Nikica Zaninovic

Weill Cornell Medical College | Cornell · Center for Reproductive Medicine and infertility (CRMI)

Study question What is the sensitivity of an embryo-grading artificial intelligence (AI) model to different focal planes and how do we obtain consistent scores across focal planes? Summary answer Test-time augmentation and ensemble modeling reduce sensitivity of the AI model to different focal planes while maintaining performance. What is known a...

Study question Is there any prognostic value to classifying 4-cell embryos according to intercellular contact points (ICPs)? Summary answer A significant association was found between the new blastomere arrangement classifications and blastulation, as well as blastocyst quality. No significant association was found for pregnancy. What is known al...

Study question Can we use focal stacks collected through Hoffman modulation contrast (HMC) microscopy to generate 3D reconstructions of preimplantation embryos? Summary answer A machine learning system was designed to generate 3D meshes that approximate the structures of embryos captured on HMC microscopes up to the 8-cell stage. What is known a...

Study question What are the acute effects of cyclophosphamide (Cp) on primordial follicles (PrFs) in human ovarian tissue? Summary answer Administration of Cp damages PrFs via DNA fragmentation and results in reduced proliferation with no increase in PrF activation markers. What is known already Alkylating agents are highly gonadotoxic, and in ca...

Objective: Men who survive cancer as children or young adults may have severe spermatogenic impairment with azoospermia requiring surgical sperm retrieval and assisted reproductive technologies. We assessed treatment outcomes from a large series of cancer patients with prior radiation and/or chemotherapy. Materials and methods: Men with non-obst...

Anti-Müllerian hormone (AMH) is produced by growing ovarian follicles and provides a diagnostic measure of reproductive reserve in women; however, the impact of AMH on folliculogenesis is poorly understood. We cotransplanted human ovarian cortex with control or AMH-expressing endothelial cells in immunocompromised mice and recovered antral follicle...

Objective To perform a series of analyses characterizing an artificial intelligence (AI) model for ranking blastocyst-stage embryos. The primary objective was to evaluate the benefit of the model for predicting clinical pregnancy, whereas the secondary objective was to identify limitations that may impact clinical use. Design Retrospective study....

The goal of an in vitro fertilization (IVF) cycle is a healthy live-born baby. Despite the many advances in the field of assisted reproductive technologies, accurately predicting the outcome of an IVF cycle has yet to be achieved. One reason for this is the method of selecting an embryo for transfer. Morphological assessment of embryos is the tradi...

Objective To report fertilization and clinical pregnancy rates based on sperm characteristics at the time of intracytoplasmic sperm injection (ICSI) in men with nonobstructive azoospermia (NOA) following microdissection testicular sperm extraction (mTESE). Design Retrospective cohort. Setting Tertiary hospital. Patient(s) Men with NOA undergoing...

Study question Is it possible to automate the process of detecting individual blastomeres within a 4-cell embryo? Summary answer Deep learning models are capable of identifying individual cells in single focal plane images of 4-cell embryos. What is known already As individual blastomeres within a 4-cell embryo maintain totipotency, their interce...

Objective To measure the influence of exogenous insulin-like growth factor 1 (IGF1) on follicle growth and maturation in human ovarian cortical xenografts. Design Xenotransplantation model Setting University-based research laboratory Patient(s)/Animal(s) Ovarian tissue was donated with consent and IRB approval by brain dead organ donors or patie...

During in vitro fertilization (IVF), the timing of cell divisions in early human embryos is a key predictor of embryo viability. Recent developments in time-lapse microscopy (TLM) have allowed us to observe cell divisions in much greater detail than previously possible. However, it is a time-consuming process that relies on a highly trained staff a...

Embryo evaluation and selection embody the aggregate manifestation of the entire in vitro fertilization (IVF) process. It aims to choose the “best” embryos from the larger cohort of fertilized oocytes, the majority of which will be determined to be not viable either as a result of abnormal development or due to chromosomal imbalances. Indeed, it is...

Artificial intelligence (AI) systems have been proposed for reproductive medicine since 1997. Although AI is the main driver of emergent technologies in reproduction, such as robotics, Big Data, and internet of things, it will continue to be the engine for technological innovation for the foreseeable future. What does the future of AI research look...

Objective To convert blastocyst (BL) morphological grade and BL day into a numeric blastocyst score (BS). Design Retrospective cohort study. Setting Academic center. Patient(s) A total of 5,653 BL of known implantation (fetal heart, FH) and 11,348 biopsied BL. Intervention(s) Based on their FH rates and/or significance, a score (1–4) was assign...

The activation, growth, and maturation of oocytes to an ovulatory phase, termed folliculogenesis, is governed by the orchestrated activity of multiple specialized cell types within the ovary; yet, the mechanisms governing diversification and behavior of discrete cellular sub-populations within follicles are poorly understood. We use bulk and single...

Visual morphology assessment is routinely used for evaluating of embryo quality and selecting human blastocysts for transfer after in vitro fertilization (IVF). However, the assessment produces different results between embryologists and as a result, the success rate of IVF remains low. To overcome uncertainties in embryo quality, multiple embryos...

Purpose To demonstrate whether the standard morphokinetic markers used for embryo selection have a similar relationship to blastocyst formation and implantation in two large clinical data sets. Methods This is a retrospective cohort analysis striving to answer two distinct questions utilizing data sets from two large IVF clinics. Blastocysts (BL)...

Background: Age-related decline in reproductive potential is mainly due to the increased incidence of aneuploidy. Furthermore, 2 recent studies have shown that euploid embryos of older women may have a lower implantation potential compared to those of younger women, suggesting that aging might compromise embryos beyond their ploidy status. However...

Abstracts of the 34th Annual Meeting of the European Society of Human Reproduction and Embryology

Morphology assessment has become the standard method for evaluation of embryo quality and selecting human blastocysts for transfer in in vitro fertilization (IVF). This process is highly subjective for some embryos and thus prone to human bias. As a result, morphological assessment results may vary extensively between embryologists and in some case...

Objective: To determine whether the blastocyst development rate, as assessed by the day of trophectoderm biopsy (day 5 vs. day 6), affects the live birth rate (LBR) of similarly graded euploid blastocysts. Design: Retrospective cohort study. Setting: Academic medical center. Patient(s): Patients who underwent frozen-thawed single euploid bla...

Infertility is a frequent side effect of chemotherapy and/or radiotherapy and for some patients, cryopreservation of oocytes or embryos is not an option. As an alternative, an increasing number of these patients are choosing to cryopreserve ovarian tissue for autograft following recovery and remission. Despite improvements in outcomes among patient...

Aneuploidy is prevalent in human embryos and is the leading cause of pregnancy loss. Many aneuploidies arise during oogenesis, increasing with maternal age. Superimposed on these meiotic aneuploidies are frequent errors occurring during early mitotic divisions, contributing to widespread chromosomal mosaicism. Here we reanalyzed a published dataset...

Study question: Is there a benefit to assessing ploidy in delayed embryos reaching the morula stage on Day 6 of development? Summary answer: Day-6 morulae should be considered for biopsy in women <40 years old undergoing preimplantation genetic testing for aneuploidy (PGT-A) because they are associated with acceptable, albeit reduced, euploidy a...

OBJECTIVE: A major obstacle to salvaging a robust pool of functional follicles from cryopreserved ovarian tissue following auto-transplantation is the global activation of the follicular pool that occurs during the ischemic window. AMH has been suggested to exert a repressive input on activation and/or growth of follicles during normal folliculogen...

Aneuploidy is prevalent in human preimplantation embryos and is the leading cause of pregnancy loss. Many aneuploidies arise during oogenesis, increasing in frequency with maternal age. Superimposed on these meiotic aneuploidies are a range of errors occurring during early mitotic divisions of the embryo, contributing to widespread chromosomal mosa...

Despite major advances in tissue cryopreservation and auto-transplantation, reperfusion ischemia and hypoxia have been reported as major obstacles to successful recovery of the follicular pool within grafted ovarian tissue. We demonstrate a benefit to follicular survival and function in human ovarian tissue that is co-transplanted with exogenous en...

Objective: To determine whether blastocyst grading can predict pregnancy outcomes in the frozen-thawed embryo transfer (FET) of euploid blastocysts. Design: Retrospective cohort study. Setting: Academic medical center. Patient(s): Women who underwent FET of euploid embryo(s) between January 2013 and December 2015, with blastocysts were divid...

Objective: To investigate the prevalence, developmental potential, chromosomal constitution and clinical outcome of embryos with direct unequal cleavages (DUC). Design: A retrospective observational study. Setting: Academic Institution. Participant: 21,261 embryos from 3,155 cycles cultured in EmbryoScope®. Results: The total incidence of...

Introduction/Objectives: Cryptorchidism is the most common genitourinary abnormality in male infants, affecting up to 6% of newborn infants. A significant concern in cryptorchidism is the potential impact on fertility, as the intra-­‐abdominal testicles rest at a higher temperature than is ideal for normal spermatogenesis. However, even when correc...

To study the outcomes of microdissection testicular sperm extraction (microTESE) among men with pure Sertoli cell-only histology on diagnostic testicular biopsy. Retrospective cohort study. Tertiary referral center. Six hundred forty patients with pure Sertoli cell-only histology on testicular biopsy who underwent microTESE by a single surgeon. Mic...

Fragile X syndrome (FXS) is caused by CGG repeat expansion that leads to FMR1 silencing. Women with a premutation allele are at risk of having a full mutation child with FXS. To investigate the mechanism of repeat expansion, we examined the relationship between a single-nucleotide polymorphism (SNP) variant that is linked to repeat expansion in hap...

Stem cells are characterized by their absolute or relative lack of specialization their ability for self-renewal, as well as their ability to generate differentiated progeny through cellular lineages with one or more branches. The increased availability of embryonic tissue and greatly improved derivation methods have led to a large increase in the...

Epigenetic gene silencing is seen in several repeat-expansion diseases. In fragile X syndrome, the most common genetic form of mental retardation, a CGG trinucleotide–repeat expansion adjacent to the fragile X mental retardation 1 (FMR1) gene promoter results in its epigenetic silencing. Here, we show that FMR1 silencing is mediated by the FMR1 mRN...

Fragile X syndrome (FXS) is caused by a CGG repeat expansion in the FMR1 gene that appears to occur during oogenesis and during early embryogenesis. One model proposes that repeat instability depends on the replication fork direction through the repeats such that (CNG)n hairpin-like structures form, causing DNA polymerase to stall and slip. Examini...

Does follicular flushing during oocyte retrieval improve the number of oocytes retrieved in the poorest responders? Follicular flushing in the poorest responders does not increase the number of oocytes retrieved and may result in lower implantation and clinical pregnancy rates. Although previous studies have shown no beneficial effect of follicular...