Antioxidants in ICSI

Male factor infertility can be caused by reasons, either related or not with total sperm production. Among causes of male infertility in cases of normal sperm count and motility, oxidative stress is one of the most relevant processes influencing fertility in vivo or in assisted reproduction treatments’ results. This chapter provides the most updated information regarding the oxidative stress situation in sperm and the relevance of antioxidants use in intracytoplasmic sperm injection results.

Value of the sperm deoxyribonucleic acid fragmentation level, as measured by the sperm chromatin dispersion test, in the outcome of in vitro fertilization and intracytoplasmic sperm injection.

To determine the prognostic value of sperm DNA fragmentation levels, as measured by the sperm chromatin dispersion (SCD) test, in predicting IVF and ICSI outcome.Double-blind prospective study.University-affiliated private IVF setting.A total of 85 couples undergoing infertility treatment with IVF/ICSI.Analysis of DNA fragmentation by the SCD test in 170 aliquots obtained from the ejaculate and from the processed semen used for assisted reproductive technologies (ART).Percentage of spermatozoa with fragmented DNA was statistically correlated with embryo quality and reproductive success.Fertilization rate was inversely correlated with DNA fragmentation (r = -0.245 P = .045). Higher DNA fragm…

Profound Transcriptomic Differences Found between Sperm Samples from Sperm Donors vs. Patients Undergoing Assisted Reproduction Techniques Tends to Disappear after Swim-up Sperm Preparation Technique

Background Although spermatozoa delivers its RNA to oocytes at fertilization, its biological role is not well characterized. Our purpose was to identify the genes differentially and exclusively expressed in sperm samples both before and after the swim-up process in control donors and infertile males with the purpose to identify their functional significance in male fertility. Materials and methods This was a nested case-control study. Ten sperm samples were obtained from infertile patients [n=5 (two aliquots each from five samples; one before the swim-up process and one after)] and donors [n=5 (two aliquots from five samples, one before the swim-up process and one after)]. Oligonucleotide m…

The use of morphokinetic as a predictor of implantation.

In recent years the increased efforts intended for improving future outcomes in the laboratory have focused mostly on the search of additional markers of embryo quality to add up present embryo selection criteria. Time-lapse system involves an alternative tool in assisted reproduction techniques, being able to improve the embryo selection from a dynamic and interactive approach while standard embryo assessment implies a subjective and static morphology evaluation and consequently reducing the information gained for embryo selection, time-lapse technology adds several morphokinetic parameters, providing additional input for embryo evaluation. This further information represents a challenge f…

A time to look back: analysis of morphokinetic characteristics of human embryo development.

Objective To describe the times associated with the morphological changes that occur in the embryo during preimplantation development based on the largest sample size described with time lapse. Design Cohort study. Setting University-affiliated private center. Patient(s) A total of 9,530 embryos from 1,806 intracytoplasmic sperm injection (ICSI) cycles. Intervention(s) None. Main Outcome Measure(s) Using a time-lapse system, embryo images were acquired for at least 68 hours, in some cases reaching 120–130 hours. Embryo cleavage time points up to 8-cell-stage (t2–t8) as well as morulae (tM) and blastocyst formation (tB) were registered in hours after ICSI. Additionally, duration of the cell …

Similar morphokinetic patterns in embryos derived from obese and normoweight infertile women: a time-lapse study.

Study question Does female obesity affect the dynamic parameters of embryo quality assessed by time-lapse analysis? Summary answer Female obesity does not affect the dynamic embryo quality as determined by image acquisition and time-lapse analysis. What is known already Female obesity impairs natural and assisted reproduction but there is no agreement on the specific contribution of gametes, embryos or endometrial receptivity. In this preliminary study the dynamic parameters of embryo quality are assessed for the first time by time-lapse analysis. Study design, size, duration Two-year cohort retrospective study comparing embryos from three groups of patients according to the presence of inf…

Smoking habits of parents and male: female ratio in spermatozoa and preimplantation embryos

BACKGROUND Previous observations have addressed a decreased male:female ratio associated with smoking. Our aim was to assess whether this effect is observed at the spermatozoa or at the early embryo development. METHODS We retrospectively assessed smoking intake habits of 56 couples included in our preimplantation genetic diagnosis (PGD) program. Three groups were established according to male or female cigarette consumption per day: non-smokers, smokers (1-19 cigarettes per day) and heavy smokers (> or =20 cigarettes per day). Fluorescence in-situ hybridization (FISH) was performed on ejaculated sperm samples to analyse chromosomes X and Y. On day 3, embryos were also analysed. Additionall…

Cigarette Consumption and X-Sperm Enrichment After Swim-Up

Let's rescue oocytes: in vitro maturation 2.0 is coming

Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: a retrospective cohort study.

Objective To quantify the effect on reproductive outcome of culturing and selecting embryos using a novel time-lapse monitoring system (TMS). Design Retrospective observational cohort study. Setting University-affiliated private center. Patient(s) Donation and autologous intracytoplasmic sperm injection (ICSI) cycles from ten IVF clinics using similar procedures, cultured in TMS (n = 1,390) or in a standard incubator (SI; n=5,915). Intervention(s) None. Main Outcome Measure(s) Clinical pregnancy rate confirmed by ultrasound in week 7. Result(s) A logistic regression analysis, which included all significant confounding factors, was used to evaluate the effect of culturing and selecting embry…

Type of culture media does not affect embryo kinetics: a time-lapse analysis of sibling oocytes

Are the morphokinetics of growing embryos affected by the type of culture media utilized?Morphokinetic parameters used for embryo selection are not affected between the two different concept culture media analyzed.Studies on the effect of culture media on human embryos have focused on evaluating different in-house and commercially available media as well as comparing outcomes among different commercial media. Nonetheless, the evaluation of embryo development in these studies was based on static observations and very little is known from a dynamic point of view.Prospective cohort study, October 2010 and April 2011.University-affiliated infertility center. Patients undergoing egg donation (n …

Embryo classification method based in time-lapse analysis is associated with blastocyst quality

groups: 87.7%(10434/11893), 87.4%(2674/3060), 80.2%(1350/1683) and 81.0%(634/783). Abnormal fertilization rate was significantly lower in 9598% group(6.9%,54/783) than other groups(16.1%,1918/11893; 13.8%,421/ 3060; 11.4%,192/1683). Good embryo, pregnancy and implantation rates were no significant differences among four groups(48.9%,61.6%,43.5%; 48.9%,62.1%,43.5%; 50.0%,57.6%,42.3%; 53.1%,62.5%,45.7%). CONCLUSION: Sperm morphology does not affect normal fertilization, embryonic development and clinical outcome.

Y chromosome microdeletions, sperm DNA fragmentation and sperm oxidative stress as causes of recurrent spontaneous abortion of unknown etiology.

Background The aim of the present study was to evaluate the implication of male factor, in terms of sperm DNA oxidation and fragmentation, and Y chromosome microdeletions in recurrent spontaneous abortion (RSA) of unknown origin in a strictly selected cohort. Methods A prospective cohort study was carried out in a private university-affiliated setting. Three groups, each comprised of 30 males, were compared. The first was formed by healthy and fertile sperm donors (SD) with normal sperm parameters (control group), the second by men presenting severe oligozoospermia (SO) without RSA history, and the third by men from couples who had experienced idiopathic RSA. Frequency of Y chromosome micro…

Microarray analysis in sperm from fertile and infertile men without basic sperm analysis abnormalities reveals a significantly different transcriptome.

Sperm analysis following World Health Organization guidelines is unable to explain the molecular causes of male infertility when basic sperm parameters are within a normal range and women do not present gynecologic pathology. Consequently, there is a need for accurate diagnostic tools in this area, and microarray technology emerges as promising. We present, for the first time, preliminary results of a comparison of sperm mRNA expression profiles between fertile and infertile men with normal semen parameters, discovering profound discrepancies between groups, with potential diagnostic and therapeutic possibilities.

Prospective validation of a time-lapse based algorithm for embryo selection

Endometrial receptivity and implantation are not affected by the presence of uterine intramural leiomyomas: a clinical and functional genomics analysis.

Uterine leiomyomas are the most frequent benign tumors during reproductive age. Whether intramural leiomyomas cause infertility and should be removed is controversial because no study has addressed the underlying mechanism of infertility.The objective of the study was to test the effect of intramural leiomyomas on endometrial function by comparing gene during the window of implantation and implantation in an oocyte donation program, in which the quality of the embryos replaced is similar and the endocrine environment of the endometrium is standardized by exogenous steroids.Human endometria of women with single intramural leiomyomas (group A,5 cm and group B,or =5 cm) and controls (group C) …

Removal of annexin V–positive sperm cells for intracytoplasmic sperm injection in ovum donation cycles does not improve reproductive outcome: a controlled and randomized trial in unselected males

Objective To determine the effect of removing presumptive apoptotic sperm cells from samples from unselected males by means of magnetic activated cell sorting (MACS) on live-birth delivery rates after intracytoplasmic sperm injection (ICSI) in couples undergoing ovum donation (OD). Design Prospective, randomized, triple-blinded, and controlled study. Setting Private university-affiliated IVF center. Patient(s) A total of 237 infertile couples undergoing ICSI as part of an OD program. Intervention(s) Semen specimens from the control group were prepared by swim-up. Samples from the study group were prepared by swim-up followed by MACS and incubation with annexin V–conjugated microbeads to rem…

Full in vitro fertilization laboratory mechanization: toward robotic assisted reproduction?

Objective To describe the current efforts made to standardize different steps of assisted reproductive technology processes by the introduction of new technologies for the nonsubjective sperm selection process, oocyte denudation by mechanical removal of cumulus cells, oocyte positioning, sperm motility screening, fertilization, embryo culture, media replacement by microfluidics, and monitoring of embryo development by time-lapse photography, embryo secretions, and/or O 2 consumption. These technologies could be integrated in a unique and fully automated device. Design Pubmed database and research and development data from authors. Setting University-affiliated private center. Patient(s) Non…

Deep learning enables robust assessment and selection of human blastocysts after in vitro fertilization

AbstractVisual 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 are often implanted resulting in undesired multiple pregnancies and complications. Unlike in other imaging fields, human embryology and IVF have not yet leveraged artificial intelligence (AI) for unbiased, automated embryo assessment. We postulated that an AI approach trained on thousands of embryos can reliably predict embryo quality with…

The effect of cancer on sperm DNA fragmentation as measured by the sperm chromatin dispersion test

The percentage of spermatozoa with fragmented DNA from cancer patients before surgery, chemotherapy, or radiotherapy treatments was compared with infertile male patients in an assisted reproduction program and with sperm donors of proven fertility. The percentages of DNA fragmentation were 34.3% in cancer patients, 30.9% in infertile men whose partners did not become pregnant, 28.8% in men who partners became pregnant, and 10.8% in fertile sperm donors. The DNA fragmentation of sperm donors was statistically significantly lower compared the other groups. No statistically significant differences were found in the levels of DNA fragmentation when comparing cancer types, including those of tes…

Sperm selection by swim-up in terms of deoxyribonucleic acid fragmentation as measured by the sperm chromatin dispersion test is altered in heavy smokers.

Toxic habits and their relationship with male factor infertility have been a matter of investigation in recent years, and smoking is one of the most common lifestyle toxic exposures to harmful substances. The analysis of sperm deoxyribonucleic acid fragmentation after capacitation detected a detrimental effect produced by tobacco, and this deleterious effect alters the sperm swim-up selection process in smokers, although the molecular and cellular basis of this phenomenon remain to be elucidated.

The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics: a time-lapse study

OBJECTIVE: To explore if the GnRH analogue used for controlled ovarian stimulation (COS) and the ovulation triggering factor (GnRH agonist + hCG triggering versus GnRH antagonist + GnRH agonist triggering) affect embryo development and kinetics.STUDY DESIGN: In a retrospective cohort study in the Instituto Valenciano de Infertilidad (IVI) Alicante and the Instituto Universitario-IVI Valencia, Spain, 2817 embryos deriving from 400 couples undergoing oocyte donation were analysed. After controlled ovarian stimulation and IVF/intracytoplamic sperm injection, the timing of embryonic cleavages was assessed by a video time-lapse system. The results were analysed using Student's t test for compari…

The significance of premature luteinization in an oocyte-donation programme

BACKGROUND: Several evidences indicate that premature luteinization (PL) may affect IVF outcome. The primary end-point of the present study was to verify the effect of PL on the pregnancy rate (PR) of our oocytedonation programme. METHODS: PL was defined as serum progesterone ³1.2 ng/ml on the day of HCG. We analysed retrospectively 240 oocyte-donation cycles in which 120 women donated twice, with PL in the first donation cycle and no PL in the following one, acting as its own control. Recipients (n = 240) were divided in two groups according to the presence of PL (n = 120) or not (n = 120). Both groups were compared regarding donor cycle parameters and recipient cycle outcome. RESULTS: The…

The most well kept secret, embryo culture media: a smart reveal from an expert.

Cigarette smoking affects specific sperm oxidative defenses but does not cause oxidative DNA damage in infertile men

Objective To evaluate the effects of tobacco consumption on the oxidative defenses of sperm, the glutathione system (GS), and sperm DNA oxidation. Design Double-blind experimental study. Setting Andrology laboratory in a university-affiliated private setting. Patient(s) One hundred seventeen semen samples from infertile males. Intervention(s) None. Main Outcome Measure(s) (a) sperm GS enzymatic activity with respect to glutathione peroxidase isoforms GPx-1 and GPx-4, glutathione reductase (GR), and cellular glutathione (GSH) content (n = 29); (b) GPx-1, GPx-4, and GR m RNA expression analysis (n = 33); (c) oxidative DNA damage quantification using OXIDNA assay kit (n = 55). Two groups were …

First report of the absence of viral load in testicular sperm samples obtained from men with hepatitis C and HIV after washing and their subsequent use.

Human immunodeficiency virus and hepatitis C infections are sexually transmitted diseases that require sperm samples to be pretreated to eliminate the viral presence before their safe use in assisted reproduction treatments. In this report we describe our experience with sperm washing protocols applied to sperm cells from testicular biopsies as well as the results obtained in subsequent assisted reproduction treatments on seropositive males that are also azoospermic.

To invade, or to observe, that is the question

Limited implantation success of direct-cleaved human zygotes: a time-lapse study.

Objective To evaluate embryos with direct cleavage (≤5 hours) from two to three cells (DC2–3) and correlate this morphokinetic parameter to implantation and ongoing pregnancy. Design Clinical multicenter retrospective study. Setting Private in vitro fertilization (IVF) centers. Patient(s) From three clinics, a total of 979 treatments including 5,225 embryos using autologous or donated oocytes, of which 1,659 embryos were transferred. Intervention(s) None. Main Outcome Measure(s) Clinical pregnancy confirmed by ultrasound in week 7. Result(s) Of the total embryo cohort, 715 (13.7%) underwent direct cleavage from two to three cells, 1,659 embryos were transferred to recipients, and 109 of the…

Clinical validation of embryo culture and selection by morphokinetic analysis: a randomized, controlled trial of the EmbryoScope.

Objective To determine whether incubation in the integrated EmbryoScope time-lapse monitoring system (TMS) and selection supported by the use of a multivariable morphokinetic model improve reproductive outcomes in comparison with incubation in a standard incubator (SI) embryo culture and selection based exclusively on morphology. Design Prospective, randomized, double-blinded, controlled study. Setting University-affiliated private in vitro fertilization (IVF) clinic. Patient(s) Eight hundred forty-three infertile couples undergoing intracytoplasmic sperm injection (ICSI). Intervention(s) No patient intervention; embryos cultured in SI with development evaluated only by morphology (control …

Testicular Sperm Extraction (TESE) and Intracytoplasmic Sperm Injection (ICSI) in Hypogonadotropic Hypogonadism with Persistent Azoospermia After Hormonal Therapy

Purpose: We aimed to retrieve testicular sperm to be employed on intracytoplasmic sperm injection (ICSI) cycles on a male affected of hypogonadotropic hypogonadism (HH) that remained azoospermic after long-time hormonal treatment. Methods: Design. We initially performed hormonal therapy using gonadotropins to achieve spermatogenesis. After several semen analyses, we weighed the possibility of looking for testicular spermatozoa for ICSI. Setting. A private university-affiliated setting. Patient. A 30-years-old man diagnosed 10 years ago to suffer from idiopathic, prepubertal HH. Interventions. Gonadotrophin treatment was initiated with hCG and follicle stimulating hormone (FSH). Testicular s…

Antral follicle count (AFC) can be used in the prediction of ovarian response but cannot predict the oocyte/embryo quality or the in vitro fertilization outcome in an egg donation program

To verify whether the antral follicle count (AFC) could predict ovarian response, oocyte/embryo quality, and IVF outcome.Prospective study.Instituto Universitario-Instituto Valenciano de Infertilidad, Valencia, Spain.One thousand seventy-four donors and 975 oocyte recipient cycles.Controlled ovarian hyperstimulation (COH), endometrial preparation, IVF/intracytoplasmic sperm injection, ET.COH and oocyte/embryo quality parameters and IVF outcome.We observed lower E(2) levels and fewer mature retrieved oocyte numbers among donors who showed an AFC that was10. These donors also showed significantly higher cancellation and no-donation rates; poor and/or insufficient response was the principal ca…

Morphokinetic analysis and embryonic prediction for blastocyst formation through an integrated time-lapse system.

Objective To describe the events associated with the blastocyst formation and implantation that occur in embryos during preimplantation development based on the largest sample size ever described with time-lapse monitoring. Design Observational, retrospective, single-center clinical study. Setting University-affiliated private IVF center. Patient(s) A total of 7,483 zygotes from 990 first treatments of intracytoplasmic sperm injection (ICSI; 627 of oocyte donor vs. 363 autologous oocyte cycles), of which 832 blastocysts were transferred. Intervention(s) No patient intervention. Embryos were cultured in a time-lapse monitoring system, and the embryos were transferred on day 5 after ICSI. Emb…

Assessment of embryo morphology and developmental dynamics by time-lapse microscopy: is there a relation to implantation and ploidy?

Time-lapse microscopy (TLM) is an exciting novel technology with great potential for enhancing embryo selection in the embryology laboratory. This non-invasive objective assessment of embryos has provided a new tool for predicting embryo development and implantation potential. TLM detects several morphological phenomena that are often missed with static observations using conventional incubators, such as irregular divisions, blastocyst collapse and re-expansion, timing of blastocoel appearance, and timing of formation and internalization of fragments. Nevertheless, it should be recognized that conventional morphological assessment has been widely accepted as the gold standard by most embryo…

Selection of high potential embryos using time-lapse imaging: the era of morphokinetics.

Incorporation of time-lapse imaging in the field of IVF has provided much information about embryo development. The combination of the embryo appearance (morphology) and the importance of when and how the cellular processes that lead to this appearance occur (kinetics) are now integrated into the unique concept of morphokinetics. At present, efforts are focused on using this information to improve embryo selection and existing success rates without losing sight of the ever-present objective of implementing a single ET strategy to avoid multiple gestations. Several investigative groups have identified predictive morphokinetic variables for embryo viability and implantation potential. Promisi…

Combination of metabolism measurement and a time-lapse system provides an embryo selection method based on oxygen uptake and chronology of cytokinesis timing.

Objective To evaluate correlations between oxygen consumption (OC) measurements before and after embryo cytokinesis, observing OC during embryo cleavages and combining that information with morphokinetics to relate to implantation potential. Design Prospective cohort study. Setting University-affiliated private IVF unit. Patient(s) A total of 1,150 injected oocytes in 86 first oocyte donation cycles with embryo transfer on day 3. Intervention(s) None. Main Outcome Measurement(s) We analyzed the embryo OC and combined this data with the cytokinesis event, exact timing (in hours) of blastomeric cleavages, with the use of an incubator equipped with time-lapse videography, gathering a total of …

Bleeding during transfer is the only parameter of patient anatomy and embryo quality that affects reproductive outcome: a prospective study.

There is very little information available regarding the relevance of the position of embryo replacement during ET and the different anatomic characteristics of the recipient in the transfer process and on the result of assisted reproduction techniques. We prospectively analyzed, using multivariate regression analysis, 375 ETs, 177 of which were from donated oocytes and 198 from patients' own oocytes, and we found no effect of the anatomic characteristics of the uterus on the chances of achieving pregnancy when data were analyzed according to patient age and embryo quality. Interestingly, there was a significant decrease in pregnancy rates when blood was present in the catheter after the pr…

Report of results obtained in 2,934 women using donor sperm: donor insemination versus in vitro fertilization according to indication.

Objective To demonstrate that the use of donor sperm leads to varying outcome rates and that its use has evolved. Design Retrospective observational cohort study. Setting University-affiliated private IVF setting. Patient(s) Women (2,934) undergoing donor insemination (DI) or IVF with donor sperm (IVF-D). Intervention(s) None. Main Outcome Measurement(s) We evaluated the distribution of the clinical indications for the use of donated sperm, studying the reproductive outcome. Result(s) A total of 1,663 DI (57%) and 1,271 IVF-D (43%) were performed. There were significant differences in the indications for the use of donated sperm (DI vs. IVF-D). Regarding pregnancy rates (PR), cases of nonob…

COVID-19 should be a novel indication for fertility preservation

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Predicting the Success of Blastocyst Implantation from Morphokinetic Parameters Estimated through CNNs and Sum of Absolute Differences

The process of In Vitro Fertilization deals nowadays with the challenge of selecting viable embryos with the highest probability of success in the implantation. In this topic, we present a computer-vision-based system to analyze the videos related to days of embryo development which automatically extracts morphokinetic features and estimates the success of implantation. A robust algorithm to detect the embryo in the culture image is proposed to avoid artifacts. Then, the ability of Convolutional Neural Networks (CNNs) for predicting the number of cells per frame is novelty combined with the Sum of Absolute Differences (SAD) signal in charge of capturing the amount of intensity changes durin…

Blastocyst formation is similar in obese and normal weight women: a morphokinetic study

Abstract STUDY QUESTION Does the embryo cleavage pattern and rate of blastocyst formation differ between normal weight and obese women undergoing IVF? SUMMARY ANSWER Embryo morphokinetic development, final blastocyst formation rate and blastocyst morphology do not differ between obese and normal weight women. WHAT IS KNOWN ALREADY Female obesity has been related to impaired IVF outcomes. Although the mechanisms responsible for this detrimental effect are thought to include impaired oocyte and embryo quality and reduced endometrial receptivity, they are yet to be confirmed. Embryo quality has been commonly assessed using static morphological criteria. Only three studies have analysed the pro…

The transcriptome of spermatozoa used in homologous intrauterine insemination varies considerably between samples that achieve pregnancy and those that do not.

Objective To differentiate transcripts' expression in the sperm from patients who achieved pregnancy in their first IUI cycle from those who did not. Basic sperm analysis is limited to forecasting pregnancies by means of assisted reproduction. New assays, such as microarray analysis, are potential predictive tools for this purpose. Design Nested case-control study. Setting University-affiliated private setting. Patient(s) Twenty sperm samples were obtained from infertile males undergoing their first IUI cycle with healthy partners. Sperm samples with which pregnancy was achieved (P; n=10) and those with which it was not achieved (NP; n=10) were identified and their respective messenger RNA …

Effect of sperm glutathione peroxidases 1 and 4 on embryo asymmetry and blastocyst quality in oocyte donation cycles

Objective To prospectively determine the impact of concrete components of the sperm oxidative glutathione stress system in terms of enzymatic activity and mitochondrial RNA (mRNA) expression on embryo quality and reproductive outcome. Human spermatozoa use the glutathione system to inactivate reactive oxygen metabolites, and there is a close correlation between some components of the glutathione system and male fertility. However, very few data are published regarding this system in sperm cells and its effect on fertilization ability and embryo development in human beings. Design An oocyte-donation model, used to homogenize the female factor. Setting University-affiliated private IVF settin…

Timing of cell division in human cleavage-stage embryos is linked with blastocyst formation and quality

Noninvasive markers of embryo quality are being sought to improve IVF success. The present study aimed to discover possible associations between embryo division kinetics in the cleavage stage, the subsequent ability of human embryos to reach the blastocyst stage and the resulting blastocyst morphology. A retrospective cohort study analysed 834 embryos from 165 oocyte donation couples using a time-lapse monitoring system that allowed the recording of the exact timings for key events related to embryo development. Timing parameters were categorized into four quartiles. The probability of an embryo developing to a blastocyst was linked to a strict chronology of development. To further evaluate…

Effect of sperm DNA fragmentation on pregnancy outcome depends on oocyte quality

Objective To quantify the effect of sperm DNA fragmentation (SDF) on reproductive outcome by evaluating the most statistically significant bias factors using logistic regression. Design Prospective blind observational cohort study. Setting University affiliated private IVF unit. Patient(s) Two hundred ten male partners of couples undergoing in vitro fertilization (IVF) or first intracytoplasmic sperm injection (ICSI) cycles with fresh or thawed sperm with the women's own or donated oocytes. Intervention(s) None. Main Outcome Measure(s) SDF determined before and after swim-up (n = 420), odds ratio calculated of the effect of an increase of one unit of SDF on pregnancy, and stratified regress…

Defining poor prognosis markers of implantation for embryo selection by time-lapse

Differential transcriptomic profile in spermatozoa achieving pregnancy or not via ICSI

Basic sperm analysis is limited as a method of estimating pregnancy. This study’s objective was use of microarray technology to differentiate the gene expressions of spermatozoa that achieved pregnancy in an intracytoplasmic sperm injection (ICSI)cycle in an oocyte donation programme with those that did not achieve pregnancy. A study of nested cases and controls was designed to evaluate fresh and frozen spermatozoa from infertile males undergoing ICSI with donor oocytes. The global genome expression of pooled samples from each group (achieving pregnancy versus those that didn’t, from fresh or frozen spermatozoa)was compared using microarray analysis. The level of expression of some of the t…

The why, the how and the when of PGS 2.0

STUDY QUESTION: We wanted to probe the opinions and current practices on preimplantation genetic screening (PGS), and more specifically on PGS in its newest form: PGS 2.0? STUDY FINDING: Consensus is lacking on which patient groups, if any at all, can benefit from PGS 2.0 and, a fortiori, whether all IVF patients should be offered PGS. WHAT IS KNOWN ALREADY: It is clear from all experts that PGS 2.0 can be defined as biopsy at the blastocyst stage followed by comprehensive chromosome screening and possibly combined with vitrification. Most agree that mosaicism is less of an issue at the blastocyst stage than at the cleavage stage but whether mosaicism is no issue at all at the blastocyst st…

In vitro fertilization and andrology laboratories in 2030

The in vitro fertilization and andrology laboratories are at the center of assisted reproductive technologies and the place where technicians and embryologists manipulate gametes and preimplantation-stage embryos with the goal of achieving the best embryo for transfer. Through the years, these laboratories have seen developments in technique, technology, and testing. The goal of this Views and Interviews series is to bring together the thought leaders in the field and envision what the laboratories will look like in the next 10 years.

Embryo morphokinetics analysis and reproductive outcomes with assisted oocyte activation by a calcium ionophore after prior fertilization failure. A multicentric retrospective study

Abstract Background Fertilization failure or low fertilization rate after ICSI is around 1–3% in IVF treatments. Several strategies have been studied in order to bypass the lack of activation. The aim of this study is to evaluate embryo morphokinetics and reproductive outcomes after intracytoplasmic sperm injection (ICSI) with assisted oocyte activation (AOA) using a calcium ionophore (CaI) in patients with previous fertilization failure or low fertilization rate (under 30%) and severe male factor. Methods Multicentric retrospective cohort study including 70 patients with fertilization failure or low fertilization rate and severe male factor (sperm concentration under 1 million/mL) who unde…

Sperm DNA fragmentation levels in testicular sperm samples from azoospermic males as assessed by the sperm chromatin dispersion (SCD) test.

Objective To analyze sperm DNA fragmentation (SDF) in testicular sperm samples from patients with azoospermia either from spermatogenic failure or from duct obstruction. Several technologies can be applied in the evaluation of SDF, but given the ease and low costs, the sperm chromatin dispersion test (SCD) has emerged as a promising standard. Design Prospective blind observational cohort study. Setting University-affiliated private IVF setting. Patient(s) Azoospermic patients from couples undergoing intracytoplasmic sperm injection cycles. Intervention(s) Testicular sperm extraction (TESE). Main Outcome Measurement(s) We determined testicular SDF, and a basic comparison between nonobstructi…

Human Endometrial Mucin MUC1 Is Up-Regulated by Progesterone and Down-Regulated In Vitro by the Human Blastocyst1

Expression of MUC1 in endometrial epithelium has been suggested to create a barrier to embryo attachment that must be lifted at the time of implantation. In this study, we investigated the hormonal regulation of human endometrial MUC1 in hormone replacement therapy cycles and in the human blastocyst. We also analyzed the embryonic regulation of MUC1 in human endometrial epithelial cells (EECs) during the apposition and adhesion phases of human implantation using two different in vitro models. Our results indicate that endometrial MUC1 mRNA and immunoreactive protein increase in receptive endometrium compared to nonreceptive endometrium. Human blastocysts express MUC1, as demonstrated by rev…

Time-lapse technology: evaluation of embryo quality and new markers for embryo selection

Current methods of embryo evaluation rely mainly on static observations of the embryo´s morphology. These observations are inevitably restricted to specific times and, considering that the development of the embryo is a dynamic process, several critical stages in between observations may go unnoticed. These methods are also very subjective, and variations between embryologists may affect critical decisions that will, in turn, affect the overall success of the IVF clinics. On the other hand, an increased number of multiple pregnancies calls for a reduction in the number of embryos transferred, making the selection procedure even more challenging for the embryologist. Therefore, new markers t…

Time-lapse: the remaining questions to be answered.

Novel noninvasive embryo selection algorithm combining time-lapse morphokinetics and oxidative status of the spent embryo culture medium.

Objective To develop a noninvasive embryo selection algorithm consisting of time-lapse morphokinetics and the oxidative status of the spent embryo culture medium determined using the Thermochemiluminescence (TCL) Analyzer. Design Retrospective cohort. Setting Not applicable. Patient(s) From women participating in the oocyte donation program, data from 505 samples of spent embryo culture media samples from 292 intracytoplasmic sperm injection cycles. Intervention(s) None. Main Outcome Measure(s) Morphokinetic parameters assessed during incubation in the time-lapse system Embryoscope. Oxidative parameters (H1sm, H2sm, and H3sm) from the spent culture medium on day 5 of incubation measured usi…

Better together than alone: the cumulus benefits.

Sperm chromosomal abnormalities and their contribution to human embryo aneuploidy.

In this work we reviewed 18 years of experience using fluorescence in situ hybridization (FISH) for sperm aneuploidy testing. We evaluated parameters associated with increased numerical sperm chromosome abnormalities and determined the male contribution to embryo aneploidies in terms of reproductive outcome by increased sperm aneuploidy. This retrospective study analyzed data from 2008 sperm samples of infertile males undergoing FISH analysis because of clinical history of repetitive implantation failure, recurrent miscarriage, impaired sperm parameters, or mixed causes. Sperm concentration was the only sperm parameter associated with FISH results—we observed a gradual increase of abnormal …

Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial

background: An efficient oocyte cryopreservation method is mandatory to establish a successful egg-banking programme. Although there are increasing reports showing good clinical outcomes after oocyte cryopreservation, there is still a lack of large controlled studies evaluating the effectiveness of oocyte cryo-banking. In this study, we aimed to compare the outcome of vitrified-banked oocytes with the gold standard procedure of employing fresh oocytes. methods: A randomized, prospective, triple-blind, single-centre, parallel-group controlled-clinical trial (NCT00785993), including 600 recipients (a ¼ 0.05 and power of 80% for sample-size calculation) selected among 1032 eligible patients fr…

Automatic time-lapse instrument is superior to single-point morphology observation for selecting viable embryos: retrospective study in oocyte donation.

Objective To correlate the different categories provided by a commercial diagnostic test with blastocyst formation, quality, implantation potential, and ongoing pregnancy (OPR) for the purpose of validating the automatic annotations and the classification algorithm. Design Observational, retrospective, multicenter cohort study. Setting University-affiliated private IVF center. Patient(s) A total of 3,002 embryos, including 521 transferred embryos with known implantation, from 626 IVF cycles that were incubated in a conventional incubator and monitored with an automatic time-lapse test. Interventions(s) None. Main Outcome Measure(s) Embryo selection was based on morphology and the classifica…

Effect of oocyte morphology on post-warming survival and embryo development in vitrified autologous oocytes.

Abstract Research question Does the presence of dysmorphisms affect post-warming survival and embryo development in vitrified autologous oocytes? Design A retrospective study comparing post-warming survival, fertilization and embryo development between morphologically normal (n = 269) and dysmorphic oocytes (n = 147). Results The survival rate was 81.4% in the morphologically normal oocytes and 87.1% in the dysmorphic oocyte group (OR 1.53; 95% CI 0.86 to 2.72). The fertilization rate was 69.9 versus 66.4% (OR 0.85; 95% CI 0.53 to 1.36), the proportion of good-quality embryos on day 3 was 30.3% versus 32.0% (OR 1.08; 95% CI 0.59 to 1.97) and the blastocyst formation rate was 54.5% versus 60…

Female obesity increases the risk of miscarriage of euploid embryos.

Objective To determine whether female body mass index (BMI) is associated with an increased risk of miscarriage after euploid embryo transfer. Design A retrospective, observational, multicenter cohort study. Setting University-affiliated in vitro fertilization center. Patient(s) In this study, 3,480 cycles of in vitro fertilization with preimplantation genetic testing for aneuploidy (PGT-A) in the blastocyst stage and euploid embryo transfer were divided into four groups according to patient BMI. Intervention(s) In vitro fertilization with PGT-A. Main Outcome Measure(s) The primary outcome was the miscarriage rate, which included both biochemical and clinical miscarriages. Secondary outcome…

GnRH agonist versus recombinant HCG in an oocyte donation programme: a randomized, prospective, controlled, assessor-blind study.

The use of gonadotrophin-releasing hormone (GnRH) agonists for triggering ovulation remains controversial. The primary objective of this study was to evaluate the incidence of ovarian hyperstimulation syndrome (OHSS) following GnRH agonist versus recombinant human chorionic gonadotrophin (HCG) as methods for triggering ovulation. A second aim was to compare the clinical outcome and embryo quality according to the two procedures. The cycle characteristics of 100 oocyte donors undergoing ovarian stimulation and IVF outcomes of their 100 oocyte recipients were analysed. Donors were prospectively randomized into two groups on the last day of ovarian stimulation: Group I received a single bolus …

Timing does not influence outcomes in double intrauterine insemination

Hormonal and embryonic regulation of chemokines IL-8, MCP-1 and RANTES in the human endometrium during the window of implantation.

Chemokines are a family of small polypeptides which specialize in the attraction of leukocytes. The presence of specific leukocyte subsets at the implantation site is an important element of the complex, and not completely understood, process of embryonic implantation. This report includes the investigation of the in-vivo immunolocalization and hormonal regulation of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and RANTES (regulated upon activation normal T-cell expressed and secreted) in the human endometrium during hormone replacement therapy cycles for oocyte recipients in an IVF programme. In addition, we have analysed the embryonic regulation of these endometrial epithelial…

Storage of human oocytes in the vapor phase of nitrogen

Objective To evaluate the effectiveness of long-term vapor-phase nitrogen storage of vitrified human oocytes as a strategy for preventing the risk of cross-contamination due to direct contact with the liquid nitrogen (LN). Design Prospective randomized study. Setting Private infertility center, IVI, Valencia. Patient(s) Oocyte donors (n = 44) and recipients (n = 46). Intervention(s) Vitrification by the Cryotop method. Storage of vitrified oocytes in a vapor-phase nitrogen storage freezer and a traditional LN storage tank. Donation of the surviving oocytes and evaluation of fertilization, embryo development, and clinical results. Main Outcome Measure(s) Survival, fertilization, and cleavage…

MUC1 in human testis and ejaculated spermatozoa and its relationship to male fertility status.

MUC1 is a cell surface glycoprotein with a previously described antiadhesive role involved in different aspects of reproductive function. We found MUC1 expressed in male germ cell line and within the ejaculated sperm, but its presence in mature sperm does not seem to be related to male fertility. This was confirmed after analysis of results from assisted reproduction techniques with oocyte donation related with MUC1, although higher MUC1 expression is related to sperm recovery after preparation.

Swim-up procedure selects spermatozoa with longer telomere length.

Telomere length and sperm DNA fragmentation were determined in sperm samples from 27 patients, using a quantitative PCR (Q-PCR) assay and the Sperm Chromatin Dispersion (SCD) test, respectively. Comparisons of the samples before and after swim-up processing demonstrated that this procedure selects a sperm population with longer average telomere size and lower frequency of sperm cells with fragmented DNA.

Collapse of blastocysts is strongly related to lower implantation success: a time-lapse study.

Study question Is there an association between blastocyst collapse patterns and implantation potential? Summary answer Embryos that exhibit collapse are as likely to hatch as those that do not, but are less likely to implant and should not be replaced if alternatives are available. What is known already Studies of blastocyst collapse in different species of mammals have found that most blastocysts, that experience consecutive weak contractions, hatch successfully whereas those that exhibit strong contractions or collapse, fail to hatch. Study design, size, duration Retrospective cohort study. Seven hundred and fifteen transferred blastocysts were analyzed from July 2012 to May 2013. Partici…

Preimplantation genetic testing for aneuploidy in patients with partial X monosomy using their own oocytes: is this a suitable indication?

Objective To describe the outcome of preimplantation genetic testing (PGT-A) using their own oocytes in patients with mosaic Turner Syndrome (MTS). The impact of the assisted reproduction technique (ART) performed (PGT-A or oocyte donation) and the type of absence of the X chromosome (total or partial) were considered. Design Retrospective observational multicenter study. Setting University-affiliated private in vitro fertilization center. Patient(s) Fifty-six patients with MTS with whom 65 ovarian stimulation cycles for PGT-A (fluorescence in situ hybridization/arrays-next generation sequencing) were performed. The study included 90 women with MTS and 20 women with pure Turner Syndrome (PT…

Oxygen consumption is a quality marker for human oocyte competence conditioned by ovarian stimulation regimens.

Objective To evaluate the effect of different ovarian stimulation protocols on oocyte respiration and to investigate the relationship between oocyte oxygen consumption and reproductive outcome. Design Prospective observational cohort study. Setting Infertility clinic in a university hospital. Patient(s) A total of 349 oocytes from 56 IVF treatment cycles in our oocyte donation program. Intervention(s) None. Main Outcome Measure(s) Average oocyte oxygen consumption rate in fmol/s. We correlated oxygen consumption values with ovarian stimulation features, fertilization, embryo quality on days 2 and 3, and implantation. Result(s) Differences in the measured oxygen consumption rates were found …

Obesity reduces uterine receptivity: clinical experience from 9,587 first cycles of ovum donation with normal weight donors

Objective To analyze the reproductive outcome of recipients of donated ova according to their body mass index (BMI). Design Twelve-year retrospective cohort analysis. Setting Fertility clinics. Patient(s) 9,587 first cycles of ovum donation with ova from normoweight donors. Intervention(s) Recipients divided according to their BMI to analyze IVF laboratory and outcome parameters: lean with BMI 2 (n = 1,458; 15.2%); normoweight with BMI 20–24.9 kg/m 2 (n = 5,706; 59.5%), overweight with BMI 25–29.9 kg/m 2 (n = 1,770; 18.5%), and obese with BMI ≥30 kg/m 2 (n = 653; 6.8%). Main Outcome Measure(s) Implantation, biochemical and clinical pregnancy, miscarriage, and live-birth rates. Result(s) In …

A prospective, randomized, controlled trial comparing three different gonadotropin regimens in oocyte donors: ovarian response, in vitro fertilization outcome, and analysis of cost minimization

Objective To compare the efficacy of three different gonadotropin regimens in an oocyte donation program. The analysis of cost minimization also was evaluated. Design Prospective, randomized, controlled study. Setting Instituto Universitario–IVI, Valencia, Spain. Patient(s) One thousand twenty-eight donors undergoing a GnRH agonist protocol were assigned randomly to one of three groups: group 1 (n = 346), only recombinant FSH (rFSH); group 2 (n = 333), only highly purified menotropin (HP-hMG); and group 3 (n = 349), rFSH plus HP-hMG. One thousand seventy-nine oocyte recipients. Intervention(s) Controlled ovarian stimulation. Main Outcome Measure(s) Controlled ovarian stimulation parameters,…

Processing Sperm Samples in HIV-Positive Patients

Human immunodeficiency virus is an important public health problem; about 40 million people around the world are actually infected with HIV type 1 virus. Furthermore, prolonged survival of patients under highly active antiretroviral therapy has given rise to a new demand from SDC couples who wish to have children. HIV serodiscordant couples with the male infected wish to make use of assisted reproduction techniques in combination with semen washing in order to decrease the risk of transmission to the partner or to the newborn. Thus it is essential to test the effectiveness of techniques aimed at reducing HIV and HCV loads in infected semen using molecular biology tests. Nevertheless, its ef…

In vitro fertilization and andrology laboratory in 2030: expert visions.

The aim of this article is to gather 9 thought leaders and their team members to present their ideas about the future of in vitro fertilization and the andrology laboratory. Although we have seen much progress and innovation in the laboratory over the years, there is still much to come, and this article looks at what these leaders think will be important in the future development of technology and processes in the laboratory.

Type of chromosome abnormality affects embryo morphology dynamics.

Objective To study the differences in the cleavage time between types of embryo chromosomal abnormalities and elaborate algorithm to exclude aneuploid embryos according to the likelihood to be euploid. Design Retrospective cohort study. Setting University affiliated private center. Patient(s) Preimplantational genetic screening patients (n = 112) including cases of advanced maternal age, repeated implantation failure, and recurrent miscarriage. A total of 485 embryos were analyzed. Intervention(s) None. Main Outcome Measure(s) All biopsied embryos were cultured in an incubator with time-lapse technology, cleavage timing from insemination to day 3 and all kinetic parameters that have been de…

Is morphokinetic analysis the answer?

Abstract Efforts aimed at improving pregnancy rates have focused on the search for additional markers of viability to supplement current criteria for embryo selection. Time-lapse technology represents a powerful tool in assisted reproduction for evaluating embryos dynamically. Whilst standard methods of embryo assessment are based on subjective morphology evaluation at discrete time points, thereby limiting the information produced for embryo selection, time-lapse recording introduces several additional morphokinetic parameters for embryo evaluation. This additional information can improve implantation rates and reproductive outcomes. This review surveys available knowledge on time-lapse im…

Study of nucleation status in the second cell cycle of human embryo and its impact on implantation rate

Objective To study nucleation status in two- and four-cell embryos and its effect on reproductive outcomes. Design Retrospective cohort study. Setting University-affiliated private center. Patient(s) A total of 1,679 embryos from 940 oocyte donation cycles from May 2012 to May 2014. Intervention(s) None. Main Outcome Measure(s) Implantation, morphokinetics, and nucleation status restoration. Result(s) Multinucleation was present in 42.53% of embryos with known implantation data at the two-cell stage; it was present in approximately 14% of them at the four-cell stage. In all, 73.4% of the embryos were multinucleated at two cells and restored their nucleation status when they cleaved into fou…

One for all or all for one? The evolution of embryo morphokinetics

Analysis of the morphological dynamics of blastocysts after vitrification/warming: defining new predictive variables of implantation

Objective To describe the morphological dynamics of vitrified/warmed blastocysts and to identify quantitative morphological variables related to implantation. Subsequently, by using the most predictive parameters, to develop a hierarchical model by subdividing vitrified/warmed blastocysts into categories with different implantation potentials. Design Observational, retrospective, cohort study. Setting University-affiliated private IVF center. Patient(s) The study included 429 vitrified/warmed blastocysts with known implantation data, which were evaluated by time-lapse imaging. Blastocysts were routinely placed in EmbryoScope (Vitrolife) immediately after warming until transfer. Intervention…

Sperm cryopreservation in oncological patients: a 14-year follow-up study.

Objective Oncologic treatments can destroy spermatogenic dividing cells and cause azoospermia which could be irreversible. Sperm banking is the best option to preserve male fertility after these treatments. It is easy, inexpensive, and safe. To date, few clinical data are available about large series of cancer patients. Our objective was to determine the usefulness of these preventive sperm freezing protocols. Design Prospective study. Setting University-affiliated private fertility center. Patient(s) One hundred eighty-six cancer patients who banked sperm samples at our center before surgery or chemo- or radiotherapy treatments from 1991 to 2004. Intervention(s) Conjugal status, age, type …

The significance of sperm DNA oxidation in embryo development and reproductive outcome in an oocyte donation program: a new model to study a male infertility prognostic factor

Objective: One byproduct resulting from free radical damage is the DNA hydroxylation also known as DNA oxidation. Our aim with this work was to determine the relevance of sperm DNA oxidation on embryo quality in oocyte donation cycles. Design: We prospectively studied pairs of oocyte donation cycles, i.e., the same oocyte donors, donating to two recipients, where the only difference between the two treatments was the use of a different sperm sample. Setting: University-affiliated private IVF setting. Patient(s): Infertile male partners from couples undergoing oocyte donation cycles (n=38): 76 semen aliquots analyzed before and after semen processing by swim up. Intervention(s): None. Main O…

Increasing the probability of selecting chromosomally normal embryos by time-lapse morphokinetics analysis

Objective To study the differences in the cleavage time between chromosomally normal and abnormal embryos and to elaborate an algorithm to increase the probability of noninvasively selecting chromosomally normal embryos. Design Retrospective cohort study. Setting University-affiliated infertility center. Patient(s) Preimplantation genetic screening patients (n = 125; n=77 with ET), including cases of repeated implantation failure or recurrent miscarriage. A total of 504 embryos were analyzed. Intervention(s) Embryo culture within a time-lapse system. Main Outcome Measure(s) Kinetic variables included the time to 2 (t2), 3 (t3), 4 (t4), and 5 (t5) cells as well as the length of the second (c…

The use of morphokinetics as a predictor of embryo implantation.

Background Time-lapse observation presents an opportunity for optimizing embryo selection based on morphological grading as well as providing novel kinetic parameters, which may further improve accurate selection of viable embryos. The objective of this retrospective study was to identify the morphokinetic parameters specific to embryos that were capable of implanting. In order to compare a large number of embryos, with minimal variation in culture conditions, we have used an automatic embryo monitoring system. Methods Using a tri-gas IVF incubator with a built-in camera designed to automatically acquire images at defined time points, we have simultaneously monitored up to 72 individual emb…

The human first cell cycle: impact on implantation.

The morphology of fertilization events has been related to successful implantation by subjective criteria (pronuclei score, pronuclei symmetry and position). This work first described these events by time-lapse technology and then compared the timings of fertilization events (second polar body extrusion, first and second pronuclei appearance, abuttal and fading) in implanted versus nonimplanted embryos in a 2-year cohort retrospective study. A total of 1448 transferred embryos from 842 patients undergoing intracytoplasmic sperm injection with oocyte donation were monitored, 212 embryos from treatments where the number of gestational sacs matched the number of transferred embryos and 687 emb…

Prediction of embryo survival and live birth rates after cryotransfers of vitrified blastocysts

Which pre-vitrification parameters are the most predictive of survival and live birth in vitrified-warmed blastocyst transfer cycles?A retrospective study including 11,936 warmed blastocysts. Pre-vitrification morphological parameters analysed for blastocysts included day of vitrification; blastocyst expansion degree; trophoectoderm grade (A, B and C); and inner cell mass grade (A, B and C). Univariate and multivariate generalized estimating equations models were used to analyse survival, clinical pregnancy and live birth rate. A stepwise regression analysis was conducted to select and classify by order which outcomes were the most predictive.The odds of survival increased almost twice for …

Improvements achieved in an oocyte donation program over a 10-year period: sequential increase in implantation and pregnancy rates and decrease in high-order multiple pregnancies

Objective To compare outcome parameters and cumulative pregnancy rates (PRs) in oocyte donation cycles over a period of 10 years. Design Retrospective study. Setting University-affiliated assisted reproductive technology program. Patient(s) Women undergoing oocyte donation (10,537 cycles) between 1995 and 2005. Intervention(s) Ovarian stimulation and oocyte retrieval in donors. Embryo transfer performed in recipients after endometrial preparation. Main Outcome Measure(s) Outcome parameters and cumulative PRs were calculated and compared in relation to indication, age, and origin of sperm used. Result(s) Overall PR, implantation rate, clinical PR, and miscarriage rate per embryo transfer per…

MUCI, glycans and the cell-surface barrier to embryo implantation

As it approaches the maternal surface, the attaching embryo encounters the epithelial glycocalyx, which contains the mucin, MUC1. A high density of MUC1 at the cell surface can inhibit cell adhesion. This raises the possibility of the existence of a uterine barrier to implantation that might allow maternal rejection of poorer quality embryos. To investigate the mechanism of implantation, human embryos were incubated with endometrial epithelial monolayers. Hatched blastocysts were found to attach readily to the epithelial surface. MUC1 was lost from epithelial cells beneath and near to the attached embryo, while normal expression persisted in neighbouring cells.

Oocyte insemination techniques are related to alterations of embryo developmental timing in an oocyte donation model

Because of the different intrinsic characteristics of the classic IVF and intracytoplasmic sperm injection (ICSI) techniques, the timing of zygote development can be influenced by the method of fertilization. However, there is no information about the relevance of the insemination procedure on embryo-quality parameters as measured through their developmental dynamics. The aim of this work was to determine if the insemination technique, IVF or ICSI, influences embryo developmental kinetics by examining 1203 embryos from 178 couples undergoing oocyte donation with IVF or ICSI. Using time-lapse information, this work calculated several developmental kinetic variables, from pronuclear fading (P…

Robust Automated Assessment of Human Blastocyst Quality using Deep Learning

AbstractMorphology assessment has become the standard method for evaluation of embryo quality and selecting human blastocysts for transfer inin 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 cases may fail to accurately predict embryo implantation and live birth potential. Here we postulated that an artificial intelligence (AI) approach trained on thousands of embryos can reliably predict embryo quality without human intervention.To test this hypothesis, we implemented an AI approach based on deep neural networks (DNNs). Our approac…

Time-dependent O2 consumption patterns determined optimal time ranges for selecting viable human embryos.

Objective To evaluate correlations between metabolic activity and implantation potential of transferred embryos in a study based on oxygen (O 2 ) consumption (OC) measurements, because O 2 uptake is directly related to the capacity of an embryo to produce energy via adenosine triphosphate. Design Retrospective cohort study. Setting Infertility institute. Patient(s) Five hundred seventy-five injected oocytes in 56 first oocyte donation cycles with embryo transfer on day 3. Intervention(s) None. Main Outcome Measure(s) We analyzed embryo destination viability and implantation depending on the embryo OC rate obtained from 47,741 measurements (up to 85 measurements per embryo, 2–3 measurements …

Simultaneous determination in situ of DNA fragmentation and 8-oxoguanine in human sperm.

Deoxyribonucleic acid fragmentation and oxidative DNA damage were simultaneously determined in the same sperm cell, incubating with an 8-oxoguanine DNA probe on human spermatozoa processed by the sperm chromatin dispersion test. The assay was validated by incubation with agents that induce DNA fragmentation with or without oxidative base damage. In all samples examined, increased levels of 8-oxoguanine were present only in those spermatozoa with fragmented DNA, suggesting a link between both DNA damage types.

High progesterone levels in women with high ovarian response do not affect clinical outcomes: a retrospective cohort study

Background The potentially detrimental role of progesterone during the follicular phase has been a matter of controversy for several years; however, few studies have analyzed the effects of combined raised estradiol and progesterone levels on pregnancy outcomes. The aim of the present study was to determine the influence of high progesterone levels on clinical outcomes in the context of high ovarian response. Methods We performed a retrospective cohort study that included 2850 women classified as high responders. The women were subdivided into six groups depending on their progesterone concentration on the day of human chorionic gonadotropin (hCG) administration: 1.81 ng/ml (>p90). Ovarian …

Effect of oocyte vitrification on embryo quality: time-lapse analysis and morphokinetic evaluation.

To analyze whether oocyte vitrification may affect subsequent embryo development from a morphokinetic standpoint by means of time-lapse imaging.Observational cohort study.University-affiliated private IVF center.Ovum donation cycles conducted with the use of vitrified (n = 631 cycles; n = 3,794 embryos) or fresh oocytes (n = 1,359 cycles; n = 9,935 embryos) over 2 years.None.Embryo development was analyzed in a time-lapse imaging incubator. The studied variables included time to 2 cells (t2), 3 cells (t3), 4 cells (t4), 5 cells (t5), morula (tM), and cavitated, early, and hatching blastocyst (tB, tEB, tHB) as well as 2nd cell cycle duration (cc2 = t3 - t2). All of the embryos were classifie…

Paving the way for a gold standard of care for infertility treatment: improving outcomes through standardization of laboratory procedures.

Infertility affects over 70 million couples globally. Access to, and interest in, assisted reproductive technologies is growing worldwide, with more couples seeking medical intervention to conceive, in particular by IVF. Despite numerous advances in IVF techniques since its first success in 1978, almost half of the patients treated remain childless. The multifactorial nature of IVF treatment means that success is dependent on many variables. Therefore, it is important to examine how each variable can be optimized to achieve the best possible outcomes for patients. The current approach to IVF is fragmented, with various protocols in use. A systematic approach to establishing optimum best pra…

Female obesity impairs in vitro fertilization outcome without affecting embryo quality.

Objective To compare embryo quality and reproductive outcome in our IVF program according to the women's body mass index (BMI). Design Retrospective study. Setting University-affiliated infertility clinic, between January 2001 and April 2007. Patient(s) Women undergoing a total of 6,500 IVF–intracytoplasmic sperm injection (ICSI) cycles. Intervention(s) Six thousand five hundred IVF-ICSI cycles were included and divided into four groups: lean ( 2 ; n=1,070; 16.5%); normal (20–24.9 kg/m 2 ; n=3,930; 60.5%); overweight (25–29.9 kg/m 2 ; n=1,081; 16.6%); and obese (≥30 kg/m 2 ; n=419; 6.4%). Main Outcome Measure(s) Comparison of embryo quality and reproductive outcome (implantation, pregnancy,…

What else can we do? The latest attempt to improve the sperm's path