Preimplantation Genetic Diagnosis Research Articles

No laser use in “flicking” embryo biopsy does not reduce the mosaicism rate

No laser use in “flicking” embryo biopsy does not reduce the mosaicism rate

A LASER-FREE, NOVEL BIOPSY SYSTEM IMPROVES TISSUE SEPARATION AND CONTROL, AND ACCURACY OF PGT-A RESULTS

Trophectoderm embryo biopsy is a highly technical procedure that requires significant training and expensive equipment. The objective of our study was to reduce the technical challenge of embryo biopsy, whilst also improving control of the tissue and quality of the acquired cells as measured by PGT-A.

Update on preimplantation genetic testing for aneuploidy and outcomes of embryos with mosaic results.

Preimplantation genetic testing for aneuploidy (PGT-A) is used as a frequent add-on for in-vitro fertilization (IVF) to improve clinical outcomes. The purpose is to select a euploid embryo following chromosomal testing on embryo biopsies. The current practice includes comprehensive chromosome screening (CCS) technology applied on trophectoderm (TE) biopsies. Despite its widespread use, PGT-A remains a controversial topic mainly because all of the RCTs comprised only good prognosis patients with 2 or more blastocysts available; hence the results are not generalizable to all groups of patients. Furthermore, with the introduction of the highly-sensitive platforms into clinical practice (i.e. next-generation sequencing [NGS]), a result consistent with intermediate copy number surfaced and is termed "Mosaic," consistent with a mixture of euploid and aneuploid cells within the biopsy sample. The optimal disposition and management of embryos with mosaic results is still an open question, as many 'mosaics' generated healthy live births with no identifiable congenital anomalies. The present article provides a complete and comprehensive up-to-date review on PGT-A. It discusses in detail the findings of all the published RCTs on PGT-A with CCS, comments on the subject of "mosaicism" and its current management, and describes the latest technique of non-invasive PGT-A.

Concordance, sensitivity, and specificity between DNA recovered in spent culture medium and blastocyst biopsies

Background and Aim: Currently, performing an embryo biopsy at the blastocyst stage is the most reliable method to obtain DNA for preimplantation genetic testing for aneuploidies (PGT-A). In spite of the increase in success rates that have been attributed to a trophectoderm (TE) biopsy, it is a time-consuming, invasive, and costly procedure. The removal of TE cells is inherently invasive, embryo biopsy techniques have not been standardized, and a sub-optimal biopsy could lead to a decrease in implantation potential.

IMPACT OF COVID-19 VACCINATION ON ART OUTCOME

To determine if COVID-19 vaccination has a significant influence on parameters considered important for Assisted reproductive technology (ART) in women. Retrospective analysis of 106 female patients, investigating BMI, donor age, TSH, AMH, LH post trigger, P4 pre trigger, eggs retrieved, number of mature eggs, fertilized eggs and E2 before HCG respectively with respect to COVID-19 vaccination status. All In vitro fertilization (IVF)/Preimplantation Genetic Testing for Aneuploidies (PGT-A) cycles resulting in embryo biopsy over a course of 12 months at a large, multicenter, private practice were included in analysis. A total of 106 patients were included in the analysis. Patients were stratified into two groups based on the COVID-19 vaccination such that 58 patients had received at least a single dose of vaccine and 48 had not received any dose of vaccine. Data recorded included BMI, donor age, TSH, AMH, LH post trigger, P4 pre trigger, eggs retrieved, number of matured eggs, fertilized eggs, and E2 before HCG respectively. Statistical analysis included two-tailed Student’s t-test for continuous variables, Chi-squared test for categorical variables, Pearson correlation for correlation matrix analysis, with p<0.05 defining statistical significance. GraphPad Prism (GraphPad Software) was used for statistical analysis. We compared BMI, donor age, TSH, AMH, HCG post trigger, LH post trigger, P4 pre trigger, eggs retrieved, number of mature eggs, fertilized eggs, and E2 before HCG respectively between the vaccinated (n=58) and non-vaccinated (n=48) groups. Results showed that there was no significant difference between the two groups for the considered parameters (p>0.05). Our findings suggest that COVID-19 vaccination does not influence the BMI, donor age, TSH, AMH, HCG post trigger, LH post trigger, P4 pre trigger, eggs retrieved, number of matured eggs, fertilized eggs and E2 before HCG. Further studies are required to find If additional parameters, such as Aneuploidy rates, antibody booster trigger, suppression and trigger type medication could influence the pregnancy in the women undergoing ART with respect to COVID-19 vaccination. Together these studies will help to overcome vaccine hesitance and establish a clear understanding about vaccines in the context of clinical variables that are considered relevant to ART for successful IVF outcomes.

DOES ANTI MULLERIAN HORMONE (AMH) AFFECT EUPLOIDY RATES IN DIFFERENT AGE GROUPS

This study pursues to determine whether patients with a low AMH undergoing ICSI with preimplantation genetic screening for aneuploidy (PGT-A) have aneuploidy rates that differ from patients with normal AMH levels.

What 18028 biopsied blastocyst show us: biopsy technique, day of embryo biopsy and blastocyst stage are related to the risk of obtaining an inconclusive chromosomal assessment after trophectoderm biopsy.

Background and Aim: PGT-A is a reliable program in the IVF Unit but, occasionally, fails to yield a diagnostic result. The prevalence of inconclusive diagnoses reported in the literature ranges from 0.8 to 6% and, regardless of the etiology, are an inherent limitation of PGT-A that pose a challenge to both patients and clinicians. The objective of our work was to identify causative factors as blastocyst features and laboratory procedures possibly associated with the probability of obtaining an inconclusive result after blastocyst trophectoderm biopsy.

Correlation of the position and status of the polar body from the fertilized oocyte to the euploid status of blastocysts.

Polar bodies are tiny cells that are extruded during oocyte meiosis and are generally considered not essential for embryonic development. Therefore, polar bodies have been widely used as important materials for the preimplantation genetic diagnosis of human embryos. Recent studies have shown that polar bodies mediate embryonic development and that their morphology is related to embryo quality and developmental potential. However, the relationship between the emission of the polar body and embryonic euploidy remains unclear. In this study, a total of 1,360 blastocyst trophectoderm (TE) biopsies were performed, and blastocyst ploidy results were correlated with the state of polar bodies. The results showed that polar body angle size and polar body status are not directly related to whether the blastocysts are euploid, aneuploid, or mosaic (p > 0.05). Therefore, in the process of clinical embryo selection, embryologists should not predict the euploidy of blastocysts based on the state of polar bodies, thus affecting embryo selection.

ESHRE survey results and good practice recommendations on managing chromosomal mosaicism.

How should ART/preimplantation genetic testing (PGT) centres manage the detection of chromosomal mosaicism following PGT? Thirty good practice recommendations were formulated that can be used by ART/PGT centres as a basis for their own policy with regards to the management of 'mosaic' embryos. The use of comprehensive chromosome screening technologies has provided a variety of data on the incidence of chromosomal mosaicism at the preimplantation stage of development and evidence is accumulating that clarifies the clinical outcomes after transfer of embryos with putative mosaic results, with regards to implantation, miscarriage and live birth rates, and neonatal outcomes. This document was developed according to a predefined methodology for ESHRE good practice recommendations. Recommendations are supported by data from the literature, a large survey evaluating current practice and published guidance documents. The literature search was performed using PubMed and focused on studies published between 2010 and 2022. The survey was performed through a web-based questionnaire distributed to members of the ESHRE special interest groups (SIG) Reproductive Genetics and Embryology, and the ESHRE PGT Consortium members. It included questions on ART and PGT, reporting, embryo transfer policy and follow-up of transfers. The final dataset represents 239 centres. The working group (WG) included 16 members with expertise on the ART/PGT process and chromosomal mosaicism. The recommendations for clinical practice were formulated based on the expert opinion of the WG, while taking into consideration the published data and results of the survey. Eighty percent of centres that biopsy three or more cells report mosaicism, even though only 66.9% of all centres have validated their technology and only 61.8% of these have validated specifically for the calling of chromosomal mosaicism. The criteria for designating mosaicism, reporting and transfer policies vary significantly across the centres replying to the survey. The WG formulated recommendations on how to manage the detection of chromosomal mosaicism in clinical practice, considering validation, risk assessment, designating and reporting mosaicism, embryo transfer policies, prenatal testing and follow-up. Guidance is also provided on the essential elements that should constitute the consent forms and the genetic report, and that should be covered in genetic counselling. As there are several unknowns in chromosomal mosaicism, it is recommended that PGT centres monitor emerging data on the topic and adapt or refine their policy whenever new insights are available from evidence. Rather than providing instant standardized advice, the recommendations should help ART/PGT centres in developing their own policy towards the management of putative mosaic embryos in clinical practice. This document will help facilitate a more knowledge-based approach for dealing with chromosomal mosaicism in different centres. In addition to recommendations for clinical practice, recommendations for future research were formulated. Following up on these will direct research towards existing research gaps with direct translation to clinical practice. Emerging data will help in improving guidance, and a more evidence-based approach of managing chromosomal mosaicism. The WG received technical support from ESHRE. M.D.R. participated in the EQA special advisory group, outside the submitted work, and is the chair of the PGT WG of the Belgian society for human genetics. D.W. declared receiving salary from Juno Genetics, UK. A.C. is an employee of Igenomix, Italy and C.R. is an employee of Igenomix, Spain. C.S. received a research grant from FWO, Belgium, not related to the submitted work. I.S. declared being a Co-founder of IVFvision Ltd, UK. J.R.V. declared patents related to 'Methods for haplotyping single-cells' and 'Haplotyping and copy number typing using polymorphic variant allelic frequencies', and being a board member of Preimplantation Genetic Diagnosis International Society (PGDIS) and International Society for Prenatal Diagnosis (ISPD). K.S. reported being Chair-elect of ESHRE. The other authors had nothing to disclose. This Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and are based on the scientific evidence available at the time of preparation. ESHRE GPRs should be used for information and educational purposes. They should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care, or be exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, or variations based on locality and facility type. Furthermore, ESHRE GPRs do not constitute or imply the endorsement, or favouring, of any of the included technologies by ESHRE.

Conception of Saviour Siblings: Religious Views in Malaysia.

The advancement of human reproductive technology has made it possible for parents with a child affected by a haematological disorder to select and bring into being, a prospective child who can act as a matched stem cell donor. This can be done through the use of preimplantation genetic diagnosis (PGD) coupled with human leukocyte antigen (HLA) typing (PGD-HLA typing), or HLA tying as a standalone procedure, where a healthy embryo, which is an HLA match to the existing sick sibling, is chosen for implantation. The creation of such a sibling (saviour sibling) is normally taken as a last resort when there is no related or unrelated matched donor. While the conception of a saviour sibling may serve as a reliable and realistic treatment option for the ailing child, it also poses new moral questions that challenge a religiously pluralistic society such as Malaysia. The use of PGD-HLA typing may be controversial as it involves creating a life to save a life, selection of compatible human embryos and destruction of the unselected embryos. At present, there is no legal framework regulating the conception of saviour siblings. The development of ethically sound and appropriate local laws and policies should consider the views of religious communities, especially when it involves a controversial subject such as the conception of saviour siblings. This article seeks to explore the perceptions of religious scholars and representatives of the major religions professed and practised in Malaysia, namely Islam, Buddhism, Christianity and Hinduism, through qualitative interviews.

Heterogeneous spectrum of CFTR gene mutations in Chinese patients with CAVD and the dilemma of genetic blocking strategy.

The genetic heterogeneity of CFTR gene mutations in Chinese patients with congenital absence of the vas deferens (CAVD) differs from the hotspot mutation pattern in Caucasians. This paper reviews and suggests a more suitable screening strategy for the Chinese considering the dilemma of CFTR genetic blocking. Congenital absence of the vas deferens (CAVD) is a major cause of obstructive azoospermia and male infertility, with CFTR gene mutation as the main pathogenesis. Other genes such as ADGRG2, SLC9A3, and PANK2 have been discovered and proven to be associated with CAVD in recent studies. Multiple CFTR hotspot mutations have been found in Caucasians in several foreign countries, and relevant genetic counseling and preimplantation genetic diagnosis (PGD) have been conducted for decades. However, when we examined research on Chinese CAVD, we discovered that CFTR mutations show heterogeneity in the Chinese Han population, and there is currently no well-established screening strategy. Therefore, we have reviewed the literature, combining domestic and international research as well as our own, aiming to review research progress on the CFTR gene in China and discuss the appropriate scope for CFTR gene detection, the detection efficiency of other CAVD-related genes, and the screening strategy applicable to the Chinese Han population. This study provides more valuable information for genetic counseling and a theoretical basis for PGD and treatment for couples with CAVD when seeking reproductive assistance.

Debate: Are We Limiting the Potential of Oocytes by Not Using ICSI for All? - ICSI for Some

Intracytoplasmic sperm injection (ICSI) was invented nearly thirty years ago and the first pregnancies in Australia were obtained at the Queen Elizabeth Hospital in the University of Adelaide’s Reproductive Medicine Program. Since then, ICSI has become the predominant method of fertilisation for IVF in cycles in Australia and in many parts of the world used for 100% of all cycles. While its value for male factor infertility, IVM egg fertilisation and injection into previously frozen eggs have been validated, the use of ICSI for non-male-factor infertility remains controversial and unproven. Given the significant concerns about the potential effects of ICSI on the health of children conceived by this method, a debate about its use in an excessive number of IVF cycles is warranted. The first randomised control trial of ICSI versus standard IVF fertilisation for unexplained infertility occurred more than twenty years ago and showed a lower ongoing pregnancy rate for those who received the ICSI form of fertilisation. Despite this evidence, ICSI continued to grow in prevalence across Europe, North America, the Middle East, Asia, and Australia for non-male factor infertility. Significant cohort studies started to emerge from the US and from Europe that showed either no benefit from ICSI for unexplained infertility, or indeed harm, in terms of ongoing pregnancy rates. This year we published in The Lancet, a randomised control trial where couples with unexplained infertility and a normal total sperm count and motility were randomised to receive either ICSI or standard IVF as a fertilisation method. No significant benefit of using ICSI was found with respect to ongoing pregnancy or live birth. The potential health benefits to the child and the cost effectiveness of the treatment weigh against the routine use of ICSI in the presence of normal sperm. Other cohort studies show that there is no benefit of ICSI for low egg numbers, advanced maternal age, or preimplantation genetic diagnosis. Examination of the use of ICSI across Australia, shows enormous variations between states and within the same state. It is clear, that members of the Society have very heterogeneous view of the use of ICSI and my intention in this talk is to encourage everyone to be more critical of its use when there is no sperm abnormality. I would encourage clinicians to use the normal natural processes of sperm selection which occur in routine IVF without sperm injection.

Investigation of the relationship between reproductive disorders and chromosomal abnormalities in a large-scale, single-center 10-year retrospective study

ObjectiveChromosomal changes are an important cause of reproductive disorders. This study investigated the chromosomal changes and prevalence of pathologies in individuals admitted to our Genetic Evaluation Center over a 10-year period due to a reproductive disorder. Materials & MethodsThe chromosomal findings of 4345 individuals with reproductive disorders who applied to our Genetic Evaluation Center at Akdeniz University in Antalya, Turkey between 2011 and 2021 were retrospectively evaluated. ResultsIn this study, an abnormal karyotype was found in a total of 138 individuals (87 males and 51 females). Although the incidence of this abnormal karyotype varied among the diseases in the reproductive disorder subgroups, it was most frequently seen in azoospermia (17.0%). Of the 138 abnormalities, 75 were numerical and 54 were structural. The remaining 9 abnormalities consisted of 6 sex reversals and 3 patients with both numerical and structural anomalies. Additionally, the X chromosome was the chromosome most frequently involved in these abnormalities, being observed in 40.6% of patients. ConclusionThis 10-year, single-center study involved one of the largest case series in the literature to investigate the subtypes of reproductive disorders and their chromosomal relationship. Although the importance of chromosome analysis has been deemphasized, it is still recommended for use by the guidelines and, as the results of this study demonstrate, is still a highly effective method in the investigation of reproductive disorders. Furthermore, chromosome analysis of individuals diagnosed with a reproductive disorder is also very important in the practice of the increasingly utilized preimplantation genetic diagnosis (PGD).

Vitrification and in-straw warming do not affect pregnancy rates of biopsied bovine embryos

In the cattle industry, in vivo or in vitro embryo production combined with genotyping and cryopreservation technologies allows the selection and conservation of embryos carrying genes for desirable traits. This study aimed to assess the efficiency of a vitrification method suitable for in-straw warming of biopsied in vivo derived (IVD) bovine embryos. Three experiments were carried out using two methodologies: the Cryotop®, the gold standard vitrification and 3-step warming methodology, or the VitTrans, a vitrification/in-straw 1-step warming method that enables direct embryo transfer to the uterus. In experiment 1, intact and biopsied in vitro produced (IVP) day 7 expanded blastocysts were vitrified using the Cryotop® and warmed in 1- or 3-steps. No differences in survival rates were recorded at 24 h after warming for intact or biopsied IVP blastocysts irrespective of the warming procedure. In experiment 2, the effect of the time from trophectoderm (TE) biopsy to vitrification/in-straw warming on post-warming survival rate was assessed. No significant differences in survival were observed when blastocysts were vitrified/in-straw warmed immediately after biopsy or after 3 h in culture when compared to intact blastocysts. In experiment 3, IVD embryos were vitrified 3 h after biopsy using the Cryotop® or the VitTrans method and pregnancy rates were assessed at day 60 after transfer. Fresh, biopsied embryos served as control. Similar pregnancy rates were observed when IVD biopsied embryos were transferred fresh or vitrified/warmed by the Cryotop® or VitTrans method. No significant effect of the embryo quality or developmental stage was detected on the percentage of pregnant recipients when IVD biopsied embryos were transferred fresh or after vitrification. While fresh female IVD embryos produced significantly higher pregnancy rates than male embryos, there were no differences in pregnancy rates when male or female vitrified/warmed embryos were transferred. About 81% from the biopsies analyzed successfully determined the embryo sex, confirming that DNA was there, and it was efficiently amplified. To conclude, our findings indicate that both vitrification methodologies produced similar post-warming outcomes for both intact and biopsied IVP embryos. Besides, vitrification/in-straw warming of biopsied IVD bovine embryos did not affect the viability to originate pregnancy, being a useful option for their direct transfer in field conditions.

The Effect of Autologous Platelet-Rich Plasma Treatment on In Vitro Fertilization/Intracytoplasmic Sperm Injection and Its Impact on the Endometrium and Clinical Pregnancy Rate.

BackgroundEndometrial thickness has been identified as a prognostic factor for improving the pregnancy rate for patients with female infertility.Study questionDoes platelet-rich plasma (PRP) treatment affect the endometrial thickness and pregnancy rate after an in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle?AimThis study aims to evaluate the effects of autologous PRP treatment on IVF/ICSI, endometrium, and clinical pregnancy rate.Materials, setting, and methodsThis is a prospective, non-blind, randomized controlled study. The ethical committee of the Jeddah IVF Center approved the study, and informed written consent was obtained from all patients. We recruited patients who consulted at the Jeddah IVF Center from September 2020 to May 2021.ResultsA total of 70 patients undergoing IVF/ICSI and embryo transfer (ET) were randomly divided by simple randomization into two groups: those who received PRP treatment after oocyte pickup (OPU) (group A) and those who did not receive PRP treatment (control, group B). The endometrial thickness was measured after OPU and before ET. The mean ages of patients in groups A and B were 35.91 ± 4.09 (range: 24-43) and 34.63 ± 4.26 (range: 25-43), respectively, which were not statistically significant (P < 0.223). In the PRP cases, the types of infertility were primary in 16 (45.7%) and secondary in 19 (54.3%), and the causes of infertility were male factors in 24 (68.6%), unexplained in five (14.3%), ovulatory factor in two (5.6%), endometriosis in two (5.6%), tubal factor in one (2.9%), and preimplantation genetic diagnosis (PGD) in one (2.9%). In the control group, the types of infertility were primary in 14 (40%) and secondary in 21 (60%), and the causes of infertility were male factors in 21 (60%), unexplained in three (8.6%), ovulatory factor in eight (22.9%), endometriosis in one (2.8), and PGD in two (5.6%). In our study, we found that the mean endometrial thicknesses after OPU were 0.594 ± 0.089 (range: 0.4-0.7) and 0.589 ± 0.090 (range: 0.6-0.9) in the treatment and control groups, respectively (odds ratio (OR): 0.005; 95% confidence interval (CI): 0.376-0.047; P < 0.791). Before ET, the mean endometrial thicknesses were 0.86 ± 0.090 (range: 0.7-0.9) and 0.7464 ± 0.06 (range: 0.7-1) in groups A and B, respectively, (OR: 0.114; 95% CI: 0.763-0.151; P < 0.001). Of the 35 patients in each group, 12 (34.3%) and five (14.3%) had confirmed pregnancies in groups A and B, respectively (OR: 0.319; 95% CI: 0.099-1.036; P < 0.05), which is statistically significant.ConclusionAutologous PRP treatment in IVF/ICSI improves the endometrial thickness and clinical pregnancy rate.

Return on Investment from the Prevention of Spinal Muscular Atrophy in Kuwait

Background: Spinal muscular atrophy (SMA) is a rare genetic disease with a devastating nature and associated with significant clinical and economic burden. Fortunately, the availability of genetic screening and prevention technologies made preventive strategy possible. The aim of this study is to assess the return on investment from a prevention program that includes premarital genetic screening, preimplantation genetic diagnosis, and in vitro fertilization pertaining to SMA, spanning five-year period from the financial perspective of the Ministry of Health (MOH) in Kuwait. Methods: A stochastic financial model was developed following a return on investment (ROI) approach spanning five-year period. Results: An average ROI estimated to be 11% with cost saving amounted to 466,159 KWD (1,524,339 USD). The financial burden if the prevention program was not implemented is 16,441,539 KWD (53,763,832 USD). Conclusion: This study is one of the very few in the region to estimate the benefits of implementing a prevention program pertaining to SMA from the financial perspective of the MOH in Kuwait.

Hemoglobinopathy screening in primary care in the Netherlands: exploring the problems and needs of patients and general practitioners

The prevalence of hemoglobinopathies in The Netherlands is increasing due to migration. Hemoglobinopathies are severe hereditary diseases. An informed reproductive choice by at-risk couples, such as pre-implantation diagnosis or termination of affected pregnancies, can be made if carriers are detected prior to conception. Using a qualitative design, the needs and wishes of patients, carriers and general practitioners were evaluated regarding carrier detection of hemoglobinopathies in primary care practice. 30 semi-structured interviews were established with 10 general practitioners, 10 patients and 10 carriers. The interviews were audio-recorded, transcribed verbatim and analysed using content analysis to identify recurring themes. Three themes were generated regarding carrier detection of hemoglobinopathies: (1) a need for more information about hemoglobinopathy, (2) a need for indications when to refer for analysis (carrier diagnostics) and (3) insight concerning organization and roles in care for hemoglobinopathy carriers and patients. These themes reflected a need to increase awareness of hemoglobinopathy, improve competences among general practitioners through better education and improvement of communication with patients and their unidentified family members. This study shows the scope of the problem and the critical need for action to improve informed reproductive decision making for the at-risk population.

The relationship between TSH levels and clinical pregnancy outcomes for patients who undergo in vitro fertilization/intracytoplasmic sperm injection: a retrospective study.

BackgroundThyroid dysfunction is linked with adverse pregnancy outcomes, an upper limit of a normal thyroid-stimulating hormone (TSH) threshold of 4.12–4.5 mIU/L should be considered for subclinical hypothyroidism in the infertile female population. Whereas, it’s controversial whether or not the infertility thresholds for upper limit of TSH threshold of 2.5 mIU/L. In our study examines the correlation of optimal TSH levels and clinical pregnancy outcomes after fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) embryo transfer cycles.MethodsPatients who underwent fresh IVF/ICSI embryo transfer cycles for the first time who presented between January 1, 2015 and December 31, 2017 at the Chongqing Institute of Reproductive and Genetic, Chongqing Health Center for Women and Children were enrolled. We excluded patients with ≥40 years, body mass index (BMI) ≤18 or ≥28 kg/m2, the man with severe oligoasthenospermia, women with poor ovarian reserve, and presence of endocrine disorders, uterine anomaly, sactosalpinx, abnormal thyroid function, preimplantation genetic diagnosis, and chromosomal abnormality or polymorphism. Baseline characteristics and clinical pregnancy outcomes were observed in our study. We detected between TSH levels and clinical pregnancy outcomes in patients undergoing IVF/ICSI by Receiver operating characteristic (ROC) curves and logical regression.ResultsA total of 6,088 patients who undergo IVF/ICSI were included. We first detected that the live birth rate had a statistically significant difference when the TSH level was 3 mIU/L. With the TSH ≤3 mIU/L group having a higher live birth rate than the TSH >3 mIU/L group (51.79% vs. 47.89%, P=0.024), meanwhile no significant difference were revealed between the early miscarriage rate (12.54% vs. 14.97%, P=0.091) and early clinical pregnancy rate (59.21% vs. 56.32%, P=0.114). There were no differences in pregnancy outcomes when the TSH threshold was at 3.5 or 4 mIU/L and no association was detected between TSH levels and clinical pregnancy outcomes in patients undergoing IVF/ICSI by ROC curves and logical regression.ConclusionsPatients undergoing IVF/ICSI with a serum TSH level ≤3 mIU/L may have a higher live birth rate rather than ≤2.5 or ≤4 mIU/L.

The principle of procreative beneficence and its implications for genetic engineering.

Molecular genetic engineering technologies such as CRISPR/Cas9 have made the accurate and safe genetic engineering of human embryos possible. Further advances in genomics have isolated genes that predict qualities and traits associated with intelligence. Given these advances, prospective parents could use these biotechnologies to genetically engineer future children for genes that enhance their intelligence. While Julian Savulescu's Principle of Procreative Beneficence (PPB) argues for the moral obligation of prospective parents to use in-vitro fertilization and preimplantation genetic diagnosis to make eugenic selections of embryos for intelligence, the PPB could imply obligations to genetically engineer selected embryos for intelligence as well. I argue that the PPB implies an additional moral obligation for prospective parents to genetically engineer the embryonic germline identity of selected embryos for genes that predict intelligence. Objections to my argument for the PPB's extension are also discussed.

Impact of cell loss after warming of human vitrified day 3 embryos on obstetric outcome in single frozen embryo transfers.

Does cell loss (CL) after vitrification and warming (V/W) of day 3 embryos have an impact on live birth rate (LBR) and neonatal outcomes? This retrospective analysis includes cleavage stage day 3 embryos vitrified/warmed between 2011 and 2018. Only single vitrified/warmed embryo transfers were included. Pre-implantation genetic screening, oocyte donation, and age banking were excluded from the analysis. The sample was divided into two groups: group A (intact embryo after warming) and group B (≤ 50% blastomere loss after warming). On the total embryos (n = 2327), 1953 were fully intact (83.9%, group A) and 374 presented cell damage (16.1%, group B). In group B, 62% (232/374) of the embryos had lost only one cell. Age at cryopreservation, cause of infertility, insemination procedure, and semen origin were comparable between the two groups. The positive hCG rate (30% and 24.3%, respectively, for intact vs CL group, p = 0.028) and LBR (13.7% and 9.4%, respectively, for intact vs CL group, p = 0.023) per warming cycle were significantly higher for intact embryos. However, LBR per positive hCG was equivalent between intact and damaged embryos (45.6% vs 38.5%, respectively, p = 0.2). Newborn measurements (length, weight, and head circumference at birth) were comparable between the two groups. Multivariate logistic regression showed that the presence of CL is not predictive for LB when adjusting for patients' age. LBR is significantly higher after transfer of an intact embryo compared to an embryo with CL after warming; however, neonatal outcomes are comparable between the two groups.