Preimplantation Genetic Diagnosis Research Articles

Concentration of hCG in Blastocoel Fluid is Independent of Embryo Morphology and PGT-A Results: Could it be a Significant Biomarker for a Competent Embryo?

The aim of this research was to develop a quantitative sandwich-strip ELISA was developed on a nitrocellulose membrane with anti-H alpha and anti-hCG beta antibodies. The detection antibody was conjugated to horseradish peroxidase, and a quantitative sandwich-strip ELISA with luminol substrate was developed following optimization with hCG. Concentration of hCG in the BF was determined for 101 embryo biopsies (Study 1) and 96 embryo biopsies (Study 2) respectively, and the results were compared with the previously recorded embryo morphology and PGT-A results. hCG was present in 73.6% of all BF specimens analysed in these two studies, and a weak correlation between hCG levels and both embryo morphology and PGT-A outcome was observed. Additionally, the receiver operating characteristic (ROC) curves show separately that both embryo morphology and PGT-A do not correlate with hCG concentrations. This indicates that the presence of hCG produced in the BF by the embryo is a separate, independent marker of embryo quality.

Religion and human rights in artificial insemination: a matter of ratio

It is pointed out that modern man is particularly sensitive to the imposition of any worldview and way of life. The only language in today’s world is the language of freedom, even if there is a substitution of this concept and its abuse. The value of freedom is not indifferent to religion. Therefore, the only way to spread the religious worldview in society is not the force of coercion, but the force of gravity.It is noted that the problem of the relationship between bioethics and religion is determined by a number of reasons, both scientific and theoretical, and socio-cultural plan. The current stage of development of scientific thought is characterized by the emergence of a new phenomenon – bioethics. Bioethics is an integrative science that synthesizes knowledge about man, which is already substantiated in medicine, psychology, psychiatry, religious anthropology, philosophical anthropology and others. The moral aspect is the center of bioethics, it is associated with its attitude to all living things, to life as such. Because of this we can talk about the formation of a bioethical worldview as a holistic system of views on the human problem. The beginning of the process of forming a bioethical worldview is closely connected with scientific progress, biomedical practices, and the aggravation of religious problems. The uniqueness of bioethical discourse creates the preconditions for the development of philosophical and methodological ground for the study of bioethical worldview. The methodological significance of the problem is related to the need to rethink the fundamental philosophical problems that relate to demental philosophical problems that relate to the definition of attributive characteristics of man.It is established that the religious problems that arise when using the IVF method are associated with several components: the production of germ cells, the lack of connection between conception and the natural idea of marital intimacy, obtaining an excessive number of embryos and manipulating them (elimination, reduction, freezing) embryos, preimplantation diagnosis), the use of germ cells of third parties. In this case, in vitro fertilization can be morally justified by religion and an acceptable method of infertility therapy for the Orthodox Christian, if it does not kill embryos and does not break the bond “in the flesh” even at the level of gametes.

Crouzon Syndrome (Congenital Craniofacial Dysostosis): from the Clinical Case to the Review of Craniosynostosis

Crouzon disease or Crouzon syndrome (CS) is a rare congenital anomaly that is caused by intrauterine premature closure of the coronal, sagittal and lambdoid sutures causing abnormal growth of the skull. It is considered an ultra-rare (ultra-orphan) disease, with an incidence of 1/50,000-60,000 neonates. We present the case of a 78-year-old woman with CS who presented congenital craniosynostosis with turricephaly, hypertelorism, external strabismus with bilateral exophthalmos and blindness (due to atrophy of the optic nerve of the right eye), maxillary hypoplasia, hearing loss, narrow palate, mandibular prognathism, malocclusion with crossbite, anosmia, parrot-beak nose, thin upper lip and facial asymmetry. It is a genetic disease with autosomal dominant inheritance, complete penetrance and variable expressivity. It is caused by mutations in the FGFR2 gene (chromosomal locus 10q25-10q26). From 30 to 60% of the cases are sporadic because they are new mutations (de novo mutations). The prenatal diagnosis of this entity is difficult, since the early welding of the sutures generally begins after birth. The diagnosis is fundamentally clinical, which must be complemented with imaging studies. Appropriate genetic counseling is necessary. In the future, with advances in clinical genetics, most craniosynostoses could be avoided if we incorporate the genetic study of the different genes involved (already known) to carrier screening. For this, it is necessary to promote assisted reproduction techniques (preimplantation genetic diagnosis). The cases that correspond to de novo mutations cannot be avoided through these strategies. Regarding treatment, an early diagnosis is required to plan a highly specialized surgery that allows the remodeling of the skull and face so as to achieve good aesthetic and functional results, and avoid some of the auditory and visual complications. In this article we review the embryology of the skull, craniosynostosis, and more specifically of CS.

Factors associated with embryo mosaicism: a systematic review and meta-analysis.

Evaluate which factors are involved in the increased rate of mosaicism in embryos. A systematic review and meta-analysis was performed. After an exhaustive search of the literature, a total of seven papers were included in the analysis. In addition, data collected from IVF cycles performed in our fertility clinic were also analysed. Day of biopsy, embryo quality, maternal and paternal age and seminal quality were the chosen factors to be studied. The results of the meta-analysis show that neither embryo quality nor seminal quality were related to mosaic embryo rate (OR: 1.09; 95% CI: 0.94-1.28 and OR: 1.10; 95% CI: 0.87-1.37, respectively). A positive association was observed for the variable "biopsy day" with embryos biopsied at day 6 or 7 having the highest rate of mosaicism (OR: 1.06; 95% CI: 1.01-1.11). In opposite to what happens with aneuploidy rate, which increases with maternal age, embryo mosaicism is higher in younger women (<34 years) rather than in older ones (≥34 years) (OR: 0.95; 95% CI: 0.92-0.98). However, for the "paternal age" factor, no association with mosaicism was found (OR: 1.04; 95% CI: 0.90-1.21). With the present study, we can conclude that the factors related to the presence of mosaicism in embryos are the embryo biopsy day and maternal age. The rest of the studied factors showed no significant relationship with mosaicism. These results are of great importance as knowing the possible causes leading to mosaicism helps to improve the clinical results of reproductive treatments.

Preimplantation Genetic Testing for Adult-Onset Neurodegenerative Disease: Considerations for Access, Utilization, and Counseling.

Preimplantation genetic testing for monogenic conditions (PGT-M), formerly called preimplantation genetic diagnosis, is a specialized assisted reproduction technique that aims to reduce the risk of a pregnancy inheriting a monogenic condition. Despite calls to increase awareness and prepare neurologists for discussing PGT-M with patients and their families, no guidelines currently exist. When introducing PGT-M to those who may be interested in using it, there are major factors for discussion, including (1) genetic considerations (e.g., requirement for a confirmed genetic diagnosis; timing of genetic test results); (2) practical considerations (e.g., access to PGT-M and genetic services); (3) technical considerations (e.g., factors that can affect the success rate of PGT-M); and (4) psychosocial and ethical considerations (e.g., predictive testing for asymptomatic family members; family dynamics and values). Here, our team of neurologists and specialized genetic counselors discusses the current state of genetic characterization in adult-onset neurodegenerative conditions and highlights the major factors that should be considered when discussing PGT-M with families.

CREATING SAVIOR SIBLINGS: MORAL OR IMMORAL?

A savior sibling is a child conceived through in-vitro fertilization for the purposes of saving a sibling, who needs an organ or cell transplant because of a fatal genetic disorder. The procedure involves pre-implantation genetic diagnosis (PGD), which analyzes the embryos to detect potential genetic disorders prior to implantation. This is to reduce the possibility of passing such disorders to offspring. However, the creation of savior siblings also raises issues of morality. The idea that a child is born for the sole purpose of saving the lives of others, even if siblings, is not acceptable to some sections of society. This is because such a child is being born not for the sake of having it, but merely to be used as an instrument by the parents to save their sick child. Different countries, such as Malaysia, the UK, U.S. and Australia take various positions on whether or not to permit PGD. This article examines the rationale for the conduct of PGD, and, specifically, whether or not the act of creating a savior child can be considered as immoral. Importantly, the examination is undertaken with a focus on Immanuel Kant’s moral theory. The notion of the end in itself by Immanuel Kant demands that we always treat humanity not only as a means to an end, but also as an end in itself. Impliedly, parents should not conceive a child solely for the purposes of serving as a donor to a sick sibling, but should also genuinely desire that child. In other words, they should also respect the savior sibling and recognize its inherent value. In this way, the savior sibling is treated not merely as a means, but also as an end. By implication, the creation of savior siblings is not unethical as such, and should be permitted. A more significant factor that should be considered is how they are treated by parents after birth. This article uses a qualitative research methodology and relies on scholarly writings, such as books, journal articles, as well as laws and decided cases.

ESHRE 2023 Abstract Highlights

The following selected highlights draw attention to numerous interesting timely abstracts presented at the European Society of Human Reproduction and Embryology (ESHRE) 39th Annual Meeting, covering topics such as obstetric and neonatal outcomes following embryo biopsy, the role of genital tract infection and pelvic surgery in endometriosis, and the impact of fertility and preservation in patients with cancer.

Single closed-tube quantitative real-time PCR assay with dual-labelled probes for improved sex determination of equine embryos

In addition to fulfilling many breeders’ curiosity, equine embryonic sex determination can have a profound commercial impact. However, the application of currently described assays for equine embryonic sexing has rendered variable diagnosis and validation rates, with sensitivity being the main problem. In addition, while pregnancy results of in vivo-flushed equine embryos following a needle aspiration biopsy equal those of non-biopsied embryos, the effect on in vitro-produced embryos is unknown. Here, we aimed to develop a highly sensitive and specific assay for equine sex determination that can be directly performed on few embryonic cells, and to test the effect of a needle aspiration biopsy on the viability of the in vitro-produced embryo. To this end, a multiplex quantitative real-time PCR (qPCR) assay with dual-labelled probes was designed to allow the simultaneous generation of both male-specific and control fragments in a single closed-tube reaction, avoiding potential sample loss or contamination. To improve sensitivity, multicopy and polymeric genes were chosen to be specifically amplified, i.e., eight copies of Y-chromosomal ETSTY5 as male-specific and four autosomal UBC monomers as control fragment. Specificity was enhanced by the equine-specific character of ETSTY5 and by using dual-labelled probes. The assay was optimised with equine male and female genomic DNA and demonstrated a 100% accuracy and a >95% qPCR efficiency down to 10 pg of DNA. The assay was subsequently applied to determine the sex of 44 in vitro-produced embryos, collecting trophectoderm biopsies by means of a needle aspiration biopsy and herniating cells. Of all trophectoderm biopsies and herniating cell samples (n = 54), 87% could be diagnosed. Assay results were validated on a second sample obtained from the biopsied embryo (n = 18) or, by ultrasound-based sex determination of the foetus (n = 7) following the transfer of the biopsied embryo to a recipient mare, with about half of the embryos being fillies and colts. The needle aspiration biopsy procedure did not impair initial pregnancy rate or early pregnancy losses as compared to non-biopsied embryos. In conclusion, we report a safe, reliable, fast, and cost-effective assay for equine sex determination which was validated for the sex determination of in vitro-produced embryos based on few embryonic cells, and needle aspiration biopsy did not impair the embryo's viability. The assay and safe biopsy strategy hold potential for other applications.

EXPLORING THE BUILDING BLOCKS OF LIFE: THE HUMAN GENOME PROJECT, ITS IMPACT IN TODAYS WORLD

The Human Genome Projects (HGP) conclusion altered a number of disciplines, including biotechnology, genetics, medicine, and forensics. Key outcomes included personalised medicine, gene therapy, and enhanced DNA profiling. The HGP increased our knowledge of hereditary illnesses and shed light on human evolution. The privacy of genetic information and the ethical application of knowledge were raised. The management and analysis of genomic data require the use of bioinformatics. The future of genetics and biology will be shaped by the HGPs substantial effects on healthcare, innovation, and the economy. In vitro fertilisation and preimplantation genetic diagnosis are two reproductive technology developments made possible by the HGP. Also, it sparked the creation of focused treatments for genetic diseases, completely altering the range of patient treatment options. These advancements have led to a new era of precision medicine and personalised healthcare, in addition to improving patient outcomes.

Current Applications and Controversies in Preimplantation Genetic Testing for Aneuploidies (PGT-A) in In Vitro Fertilization.

Preimplantation genetic testing for aneuploidy (PGT-A) has evolved over recent years, including improvements in embryo culture, biopsy, transfer, and genetic testing. The application of new comprehensive chromosome screening analysis has improved the accuracy in determining the chromosomal status of the analyzed sample, but it has brought new challenges such as the management of partial aneuploidies and mosaicisms. For the past two decades, PGT-A has been involved in a controversy regarding its efficiency in improving IVF outcomes, despite its widespread worldwide implementation. Understanding the impact of embryo aneuploidy in IVF (in vitro fertilization) should theoretically allow improving reproductive outcomes. This review of the literature aims to describe the impact of aneuploidy in human reproduction and how PGT-A was introduced to overcome this obstacle in IVF (in vitro fertilization). The article will try to analyze and summarize the evolution of the PGT-A in the recent years, and its current applications and limitations, as well as the controversy it generates. Conflicting published data could indicate the lacking value of a single biopsied sample to determine embryo chromosomal status and/or the lack of standardized methods for embryo culture and management and genetic analysis among other factors. It has to be considered that PGT-A may not be a universal test to improve the reproductive potential in IVF patients, rather each clinic should evaluate the efficacy of PGT-A in their IVF program based on their population, skills, and limitations.

A novel mutation on OCA2 gene detection and preimplantationgenetic diagnosis for oculocutaneous albinism type 2 (OCA2)

Oculocutaneous albinism (OCA) is a group of recessive genetic congenital disorders characterised by a disorder of melanin synthesis. OCA is currently classified into seven different types, of which OCA type 2 (OCA2 - OMIM 203200) ranks as the second most common type of albinism in the world and accounts for nearly 30% of albinism cases. Nowadays, there is currently no known way to treat OCA. Preimplantation genetic diagnosis (PGD) is the most effective method of disease prevention, which helps families carrying gene mutations to have healthy children. Objectives: To develop a procedure and conduct PGD for embryos of a family carrying the OCA2 mutation causing OCA2. Materials and methods: Research subjects are blood samples of four members of an OCA family, including father, mother, and two daughters; and 6 embryo biopsies on day 5 of this parents. Next-generation sequencing (NGS) was carried out on family members participating in the study. Based on the identified mutation results, primers for PCR amplification of the segments spanning the detected mutation were designed. Then, Sanger sequencing method is combined with linkage genetic analysis to detect pathogenic mutations on embryo biopsies after whole-genome amplification (WGA). Results: A novel mutation NM_000275.3:c.2323G&gt;A (NP_000266.2: p.Gly775Ser) was detected on exon 22 of the OCA2 gene. The outcomes of PGD for 6 embryos of a family carrying the OCA2 mutant gene causing OCA2 were 3 affected embryos, 2 normal embryos, and 1 carriers.

Four Decades of Carrier Detection and Prenatal Diagnosis in Hemophilia A: Historical Overview, State of the Art and Future Directions.

Hemophilia A (HA), a rare recessive X-linked bleeding disorder, is caused by either deficiency or dysfunction of coagulation factor VIII (FVIII) resulting from deleterious mutations in the F8 gene encoding FVIII. Over the last 4 decades, the methods aimed at determining the HA carrier status in female relatives of HA patients have evolved from phenotypic studies based on coagulation tests providing merely probabilistic results, via genetic linkage studies based on polymorphic markers providing more accurate results, to next generation sequencing studies enabling highly precise identification of the causative F8 mutation. In parallel, the options for prenatal diagnosis of HA have progressed from examination of FVIII levels in fetal blood samples at weeks 20-22 of pregnancy to genetic analysis of fetal DNA extracted from chorionic villus tissue at weeks 11-14 of pregnancy. In some countries, in vitro fertilization (IVF) combined with preimplantation genetic diagnosis (PGD) has gradually become the procedure of choice for HA carriers who wish to prevent further transmission of HA without the need to undergo termination of pregnancies diagnosed with affected fetuses. In rare cases, genetic analysis of a HA carrier might be complicated by skewed X chromosome inactivation (XCI) of her non-hemophilic X chromosome, thus leading to the phenotypic manifestation of moderate to severe HA. Such skewed XCI may be associated with deleterious mutations in X-linked genes located on the non-hemophilic X chromosome, which should be considered in the process of genetic counseling and PGD planning for the symptomatic HA carrier. Therefore, whole exome sequencing, combined with X-chromosome targeted bioinformatic analysis, is highly recommended for symptomatic HA carriers diagnosed with skewed XCI in order to identify additional deleterious mutations potentially involved in XCI skewing. Identification of such mutations, which may profoundly impact the reproductive choices of HA carriers with skewed XCI, is extremely important.

SCM is potential resource for non-invasive preimplantation genetic testing based on human embryos single-cell sequencing

The ongoing development of assisted reproductive technologies has provided hope to individuals struggling with infertility, promising the potential for a healthy pregnancy. One significant innovation in field of pre-implantation genetic screening (PGS) requires the biopsy of embryos or oocytes, which has potential implications for the health and development of the resultant offspring. Therefore, a non-invasive approach to preimplantation genetic screening is highly sought after. The clinical application of non-invasive preimplantation genetic testing (ni-PGT) is currently limited, with its sensitivity and specificity requiring further investigation. In this study, we used 218 human embryos for single-cell whole genome amplification (WGA), along with ni-PGT of blastocoele fluid (BF) and spent culture medium (SCM). Whole blastocyst (WB), trophectoderm biopsy (TB), and inner cell mass (ICM) from embryo biopsies were used as controls to track genomic signal alterations. Our results showed that the overall genome similarity between SCM and ICM was higher than that of BF. Apart from the Y chromosome, both SCM and ICM demonstrated numerous variant sites across other chromosomes.Further categorization of gene variants in these two sample types revealed that missense variants were the most prevalent, single nucleotide polymorphisms were more common than insertions or deletions, and C > T was the dominant single nucleotide variants in both ICM and SCM. Lastly, we found that the mutant genes in SCM and ICM had different biological functions and pathways. This study indicates that SCM provides a more effective source of embryonic DNA for preimplantation genetic screening, offering a novel reference point for genetic screening research.

Novel economical, accurate, sensitive, single-cell analytical method for mitochondrial DNA quantification in mtDNA mutation carriers.

Although a variety of analytical methods have been developed to detect mitochondrial DNA (mtDNA) heteroplasmy, there are special requirements of mtDNA heteroplasmy quantification for women carrying mtDNA mutations receiving the preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PD) in clinic. These special requirements include various sample types, large samplenumber, long-term follow-up, and the need for detection of single-cell from biopsied embryos. Therefore, developing an economical, accurate, high-sensitive, and single-cell analytical method for mtDNA heteroplasmy is necessary. In this study, we developed the Sanger sequencing combined droplet digital polymerase chain reaction (ddPCR) method for mtDNA quantification and compared the results to next-generation sequencing (NGS). A total of seventeen families with twelve mtDNA mutations were recruited in this study. The results showed that both Sanger sequencing and ddPCR could be used to analyze the mtDNA heteroplasmy in single-cell samples. There was no statistically significant difference in heteroplasmy levels in common samples with high heteroplasmy (≥ 5%), low heteroplasmy (< 5%), and single-cell samples, either between Sanger sequencing and NGS methods, or between ddPCR and NGS methods (P > 0.05). However, Sanger sequencing was unable to detect extremely low heteroplasmy accurately. But even in samples with extremely low heteroplasmy (0.40% and 0.92%), ddPCR was always able to quantify them. Compared to NGS, Sanger sequencing combined ddPCR analytical methods greatly reduced the cost of sequencing. In conclusion, this study successfully established an economical, accurate, sensitive, single-cell analytical method based on the Sanger sequencing combined ddPCR methods for mtDNA heteroplasmy quantification in aclinical setting.

Multi-level Fgf4- and apoptosis-dependent regulatory mechanism ensures the plasticity of ESC-chimaeric mouse embryo.

The preimplantation mammalian (including mouse and human) embryo holds remarkable regulatory abilities, which have found their application for example in the preimplantation genetic diagnosis of human embryos. Another manifestation of this developmental plasticity is the possibility of obtaining chimaeras by combining either two embryos or embryos and pluripotent stem cells, which enables the verification of the cell pluripotency and generation of genetically modified animals used to elucidate gene function. Using mouse chimaeric embryos (constructed by injection of embryonic stem cells into the 8-cell embryos) as a tool, we aimed to explore the mechanisms underlying the regulatory nature of the preimplantation mouse embryo. We comprehensively demonstrated the functioning of a multi-level regulatory mechanism involving the FGF4/MAPK signalling as a leading player in the communication between both components of the chimaera. This pathway, coupled with the apoptosis, cleavage division pattern, and cell cycle duration controlling the size of ESC component and giving it a competitive advantage over host embryo blastomeres, provides a cellular and molecular basis for regulative development, ensuring the generation of the embryo characterised by proper cellular composition.

Reproductive Counseling and Care in Cystic Fibrosis: A Multidisciplinary Approach for a New Therapeutic Era.

With the advent of highly effective modulator therapies, many people with cystic fibrosis (CF) are living longer, healthier lives. Pregnancy rates for women with CF more than doubled between 2019 and 2021, reflecting increases in both planned and unplanned pregnancies. For men with CF, CF-associated infertility can be mitigated with assistive reproductive technology, yet patient knowledge of these challenges and options is variable. Preconception and prenatal counseling for individuals with CF and for parents of children with CF who wish to expand their families requires nuanced discussions to promote informed reproductive decisions, drawing from a combination of standard practice recommendations and CF-specific assessments. This review article synthesizes the current literature and practice recommendations regarding reproductive counseling and care in CF, outlining the role of genetic counseling, carrier screening, teratogen counseling, in vitro fertilization and pre-implantation genetic diagnosis, and careful assessment and management of cystic fibrosis-related diabetes when present. Via a multidisciplinary, patient-centered approach, clinicians can support adults with CF and parents of children with CF as they make informed reproductive decisions and embark on family planning.

A Comprehensive Review of Pregnancy in Sickle Cell Disease.

Sickle cell hemoglobinopathies encompass a range of qualitative and quantitative hemoglobin disorders that are inherited genetically. This group of disorders includes sickle cell beta thalassemia, sickle cell trait, and sickle cell disease (SCD). Globally, SCD is the most common disorder. Even epidemiological data suggests the majority of diseases, as well as traits, are concentrated in Sub-Saharan Africa, North-East Africa, the Middle East, and India. The physiological changes in pregnancy predispose to an increased risk of catastrophic events like a vaso-occlusive crisis, thromboembolic events, and their related sequelae, leading eventually to villous infarction, necrosis, and fibrosis leading to compromising uteroplacental circulation. Conversely, the mother may exhibit exacerbated symptoms of gestational hypertension, placental abruption, preterm labor, and venous thromboembolism. Although this disease is manageable, it has the potential to adversely impact maternal and child health on a national level. The chances of severe complications in the pregnant state affecting both mother and fetus attract due attention of health services towards redefining and researching this disease and its management frequently. The literature review on the following situation advocates the general treatment to be observed under the headings of preconceptual care, strengthened antenatal care, strict intranatal care, and compliant post-natal care. Preconceptually, genetic screening of couples, with education on the adverse effects of the disease, comes as the first line of management. Newer facilities like preimplantation genetic diagnosis and celocentesis may even allow for early diagnosis as well as help patients who do not wish to terminate the pregnancy by selective transfer of unaffected embryos. This may be combined with an extensive evaluation of the psychosocial aspect and socioeconomic status of couples who administer vaccines as prophylaxis for preventable diseases. Strengthening antenatal care is associated with routine blood investigations for every registered antenatal patient with adequate awareness about the conditions that precipitate the crisis. All patients should be prophylactically treated with appropriate doses of aspirin, iron, folic acid, and multivitamins. Radiological examinations by ultrasonography may be used to monitor placenta previa, abruption, or preterm labor. Later in pregnancy, it should be recommended to performbiophysical profiling and assessment of umbilical artery flow. Intranatal care deals with strict-term institutional delivery of all sickle cell-diseased mothers with a preference for vaginal delivery. Post-natal care requires a precise assessment of blood loss during labor to initiate transfusion therapy as soon as needed. Exclusive breastfeeding, with the importance of early initiation of it, must be emphasized. Screening of neonates as quickly as possible must be done for hemoglobinopathies. Through this review, authors are trying to make aware of the complications that can be faced during pregnancy in SCD patients, its prevention, and its treatment according to various new guidelines and research available.

Outcomes of assisted reproductive technology procedures performed on weekdays versus weekends: a retrospective cohort study.

To evaluate if assisted reproductive technology (ART) outcomes are different based on whether procedures - oocyte retrieval, insemination, embryo biopsy, or embryo transfer - are performed on a weekday versus weekend/holiday. Retrospective cohort study of all patients ≥ 18years old who underwent oocyte retrieval for in vitro fertilization or oocyte banking (n = 3,197 cycles), fresh or natural-cycle frozen embryo transfers (n = 1,739 transfers), or had embryos biopsied for pre-implantation genetic testing (n = 4,568 embryos) in a large academic practice from 2015-2020. The primary outcomes were as follows: oocyte maturity for oocyte retrievals; fertilization rate for insemination; rate of no result on pre-implantation genetic testing for embryo biopsy; and live birth rate for embryo transfers. The average number of procedures performed per embryologist per day was higher on weekends/holidays than weekdays. For oocyte retrievals performed on weekdays vs. weekends/holidays, there was no difference in oocyte maturity rate (88% vs 88%). There was no difference in the fertilization rate (82% vs 80%) in cycles that had intracytoplasmic sperm injection performed on weekdays vs. weekends/holidays. No difference was found in the no result rate for embryos biopsied on weekdays vs. weekends/holidays (2.5% vs 1.8%). Finally, there was no difference by weekday vs. weekend/holiday in the live birth rate per transfer among all transfers (39.6% vs 36.1%), or when stratified by fresh (35.1% vs 34.9%) or frozen embryo transfer (49.7% vs. 39.6%). We found no differences in ART outcomes among women who had their oocyte retrievals, inseminations, embryo biopsies, or embryo transfers performed on weekdays versus weekends/holidays.

Impact of trophoectoderm biopsy for preimplantation genetic testing on serum β-hCG levels, time of delivery and birthweight following frozen embryo transfer cycles

Aim: This study investigated whether trophoectoderm (TE) biopsy adversely impacts serum β-human chorionic gonadotropin (hCG) level on the 15th day of embryo transfer (ET), delivery week and birthweight, between biopsied and unbiopsied embryo groups, in a cohort of women who delivered a singleton baby, following frozen–thawed ET. Methods: All women having had a live birth after blastocyst ETs following frozen ET cycles with preimplantation genetic testing (PGT) were included. A control group was selected among women who had a live birth following single frozen blastocyst transfer without PGT-A at the same period in our clinic Results: One hundred fifteen and 173 cycles with- and without-PGT, respectively, were included. Serum β-hCG level on the 15th day after ET was comparable between the groups (p = .336). Average birthweight of the babies born following biopsied embryos were significantly lower (3200 vs. 3380; p = .027). Women who received trophectoderm biopsied embryos had a significantly higher probability of having a baby weighing ≤1500 g and 1500–2500 g (p = .022) or ≤2500 g (p = .008). Proportion of preterm delivery was significantly higher in the biopsy group (p = .023). However, after adjusting for potential covariates, trophectoderm biopsy did not seem to increase the risk of preterm birth (OR 1.525; 95% CI, 0,644–3.611; p = .338) Conclusions: TE biopsy does not seem to impact serum β-hCG level on the 15th day after ET. Average birthweight is lower when a biopsied embryo was transferred. After adjusting for potential covariates, trophectoderm biopsy does not seem to increase the risk of preterm birth

Serum progesterone concentration on pregnancy test day might predict ongoing pregnancy after controlled ovarian stimulation and fresh embryo transfer.

Progesterone (P4) is essential for pregnancy. A controlled ovarian stimulation (COS) leads to a iatrogenic luteal defect that indicates a luteal phase support (LPS) at least until pregnancy test day. Some clinicians continue the LPS until week 8 or later, when P4 is mainly secreted by syncytiotrophoblast cells.Measuring serum P4 on pregnancy test day after a fresh embryo transfer could help to identify women who might benefit from prolonged LPS. In women with LPS based on P4 administered by the rectal route, P4 concentration on pregnancy test day was significantly higher in patients with ongoing pregnancy than in patients with abnormal pregnancy.This monocentric retrospective study used data on 99 consecutive cycles of COS, triggered with human chorionic gonadotropin, followed by fresh embryo transfer resulting in a positive pregnancy test (>100 IU/L) (from November 2020 to November 2022). Patients undergoing preimplantation genetic screening or with ectopic pregnancy were excluded. All patients received standard luteal phase support (i.e. micronized vaginal progesterone 600 mg per day for 15 days). The primary endpoint was P4 concentration at day 15 after oocyte retrieval (pregnancy test day) in women with ongoing pregnancy for >12 weeks and in patients with miscarriage before week 12 of pregnancy.The median P4 concentration [range] at pregnancy test day was higher in women with ongoing pregnancy than in women with miscarriage (55.9 ng/mL [11.6; 290.6] versus 18.1 ng/mL [8.3; 140.9], p = 0.002). A P4 concentration ≥16.5 ng/mL at pregnancy test day was associated with higher ongoing pregnancy rate (OR = 12.5, 95% CI 3.61 - 43.33, p <0.001). A P4 concentration ≥16.5 ng/mL at pregnancy test day was significantly associated with higher live birth rate (OR = 11.88, 95% CI 3.30-42.71, p <0.001).After COS and fresh embryo transfer, the risk of miscarriage is higher in women who discontinue luteal support after 15 days, as recommended, but with P4 concentration <16.5 ng/mL. The benefit of individualized prolonged luteal phase support should be evaluated.