 184 patients, and their embryos were vitrified. The percentage of euploid embryos and rates of implantation, pregnancy, and pregnancy continuity, as well as clinical and biochemical abortion rates, were compared. RESULTS: The numbers of retrieved oocytes, metaphase II oocytes, and fertilized ova were greater in the frozen-thawed group. The percentages of euploid embryos were comparable between the fresh and frozen-thawed groups (32% vs. 34.8%, respectively). The rates of implantation (46.6%vs. 62.5%), pregnancy (50% vs. 66.8%), ongoing pregnancy (38.4% vs. 53.8%), and live birth percentage (37.0% vs. 53.8%) were significantly higher in the frozen-thawed group. However, no significant differences were found in the clinical and biochemical abortion rates. CONCLUSION: The use of frozen-thawed single euploid ET is associated with increased implantation and pregnancy rates compared to fresh single euploid ET with PGS.

Preimplantation genetic testing: A remarkable history of pioneering, technical challenges, innovations, and ethical considerations.

Preimplantation genetic testing (PGT) has emerged as a powerful companion to assisted reproduction technologies. The origins and history of PGT are reviewed here, along with descriptions of advances in molecular assays and sampling methods, their capabilities, and their applications in preventing genetic diseases and enhancing pregnancy outcomes. Additionally, the potential for increasing accuracy and genome coverage is considered, as well as some of the emerging ethical and legislative considerations related to the expanding capabilities of PGT.

Acceptance of genetic editing and of whole genome sequencing of human embryos by patients with infertility before and after the onset of the COVID-19 pandemic.

RESEARCH QUESTION: Has acceptance of heritable genome editing (HGE) and whole genome sequencing for preimplantation genetic testing (PGT-WGS) of human embryos changed after the onset of COVID-19 among infertility patients? DESIGN: A written survey conducted between April and June 2018 and July and December 2021 among patients at a university-affiliated infertility practice. The questionnaire ascertained the acceptance of HGE for specific therapeutic or genetic 'enhancement' indications and of PGT-WGS to prevent adult disease. RESULTS: In 2021 and 2018, 172 patients and 469 patients (response rates: 90% and 91%, respectively) completed the questionnaire. In 2021, significantly more participants reported a positive attitude towards HGE, for therapeutic and enhancement indications. In 2021 compared with 2018, respondents were more likely to use HGE to have healthy children with their own gametes (85% versus 77%), to reduce disease risk for adult-onset polygenic disorders (78% versus 67%), to increase life expectancy (55% versus 40%), intelligence (34% versus 26%) and creativity (33% versus 24%). Fifteen per cent of the 2021 group reported a more positive attitude towards HGE because of COVID-19 and less than 1% a more negative attitude. In contrast, support for PGT-WGS was similar in 2021 and 2018. CONCLUSIONS: A significantly increased acceptance of HGE was observed, but not of PGT-WGS, after the onset of COVID-19. Although the pandemic may have contributed to this change, the exact reasons remain unknown and warrant further investigation. Whether increased acceptability of HGE may indicate an increase in acceptability of emerging biomedical technologies in general needs further investigation.

Comparison of euploid blastocyst expansion with subgroups of single chromosome, multiple chromosome, and segmental aneuploids using an AI platform from donor egg embryos.

PURPOSE: This retrospective observational study compares how different classes of blastocyst genotypes from egg donor cycles differentially blastulate and expand using a standard assay. METHODS: Quantitative measurements of expansion utilized a customized neural network that segments all sequential time-lapse images during the first 10 h of expansion. RESULTS: Analyses were performed using two developmental time perspectives using time-lapse imaging. The first was the time to blastocyst formation (tB), which broadly reflects variations in developmental rate. Euploidy peaked at 100-115 h from fertilization. In contrast, aneuploidy peaks flanked this interval bi-modally. These distributions limit ploidy discrimination based upon traditional standard grading features when assessed in real time. In contrast, from the second perspective of progressive blastocyst expansion that is normalized to each individual blastocyst's tB time, euploidy was significantly increased at expansion values > 20,000µ2 across all tB intervals studied. A Cartesian coordinate plot graphically summarizes information useful to rank order blastocysts within cohorts for transfer. Defined aneuploidy subgroups, distinguished by the number and complexity of chromosomes involved, also showed distributive differences from both euploids and from each other. A small subset of clinically significant trisomies did not show discriminating features separating them from other euploids. CONCLUSION: A standard assay of blastocyst expansion normalized to each individual blastocyst's time of blastocyst formation more usefully discriminates euploidy from aneuploidy than real-time expansion comparisons using absolute developmental time from fertilization.

Which assisted reproductive technology (ART) treatment strategy is the most clinically and cost-effective for women of advanced maternal age: a Markov model.

OBJECTIVE: To evaluate the clinical and cost-effectiveness of preimplantation genetic testing for aneuploidy, social freezing, donor and autologous assisted reproductive technology (ART) treatment strategies for women aged 35-45 following 6-12 months of infertility. METHODS: Four Markov decision-analytic models comprising: (i) Preimplantation genetic testing for aneuploidy (PGT-A); (ii) autologous ART from age 40 using oocytes cryopreserved at age 32 (social freezing); (iii) ART using donated oocytes (donor ART); (iv) standard autologous ART treatment (standard care) were developed for a hypothetical cohort of 35 to 45 years old ART naïve women with 6-12 months of infertility. Input probabilities for key parameters including live birth rates were obtained from the available literature. Deterministic and probabilistic sensitivity analyses were conducted to address uncertainty in estimating the parameters and around the model's assumptions. Cost effectiveness was assessed from both societal and patient perspectives . RESULT(S): For infertile women at age 40 and above, social freezing is the most cost-saving strategy with the highest chance of a cumulative live birth at a lowest cost from a societal perspective. PGT-A and donor ART were associated with higher treatment costs and cumulative live-birth rates compared with the autologous ART. Among the four ART strategies, standard autologous ART has the lowest cumulative live birth rate of 45% at age 35 and decreasing to 1.6% by age 45 years. At a willingness-to-pay threshold of Australian dollars (A$)50,000, our model shows all alternative treatment strategies -PGT-A, social freezing and donor ART have a higher probability of being cost-effective compared to the standard autologous ART treatment. However, higher out-of-pocket expenditure may impede their access to these alternate strategies. CONCLUSION: Given current evidence, all alternate strategies have a higher probability of being cost-effective compared to the standard autologous ART treatment. Whether this represents value for money depends on societal and individual's willingness-to-pay for children conceived with ART treatment.

Polygenic risk score for embryo selection-not ready for prime time.

Numerous chronic diseases have a substantial hereditary component. Recent advances in human genetics have allowed the extent of this to be quantified via genome-wide association studies, producing polygenic risk scores (PRS), which can then be applied to individuals to estimate their risk of developing a disease in question. This technology has recently been applied to embryo selection in the setting of IVF and preimplantation genetic testing, with limited data to support its utility. Furthermore, there are concerns that the inherent limitations of PRS makes it ill-suited for use as a screening test in this setting. There are also serious ethical and moral questions associated with this technology that are yet to be addressed. We conclude that further research and ethical reflection are required before embryo selection based on PRS is offered to patients outside of the research setting.

Validation of Non-Invasive Preimplantation Genetic Screening Using a Routine IVF Laboratory Workflow.

Embryo selection is needed to optimize the chances of pregnancy in assisted reproduction technology. This study aimed to validate non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) using a routine IVF laboratory workflow. Can niPGT-A combined with time-lapse morphokinetics provide a better embryo-selection strategy? A total of 118 spent culture mediums (SCMs) from 32 couples were collected. A total of 40 SCMs and 40 corresponding trophectoderm (TE) biopsy samples (n = 29) or arrested embryos (n = 11) were assessed for concordance. All embryos were cultured to the blastocyst stage (day 5 or 6) in a single-embryo culture time-lapse incubator. The modified multiple annealing and looping-based amplification cycle (MALBAC) single-cell whole genome amplification method was used to amplify cell-free DNA (cfDNA) from the SCM, which was then sequenced on the Illumina MiSeq system. The majority of insemination methods were conventional IVF. Low cfDNA concentrations were noted in this study. The amplification niPGT-A and conventional PGT-A was 67.7%. Based on this study, performing niPGT-A without altering the daily laboratory procedures cannot provide a precise diagnosis. However, niPGT-A can be applied in clinical IVF, enabling the addition of blastocysts with a better prediction of euploidy for transfer.

IVF outcomes of embryos with abnormal PGT-A biopsy previously refused transfer: a prospective cohort study.

STUDY QUESTION: What are the outcomes for patients who choose to move embryos diagnosed as abnormal by preimplantation genetic testing for aneuploidy (PGT-A) to a new institution for transfer after the diagnosing institution refused to transfer them? SUMMARY ANSWER: Many patients seek to have selected embryos with PGT-A abnormal trophectoderm biopsies transferred recognizing that these embryos can still offer a chance of pregnancy and live birth. WHAT IS KNOWN ALREADY: : PGT-A is a widely practiced method of selecting embryos for transfer based on biopsy of a few cells. Many clinical practices refuse to transfer PGT-A abnormal embryos even when there are no other 'normal' embryos available. STUDY DESIGN, SIZE, DURATION: This is a prospective cohort of 69 couples who, since 2014, moved a total of 444 PGT-A abnormal embryos previously refused transfer at their parent institutions to our practice. Among these, 50 patients have, thus far, undergone 57 transfer cycles of 141 embryos. PARTICIPANTS/MATERIALS, SETTING, METHODS: Embryos diagnosed at other institutions by PGT-A as abnormal (mostly using next generation sequencing) were moved to our academically affiliated private fertility and research center in New York City. Female age at retrieval was 41.35 ± 3.98 years, 74% were Caucasian, 12% Asian and 10% were of African descent. All embryos identified as PGT-A abnormal among prospectively identified couples were recorded in our center's registry. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 144 embryos transferred 102 (72.3%) had only 1 or 2 chromosomal abnormalities, 30 (21.3%) had 3 or more and 9 (6.4%) were 'undiagnosed' because of degraded DNA, yet still had been refused transfer. Transfer of PGT-A abnormal embryos resulted in 8 live births, 11 miscarriages and no voluntary terminations. One child was born with a segmental duplication and required repair of coarctation of the aorta as a newborn. Many couples with only PGT-A abnormal embryos are willing to have their PGT-A abnormal embryos transferred and such transfers can result in the establishment of ongoing euploid pregnancies and live births. LIMITATIONS, REASONS FOR CAUTION: Findings in this case series represent couples who chose to have their embryos transferred after having been refused transfer elsewhere and may not be representative of the wider population of couples undergoing IVF with PGT-A in general. Not all abnormal phenotypes present in the immediate postnatal period so it will be important to continue to follow the development of these children. WIDER IMPLICATIONS OF THE FINDINGS: PGT-A can result in a clinics refusal to transfer embryos with abnormal PGT-A biopsies, even those with mosaic findings, consequently large numbers of infertile women are prematurely advised that their only chance of motherhood is through third-party egg-donation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by intramural funds from the Center for Human Reproduction and the not-for-profit research Foundation for Reproductive Medicine, both in New York, NY, USA. N.G. and D.H.B. are listed as co-inventors on several U.S. patents. One of these patents (US Patent# 7,615,544) relates to pre-supplementation of hypo-androgenic infertile women with androgens, such as DHEA and testosterone and, therefore, at least peripherally related to the subject of this manuscript. N.G. and D.F.A. also received travel funds and speaker honoraria from several pharmaceutical and medical device companies, though none related to the here presented subject and manuscript. N.G. is a shareholder in Fertility Nutraceuticals and he and D.H.B. receive royalty payments from Fertility Nutraceuticals LLC. TRIAL REGISTRATION NUMBER: N/A.

Dual Trigger with hCG Plus GnRHa for Final Oocyte Maturation in PGT-A Cycles Results in Similar Euploidy Rates when Compared to hCG-Only Trigger.

Factors that may have an effect on euploidy rate of blastocysts have been investigated thoroughly in the literature. We aimed to assess whether dual trigger alters the ploidy chance of a blastocyst in preimplantation genetic screening for aneuploidy (PGT-A) cycles. This retrospective cohort study was conducted in a total of 385 PGT-A cycles at a single tertiary center for various indications. Final oocyte maturation was triggered using human chorionic gonadotropin (hCG) or the combination of hCG and gonadotropin-releasing hormone agonists (GnRHa) (dual trigger). Participants were divided based on triggering method and all demographic and clinical characteristics of the patients were compared. Final oocyte maturation was triggered in 143 cycles with hCG (37.1%), and in 242 cycles with dual trigger (62.9%). The duration of stimulation was shorter in the dual trigger arm compared to the hCG trigger group (10.0 ± 1.6 vs. 9.4 ± 1.4 days, p ≤ .001). Euploidy rates per blastocyst tested were 23.4% and 26.1% respectively for hCG and dual trigger groups without significance. Similar rates of euploidy were noted, even after age stratification. There was no significant difference between the groups regarding positive pregnancy result and ongoing pregnancy rates (p = .779 vs. p = .188). Although dual triggering, compared to hCG triggering, does not provide an additional superiority on blastocyst euploidy rate, further studies in women with different infertility etiology are needed to specifically evaluate the impact of triggering method on ploidy rates.

Application of cell free DNA in ART.

Various biopsy and sampling methods are used for preimplantation genetic diagnosis (PGD) of embryo. This method benefits blastomer/trophectoderm biopsy to improve the clinical outcome of in vitro fertilization (IVF). However, all of these procedures are invasive and have adverse effects on embryo development. Additionally, these procedures require expensive equipment and well-experienced technicians. Regarding these limitations, designing non-invasive methods is necessary. One of the recently proposed non-invasive and applicable methods is cell free DNA (cfDNA) molecule evaluation that have opened up exciting opportunities in the molecular diagnosis of embryo and fetus chromosomal aneuploidy. cfDNA is present in body fluids; especially blood, follicular fluid, amniotic fluid, spent embryo culture medium (SCM) and blastocoel fluid. Overall, this review highlights the cfDNA biomarker might constitute a supplemental tool for improving IVF and pregnancy outcomes, female infertility management. However, the successful application of cfDNA demands an understanding of its biological properties, kinetics, time of collection, high sensitivity and specificity cfDNA detection methods, and their limitation and challenges in the clinical settings. In this review we also describe ethical aspects of cfDNA testing.

Chromosome aneuploidy analysis in embryos derived from in vivo and in vitro matured human oocytes.

BACKGROUND: In vitro oocyte maturation (IVM) is being increasingly approached in assisted reproductive technology (ART). This study aimed to evaluate the quality of embryos generated by in-vitro matured immature follicles, as a guideline for further clinical decision-making. METHODS: A total of 52 couples with normal karyotypes underwent in vitro fertilization, and 162 embryos were donated for genetic screening. Embryos in IVF group were generated by mature follicles retrieved during gonadotrophin-stimulated in vitro fertilization (IVF) cycles. And embryos in IVM group were fertilized from IVM immature oocytes. RESULTS: The average age of the women was 30.50 ± 4.55 years (range 21-42 years) with 87 embryos from IVF group and 75 embryos from IVM group. The rate of aneuploid with 28 of the 87 (32.2%) embryos from IVF group and 21 of the 75 (28%) embryos from IVM group, with no significant difference. The frequency of aneuploid embryos was lowest in the youngest age and increased gradually with women's age, whether in IVF group or IVM group and risen significantly over 35 years old. The embryos with morphological grade 1 have the lowest aneuploidy frequency (16.6%), and increase by the grade, especially in IVF group. In grade 3, embryos in IVM group were more likely to be euploid than IVF group (60% vs 40%, respectively). CONCLUSIONS: IVM does not affect the quality of embryos and does not increase the aneuploidy rate of embryos. It is clinically recommended that women more than 35 years have a high aneuploidy rate and recommended to test by PGS (strongly recommended to screened by PGS for women more than 40 years). Women aged less than 35 years old for PGS according to their physical and economic conditions. Embryo with poor quality is also recommended to test by PGS, especially for grade III embryos.

A Non-invasive Chromosome Screening Strategy for Prioritizing in vitro Fertilization Embryos for Implantation.

Preimplantation genetic testing for aneuploidy (PGT-A) is widely used to select embryos having normal ploidy for transfer, but they require an invasive embryo biopsy procedure that may cause harm to the embryos and offspring. Therefore, a non-invasive approach to select embryos with normal ploidy for implantation is highly demanded. Non-invasive chromosome screening (NICS) methods have been proposed and applied in clinical practices, but a large-scale validation versus invasive preimplantation genetic testing (PGT) and the whole embryo ploidy has not yet been reported. In this study, by using the whole embryo as a gold standard, we validated NICS assay in a total of 265 donated human embryos and compared its performance with conventional trophectoderm (TE) biopsy PGT. The NICS assay showed promising performance, which is comparable to PGT-TE [sensitivity: 87.36 versus 89.66%; specificity: 80.28 versus 82.39%; negative predictive value (NPV): 91.2 versus 92.86%; positive predictive value (PPV): 73.08 versus 75.73%]. Additionally, NICS provides a scoring system for prioritizing embryo: embryos can be categorized into three groups with euploid prediction probabilities of 90.0, 27.8, and 72.2% for group euploid (A), aneuploid (B), and multiple abnormal chromosomes (MAC) (C), respectively. When an addition of TE assay is provided as a secondary validation, the accuracy significantly increases from 72.2 to 84.3% for group B and from 27.8 to 83.3% for group C. Our results suggest that NICS is a good rule in assay for identifying chromosomal normal embryos for transfer and might serve as a non-invasive approach for prioritizing embryos instead of preventing transfer of aneuploid and MAC embryos. It will help to ensure the safety of offspring and efficient utilization of embryos.

Reproductive outcomes after preimplantation genetic testing in mosaic Turner syndrome: a retrospective cohort study of 100 cycles.

PURPOSE: The purpose of this study is to explore the reproductive outcomes of women with Turner syndrome (TS) in preimplantation genetic testing (PGT) cycles. METHODS: A retrospective study of 100 controlled ovarian stimulating cycles, 68 TS (sixty-four mosaic Turner syndrome (MTS) and four pure Turner syndrome (PTS)) women underwent PGT was conducted from 2013 to 2018. RESULTS: Embryo X chromosome abnormal rates of TS women were significantly higher than women with normal karyotype (7.04 vs 1.61%, P<0.01). Cumulative live birth rates (CLBR) after PGT-NGS treatment were lower in TS than control (31.15 vs 45.59%, P<0.05). Clinical pregnancy rates per transfer (CPR), miscarriage rates (MR) and live birth rates per transfer (LBR) remained comparable between TS and control group. Reproductive outcomes (X chromosome abnormal rates, CPR, MR, LBR and CLBR) among low (<10%), medium (10-50%) and high (>50%) level 45,X mosaicism groups were not statistically different. CONCLUSIONS: To avoid high risk of embryo X chromosome abnormalities, prenatal or preimplantation genetic testing should be recommended to mosaic or pure TS patients.

Successful fertility outcome in a couple with recurrent implantation failure and testicular cancer survivor: A case report.

A couple of Indo-American descent, presented to our clinic with a history of primary infertility and repeated IVF implantation failure. Male was a testicular cancer survivor who had erectile dysfunction and azoospermia. Female partner had polycystic ovarian syndrome (PCOD). She had three unsuccessful attempts of embryo transfer at another fertility clinic. At our clinic, she underwent controlled ovarian stimulation, COH started from day two period with rFSH (follicle stimulating hormone) followed by HMG (human menopausal gondadotropin) with antagonist protocol followed by preimplantation genetic screening of embryos. Subsequently, she began HRT (hormone replacement Therapy) protocol for ERA cycle from day 2, where she also underwent hysteroscopy on day 7. After five days of progesterone supplementation, she underwent endometrial biopsy for ERA (endometrial receptivity assay). Frozen embryo transfer cycle was started with the same HRT protocol used in her previous ERA cycle. Post embryo transfer, immunotherapy with steroids and fortnightly intralipids was given. Pregnancy test was positive with a BHCG value of 290 mIU/mL. and she delivered naturally after 39 completed weeks of gestation. A stepwise personalized treatment approach maximizes the chances of a successful outcome in presence of both male and female factors. Frozen or fresh sperms for ICSI with PGS along with hysteroscopy, ERA and under cover of immune modulation yielded positive results.

Preimplantation Genetic Screening and The Success Rate of In Vitro Fertilization: A Three-Years Study on Iranian Population.

OBJECTIVE: In vitro fertilization (IVF) is one of the most efficient approaches within the context of assisted reproductive technology (ART) to treat infertility. High pregnancy rates have become the major index of successful IVF in clinical studies. It is not clear yet which factors are certainly responsible for IVF success, as various outcomes were obtained in different IVF centers with different settings. In this study, we aimed to address controversies in the interpretation of promising results of IVF with respect to preimplantation genetic screening (PGS). MATERIALS AND METHODS: In this retrospective case series study, we built a dataset containing data from 213 IVF patient candidates for PGS (654 embryos) with blastomere biopsy at day 3 and trophectoderm biopsy in day 5, referred to Royan Institute, Tehran, Iran from 2015 to 2018. Next, the data were analyzed to find influential factors affecting success rate of ART cycles. RESULTS: Data analyses showed that regardless of PGS indications (ART failures, recurrent miscarriage, chromosomal abnormalities, etc.), the pregnancy rate is influenced by maternal and embryonic factors such as the age of mother as well as quantity and quality of transferred embryos. Furthermore, genotyping of embryos using array comparative genomic hybridization (aCGH) depicted the highest rate of chromosomal aberrations for chromosomes 1, 16 and 19 while the lowest frequency for chromosomes 11 and 17. Similarly, we detected 463 genetically abnormal embryos by aCGH, among which only 41.9% could be detected by classical fluorescent in situ hybridization (FISH) method. CONCLUSION: This study not only highlighted the advantages of aCGH over the FISH method in detection of chromosomal abnormalities, but also emphasized the importance of genetic abnormality as an indication for determination of IVF success rate.

Preimplantation Genetic Testing: Where We Are Today.

BACKGROUND: Preimplantation genetic testing (PGT) is widely used today in in-vitro fertilization (IVF) centers over the world for selecting euploid embryos for transfer and to improve clinical outcomes in terms of embryo implantation, clinical pregnancy, and live birth rates. METHODS: We report the current knowledge concerning these procedures and the results from different clinical indications in which PGT is commonly applied. RESULTS: This paper illustrates different molecular techniques used for this purpose and the clinical significance of the different oocyte and embryo stage (polar bodies, cleavage embryo, and blastocyst) at which it is possible to perform sampling biopsies for PGT. Finally, genetic origin and clinical significance of embryo mosaicism are illustrated. CONCLUSIONS: The preimplantation genetic testing is a valid technique to evaluated embryo euploidy and mosaicism before transfer.

The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A.

BACKGROUND: A recently published Position Statement (PS) by the Preimplantation Genetics Diagnosis International Society (PGDIS) regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF) contained inaccuracies and misrepresentations. Because opinions issued by the PGDIS have since 2016 determined worldwide IVF practice, corrections appear of importance. METHODS: The International Do No Harm Group in IVF (IDNHG-IVF) is a spontaneously coalesced body of international investigators, concerned with increasing utilization of add-ons to IVF. It is responsible for the presented consensus statement, which as a final document was reached after review of the pertinent literature and again revised after the recent publication of the STAR trial and related commentaries. RESULTS: In contrast to the PGDIA-PS, we recommend restrictions to the increasing, and by IVF centers now often even mandated, utilization of PGT-A in IVF cycles. While PGT-A has been proposed as a tool for achieving enhanced singleton livebirth outcomes through embryo selection, continued false-positive rates and increasing evidence for embryonic self-correction downstream from the testing stage, has led IDNHG-IVF to conclude that currently available data are insufficient to impose overreaching recommendations for PGT-A utilization. DISCUSSION: Here presented consensus offers an alternative to the 2019 PGDIS position statement regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF). Mindful of what appears to offer best outcomes for patients, and in full consideration of patient autonomy, here presented opinion is based on best available evidence, with the goal of improving safety and efficacy of IVF and minimizing wastage of embryos with potential for healthy births. CONCLUSIONS: As the PGDIS never suggested restrictions on clinical utilization of PGT-A in IVF, here presented rebuttal represents an act of self-regulation by parts of the IVF community in attempts to control increasing utilization of different unproven recent add-ons to IVF.